Evidence Report/Technology Assessment

Number 73

Criteria for Determining Disability in Infants 

and Children: Short Stature

Prepared for: 

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

2101 East Jefferson Street

Rockville, MD 20852

www.ahrq.gov

Contract No. 290-97-0019

Prepared by:

Tufts-New England Medical Center EPC, Boston, MA

Investigators

Patricia Wheeler, MD

Karen Bresnahan, MD

Barbara Shephard, MD

EPC Staff

Joseph Lau, MD, Director

Ethan Balk, MD, MPH, Project Leader

Deirdre DeVine, M Litt, Project Manager

Mei Chung, MPH, Research Associate

Kimberly Miller, BA, Research Assistant

AHRQ Publication No. 03-E025

March 2003
This report may be used, in whole or in part, as the basis for development of clinical practice 

guidelines and other quality enhancement tools, or a basis for reimbursement and coverage 

policies. AHRQ or U.S. Department of Health and Human Services endorsement of such 

derivative products may not be stated or implied.

AHRQ is the lead Federal agency charged with supporting research designed to improve the 

quality of health care, reduce its cost, address patient safety and medical errors, and broaden access 

to essential services. AHRQ sponsors and conducts research that provides evidence-based 

information on health care outcomes; quality; and cost, use, and access. The information helps 

health care decisionmakers—patients and clinicians, health system leaders, and policymakers—

make more informed decisions and improve the quality of health care services.
ii

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

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Suggested Citation:

Wheeler P, Balk E, Cole C, et al. Criteria for Determining Disability in Infants and Children: 

Short Stature. Evidence Report/Technology Assessment No. 73 (Prepared by Tufts-New 

England Medical Center Evidence-based Practice Center under Contract No. 290-97-0019). 

AHRQ Publication No. 03-E025. Rockville, MD: Agency for Healthcare Research and Quality. 

March 2003.
iii

Preface

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. The reports and assessments provide organizations 

with comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director, 

Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 

6010 Executive Blvd., Suite 300, Rockville, MD 20852.

Carolyn M. Clancy, M.D.

Director

Agency for Healthcare Research and Quality

Jean Slutsky, P.A., M.S.P.H.

Acting Director, Center for Practice and 

 Technology Assessment 

Agency for Healthcare Research and Quality

The authors of this report are responsible for its content. Statements in the report 

should not be construed as endorsement by the Agency for Healthcare Research and 

Quality or the U.S. Department of Health and Human Services of a particular drug, 

device, test, treatment, or other clinical service.
iv
v

Structured Abstract

Objectives. The evidence report provides a systematic review of the scientific evidence to 

answer three questions of whether short stature in a child 1) due to a medically determinable 

cause or 2) due to skeletal dysplasia may be associated with disability, and 3) whether decreasing 

growth velocity in a child with a chronic disease may serve as an indicator of severity of the 

disease.

Search Strategy. Systematic searches were performed for relevant articles in MEDLINE® from 

1966 through February 2001, with updates through October 2001. Additional studies were 

identified from other databases, reference lists of review and primary articles, and from domain 

experts.

Selection Criteria. Eligibility criteria for study inclusion included: primary articles reporting 

original data on at least 10 children; in studies of children with short stature, data on association 

between height and functional ability or limitation; in studies of children with chronic diseases, 

association between a measure of severity of disease and either height or height velocity. Studies 

could be cross-sectional or longitudinal, prospective or retrospective, comparative or not.

Main Results. A total of 13,537 English language citations were reviewed. Of these, 825 articles 

were reviewed for inclusion. For Question 1, 31 studies met inclusion criteria; for Question 2, 31 

studies; and for Question 3, 53 studies. Detailed data extraction was performed on these 115 

studies. 

Based on the reviewed articles, no severe functional limitations were found in children with 

short stature due to isolated short stature, growth hormone deficiency, multiple hormone 

deficiency, Turner syndrome, or Russell-Silver syndrome. The studies reviewed focused on 

intelligence, academic achievement, behavior, visual-motor perception, and psychomotor 

development. In each of these categories, children with short stature either had testing that was 

not significantly different from the controls or from the population mean, or if the testing were 

significantly poorer, it was generally within 1 standard deviation (SD) of the population mean. 

Based on the articles reviewed, children with skeletal dysplasias were not at increased risk of 

having severe impairments in intelligence, academic achievement, or psychological outcome. 

There was an increased risk for delay in achievement of motor skills in children with 

achondroplasia and osteogenesis imperfecta, and decreased ambulation, range of motion and 

mobility in children with more severe forms of osteogenesis imperfecta. The results for hearing 

impairment, respiratory dysfunction and spinal curvature appear to indicate an increased risk for 

impairment in these three areas, but the studies were limited in the number of children evaluated 

and how the samples were selected.

The evidence from four conditions (congenital heart disease, juvenile rheumatoid arthritis, 

Crohn’s disease and human immunodeficiency virus (HIV) infection) appear to indicate that a 

sustained decrease in linear growth velocity can be used as a marker of the severity of these 

underlying conditions. Evidence is less clear for asthma, atopic dermatitis, diabetes, ßthalassemia, and chronic kidney disease. There was only one study each for sickle cell disease, 

congenital adrenal hyperplasia and cerebral palsy so it is difficult to draw conclusions for these 

conditions. No study addressed whether the process of having a decreasing height velocity was 

likely to be disabling.
vi

Conclusions. No severe functional limitations were found in children with short stature due to 

growth hormone deficiency, multi-hormone deficiency, Turner syndrome, Russell-Silver 

syndrome or isolated short stature. These children generally scored within 1 SD of the population 

mean. Children with skeletal dysplasias were not at increased risk of having severe impairments 

in intelligence, academic achievement, or psychological outcome. Sustained decrease in linear 

growth velocity has been shown to be associated with the severity of congenital heart disease, 

juvenile rheumatoid arthritis, Crohn’s disease, and HIV.
vii

Contents

Summary........................................................................................................................................ 1

Evidence Report

Chapter 1. Introduction.................................................................................................................. 15

Scope of the Problem............................................................................................................... 15

Causes of Short Stature in Children.......................................................................................... 15

 Definition of Disability........................................................................................................ 16

 Evaluation of Children With Short Stature Due to a Medically Determinable Cause.........17

 Evaluation of Children With Short Stature Secondary to a Skeletal Dysplasia.................. 17

 Evaluation of Children With Decreased Growth Velocity Secondary to Chronic Disease. 18

Chapter 2. Methodology.................................................................................................................19

Key Questions Addressed by the Evidence Report...................................................................19

 Question 1. Definition of Short Stature as a Result of Medically Determinable 

Impairment............................................................................................. 20

 Question 2. Definition of Short Stature as a Result of Skeletal Dysplasia......................... 20

 Question 3. Chronic Disease and Linear Growth Velocity..................................................20

Search Strategies....................................................................................................................... 21

Study Selection......................................................................................................................... 21

Data Abstraction....................................................................................................................... 21

Summary Tables....................................................................................................................... 22

 Study Quality...................................................................................................................... 22

 Applicability....................................................................................................................... 23

 Study Size............................................................................................................................23

 Results.................................................................................................................................

Limitations................................................................................................

23

24

Chapter 3. Results.......................................................................................................................... 25

Search Results........................................................................................................................... 25

 Evidence Found Regarding Key Questions.............................................................................. 25

 Question 1. Is Short Stature as a Result of a Medically Determinable Impairment 

Associated With Severe Functional Limitations, According to, But Not Limited to, 

SSA’s Definition of Disability?.......................................................................................... 25

 Question 2. What is the Evidence That Short Stature Due to a Skeletal Dysplasia is

Disabling According to, But Not Limited to, SAA’s Definition of Disability? If So, 

Are Children Disabled by Virtue of Their Size or Other Features of Their Conditions?... 41

 Question 3. What is the Evidence That a Sustained Decrease in Linear Growth Velocity 

Can Be Used as a Marker of Severity of an Underlying Disease? Is Such a Process 

Likely To Be Disabling? ........................................................................... 62

Chapter 4. Conclusions.................................................................................................................. 83

Overview................................................................................................................................... 83
viii

 Question 1. Is Short Stature as a Result of a Medically Determinable Impairment 

Associated With Severe Functional Limitations, According to, But Not limited to, 

SSA’s Definition of Disability?.......................................................................................... 83

 Question 2. What is the Evidence That Short Stature Due to a Skeletal Dysplasia is 

Disabling According to, But Not Limited to, SSA’s Definition of Disability? If So, Are 

Children Disabled by Virtue of Their Size or Other Features of Their Conditions?.......... 85

 Question 3. What is the Evidence That a Sustained Decrease in Linear Growth Velocity 

Can Be Used as a Marker of Severity of an Underlying Disease? Is Such a Process 

Likely To Be Disabling?..................................................................................................... 88

 Limitations.......................................................................................................................... 91

Chapter 5. Future Research............................................................................................................ 93

 Questions 1 and 2........................................................................................

 Question 3.................................................................................................

93

93

References and Bibliography.......................................................................................................... 95

Evidence Tables

Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical 

Impairment..................................................................................................103

Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia............129

Evidence Table 3. Association of Decreased Growth Velocity With Severity of Disease.......163

Appendixes

Appendix A. Main Search Performed in MEDLINE®..............................................................229

Appendix B. Acronyms and Abbreviations.............................................................................. 231

Appendix C. Acknowledgements............................................................................................. 235

Tables

Table 1. Mean Academic Achievement Scores of Children With Short Stature Due to 

Medical Impairment................................................................................................ 26

Table 2. Mean Intelligence Quotients of Children With Short Stature Due to Medical 

Impairment.............................................................................................................. 30

Table 3. Association of Height to Visual-Motor Skills Among Children With Short 

Stature Due to Medical Impairment........................................................................37

Table 4. Association of Height to Psychomotor Development Among Children With 

Short Stature Due to Medical Impairment.............................................................. 38

Table 5. Association of Height to Teacher-Graded Behavior Problems Among Children 

With Short Stature Due to Medical Impairment..................................................... 39

Table 6. Academic Achievement Score of Children With Short Stature due to Skeletal 

Dysplasia................................................................................................................. 41
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Table 7. Intelligence Quotient of Children With Short Stature Due to Skeletal 

Dysplasia................................................................................................................. 43

Table 8. Visual Motor Skills in Children With Short Stature Due to Skeletal 

Dysplasia................................................................................................................. 45

Table 9. Motor Development in Children With Short Stature Due to Skeletal 

Dysplasia................................................................................................................. 45

Table 10. Motor Development Patterns in Children With Short Stature Due to Skeletal 

Dysplasia................................................................................................................. 45

Table 11. Neuromuscular Findings in Chldren With Skeletal Dysplasia............................... 48

Table 12. Ambulation/Mobility of Children With Short Stature Due to Skeletal 

Dysplasia..................................................................................... 50

Table 13. Limb Range of Motion in Children With Skeletal Dysplasia.................................54

Table 14. Spinal Curvature in Children With Skeletal Dysplasia...........................................55

Table 15. Heating Loss in Children With Short Stature Due to Skeletal Dysplasia...............57

Table 16. Sleep Apnea in Children With Short Stature Due to Skeletal Dysplasia................59

Table 17. Pulmonary Function in Children With Short Stature Due to Skeletal 

Dysplasia................................................................................................................. 60

Table 18. Psychological Outcomes in Chldren With Skeletal Dysplasia............................... 61

Table 19. Height Association With Severity of Asthma...........................................63

Table 20. Growth Retardation Association With Severity of Congenital Heart Disease....... 66

Table 21. Growth Retardation Association With Control/Severity of Insulin Dependent 

Diabetes Mellitus.................................................................................................... 69

Table 22. Growth Retardation Association With Hemoglobin Level/Severity of ßThalassemia.............................................................................................................71

Table 23. Growth Retardation Association With Severity of Inflammatory Bowel 

Disease.................................................................................................................... 73

Table 24. Growth Retardation Association With Subtypes/Severity of Juvenile 

Rheumatoid Arthritis...............................................................................................74

Table 25. Growth Retardation Association With Severity of Chronic Kidney Disease......... 76

Table 26. Growth Retardation Association With Severity of Human Immunodeficiency 

Virus........................................................................................................................79

Table 27. Growth Retardation Association With Severity of Atopic 

Dermatitis/Eczema.................................................................................................. 80

Table 28. Growth Retardation Association With Severity of Miscellaneous Chronic 

Diseases...................................................................................................................81
Overview

The Social Security Administration (SSA)

requested that the Agency for Healthcare

Research and Quality (AHRQ), through its

Evidence-based Practice Center (EPC) program,

provide a systematic review of the scientific

evidence about whether short stature in a child

due to a medically determinable cause may be

associated with disability, whether skeletal

dysplasias in a child may be considered a

disability, and whether decreasing growth

velocity in a child with a chronic disease may

serve as an indicator of severity of the disease.

The population of interest includes children age

17 years or younger, both male and female, of

all racial, ethnic, and socioeconomic groupings.

The evidence report was prepared to assist

SSA in updating its Listing of Impairments and

revising its disability policy, as may be

appropriate. 

Causes of Short Stature in

Children

There are multiple causes of short stature.

The most common causes are familial short

stature (FSS) and constitutional growth delay

(CGD). FSS occurs when a child has height

below the third percentile due to a genetic

tendency to short stature in his or her family.

Children with FSS typically reach adult height

consistent with their family background. CGD

occurs when a child is shorter than would be

expected by her or his genetic background and

no determinable medical cause of the short

stature can be found. Often children with CGD

experience a delayed onset of pubertal

development and usually obtain normal or near

normal adult height. Neither FSS nor CGD is

considered to be due to medically determinable

causes in most cases. Since it can be difficult to

differentiate between these two conditions, the

term isolated short stature (ISS), is often used

interchangeably for both FSS and CGD.

Medically determinable causes of short stature

include abnormalities in the growth hormone

axis such as decreased growth hormone

production and diminished response to growth

hormone. Other endocrine abnormalities such

as hypothyroidism and Cushing disease may

lead to short stature and a variety of genetic

disorders including chromosomal, metabolic,

and single gene disorders can also result in short

stature. 

Skeletal dysplasias are genetic disorders that

result in abnormal formation of part or all of the

skeleton. Not all skeletal dysplasia will result in

short stature. The skeletal dysplasias most likely

to lead to short stature are those that involve

formation and growth of the long bones and/or

the spine.

The presence of a chronic disease in a child

has long been known to be a risk factor for

decreased growth to a varying degree. However,

the underlying cause of the decreased growth

has not been determined in all chronic diseases. 

Reporting the Evidence

The following key questions were refined by

the EPC Evidence Review Team and technical

experts from those posed by the SSA.

Question 1. Is short stature (height < 5th

percentile) as a result of a medically

determinable impairment associated with severe

functional limitations, according to, but not

limited to, SSA’s definition of disability?

Question 2. What is the evidence that short

stature (height < 5th percentile) due to a skeletal

Evidence Report/Technology Assessment

Number 73

Criteria for Determining Disability in Infants and Children:

Short Stature

Summary

Agency for Healthcare Research and Quality

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service
dysplasia is disabling according to, but not limited to, SSA’s

definition of disability? If so, are children disabled by virtue of

their size or other features of their conditions?

Question 3. What is the evidence that a sustained decrease

in linear growth velocity can be used as a marker of severity of

an underlying disease? Is such a process likely to be disabling?

Methodology

Definition of Short Stature

A range of definitions of short stature among children

exists. In general, short stature has been defined as a height less

than the 3rd percentile. This corresponds to a value of 1.9

standard deviations below the mean height (which is

commonly rounded up to 2.0). However, many studies use a

variety of definitions including height less than the 5th and

10th percentiles (corresponding to 1.65 and 1.3 standard

deviations below the mean, respectively). The total number of

children who have short stature due to either a medically

determinable cause or a skeletal dysplasia as opposed to FSS

has not been reported. However, by definition, approximately

2.2 million American children have short stature (US Census,

2001).

Literature Search 

Systematic searches were performed for full journal articles

of original data. The primary search for the literature review

consisted of a MEDLINE® search from 1966 through

February 2001, with updates through October 2001.

Supplemental searches were also performed in ERIC, PsycInfo,

Healthstar and EMBASE. Additional studies were identified

from reference lists of review and primary articles, and from

domain experts.

Development of the search strategies was an iterative

process that included input from domain experts. Keywords

from known relevant studies were used to refine and focus the

final search strategies used. 

Study Selection

Including studies found from other sources, a total of

13,537 English language citations were reviewed. Screening of

the abstracts and titles identified 825 articles potentially useful

to address the three report questions. A set of minimum

inclusion criteria were used in this initial screening: primary

articles reporting original data on at least 10 children that

provided primary or secondary evaluation of growth failure

and had a primary or secondary outcome of a potential

functional limitation. Studies could be cross-sectional or

longitudinal, prospective or retrospective, comparative or not.

Summarizing the Literature

A total of 825 studies were retrieved for careful evaluation.

Detailed examination of these articles identified 31 studies

that met inclusion criteria for Question 1, 31 studies for

Question 2, and 53 studies for Question 3. Detailed data

extraction was performed on these 115 studies. 

Findings

Question 1. Is short stature (height < 5th percentile) as a

result of a medically determinable impairment associated

with severe functional limitations, according to, but not

limited to, SSA’s definition of disability? 

We reviewed 31 papers that provided information on

functional abilities among children with short stature due to

medically determinable impairments. A number of these

papers provided analyses from the same samples of children.

One study reported on different outcomes in two separate

papers. Therefore, 24 papers from 23 studies are summarized

here. Few studies explicitly examined functional impairment,

per se. Data are reported on the association of short stature

with academic achievement, intelligence, visual-motor skills,

psychomotor development, and teacher-graded behavior.

Fifteen of the 23 studies were prospective cross-sectional

studies; seven were prospective longitudinal studies; and one

was a retrospective longitudinal study. Two were of good

quality, eleven were of fair quality, and nine were of poor

quality. One study was of fair quality in its analysis of

intelligence, but of poor quality in its analysis of academic

achievement.

Based on the reviewed articles, no severe functional

limitations were found in children with short stature due to

growth hormone deficiency, multi-hormone deficiency, Turner

syndrome, Russell-Silver syndrome, or isolated short stature.

These specific causes of short stature were chosen because they

allowed us to isolate the effect of short stature and thus enable

us to determine if there was an increased risk for disability

related problems just due to short stature. The articles focused

on intelligence, academic achievement, behavior, visual-motor

perception, and psychomotor development. In each of these

categories, children with short stature either had testing that

was not significantly different from the controls or from the

population mean, or if the testing were significantly poorer it

was still for the most part within one standard deviation (SD)

of the population mean. 

Association of short stature with academic achievement.

Eleven studies evaluated academic achievement in

approximately 996 children with short stature as a result of a

medically determinable impairment. Five of the studies found

that children with short stature had academic achievement

scores at or above the population norm. The other six studies

found scores below the population norm but the great

majority was still within one SD of the mean. These results

imply that children with short stature do not have enough

difficulties with academic achievement to qualify as a

disability. A major limitation in five of the studies was the

exclusion of children with a low intelligence quotient (IQ). 

2
Association of short stature with intelligence. Twentyone studies evaluated IQ in approximately 1,156 children with

short stature as a result of a medically determinable

impairment. Fifteen studies found short stature children to

have IQs at or above the population mean, while the

remaining studies reported IQs for the most part less then one

SD below the mean. Three of the studies that found IQs at or

above the mean excluded children with low IQs. The studies

were limited by the IQ exclusion and also by an absence of a

control population in many of the studies. Future studies are

required to better delineate this question.

Association of short stature with visual-motor skills.

Only three studies involving 81 patients could be found that

evaluated visual-motor perception in children with short

stature. All three found significantly lower visual-motor skills

in the evaluated children. These studies, however, were limited

by their reporting of the data. Furthermore, it is not clear how

a decrease in visual-motor skill can be correlated with the SSA

definition of disability. Future studies are needed to evaluate

disabilities caused by functional limitations in visual-motor

skills.

Association of short stature with psychomotor

development. One poor quality study evaluated 14 children

with short stature due to Russell-Silver syndrome for

psychomotor development by the Denver Developmental

Screening Test. These children were found to have delays in

meeting their developmental landmarks. However, the value of

this finding in relation to disability is questionable since the

children did eventually meet their developmental landmarks

(e.g., walking). Future studies are needed to determine the

significance of these findings.

Association of short stature with behavior. Teacher-based

evaluation of behavior in children with short stature was

reported in five studies involving 274 children. In general,

behavior in the children with short stature was not

significantly different from the controls. Exceptions to this

were increased hyperactivity reported in one study, increased

locus of control in another study, and general increased

behavior problems in a third study. It is difficult to extrapolate

behavior in general from these studies since they tended to use

different tests, and the test results do not always overlap. In

addition, sub-group results were not given for each study.

Furthermore, the value of behavioral impairments for

determining a child’s level of disability is questionable. Further

studies are needed that evaluate large groups of non-selected

short stature children, use the same behavior-based test,

compare results to matched controls, and determine likelihood

of disability.

Question 2. What is the evidence that short stature

(height < 5th percentile) due to a skeletal dysplasia is

disabling according to, but not limited to, SSA’s definition

of disability? If so, are children disabled by virtue of their

size or other features of their conditions?

There were 31 papers from 25 study groups that provided

information on functional abilities among children with short

stature due to skeletal dysplasia. Of the studies, 22 were

prospective cross-sectional studies; 5 were prospective

longitudinal studies; 2 were retrospective longitudinal; and 2

were retrospective cross-sectional. One was of good quality, 16

were of fair quality, and 12 were of poor quality. One study

was of good quality in its analysis of academic achievement,

but of fair quality in its analysis of ambulation and mobility.

One study was of fair quality in its analysis of neuromuscular

function and range of motion, but of poor quality in its

analysis of ambulation and mobility.

Based on the articles reviewed, children with skeletal

dysplasias were not at increased risk of having severe

impairments in intelligence, academic achievement, or

psychological outcome. There was an increased risk for delay

in achievement of motor skills in children with achondroplasia

and osteogenesis imperfecta, and decreased ambulation, range

of motion, and mobility in children with more severe forms of

osteogenesis imperfecta. The results for hearing impairment,

respiratory dysfunction, and spinal curvature appear to

indicate an increased risk for impairment in these three areas,

but the studies were limited in the number of children

evaluated and how the samples were selected, thus making it

difficult to arrive at a definitive conclusion in these areas.

Association with academic achievement. Three studies

examined academic achievement among 84 children with

achondroplasia or osteogenesis imperfecta. In two studies,

achondroplasia patients scored lower than control groups, yet

remained in the normal range. Further studies on this issue are

needed to evaluate a larger population of children with

achondroplasia, osteogenesis imperfecta, and other types of

skeletal dysplasias.

Association with intelligence. Five studies with 116

children evaluated intelligence in children with

achondroplasia, osteogenesis imperfecta, and other skeletal

dysplasias. No evidence of significantly impaired intelligence

was found in any of the skeletal dysplasias by intelligence

testing with all scores either above the population norm or

within 0.5 SD of the norm. These studies were generally small

for the comparisons made. Further studies on this issue are

needed to evaluate a larger population with skeletal dysplasias

clearly defined by up-to-date standards.

Association with psychomotor development. Six studies

involving a total of 196 children found generally delayed

achievement of psychomotor abilities or development in

children with achondroplasia and osteogenesis imperfecta.

Each group evaluated was small, used different testing

instruments, and had varying ages of subjects. Furthermore,

none was followed longitudinally. Clinically useful conclusions

about ultimate motor function in children with skeletal

dysplasias cannot be made from these studies. Larger,

longitudinal studies are needed that test psychomotor

functional abilities.

3
Association with neuromuscular function. From review of

the available literature, children with short stature due to

various skeletal dysplasias appear to be at risk for

neuromuscular abnormalities. Six studies with 185 children

evaluated neuromuscular function in children with skeletal

dysplasias. The four studies that looked solely at children with

achondroplasia found varied abnormalities. The three that

measured strength found substantial weakness and hypotonia.

Asymmetry, sensory deficits, poor coordination, and seizures

were found in frequencies higher than controls or than are

expected in the healthy population. All studies highlighted the

significant risk of often occult cervical cord compression in

these young children. The one paper that evaluated

osteogenesis imperfecta found substantial muscle weakness in

children who are moderately to severely affected by their

disease. The one paper that reviewed other skeletal dysplasias

found cervical cord complications in children with Morquio

disease. Further studies of children with skeletal dysplasias,

especially achondroplasia, are needed to better delineate the

extent of neuromuscular impairment.

Association with ambulation and mobility. Of the eight

papers considering ambulation and mobility in children

(N=345) with short stature due to skeletal dysplasia, all

considered children with osteogenesis imperfecta. All found

significant impairment in ambulation, with greater

impairment, as expected, in patients with more severe disease.

Children with the less severe types of osteogenesis imperfecta

(tarda, Type I, Type IV) were more likely to attain some

walking capability, although a substantial proportion of these

children did require assistance. Orthopedic abnormalities such

as scoliosis, decreased range of motion, decreased muscle

strength, and fracture contribute to limitations of ambulation.

All of the studies were of small size; although given the rarity

of osteogenesis imperfecta, the studies were of reasonable size.

Definitions of levels of ambulation were consistent and fairly

objective. Studies of ambulation and mobility disabilities are

necessary for children with skeletal dysplasias other than

osteogenesis imperfecta.

Association with limb range of motion. Two studies

evaluated upper and lower range of motion (ROM)

abnormalities in children with various types of osteogenesis

imperfecta (N=40) and with achondroplasia (N=41).

Decreased ROM was found in children with osteogenesis

imperfecta, but no such correlation was seen in children with

achondroplasia. Decreased lower extremity ROM may impact

on ability to independently ambulate. Decreased upper

extremity ROM may limit an individual’s independence by

reducing his or her ability to engage in self-care. Further

studies are necessary to better delineate the connection

between limb ROM and various skeletal dysplasias.

Association with spinal curvature. Four papers assessed

spinal deformities in 209 children with short stature due to

skeletal dysplasia. Three studied children with osteogenesis

imperfecta, and one studied children with diastrophic

dysplasia. A high prevalence of scoliosis was found in children

with both conditions. One study also found a high prevalence

of pathologic kyphosis. All studies, however, likely represent a

selected, perhaps more severe, population of patients followed

by academic medical centers. Thus to find prevalence in the

general population of individuals with skeletal dysplasias, it

will be necessary to evaluate scoliosis and kyphosis in a group

of unselected individuals with skeletal dysplasias.

Association with hearing loss. Of the six studies that

reported on hearing loss in 151 children with skeletal

dysplasia, only three performed objective hearing testing. All

papers that reported actual hearing testing in young

osteogenesis imperfecta patients reported a sizable proportion

with hearing loss, although the prevalence varied due to

selection and cohort size differences. Subjective reports of

hearing problems in achondroplasia patients were common.

However, one study found no difference in self-reported

hearing function between children with a mix of skeletal

dysplasias, including achondroplasia, and control children. The

available literature supports that children with at least some

skeletal dysplasias, specifically achondroplasia and osteogenesis

imperfecta, are at risk for hearing problems. Further studies

with a larger, unselected population of children with skeletal

dysplasia are needed to better define the extent, severity, and

type of hearing loss. 

Association of short stature with respiratory

dysfunction. Of the four papers evaluating sleep and

respiratory dysfunction in 94 children with achondroplasia, all

found a high incidence of abnormality, including central

hypopnea, central apnea, and obstructive apnea. All four

papers, however, reported on small numbers of children. Two

of the groups contained patients referred for their respiratory

or neurologic symptoms, and therefore may not represent the

general achondroplasia population. Further studies that look at

larger groups of non-selected achondroplasia patients are

needed to define the prevalence of apnea in this population.

Little information on pulmonary function in children with

skeletal dysplasia was found. One group found abnormal

pulmonary function in a small group of children with

achondroplasia, and one found no significant abnormality in a

smaller group of children with osteogenesis imperfecta. More

data are required before meaningful conclusions can be drawn.

Association of short stature with psychological

outcomes. Only one paper adequately studied the association

of short stature due to skeletal dysplasia with psychological

outcomes. The study found no evidence for increased rates of

depression or anxiety in children with skeletal dysplasia.

Further studies that evaluate psychological problems such as

depression and anxiety are needed to validate these results.

Question 3. What is the evidence that a sustained decrease

in linear growth velocity can be used as a marker of

severity of an underlying disease? Is such a process likely to

be disabling?

We reviewed 53 articles that evaluated whether a sustained

decrease in linear growth velocity can be used as a marker of

4
5

the severity of 12 medical conditions and whether such a

process is likely to be disabling. One study separately evaluated

children with both asthma and congenital heart disease. The

evidence from four conditions—congenital heart disease,

Crohn’s disease, juvenile rheumatoid arthritis, and human

immunodeficiency virus (HIV) infection—appears to indicate

that a sustained decrease in linear growth velocity can be used

as a marker of the severity of these underlying conditions.

Evidence is less clear for asthma, diabetes, β-thalassemia,

chronic kidney failure, and atopic dermatitis. There was only

one study each for cerebral palsy, sickle cell anemia, and

congenital adrenal hyperplasia, so it is difficult to draw

conclusions for these conditions. None of the studies

addressed the question of whether the process of having a

decreasing linear growth velocity was likely to be disabling.

Association of severity of asthma. Eleven studies evaluated

the association between severity of asthma and height or

height velocity in 3,778 children. Overall, the studies did not

find a consistent result. Six of the studies found no association

between severity of asthma and growth retardation. No study

found an association between mild asthma and growth

retardation.

Studies were limited by poorly defined samples, limited data

and analysis, missing data and, frequently, by the fact that

severity of disease was measured by steroid treatment. These

studies do not clearly provide evidence that a sustained

decrease in linear growth velocity can be used as a marker of

severity of asthma or whether a decrease in growth velocity is

likely to be disabling. Future well-designed studies are needed.

Congenital heart disease. Six studies evaluated the

association between severity of congenital heart diseases and

height or height velocity in 1,784 children. Many studies were

limited by incomplete data and statistical analysis and some

studies were limited because they excluded children with the

most severe congenital cardiac defects. Given the limitations,

the results do suggest that height and height velocity

retardation is seen in children with severe congenital heart

defects and may be a marker for more severe disease. Whether

the decrease in height or height velocity in itself is disabling is

not answered.

Insulin-dependent diabetes mellitus. Eleven studies

involving 1,099 children evaluated the relationship between

growth retardation and control or severity of insulindependent diabetes mellitus. Overall, the studies showed

mixed results with five studies demonstrating a positive

relationship between poor diabetes control or increased

severity of disease and decreased growth velocity. Several

studies associated growth deceleration with peripubertal onset

of illness. Some studies were limited because they did not use a

well-defined, objective measure, such as glycohemoglobin

(Hgb A1c), to assess severity or control. Some studies were

limited by unclear statistical analysis, lack of specific data

included, or summary results. These studies did not find clear

evidence that a sustained decrease in linear growth velocity can

be used as a marker of severity of diabetes or whether a

decrease in linear growth velocity is in itself disabling. Further

prospective, longitudinal studies of the linear growth of

children with diabetes mellitus, using objective measures of

control like Hgb A1c, are needed to clarify whether a decrease

in linear growth velocity may be a marker for severity of

disease. 

β-Thalassemia. There were three studies involving 295

children that evaluated the relationship between growth

retardation and severity of anemia in β-thalassemia. One study

showed a relationship between increased severity of anemia

and reduced height, and one study showed a trend toward

increased severity of disease and decreased growth. The studies

were limited by incomplete data reporting and by inconsistent

definitions of severity. These studies do not show clear

evidence that a sustained decrease in linear growth velocity can

be used as a marker of the severity of the disease. Prospective

longitudinal cohort studies with clear definitions of severity

(i.e., hemoglobin levels) and measurements of height velocity

may answer the question. 

Inflammatory bowel disease. There were three studies

involving 660 children that evaluated the relationship between

growth retardation and the severity of inflammatory bowel

disease. Two studies included only children with Crohn’s

disease. The other two studies included children with both

Crohn’s disease and ulcerative colitis. Disease severity was

associated with height velocity among children with both

Crohn’s disease and ulcerative colitis; however, height was not

significantly associated with disease severity in any study.

There are no data presented to suggest that the process of

growth failure is likely to be disabling. Further prospective

longitudinal studies that include larger numbers of patients

who have ulcerative colitis and Crohn’s disease, and that

compare both with population standards and with each other,

may clarify whether growth retardation is a marker associated

with severity of all inflammatory bowel diseases, or is related

to one in particular.

Juvenile rheumatoid arthritis. Three studies involving 153

children evaluated the relationship between growth retardation

and the subtypes or severity of juvenile rheumatoid arthritis.

All studies indicated an association between decreased growth

velocity and increased severity of the disease. One study noted

that height velocity normalized after the first year of treatment.

The studies were limited in two cases by excluding children

with the most severe disease, by incomplete statistical analyses

in one, and by poorly defined outcomes in another. With

these caveats, the studies suggest that a decrease in linear

growth velocity is associated with more severe disease and may

serve as a marker of severity of the underlying disease. There

are no data reported addressing the question of whether

decreased growth velocity is in itself disabling. Future welldesigned studies with broad inclusion criteria are needed to

clarify the issue.

Chronic kidney disease. Ten studies involving 684

children evaluated the relationship between growth retardation

and severity of chronic kidney disease. Eight of the studies
6

found a positive relationship between increased severity of

kidney failure and decreased height or height velocity. Single

studies of sub-populations of children with autosomal recessive

polycystic kidney disease (ARPKD) and very young children

with chronic kidney disease found no association of disease

severity with height velocity. There was conflicting evidence

about the role of steroid use in causing growth retardation.

Some studies were limited by using a severity marker other

than glomerular filtration rate, by small sample sizes, or by

incomplete data reporting. Overall, the studies suggest that a

decrease in linear growth velocity is associated with the severity

of the underlying disease but this finding was not universal.

No data were available to assess if a decreased height velocity is

in itself disabling. Additional prospective, longitudinal studies

that evaluate whether a decrease in linear growth velocity can

be used as a marker of severity of underlying kidney disease are

needed.

Human immunodeficiency virus infection. There were

two studies evaluating the relationship between growth

retardation and progression to disease in 60 HIV-positive

children. Both studies found that linear growth retardation is a

marker for progression to active disease in HIV-positive

children and linear growth deceleration may precede the onset

of symptoms of active disease. These studies were limited by

incomplete data reporting and poorly defined methods,

predictors, and outcomes. Despite the limitations, the studies

do indicate that a sustained decrease in linear growth velocity

is a marker for progression from seropositive status to active

disease. No data were included that assess whether a decreased

linear growth velocity is in itself likely to be disabling. Larger,

prospective, longitudinal studies of the relationship between

decreasing linear growth velocity and progression of disease

could confirm the usefulness of decreased linear growth

velocity as a marker for increasing severity of disease.

Atopic dermatitis. Two studies involving 148 children

evaluated the relationship between growth retardation and

severity of atopic dermatitis. The studies reported conflicting

results with one study reporting a positive association between

increased severity and decreased height and the other study

showing no association between increased severity and

decreased height or height velocity. In the first study the more

severely affected group had higher steroid use and some used

systemic steroids. In the second study, those using systemic

glucocorticoids were excluded from analysis. This study was

also limited by a failure to report complete results and a failure

to report statistical analyses. These studies do not clearly

provide evidence that a sustained decrease in linear growth

velocity is a marker for the severity of the underlying disease.

No data were provided that look at whether the process of a

decreasing linear growth velocity is in itself disabling. Further

prospective longitudinal studies are needed to clarify whether

growth velocity is affected by the severity of atopic dermatitis,

or whether the apparent effect is related to steroid treatment.

Cerebral palsy. There was only one study with 81 subjects

that looked at the relationship between growth retardation and

cerebral palsy. The study did not find a significant association

between the type of cerebral palsy and decreased growth

velocity but cognitive impairment, and non-ambulatory status

were associated with decreased growth velocity. This suggests

that those more severely affected by both motor and nonmotor neurological deficits have decreased growth velocity.

This study was limited by the exclusion criteria, which likely

excluded the most severely affected children. No data were

presented to answer the question about whether the process of

having a decreasing linear growth velocity is in itself disabling.

Further prospective longitudinal studies of children with

varying severity of cerebral palsy are needed to confirm

whether a decreasing linear growth velocity is a marker for the

severity of the underlying disorder. 

Sickle cell disease. There was only one study with 24

subjects that evaluated the association of growth retardation

with the severity of sickle cell disease. That study found a

positive association between severe sickle cell disease (measured

by need for transfusions and the number of crises) and

decreased height percentile compared to controls. The study

was small and did not explicitly compare less severe sickle cell

disease to more severe disease. The study also did not look at

height velocity as a predictor of more severe disease. Further

prospective longitudinal studies that compare larger numbers

of patients with mild, moderate, and severe sickle cell disease

are needed to determine if a decreasing linear growth velocity

can serve as a marker for the severity of the underlying disease.

Congenital adrenal hyperplasia. There was only one study

with 9 subjects that looked at the relationship between growth

retardation and congenital adrenal hyperplasia. It did not find

an association between number of escapes (more severe

disease) and decreased growth velocity. The study was limited

by its small size and by its reporting of results in graphic form

only. There is not clear evidence that a decreasing linear

growth velocity can be used as a marker for the underlying

severity of congenital adrenal hyperplasia. No data were

presented that look at whether the process of a decreasing

linear growth velocity is in itself disabling. Further prospective

longitudinal studies of larger numbers of patients with

congenital adrenal hyperplasia are needed to answer the

question of whether decreasing linear growth velocity can be

used as a marker for severity of the underlying disease.

Limitations 

There were several limitations encountered in evaluating

Questions 1 and 2. Very few studies looked specifically at

disability as defined by SSA. Most studies in fact were looking

at functional ability such as IQ or academic achievement. Such
areas are focused on in the published literature because they

allow for acquisition of data that can be compared to

published norms. Results from such studies have to be

extrapolated to determine if the children evaluated meet the

SSA definition of disability. For example, one SSA criterion of

disability includes acquiring and using information. Reduced

IQ in a child may lead to limitations in acquiring or using

information, but there is not a linear relationship between

decreased IQ and reduced ability to acquire and use

information. Even those studies that evaluated functional

impairment, such as those that evaluated inability or limitation

of walking, do not necessarily correlate directly with SSA’s

definitions of disability.

One limitation to evaluating Question 3 relates to

difficulties in trying to correlate the severity of disease with

decreasing growth velocity. Frequently a report that details

height in a specific disorder does not directly correlate this

with severity of disease. Also the way in which severity of

disease was reported may vary between reports discussing the

same disease. The same problem was seen with reporting of

growth data, which is given in a variety of different formats

(e.g., one-time height, growth velocity, and standard deviation

from the mean). This makes it more difficult to determine the

overall validity of the results. 

Future Research

Further research is needed to better define the relationships

both between short stature and disability and between growth

velocity and severity of chronic disease. Research on disability

should focus on functional deficits rather than functional

ability. Studies that examine physical limitations directly

related to short stature are needed. Further prospective

longitudinal studies of growth velocity in chronic disease are

needed. Studies are needed of children of various ages,

including puberty. Studies need to clearly define severity of

disease and avoid confounding severity with treatment options.

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for AHRQ by Tufts-New England Medical

Center Evidence-based Practice Center under Contract No.

290-97-0019. It is expected to be available in spring 2003.

At that time, printed copies may be obtained free of charge

from the AHRQ Publications Clearinghouse by calling 800-

358-9295. Requesters should ask for Evidence

Report/Technology Assessment No. 73, Criteria for

Determining Disability in Infants and Children: Short Stature.

Internet users will be able to access the report online through

AHRQ’s Web site at www.ahrq.gov.

7
AHRQ Pub. No. 03-E025

March 2003

ISSN 1530-440X
15

Chapter 1. Introduction

The Social Security Administration (SSA) of the Department of Health and Human Services 

requested that the Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based 

Practice Center (EPC) program, provide the scientific basis for SSA to determine disability claims for 

children with short stature, with skeletal dysplasias, and with chronic disease in which decreasing growth 

velocity may be a component. This evidence report is prepared to assist SSA in updating its Listing of 

Impairments and revising its disability policy, as may be appropriate. 

This report summarizes the scientific evidence about whether short stature in a child due to a 

medically determinable cause may be associated with disability, whether skeletal dysplasias in a child 

may be considered a disability, and whether decreasing growth velocity in a child with a chronic disease 

may serve as an indicator of severity of the disease. The population of interest includes children age 17 

years or younger, both male and female, of all racial, ethnic and socioeconomic groupings.

Scope of the Problem

A range of definitions of short stature among children exists. In general, short stature has been 

defined as a height less than the 3rd percentile (Plotnick, 1990). This corresponds to a value of 1.9 

standard deviations below the mean height (which is commonly rounded up to 2.0). However, many 

studies use a variety of definitions including height less than the 5th and 10th percentiles (corresponding 

to 1.65 and 1.3 standard deviations below the mean, respectively). The total number of children who 

have short stature due to either a medically determinable cause or a skeletal dysplasia as opposed to 

familial short stature has not been reported. However, by definition, approximately 2.2 million American 

children have short stature (US Census, 2001). 

Causes of short stature in children

There are multiple causes of short stature. The most common causes are familial short stature (FSS) 

and constitutional growth delay (CGD). FSS occurs when a child has height below the third percentile 

due to a genetic tendency to short stature in his or her family (Mahoney, 1987). Children with FSS 

typically reach adult height consistent with their family background. CGD occurs when a child is shorter 

than would be expected by her or his genetic background and no determinable medical cause of the 

short stature can be found. Often children with CGD experience a delayed onset of pubertal 

development and usually obtain normal or near normal adult height (Plotnick, 1990). Neither FSS nor 

CGD is considered to be due to medically determinable causes in most cases (Attie, 2000). Since it can 

be difficult to differentiate between these two conditions, the term isolated short stature (ISS), is often 

used interchangeably for both FSS and CGD.

Medically determinable causes of short stature include abnormalities in the growth hormone axis 

such as decreased growth hormone production and diminished response to growth hormone. Other 

endocrine abnormalities such as hypothyroidism and Cushing disease may lead to short stature (Bacon, 

Spencer, Hopwood, et al., 1990). A variety of genetic disorders including chromosomal disorders, 
16

metabolic disorders and single gene disorders can also result in short stature (Bacon, Spencer, 

Hopwood, et al., 1990). 

Skeletal dysplasias are genetic disorders that result in abnormal formation of part or all of the 

skeleton. Not all skeletal dysplasia will result in short stature. The skeletal dysplasias most likely to lead 

to short stature are those that involve formation and growth of the long bones and/or the spine. The 

most common skeletal dysplasias that typically result in short stature include achondroplasia, 

hypochondroplasia, and osteogenesis imperfecta (Taybi and Lachman, 1996). There are more than 200 

described skeletal dysplasias, many of which may lead to short stature, but each of these conditions 

individually is quite rare (Online Mendelian Inheritance in Man, 2002). 

The presence of a chronic disease in a child has long been known to be a risk factor for decreased 

growth to a varying degree (Plotnick, 1990). However, the underlying cause of the decreased growth 

has not been determined in all chronic diseases. Diseases that affect a child’s nutritional status 

(inflammatory bowel disease, celiac disease) may lead to a decrease in growth velocity secondary to 

caloric and general nutritional insufficiency (Kelts, Grand, Shen, et al., 1979; Oliva and Lake, 1996). 

Other diseases such as asthma, which do not appear to directly affect nutritional status, have also been 

reported to lead to decreased growth velocity (Abrams, 2001). 

Definition of Disability

The definition of disability in children used for the purposes of this report came from the SSA and 

was based on a definition passed by Congress in 1996. Under Title XVI, a child under age 18 years 

will be considered disabled if he or she has a medically determinable physical or mental impairment or 

combination of impairments that causes marked and severe functional limitations, and that can be 

expected to cause death or that has lasted or can be expected to last for a continuous period of not less 

than 12 months (Disability evaluation under Social Security, 1999). 

Specific areas of functioning include: 1) acquiring and using information, 2) attending and completing 

tasks, 3) interacting and relating with others, 4) moving about and manipulating objects, 5) caring for 

yourself, 6) health and physical well-being. Disability is based on the degree to which the above 

functions are interfered with. Disability is established if there are marked limitations in at least two areas 

or there is an extreme limitation in one area of functioning. Where standardized tests of function exist, 

the regulations define a “marked” degree of functional limitation as more than two but less than three 

standard deviations below the mean and an “extreme” limitation as three or more standard deviations 

below the mean. (Disability evaluation under Social Security, 1999).

However, SSA’s definition of disability is an administrative one, which is not commonly used by 

clinicians or researchers. In general, disability is defined differently by different researchers for different 

diseases. Furthermore, studies of children with short stature frequently focus on differences of ability, 

rather than on disability per se. Thus, any analysis of the literature to evaluate disability for SSA will be 

limited by the fact that few studies have primary analyses of disability that correspond to SSA’s 

definition.

Evaluation of children with short stature due to a medically 

determinable cause
17

The evaluation of the association of short stature due to medically determinable causes with 

disability is complicated by the fact that it is often hard to distinguish whether the disability is due directly 

to short stature or to the underlying medical problem. As an example, Turner syndrome, which is caused 

by the absence of part or all of one X chromosome in a female, results in short stature in the majority of 

girls affected. These girls often have difficulties in visual-spatial relationships, but these difficulties are 

believed to be secondary to their genetic defect and not related to their short stature (Ross, Stefanatos, 

Roeltgen, et al., 1995). Similarly in Down syndrome, which is caused by chromosome 21 trisomy, 

children generally have short stature; however the significant mental retardation in these children is not 

thought to be secondary to their stature (Tolmie, 1997). 

Evaluation of children with short stature may be done by a variety of medical specialties including 

endocrinology, gastroenterology, and genetics and depending on the specialty, different evaluations may 

be done. In general, research done on children with short stature has tended to focus on intelligence and 

psychological concerns, which fall into the first three areas of functioning discussed above (acquiring and 

using information, attending and completing tasks, and interacting and relating with others). 

Evaluation of disability among children with short stature due to medically determinable causes is 

limited in that few studies examine disability per se, but instead compare different levels of ability (e.g. 

cognitive ability). In addition, direct associations between ability and height are often not reported.

Evaluation of children with short stature secondary to a skeletal 

dysplasia

Skeletal dysplasias are a relatively heterogeneous group of diseases that cause abnormalities in 

development of one or more parts of the skeleton. For the most part skeletal dysplasias tend to affect 

only bony development, specifically metaphyseal or epiphyseal development. However, certain skeletal 

dysplasias may also have other associated anomalies, such as severe myopia and cleft palate in 

diastrophic dysplasia, which may impact on a disability evaluation. Most, but not all, skeletal dysplasias 

will lead to stature below the third percentile. The most common skeletal dysplasias include 

achondroplasia, hypochondroplasia, osteogenesis imperfecta, and diastrophic dysplasia (Taybi and 

Lachman, 1996). The research on disability and skeletal dysplasia has tended to focus on structural 

abnormalities of the bones and short stature and has looked at problems such as difficulties in acquiring 

and using information, moving about and manipulating objects, caring for self, and health and physical 

well-being. 

Evaluation of disability among children with skeletal dysplasia, as with children with short stature due 

to medically determinable causes, is limited in that few studies examine disability per se, but instead 

compare different levels of ability (e.g. cognitive ability). The main exception to this are studies of 

ambulation and mobility. In addition, direct associations between ability and height and between severity 

of short stature within a particular skeletal dysplasia are often not reported.

Evaluation of children with decreased growth velocity secondary to 

chronic disease
18

Some chronic diseases (e.g., inflammatory bowel disease, asthma, congenital heart disease) have 

been associated with poor growth in the affected child. The poor growth may lead to height less than the 

third percentile in some, or the height may stay within the normal range but with a decreased growth 

velocity (Mahoney, 1987). Of interest is whether decreased growth velocity can be used as a marker to 

indicate worsening severity of disease. This question does not directly relate to disability. 

Certain chronic diseases, such as diabetes or chronic kidney disease, have clearly defined methods 

of measuring severity of disease (i.e., HgbA1c and glomerular filtration rate, respectively). However, 

most chronic diseases have less well-defined measures of severity (e.g., asthma, congenital heart 

disease, sickle cell anemia). Therefore, different studies use different, non-standard definitions of 

severity, making comparisons across studies difficult. For some chronic diseases, severity of disease 

may just be a proxy for different categories or sub-types of the disease (e.g., congenital heart disease, 

juvenile rheumatoid arthritis). Growth may be affected differently by the different categories of the 

chronic disease, which may not be associated with the “severity” of the disease. 

To properly evaluate the association between chronic disease severity and growth, studies must be 

longitudinal and measure height velocity. However, much of the research on severity of chronic disease 

has been cross-sectional. Therefore, height, rather than height velocity, has frequently been analyzed.
19

Chapter 2. Methodology

This evidence report is based on a systematic review of the literature. A series of 

teleconferences was held with the science partner representatives from the Social Security 

Administration (SSA), the American Academy of Pediatrics (AAP), the internal technical 

experts from the Evidence-based Practice Center (EPC), and a representative of the Disability 

Law Center to formulate the key questions addressed by this report. A comprehensive search of 

the medical literature was conducted to identify the evidence available to address the questions.

Detailed information about each study used in the systematic review was abstracted. The 

results are presented in evidence tables. Information directly pertinent to answer each aspect of 

the key questions addressed is presented in summary tables within the Results section (Chapter 

3). A list of abbreviations is presented in Appendix 2.

Key Questions Addressed by the Evidence Report

The EPC staff, pediatric experts, and representatives of SSA arrived at consensus on three 

key questions following discussions and between-meeting solicitation of comments from the 

group members. The key questions were refined to ensure that the answers would be useful to 

SSA, would be of interest to the technical experts, would be appropriate for literature review, and 

would likely be available in the literature. The final key questions are:

1. Is short stature (height < 5th percentile) as a result of a medically determinable 

impairment associated with severe functional limitations, according to, but not limited to, 

SSA’s definition of disability?

2. What is the evidence that short stature (height < 5th percentile) due to a skeletal dysplasia 

is disabling according to, but not limited to, SSA’s definition of disability? If so, are 

children disabled by virtue of their size or other features of their conditions?

3. What is the evidence that a sustained decrease in linear growth velocity can be used as a 

marker of severity of an underlying disease? Is such a process likely to be disabling?

For all key questions, the populations of interest are boys and girls under age 18 years who 

have short stature. Children of all ethnicities, nationalities, racial, and socioeconomic groups 

were included.

For key questions 1 and 2, short stature was defined as height less than the 5th percentile (or 

less than –1.67 standard deviations (SD) below the mean) for age. However, given the variability 

of definitions of short stature in the literature, we accepted definitions of short stature up to the 

25th percentile.

For key questions 1 and 2, disability was defined based on SSA definitions published in 

“Disability Evaluation Under Social Security” (Disability Evaluation Under Social Security, 

1999), as discussed in the Introduction. The list of impairments provided by SSA was reviewed 

to determine the possible disabilities of interest. However, SSA’s definition of disability is based 

on a need to determine an administrative definition to comply with Federal law. Clinicians and 

researchers, though, use various definitions of ability and disability to care for patients. Thus, 
20

very few studies have examined the association between short stature and (SSA-defined) 

disability, per se. This report therefore focuses on assessments of functional limitations, as 

defined by study authors. Objective and teacher- or clinician-scored assessments were included. 

Parent or child determinations of functional ability were excluded. 

Question 1. Definition of short stature as a result of medically 

determinable impairment.

The primary categories (or causes) of short stature considered included isolated or idiopathic 

short stature, constitutional growth delay, growth hormone deficiency, multiple hormone 

deficiency, Russell-Silver syndrome, and Turner syndrome. No predetermined definitions for 

each of the causes of short stature were used; instead, definitions used by study authors were 

accepted. Studies that focused on children with Down syndrome were not reviewed as SSA 

already defines such children as disabled from birth.

The associations between short stature due to medically determinable impairment and 

functional ability included academic achievement, intelligence, academic advancement, visual 

motor skills, psychomotor development, and teacher-graded behavioral problems.

Question 2. Definition of short stature as a result of skeletal 

dysplasia.

The primary skeletal diseases resulting in short stature considered included osteogenesis 

imperfecta, achondroplasia, diastrophic dysplasia, and other skeletal dysplasias. No 

predetermined definitions for each skeletal dysplasia were used; instead, definitions used by 

study authors were accepted. 

The associations between short stature due to skeletal dysplasia and functional ability 

included academic achievement, intelligence, psychomotor development (visual-motor skills, 

motor development, and motor development patterns), neuromuscular function, ambulation and 

mobility, limb range of motion, spinal curvature, hearing loss, respiratory dysfunction (sleep 

apnea and pulmonary function), and psychological outcomes.

Question 3. Chronic disease and linear growth velocity

Attention was paid to addressing the association between disease severity and decreased 

linear growth velocity. Thus, only studies that categorized children with chronic diseases by 

disease severity and that also directly compared height to disease severity were included. Studies 

that investigated only the association between disease presence and height were not reviewed. 

No predetermined definitions of disease severity were used; instead definitions used by study 

authors were accepted. To capture the full range of data available on growth in children with 

chronic disease, we included both studies that evaluated height velocity as well as height alone. 

The review focused on chronic diseases that either are associated with, or may result in, 

disability, as defined by SSA. We did not review studies that evaluated the association between 

treatment for chronic disease and height, unless sufficient data were available to answer the 

primary question. Thus, studies of steroid use for gastrointestinal and most other diseases were 

generally excluded. For studies of children with asthma, we excluded those that explicitly 

examined the effect on growth of steroid use. However, we included studies that used medication 
21

requirement (including steroids) as a marker of severity, since this was a common method of 

analysis. Cancer and cardiac diseases requiring surgery were not considered because separating 

the effect on height of treatment from the underlying disease is not possible.

Search Strategies

Systematic searches were performed for full journal articles of original data. The primary 

search for the literature review consisted of a MEDLINE® search from 1966 through February 

2001, with updates through October 2001. Supplemental searches were also performed in ERIC, 

PsycInfo, Healthstar and Embase. Additional studies were identified from reference lists of 

review and primary articles, and from domain experts.

Development of the search strategies was an iterative process that included input from 

domain experts. Keywords from known relevant studies were used to refine and focus the final 

search strategies used. 

The details of the literature searches performed in MEDLINE® are presented in Appendix 1. 

The primary search strategy for key questions 1 and 2 retrieved articles with the keywords or text 

words developmental bone diseases, growth disorders, body height, or short stature, along with 

variations of disability, limitation, handicap, or impairment (Appendix Table 1, lines 1-11). The 

primary search strategy for key question 3 retrieved articles with the keywords or text words 

developmental bone diseases, short stature, skeletal dysplasia, growth velocity, retardation, delay 

and restriction, and growth disorders (Appendix Table 1. lines 12-50). Studies that focused on 

growth disorders that do not cause short stature, that affect neonatal development or that are 

rapidly fatal were not included. These topics included fetal development, pregnancy, failure to 

thrive, facial bones, thanatropic dysplasia, and various forms of gigantism or other bone diseases 

that do not cause short stature. To capture additional studies of common chronic diseases that 

affect growth, supplemental searches were performed for heart diseases, arthritis, and asthma in 

children, as summarized in Appendix Table 2.

Only articles that included human children under age 18 years and that were published in 

English were included. Case reports, review articles, commentaries, letters, and abstracts were 

excluded.

Study Selection

Pediatrician domain experts and EPC staff manually screened the titles and abstracts of the 

search results to identify potentially useful articles to address each of the key questions. A set of 

minimum inclusion criteria were used in this initial screening: primary articles reporting original 

data on at least 10 children that provided primary or secondary evaluation of growth failure and 

had a primary or secondary outcome of a potential functional limitation. Studies could be crosssectional or longitudinal, prospective or retrospective, comparative or not. Full articles of 

abstracts found potentially useful were retrieved for more careful evaluation.

Data Abstraction

Data abstraction forms were developed in an iterative process by EPC staff with the 

pediatrician experts. The forms were designed to capture information of various aspects of the 
22

primary articles. Individual forms were developed for each key question. Forms included study 

setting, demographics (including such information as age, height, sex, race, and socioeconomic 

status), eligibility criteria, number of subjects, study design, funding source, relevant 

measurements and outcomes evaluated, statistical methodology, results, potential biases, and 

study quality. 

Pediatrician domain experts performed all the data abstraction. Abstractors were trained by 

the EPC staff. As part of the training, each Team Member abstracted three studies in duplicate 

with the Team Leader and meetings were held to discuss discrepancies. After training, all 

remaining studies were abstracted by one pediatrician. All abstracted data were reviewed by two 

members of the EPC staff when data were transferred to evidence and summary tables. 

Articles that reported data on the same or overlapping sets of children were grouped together 

in the evidence and summary tables, or noted to contain duplicate data, to avoid duplication of 

results. One study author (RHH Engelbert) was contacted by email to clarify the overlap of a 

number of studies. 

Summary Tables

Summary tables were created to describe studies reviewed for each topic. The tables describe 

the strength of the evidence according to four dimensions: study size, study sample applicability, 

results, and methodological quality. For questions 1 and 2, studies are grouped first by study 

sample disease type. Within each section, studies are ordered first by methodological quality 

(best to worst), then by study size (largest to smallest). For question 3, studies are grouped first 

by methodological quality, then by applicability of study sample to children with the given 

chronic disease, then by study size.

Study Quality

Methodological quality (also known as internal validity) refers to the design, conduct, and 

reporting of the clinical study. Because studies with a variety of design types were evaluated, a 

three-level classification of study quality, used in previous reports, was modified. All studies 

were graded on the following scale:

=Good quality. Least bias. Results are valid. A study that mostly adheres to the commonly 

held concepts of high quality, including the following: a formal study; prospective 

design, clear description of the population and setting; proper measurement techniques; 

appropriate statistical and analytic methods; no reporting errors; no obvious bias.

£ Fair quality. Susceptible to some bias, but not sufficient to invalidate the results. A study 

that does not meet all the criteria of category A. It has some deficiencies but none likely 

to cause major bias.

° Poor quality. Significant bias likely that may invalidate the results. A study with serious 

errors in design or reporting. These studies may have large amounts of missing 

information or discrepancies in reporting. 

In general, studies that reported data relevant to multiple topics of interest were given the 

same quality rating for each topic; however, some studies were rated differently for different 

topics, depending on the quality of the data for each topic. For example, a study may have 
23

performed a complete and valid statistical analysis of intelligence but may not have performed a 

statistical analysis of academic achievement. The study may therefore receive a lower quality 

rating for its analysis of academic achievement than for intelligence.

Applicability

Applicability (also known as generalizability or external validity) addressed the issue of 

whether the study sample is sufficiently broad so that the results of the study can be generalized 

to the population of interest at large. The study population is typically defined by the eligibility 

criteria. Restrictive eligibility criteria (e.g., single sex, limited range of disease severity) or small 

sample size may reduce the applicability of a given study.

For questions 1 and 2 the applicability of each study is described by the type of disease 

causing short stature. The few studies that had particularly restrictive eligibility are noted in each 

table’s footnotes. For certain disability topics (e.g., hearing loss and ambulation) where separate 

results are reported for different sub-populations of children, columns were added to the tables to 

describe the populations. For each study, the mean, median, or threshold height (generally 

expressed in age and sex standard deviations from the mean, or standard deviation score (SDS) 

were recorded.

For question 3, where all studies within a given table evaluate children with the same (or 

similar) diseases, a designation for applicability was assigned to each article, according to the 

following three-level scale:

ÇÇÇ Study is representative of all children with the given chronic disease. Study sample 

includes both sexes, the full range of disease severity, a sufficient number of subjects. 

There are no substantial eligibility restrictions.

ÇÇ Sample is representative of a relevant sub-group of children with the given chronic 

disease. There were eligibility restrictions that may limit the applicability, such as 

single sex, disease severity, or co-morbidities.

ÇSample is representative of a narrow subgroup of children with the given chronic disease. 

There were substantial eligibility restrictions that limit applicability.

To complement the applicability scale, each table has a column describing the diseases of the 

study population.

Study Size

The study (sample) size is used as a measure of the weight of the evidence. In general, large 

studies provide more precise estimates of prevalence and associations. In addition, large studies 

are more likely to have wide applicability, depending on eligibility criteria. However, large study 

size does not guarantee applicability. 

Results

The type of results available is determined by each study’s design, the purpose of the study, 

and the question(s) being asked. Therefore, the results presented vary across summary tables. For 
24

questions 1 and 2 most summary tables present either the mean test results of a given test or the 

prevalence of a given condition. When necessary, the test or condition evaluated in each study is 

included. When available, the results for a control group are also included. Summary tables for 

question 3 include separate columns for association of disease severity with height and with 

height velocity. For appropriate topics in questions 1 and for all topics in question 3, associations 

are described with the following arrows:

Statistically significant positive association between severity of chronic disease and 

height or height velocity. More severe chronic disease associated with growth retardation. 

If statistical analysis was not reported, but a large clinical difference in growth based on 

disease severity was, statistical significance was assumed to be likely. This symbol was 

used only in studies evaluated for question 3.

Statistically significant negative association between ability and disease causing short 

stature. This symbol was used only in studies evaluated for visual-motor skills in question 

1. 

Trend toward positive association between severity of chronic disease and height or 

height velocity. Some indication that children with more severe chronic disease may be 

associated with growth retardation. However, association either is not statistically 

significant or statistical analysis was not reported. This symbol was used only in studies 

evaluated for question 3.

No association between severity of chronic disease and height or height velocity. This 

symbol was used only in studies evaluated for question 3.

Limitations

While literature searches were intended to be comprehensive, they may not have been 

exhaustive. As noted above, search strategies were limited to focus on studies likely to be 

relevant. Searches were limited to English language publications. Hand searches of journals were 

not performed, and review articles and textbook chapters were not systematically searched. 

However, important studies known to the domain experts and studies found in reference lists 

were included in the review.
25

Chapter 3. Results

Search Results

The results of the primary and supplemental Medline search strategies are shown in 

Appendix Tables 1 and 2 (Appendix 1). Including studies found from other sources, a total of 

13,537 English language citations were reviewed. Screening of the abstracts and titles identified 

825 articles potentially useful to address the three questions formulated by the Evidence-based 

Practice Center (EPC) staff, pediatric experts, and representatives of the Social Security 

Administration (SSA). These studies were retrieved for review. Detailed examination of these 

articles identified 31 studies that met inclusion criteria for Question 1, 31 studies for Question 2, 

and 53 studies for Question 3. Detailed data extraction was performed on these 115 studies. The 

results of the detailed data extraction are presented in the evidence tables. 

Evidence Found Regarding Key Questions

Question 1. Is short stature (height less than the 5th percentile) as a 

result of a medically determinable impairment associated with severe 

functional limitations, according to, but not limited to, SSA’s 

definition of disability? 

See Evidence Table 1.

We reviewed 31 papers that provided information on functional abilities among children with 

short stature due to medically determinable impairments. As described in Evidence Table 1, a 

number of these papers provided analyses from the same samples of children. One study reported 

on different outcomes in two separate papers. Therefore, 24 papers from 23 studies are 

summarized here. Few studies explicitly examined functional impairment, per se. Data are 

reported on the association of short stature with academic achievement, intelligence, visualmotor skills, psychomotor development, and teacher-graded behavior. Detailed information on 

all 31 papers is reported in Evidence Table 1. 
26

Association of Short Stature with Academic Achievement

Table 1. Mean Academic Achievement Scores of Children with Short Stature due to Medical 

Impairment

Mean Academic Achievement Score

Author Year Sample N

(Controls)

Mean 

Height, 

SDS 

Test Math Reading Comprehension Spelling Bias a Quality b

Isolated Short Stature or Constitutional Growth Delay

Downie 1997 106 (119) < –2 BAS 40 [44] 44 [48] =

Wilson 1986 ~350 (~6,400) < –1.6 WRAT ~92

c £

Stathis 1999 113 (3,178) < –2 PPVT-R 92 [97] >IQ °

Siegel 1994 90 (90) –2.8 WRAT 96

22% <80 d

102 98 >IQ °

Kranzler 2000 34 (29) e –1.7 KTEA 105 [121] 106 [115] 107 [114] 

Total f

104 [101] >IQ °

Kranzler 2000 27 (29) g –2.7 KTEA 107 [121] 104 [115] 106 [114] 

Total f

105 [101] >IQ °

Gordon 1984 24 (23) < –1.6 PIAT 103 102 102 Matched °

Isolated Growth Hormone or Multiple Hormone Deficiency

Siegel 1986 42 < –2 WRAT 85 96 >IQ £

Abbott 1982 11 ND WRAT 83 88 85 No stat £

Siegel 1994 87 (90) –2.7 WRAT 99 103 98 >IQ °

Isolated Short Stature or Growth Hormone Deficiency

Siegel 1998 25 (25) –3.1 WRAT 102 105 99 =

Turner Syndrome

Siegel 1998 22 (25) –3.3 WRAT 90 98 95 =

Ross 1997 20 w/GH h ND WRAT 100 No stat £

Ross 1997 20 w/o GH i ND WRAT 97 No stat £

Russell-Silver Syndrome

Lai 1994 25 –2.2 Neale j

Delay

7 mo

Delay

15 mo No stat °

Mean scores in bold were significantly different than normal population; results not in bold not significantly different, except as 

noted in bias column.

Mean score for normal population for each test is 100, unless otherwise noted in brackets

BAS = British Ability Scales; KTEA = Kaufman Test of Educational Achievement; Neale = Neale analysis of reading ability, 

British edition; PIAT = Peabody Individual Achievement Test; PPVT-R = Peabody Picture Vocabulary Test-Revised; WRAT = 

Wide Range Achievement Test

a Studies noted with “>IQ” excluded subjects with low intelligence quotient or known mental impairment excluded.

Studies noted with “No stat” did not perform statistical analysis comparing IQ of subjects to normal controls.

Study noted with ”Matched” used controls that were matched for IQ among other factors.

b See Methods, Summary Tables, Study Quality.

c Significant correlation between height and reading and arithmetic subtests of WRAT. WRAT score reported graphically.

d Significantly more children with ISS had an arithmetic score less than 80 than controls (7%).

e Non-referred subjects, shortest 10% at school.

f Control children had math and reading scores of 121 and 115, respectively

g Referred to endocrinology clinic for short stature.

h Subjects with Turner syndrome, treated with growth hormone

i Subjects with Turner syndrome, not treated with growth hormone

j Neale assessment of reading ability measured reading competence. No data clearly provided on how arithmetic competence 

was measured.
27

Eleven studies evaluated academic achievement in approximately 996 children with short 

stature as a result of a medically determinable impairment (Table 1). Six studies evaluated 

children with isolated short stature (ISS) or constitutional growth delay (CGD); three evaluated 

children with isolated growth hormone deficiency (GHD) or multiple hormone deficiency 

(MHD); one evaluated children with either ISS or GHD; two evaluated children with Turner 

syndrome; and one evaluated children with Russell-Silver syndrome.

Isolated Short Stature / Constitutional Growth Delay

Six studies evaluated academic achievement in approximately 744 children with ISS or 

CGD. Academic achievement was measured with a variety of tests, including the Wide Ranging 

Achievement Test (WRAT), the Peabody Picture Vocabulary Test – Revised (PPVT-R), the 

British Ability Scales (BAS), the Kaufman Test of Educational Achievement (KTEA), and 

Peabody Individual Achievement Test (PIAT). The scores of the children with short stature were 

all compared to controls. All studies analyzed prospective data. Two were longitudinal, four 

were cross-sectional. One study was of good quality, one was of fair quality, and four were rated 

poor quality because they excluded children with low intelligence quotients (IQ) for analyses of 

cognitive function or analyzed cognitive function despite matching subjects and controls by IQ.

In four prospective, longitudinal papers (Downie, Mulligan, McCaughey, et al., 1996; 

Downie, Mulligan, Stratford, et al., 1997; Voss, Bailey, Mulligan, et al., 1991; Voss and 

Mulligan, 1994) children with ISS were tested repeatedly at different ages. In the final analysis 

(Downie, Mulligan, Stratford, et al., 1997) 106 13 year old children with ISS had significantly 

lower reading and mathematics attainment scores on BAS than the same aged controls. The 

scores remained significantly lower than for controls after adjusting for social class. However the 

absolute difference in scores were within 1 standard deviation (SD) of the average control 

subjects’ scores. 

Wilson, Duncan, Dornbusch, et al. (1986) reported on a prospective, longitudinal study of 

6,768 adolescents, aged 12 to 17 years old, who were in Cycle III of the National Health 

Examination Survey from 1966-1970. Approximately 350 of these children had height below the 

5

th percentile. There was a small but significant correlation between standardized height and 

WRAT score. Mean WRAT score for different height percentile groups of children rose 

consistently with height. Similar results were found for the same children when they were 6 to 11 

years old.

Stathis, O'Callaghan, Williams, et al. (1999), in a prospective, cross-sectional analysis of 113 

4 to 6 year old children with height less than the 3rd percentile, found that receptive vocabulary, 

measured with PPVT-R, was significantly lower among both boys and girls than among children 

of normal height. However, the absolute differences in scores were within 1 SD of the mean for 

normal children. The value of this study is limited, though, since 14 children with PPVT-R 

scores less than 50, with cerebral palsy, or with other neurological disorders were excluded from 

the analysis.

In a prospective, cross-sectional study, Siegel, Clopper, Stoppani, et al. (1994) evaluated 

WRAT-R in 90 children with ISS with a mean age of 11 years old. There were no significant 

differences between mean reading, spelling, and math scores in the children with ISS and the 

normal controls. However, significantly more ISS children (22 percent) had a skill deficit in 

mathematics (score less than 80) compared to both GHD children (10 percent) and normal 
28

children (7 percent). The value of this study is limited, though, since children with “known 

mental impairments” were excluded.

Kranzler, Rosenbloom, Proctor, et al. (2000) evaluated two groups of 6 to 12 year old 

children with ISS in a prospective, cross-sectional study. One group consisted of 34 children who 

were identified in local public schools as being in the shortest 10 percent of the class (“nonreferred”). The second group consisted of 27 children with ISS who had been referred to 

pediatric endocrinology because of short stature. Among both groups, children with ISS scored 

significantly lower than normal height controls on both mathematics and reading KTEA. For 

both groups, spelling and composite achievement scores were similar to controls. However, 

mean scores for all groups of children were above standardized norms. The value of this study is 

limited, though, since children with IQ less than 75 were excluded.

Gordon, Post, Crouthamel, et al. (1984) evaluated 24 6 to 12 year old children with height 

less than the 5th percentile due to CGD in a prospective, cross-sectional study. The children had 

normal scores on math, reading recognition, and comprehension PIAT. These scores were not 

significantly different from controls; however the controls were matched for Full Scale IQ.

Growth Hormone Deficiency / Multiple Hormone Deficiency

Three studies evaluated academic achievement in children with GHD and multiple hormone 

deficiency (MHD). A total of 140 children were evaluated by WRAT. The test results were 

either compared to controls or population norms. Two of the studies (Siegel, Clopper, Stoppani, 

et al., 1994; Siegel and Hopwood, 1986) excluded subjects with low IQ or known mental 

impairment. All were prospective; one was longitudinal, two were cross-sectional. Two were 

rated as fair quality; one poor.

Siegel and Hopwood (1986) evaluated 42 children with short stature due to hypopituitarism 

(28 with isolated GHD and 14 with MHD) and a mean age of 12 years. Academic achievement 

was evaluated by WRAT and was compared to population norms in a prospective, crosssectional study. A significant decrease in math scores was found in the hypopituitary children but 

no difference in reading scores. The children with hypopituitarism had WRAT scores within 1 

SD of the mean. Of note, the study excluded one child with hypopituitarism because severe 

mental retardation prevented using some of the tests.

Eleven children, aged 4 to 18 years old, with short stature due to GHD and/or other pituitary 

hormone deficiency were evaluated in a longitudinal, prospective study by Abbott, Rotnem, 

Genel, et al. (1982). Their academic achievement tests (WRAT) were less than the mean but 

within 1 SD of the mean (except for WRAT arithmetic scores, which were within 1.5 SD of the 

mean) when compared to population norms.

Siegel, Clopper, Stoppani, et al. (1994) evaluated 87 children with height less than the 3rd

percentile either due to GHD and mean age of 11 years. The children were compared to average 

stature control children matched for age, sex and socioeconomic status in a prospective, crosssectional study. Academic achievement in the children with short stature tested by the WRAT-R 

test was not significantly different from the results of the controls. However, children with 

known mental impairment were excluded from this study. 
29

Combined Isolated Short Stature and Growth Hormone Deficiency

One study evaluated academic achievement with WRAT in 25 girls with a mean age of 10 

years who had either ISS or short stature due to GHD. In a longitudinal, prospective study, 

Siegel, Clopper, and Stabler (1998) compared the girls with ISS/GHD to a group of girls with 

short stature due to Turner syndrome and a control group of girls with average stature. The girls 

with short stature had similar academic achievement testing, measured by WRAT, compared to 

control girls of average stature and girls with Turner syndrome. These results were from the 

baseline study for an evaluation of the effects of growth hormone on girls with short stature. The 

study was of good quality.

Turner Syndrome

Two studies evaluated academic achievement (WRAT) in 62 girls with short stature 

secondary to Turner syndrome. The test results were compared to population norms or to 

controls. Both were longitudinal, prospective studies. One was of good quality; one of fair 

quality.

Siegel, Clopper, and Stabler (1998) tested 22 girls with Turner syndrome with a mean age of 

10 years for academic achievement (WRAT). Test scores for the girls with Turner syndrome 

were not significantly different from control girls of average stature. This was a longitudinal, 

prospective study.

In a prospective study that was part of a double-blind randomized controlled trial of growth 

hormone for the treatment of Turner syndrome, Ross, Feuillan, Kushner, et al. (1997) evaluated 

40 girls with a mean age of 9 years. The study found that girls with Turner syndrome had WRAT 

scores that were at or just below the population average, whether they received growth hormone 

or a placebo.

Russell-Silver Syndrome

One study evaluated academic achievement in 25 children with Russell-Silver syndrome. 

Lai, Skuse, Stanhope, et al. (1994) tested children aged 6 to 12 years old with the clinical 

diagnosis of Russell-Silver syndrome with the Neale analysis of reading and an undefined test of 

arithmetic competence in a prospective, cross-sectional study. The children with Russell-Silver 

syndrome were found to have substantial delays in both reading and arithmetic competence. 

Because of the poor reporting and the lack of statistical analysis, the study was graded poor 

quality.

Short Stature and Academic Achievement

Six studies examined academic achievement among children with ISS or CGD. Four found 

that the short children had significantly lower scores on various tests of academic achievement 

than normal height children. Two studies found that, overall, short children had similar scores as 

normal controls. Among all the studies, short children scored either above population norms or 

within 1 SD of normal scores. One study found that short children were significantly more likely 

to have a skill deficit (in mathematics) than normal height children even though mean scores 
30

were similar. Three of the studies excluded children with low IQ and a fourth matched short 

children with normal children with similar IQs.

Three studies examined academic achievement among children with GHD or MHD. One 

found that short children had significantly lower mathematics test scores than normal height 

controls. All three found that test scores among short children were within 1.5 SD of population 

means. One study excluded one child with severe mental retardation; another excluded children 

with low IQs.

A single study examined academic achievement among children with either ISS or GHD. 

These children scored at or above population means. 

Two studies examined academic achievement among children with Turner syndrome. One 

study found no significant difference between girls with Turner syndrome and controls. Both 

studies found that girls with Turner syndrome scored within 1 SD of population norms.

One study examined academic achievement among children with Russell-Silver syndrome. 

These children were found to have substantial delays in both reading and arithmetic competence.

Association of Short Stature with Intelligence

Table 2. Mean Intelligence Quotients of Children with Short Stature due to Medical Impairment

Mean IQ

Author Year

Sample N

(Controls

)

Mean 

Height, 

SDS Full Verbal Performance Bias a Quality b

Isolated Short Stature or Constitutional Growth Delay

Downie 1997 106 (119) <–2 103 d =

Wilson 1986 ~350 (~1800) < –1.6 ~93 c £

Rovet 1985 25 < -2 101 98 102 No stat £

Siegel 1994 90 (90) –2.8 107

18%<90 e

>IQ °

Kranzler 2000 34 (29) f –1.7 105 104 105 Matrices >IQ °

Kranzler 2000 27 (29) g –2.7 103 101 h 106 Matrices >IQ °

Gordon 1984 24 (23) < –1.6 108 107 108 Matched °

Holmes 1985 21 <–2 104 No stat °

McCauley 1987 16 –4.5 100 108 >IQ

No stat °

Isolated Growth Hormone or Multiple Hormone Deficiency

Siegel 1986 42 < -2 94 94 >IQ £

Frisch 1990 23 –2.5 115 104 114 £

Meyer-Bahlburg 1978 13 w/GHD –3.7 101 No stat £

Abbott 1982 11 ND 88 89 89 No stat £

Meyer-Bahlburg 1978 9 w/MHD –4.0 102 No stat £

Siegel 1994 87 (90) –2.7 110

9%<90 e

>IQ °

Holmes 1985 17 < –2 97 °

 (continued)
31

Table 2. cont.

Mean IQ

Author Year Sample N

(Controls)

Mean 

Height, 

SDS Full Verbal Performance Bias a Quality b

Combined Isolated Short Stature, Constitutional Growth Delay, and Growth Hormone Deficiency

Siegel 1998 25 (25) –3.1 105 =

Steinhausen 1976 32 –3.7 103 102 103 No stat £

Pollitt 1964 13 –6.9 103 103 102 £

Young-Hyman 1986 27 < –2 110 >IQ °

Turner Syndrome

Siegel 1998 22 (25) –3.3 102 =

Ross 1997 20 w/ GH i ND 98 104 92 No stat £

Ross 1997 20 w/o GH j ND 99 102 96 No stat £

Robinson 1983 9 (17) ND 87 93 83 £

McCauley 1987 17 –5.0 95 91 >IQ

No stat °

Holmes 1985 9 < –2 103 No stat °

Russell-Silver Syndrome

Lai 1994 25 –2.2 86 89 84 £

Tanner 1975 11 –2.6 103 No stat °

Angehrn 1979 9 k –4.4 91 No stat °

Combined Isolated Short Stature and Russell-Silver Syndrome

Skuse 1996 22 (21) –2.5 96 95 97 >IQ °

Mean IQ results in bold were significantly different than normal population; results not in bold not significantly different, except 

as noted.

w/ GHD = Children with growth hormone deficiency; w/MHD = Children with multiple hormone deficiency

a Studies noted with “>IQ” excluded subjects with low IQ or known mental impairment excluded.

Studies noted with “No stat” did not perform statistical analysis comparing IQ of subjects to normal controls.

Study noted with ”Matched ” used controls that were matched for IQ among other factors.

b See Methods, Summary Tables, Study Quality.

c Significant correlation between height and IQ. IQ value reported graphically.

d Controls had mean IQ of 109

e Significantly more children with ISS and with GHD had IQ < 90 than controls (3%).

f Non-referred subjects, shortest 10% at school.

g Referred to endocrinology clinic for short stature.

h Controls had mean verbal IQ of 110

i Subjects with Turner syndrome, treated with growth hormone

j Subjects with Turner syndrome, not treated with growth hormone

k 5 additional children who were not tested were “probably of normal intelligence.” No data on 6 other children in study.

Twenty-one studies evaluated IQ in approximately 1,156 children with short stature as a 

result of a medically determinable impairment (Table 2). Eight studies evaluated children with 

ISS or CGD; six evaluated children with GHD or MHD; four evaluated children with either ISS, 

GHD or GHD; five evaluated children with Turner syndrome; three evaluated children with 

Russell-Silver syndrome; and one evaluated children with either ISS or Russell-Silver syndrome.
32

Isolated Short Stature / Constitutional Growth Delay

Eight studies evaluated intelligence in children with ISS or CGD with approximately 693 

subjects. Tests included Wechsler Intelligence Scale for Children (WISC), British Ability Scales 

(BAS), Kaufman-Brief Intelligence Test (K-BIT), and Slosson Intelligence Test (SIT). Test 

results were either compared to controls or to population norms. All studies analyzed prospective 

data. Three were longitudinal; five were cross-sectional. One study was of good quality; two 

were of fair quality; and five were of poor quality, primarily because of excluding subjects with 

low IQ or known mental impairment.

In four prospective, longitudinal papers (Downie, Mulligan, McCaughey, et al., 1996; 

Downie, Mulligan, Stratford, et al., 1997; Voss, Bailey, Mulligan, et al., 1991; Voss and 

Mulligan, 1994) children with ISS were tested repeatedly at different ages. In the final analysis 

(Downie, Mulligan, Stratford, et al., 1997) 106 13 year old children with ISS had IQ measured 

with BAS. Children with short stature had significantly lower IQ than normal height controls, 

even after adjusting for socioeconomic status. However, mean IQ among study subjects was 

greater than 100.

Wilson, Duncan, Dornbusch, et al. (1986) reported on a prospective, longitudinal study of 

6,768 adolescents, aged 12 to 17 years old, who were in Cycle III of the National Health 

Examination Survey from 1966-1970. Approximately 350 of these children had height below the 

5

th percentile. These children had significantly lower IQ scores, measured by WISC, than the 

general population mean. IQ was significantly correlated with height for all children. However, 

average WISC scores for short children were within 1 SD of the mean. Similar results were 

found for the same children when they were 6 to 11 years old.

Rovet, Netley, and MacLeod (1986) evaluated 25 boys with a mean age of 14 years who had 

ISS in a prospective, cross-sectional study. Verbal, performance and full-scale IQs, measured by 

WISC, were similar to the population average. 

In a prospective, cross-sectional study Siegel, Clopper, Stoppani, et al. (1994) evaluated 

intelligence with SIT in 90 children with ISS and a mean age of 11 years old. There were no 

significant differences between mean IQ in the children with ISS and the normal controls. 

However, significantly more ISS children (18 percent) had an IQ less than 90 than normal 

children (3 percent). The value of this study is limited, though, since children with “known 

mental impairments” were excluded.

Kranzler, Rosenbloom, Proctor, et al. (2000) evaluated two groups of 6 to 12 year old 

children with ISS in a prospective, cross-sectional study. One group consisted of 34 children who 

were identified in local public schools as being in the shortest 10 percent of the class (“nonreferred”). The second group consisted of 27 children with ISS who had been referred to 

pediatric endocrinology because of short stature. Among both groups, children with ISS had 

similar composite and matrices IQ measured by K-BIT as normal height controls. Non-referred 

short children had similar verbal IQ as controls, while referred short children had significantly 

lower IQ than controls. However, the mean verbal IQs for all groups of children were above 100. 

The value of this study is limited, though, since children with IQ less than 75 were excluded.

Gordon, Post, Crouthamel, et al. (1984) evaluated 24 6 to 12 year old children with height 

less than the 5th percentile due to CGD in a prospective, cross-sectional study. The children had 

above normal scores on full, verbal, and performance IQ by WISC. These scores were not 

significantly different from controls; however the controls were matched for Full Scale IQ.
33

Holmes, Karlsson, and Thompson (1985) evaluated 21 children with short stature due to 

CGD who were age 12 years at the start of a prospective longitudinal study. The verbal IQs, 

measured by WISC, of these children were slightly above the population mean. No statistical 

analysis was performed and the study suffered from incomplete reporting.

In a prospective, cross-sectional study, McCauley, Kay, Ito, et al. (1987) evaluated 16 girls 

with ISS and a mean age of 13 years. These girls had scored at or above the population mean for 

both verbal and performance IQ measured by WISC. However, children with IQ less than 79 

were excluded.

Growth Hormone Deficiency / Multiple Hormone Deficiency

Six studies evaluated intelligence in children with short stature due to GHD or MHD with a 

total of 202 subjects. The tests used included the WISC and SIT. Test results for children with 

short stature due to GHD/MHD were either compared to average stature controls or to population 

norms. All of the studies were prospective. Two were longitudinal; four were cross-sectional. No 

study was of good quality; four were of fair quality; and two were of poor quality.

Siegel and Hopwood (1986) evaluated 42 children with short stature due to hypopituitarism 

(28 with isolated GHD and 14 with MHD) and a mean age of 12 years. IQ was evaluated by 

WISC and was compared to population norms in a prospective, cross-sectional study. Their 

verbal and performance IQs were significantly less than the population average, but within 1 SD 

of the population average. Of note, the study excluded one child with hypopituitarism because 

severe mental retardation prevented using some of the tests.

Frisch, Hausler, Lindenbauer, et al. (1990) evaluated 23 children aged 7 to 16 years old with 

isolated GHD or MHD who were evaluated by IQ testing with the German language version of 

WISC in a prospective, cross-sectional study. The children scored statistically higher on full 

score and performance IQ tests than the population at large. Verbal IQ scores were similar to 

controls. No correlation was found between standardized height and IQ score. 

In a prospective, cross-sectional study, 13 children with short stature due to isolated GHD 

and nine children with MHD were evaluated by Meyer-Bahlburg, Feinman, MacGillivray, et al. 

(1978) by IQ testing (WISC). The children ranged in age from about 4 to 18 years old. Both 

groups of children had normal full score IQs.

Eleven children, aged 4 to 18 years old, with short stature due to GHD and/or other pituitary 

hormone deficiency were evaluated in a longitudinal, prospective study by Abbott, Rotnem, 

Genel, et al. (1982). The children had verbal, performance and full-scale IQs that were less then 

the general population mean but within 1 SD of the mean. No statistical analysis was reported. 

The study found that overall IQ scores were more related to socioeconomic level and specific 

physical dysfunction, such as eye defects, than to hypopituitarism. 

In a prospective, cross-sectional study Siegel, Clopper, Stoppani, et al. (1994) evaluated 

intelligence with SIT in 87 children with GHD and a mean age of 11 years old. There were no 

significant differences between mean IQ in the children with GHD and the normal controls. 

However, significantly more GHD children (9 percent) had an IQ less than 90 than normal 

children (3 percent). The value of this study is limited, though, since children with “known 

mental impairments” were excluded.

Holmes, Karlsson, and Thompson (1985) evaluated 17 children with short stature due to 

GHD who were age 12 years at the start of the study in a prospective longitudinal study. The 
34

verbal IQs, measured by WISC, of these children were slightly below the population mean. No 

statistical analysis was performed and the study suffered from incomplete reporting.

Combined Isolated Short Stature, Constitutional Growth Delay, and Growth 

Hormone Deficiency

Four studies evaluated intelligence with WISC or SIT in 97 subjects with ISS, CGD and 

GHD. The test results were compared to controls of average stature or to population norms. One 

study excluded subjects with low IQ or known mental impairment. All of the studies were 

prospective. One was longitudinal; three were cross-sectional. One study was of good quality; 

two were of fair quality; and one was of poor quality.

Siegel, Clopper, and Stabler (1998) evaluated IQ with SIT in 25 girls with a mean age of 10 

years who had either ISS or short stature due to GHD. This longitudinal, prospective study, 

compared the girls with ISS/GHD to a group of girls with short stature due to Turner syndrome 

and a control group of girls with average stature. These results were from the baseline study for 

an evaluation of the effects of growth hormone on girls with short stature. No significant 

difference was found in the IQ of girls with GHD/ISS compared to control girls of average 

stature. 

Steinhausen and Stahnke (1976) reported IQ testing (WISC) in 32 children ranging from 9 to 

17 years old with height less than the 3rd percentile due to either hypopituitarism or familial 

reasons and compared these children to age-matched children of “normal” height. Performance, 

verbal and full-scale IQ testing scores were similar among these children and controls. This was 

a prospective, cross-sectional study. 

Intelligence testing was performed in 13 children aged 3 to 16 years with short stature due to 

GHD, CGD, or Turner syndrome by Pollitt and Money (1964) in a prospective, cross-sectional 

study. Average full-scale, verbal and performance IQ scores (measured by WISC) were normal.

Results were all slightly above the population mean (verbal 103, performance 101, full-scale 

102). The 2 children who were tested with the Stanford-Binet, revised had IQs (48), which were 

slightly below the population norm. The study did not find a significant difference in intelligence 

in children with short stature. 

Young-Hyman (1986) evaluated 27 children with ISS, GHD or CGD and a mean age of 12 

years in a prospective, cross-sectional study. The full-scale IQs (WISC) were on average above 

the normal range. However, no statistical analysis was performed and the study excluded 

children with mental disability or learning problems. 

Turner Syndrome

Five studies evaluated intelligence in girls with short stature secondary to Turner syndrome 

with a total of 97 subjects. Tests used included WISC and SIT. The test results were compared 

either to controls or to population norms. One study excluded subjects with low IQ or known 

mental impairment. All studies were prospective. Three were longitudinal; two were crosssectional. One study was of good quality; two were of fair quality; and two were of poor quality.

Siegel, Clopper, and Stabler (1998) evaluated IQ with SIT in 22 girls with a mean age of 10 

years who had Turner syndrome. This longitudinal, prospective study, compared these girls to 

girls with ISS/GHD and to a control group of girls with average stature. These results were from 

the baseline study for an evaluation of the effects of growth hormone on girls with short stature. 
35

The girls with Turner syndrome had IQ scores that were slightly above the population mean, but 

slightly less than the scores for the control girls of average height (108).

In a prospective study that was part of a double-blind randomized controlled trial of growth 

hormone for the treatment of Turner syndrome, Ross, Feuillan, Kushner, et al. (1997) evaluated 

40 girls with a mean age of 9 years. The study found that girls with Turner syndrome had IQ 

scores (measured by WISC) that were similar to the population norm, whether they received 

growth hormone or a placebo.

Robinson, Bender, Borelli, et al. (1983), in a small prospective, cross-sectional study, 

evaluated nine girls with Turner syndrome who ranged from 7 to 15 years old. Measured by 

WISC, the average full-scale and verbal IQs of these girls were significantly below normal, 

although still within 1 SD of normal mean. The mean verbal IQ was not significantly lower than 

normal.

McCauley, Kay, Ito, et al. (1987) tested IQ in 17 3 to 16 year old girls with short stature due 

to Turner syndrome. The girls had somewhat low verbal and performance IQs (measured by 

WISC) that were within 1 SD of the mean. No statistical analyses were performed in this 

prospective, cross-sectional study. Children with IQ less than 79 were excluded from the study.

Holmes, Karlsson, and Thompson (1985) evaluated 9 children with Turner syndrome who 

were age 12 years at the start of a prospective longitudinal study. The verbal IQs, measured by 

WISC, of these children were slightly above the population mean. No statistical analysis was 

performed and the study suffered from incomplete reporting.

Russell-Silver Syndrome

Three studies evaluated intelligence in children with short stature due to Russell-Silver 

syndrome with 45 total subjects. The test scores were compared to population norms. Two were 

prospective; one was retrospective. Two were longitudinal; one was cross-sectional. One study 

was of fair quality; two were of poor quality.

Lai, Skuse, Stanhope, et al. (1994) evaluated IQ with WISC in 25 children with RussellSilver syndrome in a prospective, cross-sectional study. The children were 6 to 12 years old and 

had significantly lower full-scale, verbal, and performance IQs than the general population norm. 

However, the scores were within 1 SD of the general population mean. The full-scale IQ range 

was 46-130 with 8 children (32 percent) having IQs less than 70.

A longitudinal, retrospective study by Tanner, Lejarraga, and Cameron (1975) evaluated 39 

children with Russell-Silver syndrome aged 11⁄2 to 10 years old in an attempt to understand the 

natural history of this condition. IQ testing was only available for 11 of the children and the 

specific test used was not reported . The mean full-scale IQ was slightly above the population 

mean of 100.

A longitudinal, prospective study by Angehrn, Zachmann, and Prader (1979) evaluated 

growth and development in 20 children with Russell-Silver syndrome and a mean age of 4 years 

old. IQs (specific test not reported) were reported for only nine of the children. Six of them had 

IQs in the normal range (mean of 102) and 3 had IQs less than 86 (85, 83 and 38).

Combined Isolated Short Stature and Russell-Silver Syndrome

One study evaluated intelligence via WISC in 22 children with either ISS or Russell-Silver 

syndrome. The test scores were compared to the average stature control group. Skuse and 
36

Gilmour (1997) evaluated seven children with Russell-Silver syndrome and 15 with ISS in a 

prospective, cross-sectional study. The children with short stature had significantly lower 

average full-scale and performance IQ scores and lower verbal IQ than control children who had 

mean IQ scores from 105 to 108. However, the mean scores of the short children were within 1 

SD of the population mean. The study was graded to be of poor quality because it excluded 

children with IQ less than 72.

Short Stature and Intelligence

Eight studies evaluated intelligence among children with ISS or CGD. Three studies found 

that short children had significantly lower IQs than normal controls. All studies found that, 

overall, short children had IQs that were either above or within 1 SD of population norms. One 

study found that short children were significantly more likely to have some intelligence deficit 

(IQ less than 90) even though mean scores were similar. Four studies excluded children with low 

IQ and one study matched short children with normal height children with similar IQs.

Seven studies evaluated intelligence among children with GHD or MHD. Two studies found 

that short children had significantly lower IQs than normal controls. All studies found that, 

overall, short children had IQs that were either above or within 1 SD of population norms. One 

study found that short children were significantly more likely to have some intelligence deficit 

(IQ less than 90) even though mean scores were similar. One study excluded one child with 

severe mental retardation; one excluded children with low IQs.

Four studies evaluated intelligence among children with either ISS, CGD or GHD. None 

found that short children had significantly lower IQs than normal controls. All found that, 

overall, short children had IQs that were above population norms. One study excluded children 

with low IQs.

Five studies evaluated intelligence among girls with Turner syndrome. One small study 

found that girls with Turner syndrome had significantly lower IQs than normal height controls 

and that their IQs were, on average, about 1.5 SD below population norms. The remaining 

studies found that girls with Turner syndrome had IQs that were within 1 SD of population 

norms. Ones study excluded girls with low IQ.

Three studies evaluated children with Russell-Silver syndrome and one with either RussellSilver syndrome or ISS. Two studies found that the short children had significantly lower IQs 

than normal height controls. One excluded children with low IQs. All studies found that children 

with Russell-Silver syndrome, overall, had IQs within 1.5 SD of population norms.
37

Association of Short Stature with Visual-Motor Skills

Table 3. Association of Height to Visual-Motor Skills Among Children with Short Stature due to 

Medical Impairment

Author, Year Sample N

(Controls) Mean Height Measure Results Quality a

Isolated Short Stature

Bender Visual Motor – 2 y 1 mo b

Abbott 1982 11 81-132 cm Beery Visual Motor Integration –3 y 8 mo b £

Young-Hyman 

1986 27 ND Bender Visual Motor – 2 y 6 mo b °

Growth Hormone or Multiple Hormone Deficiency

Siegel 1986 42 < -2 SDS

Bender Visual Motor 

Score < 16th percentile &

≥ 4 brain injury indicators

26% £

Results in bold were significantly different than normal population.

a See Methods, Summary Tables, Study Quality.

b Discrepancy between chronological age and age equivalence, in years and months.

Three studies evaluated 81 patients with ISS, GHD or MHD for visual-motor skills with 

either the Developmental Test of Visual-Motor Integration or the Bender Visual-Motor Gestalt 

Test (Table 3). The testing used estimates a child’s level of perceptual-motor integration as 

evaluated by their ability to copy a series of designs. All were prospective. One was longitudinal; 

two were cross-sectional. Two were of fair quality; one was of poor quality.

Isolated Short Stature

Eleven children, aged 4 to 18 years old, with short stature due to GHD and/or other pituitary 

hormone deficiency had Bender Visual Motor Gestalt testing done by Abbott, Rotnem, Genel, et 

al. (1982) in a longitudinal, prospective study. Visual integration skills were significantly 

delayed in these children compared to population norms.

Young-Hyman (1986) evaluated 27 children with short stature who had presented to an 

endocrine clinic in a prospective, cross-sectional study. Perceptual motor skills as assessed by 

the Bender visual-motor skills were significantly delayed. The tested children had skills rated at 

9.2 y compared to their chronological age of 11.8 years. Reporting of the analysis was poor.

Growth Hormone Deficiency / Multiple Hormone deficiency

Siegel and Hopwood (1986) evaluated Bender visual-motor integration testing in 42 children 

who were 6 to 16 years old and had short stature due to hypopituitarism. Significant visual-motor 

integration deficits occurred in one-quarter of the children. This was a prospective, crosssectional study. Reporting of the analysis was poor.
38

Short Stature and Visual-Motor Skills

Three studies evaluated visual-motor skills in children with either ISS, GHD, or MHD. All 

three found that short children were significantly more likely to a reduction in visual-motor 

skills. The degree of functional deficit or disability in visual-motor skills was not reported.

Association of short stature with psychomotor development

Table 4. Association of Height to Psychomotor Development Among Children with Short Stature 

due to Medical Impairment

Author Year Sample N

(Controls)

Mean Height, 

SDS Measure Association Quality a

Russell-Silver Syndrome

Angehrn 1979 14 –4.4 DDST >90th %ile in >50% 

subjects °

DDST = Denver developmental screening test

a See Methods, Summary Tables, Study Quality.

One poor quality study evaluated 14 children with short stature due to Russell-Silver 

syndrome for psychomotor development by the Denver Developmental Screening Test (Table 4). 

Angehrn, Zachmann, and Prader (1979) conducted a prospective, longitudinal study of children

with Russell-Silver syndrome. In these children, more than half of the developmental landmarks 

evaluated by the Denver Developmental Screening Test were met at or after the age when 90% 

of average children had met that landmark.

Short Stature and Psychomotor Development

One study evaluated psychomotor development among children with Russell-Silver 

syndrome. This study found that these children tended to be delayed in meeting their early 

developmental landmarks.
39

Association of Short Stature with Behavior

Table 5. Association of Height to Teacher-Graded Behavior Problems Among Children with Short 

Stature due to Medical Impairment

Author Year Sample N

(Controls)

Mean 

Height, 

SDS

Test Total 

(Control)

Internalizing 

(Control)

Externalizing 

(Control)

School 

(Control) Quality a

Isolated Short Stature

Voss 1991 b 140 (140) RBQ 29% >9 (21%)

Disturbance

16% >3 (8%)

Hyperactivity

Voss 1994 b 132 (132) RBQ 6.2 (5.1) 1.2 (1.0)

Conduct

1.2 (1.2)

Emotion

1.7 (1.1)

Activity

Downie 1997 b 98 (115)

< –2.0

N&S 17 (14)

Locus of control

=

Gordon 1984 24 (23) –1.7 CBCL 31 (28) £

Kranzler 2000 34 (29) c –1.7 BASC 51 (50) 47 (48) 47 (46) °

Kranzler 2000 27 (29) d –2.7 BASC 50 (50) 51 (48) 50 (46) °

Growth Hormone Deficient or Constitutional Growth Delay

Steinhausen 

1976 32 (32) –2.0 HANES 13 (16)Neuroticism

11 (12)

Extraversion £

Isolated Short Stature or Russell-Silver Syndrome

Skuse 1994 17 (15) –2.5 CBCL 49 (42) NS e NS e °

Bold = significantly different from control

BASC = Behavior Assessment System for Children; CBCL = Child Behavior Checklist; HANES = Hamburg Neuroticism 

Extraversion Scale; RBQ = Rutter’s Behavior Questionnaire ; N&S = Nowicki and Strickland Locus of control scale; NS = Nonsignificant

a See Methods, Summary Tables, Study Quality.

b Voss 1991, Voss 1994, and Downie 1997 included same overall sample of subjects.

c Non-referred subjects, shortest 10% at school.

d Referred to endocrinology clinic for short stature.

e Exact data not reported.

Five studies evaluated behavior in children with short stature by a variety of tests (Table 5). 

Included tests were Child Behavior Checklist (CBCL), Hamburg Neuroticism Extraversion Scale 

(HANES), Rutter’s Behavior Questionnaire (RBQ), Nowicki and Strickland Locus of Control 

Scale (N&S), and Behavior Assessment System for Children (BASC). Only results of teachergraded tests are evaluated. A total of 274 children were evaluated and compared to controls. All 

the studies were prospective. One was longitudinal; four were cross-sectional. One set of studies 

was of good quality; two studies were of fair quality; two studies were of poor quality.

Isolated Short Stature

In three prospective, longitudinal papers (Downie, Mulligan, Stratford, et al., 1997; Voss, 

Bailey, Mulligan, et al., 1991; Voss and Mulligan, 1994) children with ISS were tested 

repeatedly at different ages. In the first study (Voss, Bailey, Mulligan, et al., 1991) of 140 short 

children between 7 and 9 years old, 29 percent were found to have a behavior disturbance 

(defined as total RBQ score greater than 9), which was somewhat higher than among control 

children (21 percent); the difference was not significant. In these same children, hyperactivity 
40

(defined as activity sub-scale score of greater than 3) occurred in significantly more short 

children than controls (16 percent versus 8 percent). As reported in Voss and Mulligan (1994) for 

a subset of 132 of the children with short stature, mean behavior scale scores for short children 

were non-significantly higher than for control children for total behavior, conduct, emotion, and 

activity, after controlling for socio-economic status. In Downie, Mulligan, Stratford, et al. (1997) 

98 of the children were evaluated at age 13 years with N&S. Locus of control score was 

significantly higher among the children with short stature.

Gordon, Post, Crouthamel, et al. (1984) evaluated 24 children aged 6 to 12 years old with 

CGD in a prospective, cross-sectional study. Behavior was assessed with CBCL. There was no 

significant difference in behavior between short stature children and controls. 

Kranzler, Rosenbloom, Proctor, et al. (2000) evaluated two groups of 6 to 12 year old 

children with ISS in a prospective, cross-sectional study. One group consisted of 34 children who 

were identified in local public schools as being in the shortest 10 percent of the class (“nonreferred”). The second group consisted of 27 children with ISS who had been referred to 

pediatric endocrinology because of short stature. Behavioral functioning was assessed with 

BASC. Both the referred and non-referred children had behavior functioning scores that were 

similar to controls.

Growth Hormone Deficient or Constitutional Growth Delay

Steinhausen and Stahnke (1976) evaluated 32 children ranging from 9 to 17 years old with 

height less than the 3rd percentile due to either hypopituitarism or familial reasons and compared 

these children to age-matched children of “normal” height. Extraversion and neuroticism were 

measured with HANES. The children with short stature had similar scores as controls. This was 

a prospective, cross-sectional study. 

Isolated Short Stature or Russell-Silver Syndrome

Skuse and Gilmour (1997) evaluated 22 children aged 6 to 12 years with Russell-Silver 

syndrome or ISS in a prospective, cross-sectional study. Among a subset of 17 short children, 

they had statistically higher total behavior scores, but similar internalizing and externalizing 

scores compared to controls. However, this was only a preliminary analysis of available data on 

a subset of the total sample. Reporting of the results was also incomplete.

Short Stature and Behavior

Three studies evaluated teacher-graded behavior among children with ISS. One study found 

that short children scored significantly worse in terms of locus of control and that significantly 

more short children were likely to have hyperactivity than normal height controls. Other tests of 

behavior were found to be similar among short and normal height children. No study described 

any functional limitations or disabilities based on behavior.

One study evaluated behavior among children with either GHD or CGD and found that 

neuroticism and extraversion scores were similar among short children and normal height 

controls. One study evaluated children with either ISS or Russell-Silver syndrome and found that 

short children had significantly more total behavior problems than normal height controls. 

Neither study described any functional limitations or disabilities based on behavior.
41

Question 2. What is the evidence that short stature (height < 5th

percentile) due to a skeletal dysplasia is disabling according to, but 

not limited to, SSA’s definition of disability? If so, are children 

disabled by virtue of their size or other features of their conditions? 

See Evidence Table 2.

We reviewed 31 papers that provided information on functional abilities among children with 

short stature due to skeletal dysplasias. As described in Evidence Table 2, a number of these 

papers probably provided analyses from the same samples of children. Two studies reported on 

different outcomes in two sets of two separate papers. One set of five papers probably included 

data from overlapping groups of the same overall sample of children. Therefore, 31 papers from 

25 study groups are summarized here. Few studies explicitly examined functional impairment, 

per se. Data are reported on the association of short stature with academic achievement, 

intelligence, psychomotor development (visual-motor skills, motor development, and motor 

development patterns), neuromuscular function, ambulation and mobility, limb range of motion, 

spinal curvature, hearing loss, respiratory dysfunction (sleep apnea and pulmonary function), and 

psychological outcomes. Detailed information on all 31 papers is reported in Evidence Table 2. 

Association of Short Stature Due to Skeletal Dysplasia with Academic 

Achievement

Table 6. Academic Achievement Score of Children with Short Stature Due to Skeletal dysplasia

Mean Academic Achievement Score

Author Year Sample N

(Controls) Test Math Reading Comprehension

Spelling Bias a Quality b

Achondroplasia

Brinkman, 1993 30 (30) c CAS 49 [55] 46 [54] d 51 [55] e 48 [56] f £

Thompson, 1999 12-15 (17) g WRAT 89 [96] 80 [95] h 88 [97] >IQ £

Osteogenesis Imperfecta

Alston, 1983 40 (40) Multi i 104 [105] j 100 [102] 102 [104] =

Mean scores in bold were significantly different than normal population; results not in bold not significantly different, except as 

noted in bias column.

Mean score for normal population for each test is 100, unless otherwise noted in brackets

CAS = Cognitive abilities score, WRAT = Wide range achievement test

a Studies noted with “>IQ” excluded subjects with low IQ or known mental impairment excluded.

Studies noted with “No stat” did not perform statistical analysis comparing IQ of subjects to normal controls

b See Methods, Summary Tables, Study Quality.

c 30 normal height controls. Also had 30 sibling controls and 30 short stature controls.

d Verbal

e Reasoning

f Total

g 17 normally developing controls. Also had 19 premature arrested hydrocephalus controls.

h Sentence writing

i Raven’s Progressive Matrices, Primary Reading Test, Wide Span Reading Test, Gapadol Reading Test, Graded Word Spelling 

Test

j Non-verbal Intelligence
42

Three studies evaluated academic achievement in 84 children with skeletal dysplasia (See 

Table 6). Two studies evaluated children with achondroplasia; one evaluated children with 

osteogenesis imperfecta.

Achondroplasia

Two studies evaluated academic achievement in approximately 43 children with 

achondroplasia. Academic achievement was measured with either the Cognitive Abilities Score 

or WRAT. The scores of the children with skeletal dysplasia were compared to controls. Both 

were prospective cross-sectional studies. Both were of fair quality.

Brinkmann, Schlitt, Zorowka, et al. (1993) performed cognitive testing, including verbal 

comprehension, arithmetic thinking, and reasoning, on children with achondroplasia. In a 

prospective, cross-sectional study, 30 subjects with a mean age of 9 years old were compared 

with 30 of their own siblings, 30 children with short stature not due to skeletal dysplasia. 

Controls were matched for age, sex, and socioeconomic status. The children with achondroplasia 

were found to have testing within the normal range, although they did score significantly lower 

than all three control groups. 

Thompson, Hecht, Bohan, et al. (1999) prospectively examined children with a mean age of 

7 years old with achondroplasia with WRAT-R, comparing them with normally developing 

controls in a cross-sectional study. In order to separate out the effect of the common 

neuroanatomic defect, hydrocephalus, from the effect of the dwarfing condition itself, they were 

also compared with 19 children born prematurely with low birthweight who had arrested, 

unshunted hydrocephalus. All results were age-corrected. The different sub-test results of the 

WRAT-R were reported for between 12 and 15 children with achondroplasia. In general, 

achondroplasia children had average cognitive abilities within 1 SD of population norms. The 

three groups had statistically similar in academic achievement. However, the small sample size 

minimized the possibility of finding statistically significant differences and children with low 

IQs were excluded.

Osteogenesis Imperfecta

One study evaluated academic achievement in children with osteogenesis imperfecta. The 

study was a prospective cross-sectional analysis of good quality. Alston (1979) evaluated 40 

children ranging from 5 to 16 years old for nonverbal intellectual ability including reading and 

spelling. The controls were chosen from the same class or neighborhood as subjects, and were 

matched for age, sex, and social class. Children with osteogenesis imperfecta had normal scores 

that were not significantly different than controls. 

Skeletal Dysplasia and Academic Achievement

Three studies examined academic achievement among children with achondroplasia or 

osteogenesis imperfecta. One found that children with achondroplasia had significantly lower 

scores on academic achievement tests than normal height children. However, among all the 

studies, children with skeletal dysplasias scored either above population norms or within 1 SD of 

normal scores. One of the studies excluded children with low IQ.
43

Association of Short Stature Due to Skeletal Dysplasia with Intelligence

Table 7. Intelligence Quotient of Children with Short Stature Due to Skeletal Dysplasia

Mean IQ Author, Year Sample N

(Controls) Test Full Verbal Performance Bias a Quality b

Achondroplasia

19 c WISC 96 95 100 Rogers, 1979 15 d BSID/SB 97 No stat £

Thompson, 1999 16 WISC 94 101 >IQ

No stat £

Hecht, 1991 13 BSID 97 No stat °

Osteogenesis Imperfecta

Reite, 1972 12 WISC 107 No stat °

Skeletal Dysplasia

22 e WISC 104 104 103 Rogers, 1979 12 f BSID/SB 100 No stat £

Shurka, 1976 7 WISC 102 103 99 No stat °

Mean scores in bold were significantly different than normal population; results not in bold not significantly different, except as 

noted in bias column.

Mean score for normal population for each test is 100, unless otherwise noted in brackets

IQ = Intelligence quotient, BSID = Bayley Scales of Infant Development, SB = Stanford-Binet Intelligence Scale; WISC = 

Wechsler Intelligence Scale for Children

a Studies noted with “>IQ” excluded subjects with low IQ or known mental impairment excluded.

Studies noted with “No stat” did not perform statistical analysis comparing IQ of subjects to normal controls

b See Methods, Summary Tables, Study Quality.

c School age children

d Preschool age children

e School age children with skeletal dysplasias other than achondroplasia

f Preschool age children with skeletal dysplasias other than achondroplasia

Five studies tested IQ in 116 children with skeletal dysplasia (See Table 7). Three studies 

evaluated children with achondroplasia; one evaluated children with osteogenesis imperfecta; 

and two evaluated children with a variety of skeletal dysplasias.

Achondroplasia

Three studies evaluated intelligence in 63 children with achondroplasia. IQs were measured 

with either Wechsler Intelligence Scale for Children, Bayley Scales of Infant Development, or 

the Stanford-Binet Intelligence Scale. The scores of the children with skeletal dysplasia were 

compared to population norms. All were prospective cross-sectional studies. Two were of fair 

quality; one was of poor quality.

In a prospective cross-sectional study by Rogers, Perry, and Rosenberg (1979), 34 children 

aged from 6 months to 15 years with achondroplasia were studied with intelligence testing. The 

mean IQ scores for both the pre-school and school age children were within the normal range. 

Thompson, Hecht, Bohan, et al. (1999) prospectively examined 16 children with a mean age 

of 7 years old with achondroplasia with intelligence testing in a cross-sectional study. 

Achondroplasia children had average cognitive abilities within 1 SD of population norms. Of 

note, though, children with low IQ were excluded from analysis.
44

In a paper by Hecht, Thompson, Weir, et al. (1991), 13 infants with achondroplasia were 

evaluated for intelligence in a prospective cross-sectional study. The children with 

achondroplasia had a mean mental developmental index within the normal range. However, a 

wide range of scores was obtained. Their results were correlated with ventricular size, degree of 

cortical atrophy, and neurological and respiratory complications. Three of the infants were also 

found to have abnormal polysomnograms showing obstructive apnea or hypoxemia. There was a 

significant correlation between an abnormal polysomnogram and a low test score. They 

concluded that the mental performance in the children with achondroplasia was average, and that 

the respiratory complications, not the achondroplasia itself, may contribute to decreased 

intellectual potential.

Osteogenesis Imperfecta

One study evaluated intelligence in children with osteogenesis imperfecta. The study was 

prospective, cross-sectional and of poor quality. Reite, Davis, Solomons, et al. (1972) evaluated 

12 6 to 17 year old children with severe osteogenesis imperfecta. The children’s mean IQ was 

somewhat above normal.

Skeletal Dysplasias

Two studies evaluated intelligence in children with a variety of skeletal dysplasias. Both 

were prospective cross-sectional studies. One was of fair quality; one was of poor quality.

In a prospective cross-sectional study by Rogers, Perry, and Rosenberg (1979), 34 children 

aged from 6 months to 15 years with skeletal dysplasias other than achondroplasia were studied 

with intelligence testing. The mean IQ scores for both the pre-school and school age children 

were within the normal range. 

In a small prospective cross-sectional study, Shurka and Laron (1976) measured IQ in 7 

children with skeletal dysplasia and a mean age of 14 years old. The children had mean IQs that 

were within the normal range. 

Skeletal Dysplasia and Intelligence

Five studies evaluated intelligence among children with achondroplasia, osteogenesis 

imperfecta and other skeletal dysplasias. The studies found no evidence of significantly impaired 

intelligence in the children. The mean IQs were all within 1 SD of population norms. None of the 

studies performed statistical analyses or reported comparisons with control groups. One study 

excluded children with low IQ from evaluation.
45

Association of Short Stature Due to Skeletal Dysplasia with Psychomotor 

Development

Table 8. Visual Motor Skills in Children with Short Stature Due to Skeletal Dysplasia

Author, Year Sample N

(Controls) Population Measure Results Quality a

Achondroplasia

Beery Visual Motor Integration 82 [92] 13 (12) Thompson, 1999 Judgment of Line Orientation 85 [100]

12 (17)

All

Fine Motor Skills (various tests) No significant difference

£

Hecht, 1991 13 Infants Psychomotor Development Index 63 (62% < 50) b °

Results in bold were significantly different than control; results not in bold were not statistically analyzed.

Results in brackets are those of normal controls.

a See Methods, Summary Tables, Study Quality.

b Population norm = 100

Table 9. Motor Development in Children with Short Stature Due to Skeletal Dysplasia

Months to Milestone, Mean Author, Year Sample N

(Controls) Population Sit Alone Stand Alone Walk Alone Quality a

Achondroplasia

Brinkmann, 1993 30 (90) All 12 [7] b 14 [10] b 18 [12] b £

Fowler, 1997 c 21-37 All 12 19 d 18 d °

Results in bold were significantly different than population means. Those not in bold were not statistically different than controls.

Results in brackets are those of normal controls.

a See Methods, Summary Tables, Study Quality.

b Results presented for normal controls (n=30). Results for sibling and other short controls were similar.

c Probable overlap of subjects with those in Pauli, Horton, Glinski, et al. (1995) in Table 10.

d Walking alone appears to have occurred earlier than standing alone due to “statistical aberration” due to different subjects’ 

parents responding to questionnaire.

Table 10. Motor Development Patterns in Children with Short Stature Due to Skeletal Dysplasia

Patterns of Development (%)

Author, Year Sample N

(Contro ls) Population Abnormal 

Arrested

Delayed 

Arrested

Normal 

Arrested Delayed Normal

Quality a

Achondroplasia

Pauli, 1995 b 52 All 10% had “disproportionate developmental delays” °

Osteogenesis Imperfecta

31 Congenita B 19 19 29 29 3

15 Tarda A 0 27 7 20 47

4 Tarda B 0 0 0 0 100

15 Type I 0 0 7 27 67

29 Type III 21 34 28 17 0

Daly, 1996

7 Type IV 0 14 14 43 29

£

a See Methods, Summary Tables, Study Quality.

b Probable overlap of subjects with those in Fowler, Glinski, Reiser, et al. (1997) in Table 9.
46

Six studies investigated psychomotor development in up to 196 children with skeletal 

dysplasia (Tables 8-10). Five considered children with achondroplasia, and one evaluated 

children with osteogenesis imperfecta. 

Achondroplasia

Five studies evaluated psychomotor development in children with achondroplasia. All were 

prospective. One was longitudinal; four were cross-sectional. Two were of fair quality; three 

were of poor quality.

Thompson, Hecht, Bohan, et al. (1999) prospectively examined 13 children with 

achondroplasia who had a mean age of 7 years old with neuropsychological testing, comparing 

them with normal controls in a cross-sectional study (See Table 8). All results were agecorrected. Achondroplasia subjects performed significantly less well in visual-motor integration 

skills than controls. Fine motor skills were not significantly different between groups, but 

children in the achondroplasia performed below average. Small sample size may have prevented 

statistical significance for some of these comparisons.

In a prospective cross-sectional study by Hecht, Thompson, Weir, et al. (1991), 13 infants 

with achondroplasia underwent psychometric testing using the Bayley Scales of Infant 

Development as part of a comprehensive neurological assessment (See Table 8). The mean 

Psychomotor Development Index component score was more than 2 SD below normal and 

almost two-thirds of subjects had scores below 50. However, psychomotor testing was not 

predictive of cognitive function in these children.

In Brinkmann, Schlitt, Zorowka, et al. (1993), a prospective, cross-sectional study, 30 

children with achondroplasia who had a mean age of 9 years old, were compared with 30 of their 

own siblings, 30 children with different skeletal dysplasias, and 30 children with short stature not 

due to skeletal dysplasia (See Table 9). Controls were matched for age, sex, and socioeconomic 

status. According to parental reports, the average age of sitting unassisted, standing alone, and 

walking alone were all delayed when compared to controls. However, statistical analyses were 

not presented. 

In a paper primarily intended to describe prospective observations of aberrant, but probably 

adaptive, pre-walking movements in children with achondroplasia, Fowler, Glinski, Reiser, et al. 

(1997) presented a cross-section of gross motor and fine motor developmental milestones for 

their patients, aged 1 to 60 months old (See Table 9). Although 93 subjects were included, only 

some children had results reported for any given item, ranging from 6 to 38 children per item. 

Subjects evaluated in this study appear to overlap with subjects included in report by Pauli, 

Horton, Glinski, et al. (1995), below. The Standard Denver Developmental Screening Test and 

Denver II Test, which rely on parent recollection and report, were used. All parameters for both 

gross motor and fine motor function were delayed when compared with published percentiles for 

average children. Specifically, the median ages at which 37, 21, and 24 children, respectively, 

were able to sit, stand, and walk unsupported were all significantly older than normal. These 

authors concluded that these delays are aberrant but not maladaptive, and different but not 

defective, representing adaptation because of biophysical abnormalities. However, their 

conclusions are hypotheses, not based on results presented in this paper.

Pauli, Horton, Glinski, et al. (1995) reported on 52 infants and young children with 

achondroplasia in a prospective longitudinal study (See Table 10). The subjects reported in this 
47

paper appear to overlap with the patients examined in Fowler, Glinski, Reiser, et al. (1997), 

described above. By history, 10 percent had disproportionate developmental delay. Many had 

other neurological abnormalities by history or by exam discussed elsewhere in this report.

Osteogenesis Imperfecta

One study evaluated psychomotor development in children with osteogenesis imperfecta. 

The study was prospective cross-sectional in design, and was of fair quality. Daly, Wisbeach, 

Sanpera, Jr., et al. (1996) compared the ability of two commonly used classifications of 

osteogenesis imperfecta to predict motor development of the child (See Table 10). By 

questionnaire, 51 children with osteogenesis imperfecta who had a mean age of 7 years old, were 

evaluated for pattern of development. Children were classified into categories described by 

Shapiro based on radiographic appearance of bones and history of fractures (Congenita A, 

Congenita B, Tarda A, and Tarda B) and into categories described by Sillence (I, III, and IV). 

Five patterns of development were described: abnormal/arrested, delayed/arrested, 

normal/arrested, delayed, and normal. Overall, approximately half the children had normal or 

only slightly delayed motor development. Only one child with osteogenesis imperfecta 

Congenita had normal development and became a walker. Only half the children with 

osteogenesis imperfecta Tarda A had normal development; the others were delayed and/or 

arrested. All four with osteogenesis imperfecta Tarda B had normal development. All children 

with Type I disease had either normal or slightly delayed development. None of those with 

osteogenesis imperfecta Type III had normal development. Of those with Type IV, 

approximately three-quarters had delayed and/or arrested development.

Skeletal Dysplasia and Psychomotor Development

Among the reviewed studies, substantial proportions of children with achondroplasia were 

found to have delayed and/or abnormal gross, fine, or visual motor development. The one study 

of children with osteogenesis imperfecta similarly found abnormal patterns of development in 

the more severely affected patients. All studies are small and used different testing instruments, 

making comparisons among studies difficult. Two studies (Fowler, Glinski, Reiser, et al., 1997; 

Pauli, Horton, Glinski, et al., 1995) reported on similar outcomes in samples of children that 

probably overlapped.
48

Association of Short Stature Due to Skeletal Dysplasia with Neuromuscular 

Function

Table 11. Neuromuscular Findings in Children with Skeletal Dysplasia

Author Year Population Sample N

(Controls) Outcome Result Quality a

Achondroplasia

Gross Motor Arm Coordination score 73 [93] b

Thompson, 1999 All 13 (13)

Gross Motor Leg Coordination score 79 [104] b

£

52 Weakness by history 14%

52 Sensory abnormality by history 4%

52 “Abnormality” by history 42%

52 Asymmetry by history 21%

52 Seizures by history 8%

44 Decreased limb tone by exam 70%

40 Abnormal arm strength by exam 32%

40 Abnormal leg strength by exam 50%

Pauli, 1995 All

39 Decreased truncal tone by exam 70%

°

Weakness by exam 31% (26%) c

Sensory deficit by exam 10% (5%) c

Hypotonia by exam 59% (49%) c

Quadriparesis by exam 15% (13%) c

Ruiz-Garcia, 1997 All 39

Compressive neural syndrome 31%

°

Reid, 1988 All 26 Paresis 42% °

Osteogenesis Imperfecta

Type I 17 4.5

Type III 11 3.5

Type IV 12

Arm strength score

4.5

Type I 17 4.8

Type III 11 3.6

Engelbert, 2001

Type IV 12

Leg strength score

0=None

5=Normal

3.8

£

Morquio Disease

Skeletal Dysplasia 

Group, 1989 All 15 “Known neurological complications” 33% °

a See Methods, Summary Tables, Study Quality.

b Significantly lower than controls

c Reported results differ in table and text (in parentheses).

Six studies evaluated neuromuscular function in 185 children with skeletal dysplasia (Table 

11). Four studies evaluated children with achondroplasia; one evaluated children with 

osteogenesis imperfecta; and one evaluated children with Morquio disease. Each study used 

different methods to measure neuromuscular function.

Achondroplasia

Four studies evaluated neuromuscular function in children with achondroplasia. All were 

prospective. Two were longitudinal; two were cross-sectional. One was of fair quality; three 

were of poor quality. 
49

Thompson, Hecht, Bohan, et al. (1999) prospectively examined 13 children with 

achondroplasia who had a mean age of 7 years old for gross motor coordination, comparing them 

with normal controls in a cross-sectional study. All results were age-corrected. Sample size for 

gross motor skills were reduced because some children were unable to complete the testing due 

to fatigue or time constraints. Achondroplasia subjects performed significantly less well in gross 

motor arm and leg coordination skills than control children.

Pauli, Horton, Glinski, et al. (1995) reported on 52 infants and young children with 

achondroplasia in a prospective longitudinal study. By history and neurological examination, 

neurological abnormalities referable to the upper cervical cord were found to be common. 

Seizures occurred in a small percentage of subjects.

Ruiz-Garcia, Tovar-Baudin, Castillo-Ruiz, et al. (1997) prospectively evaluated 39 children 

with achondroplasia who had a mean age of 4 years old in a cross-sectional study. Children who 

had had prior neurosurgery were excluded. Each had comprehensive neurological examination 

including history, physical examination, and CT imaging. The reported results for findings on 

neurological examination differed in the text from the summary table. Both sets of results are 

presented in Table 11. Hypotonia, weakness, and even quadriparesis were common. 

Furthermore, nearly a third had compressive neural syndromes confirmed by neurological 

examination, neurophysiological and neuroimaging studies. Sensory deficits were also found.

Reid, Pyeritz, Kopits, et al. (1988) conducted a prospective longitudinal evaluation of 26 

children less than 7 years old with achondroplasia. Of note, about three-quarters of the subjects 

were referred to the study because they were symptomatic. By neurological exam, 42 percent had 

varying forms of paresis, some of these children were asymptomatic. For some, this was the clue 

to the presence of cervicomedullary compression, in that the children were otherwise 

asymptomatic. The findings in this study may not be applicable to all children with 

achondroplasia because the subjects were highly selected.

Osteogenesis Imperfecta

One study evalua ted neuromuscular function in children with osteogenesis imperfecta. The 

study was of fair quality. Engelbert, Gulmans, Uiterwaal, et al. (2001), in a prospective, crosssectional study, measured muscle strength in 40 children with osteogenesis imperfecta who had a 

mean age of 12 years old. Muscle strength of upper and lower extremity muscle groups was 

measured using standardized criteria using a six point scale. All subjects had some degree of 

weakness. In children with osteogenesis imperfecta Type I, muscle strength was almost 

comparable to the healthy population. In children with osteogenesis imperfecta Type III, muscle 

strength was severely decreased in both upper and lower extremities. In those with osteogenesis 

imperfecta Type IV, muscle strength was also decreased, particularly in the lower extremities. Of 

note, the level of ambulation and functional skills regarding mobility correlated highly with 

muscle strength.

Morquio Disease

One study evaluated neuromuscular function in children with Morquio disease. The study 

was of poor quality. In a retrospective cross-sectional review of cervical spine anomalies in all 

patients on the register of the Skeletal Dysplasia Group (1989), 15 children, between ages 1 and 

15 years old, had Morquio disease. All had either hypoplasia or absence of the odontoid. Of 
50

these children, 1/3 had known neurological complications related to the odontoid abnormalities. 

The descriptions of the neurological complications were not reported.

Skeletal Dysplasia and Neuromuscular Function

Four papers that reviewed neuromuscular function in children with achondroplasia all found 

abnormalities. The three that measured strength found substantial weakness and hypotonia. 

Asymmetry, sensory deficits, poor coordination, and even seizures were found in frequencies 

higher than either controls or than expected in the healthy population. All highlighted the 

significant risk of often occult cervical cord compression in these young children. The one paper 

that evaluated osteogenesis imperfecta also found significant weakness in children who are 

moderately to severely affected. The one paper that reviewed other skeletal dysplasias found 

cervical cord complications in children with the mucopolysaccharidosis Morquio disease.

Association of Short Stature Due to Skeletal Dysplasia with Ambulation and 

Mobility

Table 12. Ambulation/Mobility of Children with Short Stature due to Skeletal Dysplasia

Ambulation Ability (%)

Author Year Without Assistance Assistance Needed Wheelchair Sample 

N

Population

C N H Th C N H Th

Quality a

Osteogenesis Imperfecta

41 Type I 59 10 12 0 5 0 7 7 0 e

11 Type III 0 0 0 0 0 9 27 19 45 Engelbert, 2000 b e

18 Type IV 28 0 0 0 11 6 11 22 22 e

=

31 Congenita B 13 0 87

15 Tarda A 60 13 27

15 Type I 93 7 0

29 Type III 3 0 97

Daly, 1996

7 Type IV 29 14 57

£

19 Type I 53c 26c 16c 5 c c c c c 0 d

13 Type III 0 0 31c 8 c 0 0

c c 61 Engelbert, 1999 b d

10 Type IV 10c 10c 10c 40c c c c c 30 d

£

Alston, 1983 40 All 38 £

17 Type I 50f

11 Type III 50 Engelbert, 2001 b f

12 Type IV 50f

°

8 Congenita 0 62 38 Norimatsu, 1982 14 Tarda 0 86 14 °

Result g Scale

Mobility = 31 16 h Type I h

Self-care = 39

Mobility = 5 8 h Type III h

Self-care = 31

Mobility = 10 6 h Type IV h

Self-care = 37

PEDI: Median of healthy children ≤ 7.5 y = 50

Mobility = 100 16 i Type I i

Self-care = 100

Engelbert, 1997 b

6 i Type III i Mobility = 70

PEDI: Normal healthy children > 7.5 y = 100

£
51

Self-care = 41

Mobility = 93 9 i Type IV i

Self-care = 62

Ambulation = 0.7 0 = None 4 = Community walker

Mobility = 3.0 0 = None 4 = Travel beyond community

Indep = 2.6 0 = None 4 = Normal activity 12 Severe 

Congenita

ADL = 2.5 0 = None possible 4 = Normal ADL

Ambulation = 2.8 0 = None 4 = Community walker

Mobility = 3.8 0 = None 4 = Travel beyond community

Indep = 3.4 0 = None 4 = Normal activity

Bleck, 1981

12 Tarda

ADL = 3.7 0 = None possible 4 = Normal ADL

£

C = Community walker, N = Neighborhood walker, H = Home walker, Th = Therapy/exercise walker

PEDI = Pediatric Evaluation of Disability Inventory; Indep = Independence, ADL = Activities of daily living

a See Methods, Summary Tables, Study Quality.

b Likely overlap in subjects among studies by Engelbert

c No distinction made between those who require assistance and those who can walk independently

d Bottom shufflers, Sit unsupported only, Sit supported only.

e Non-walkers

f Average child fell into reported category

g Engelbert, 1997: Median scores. Bleck, 1981: Mean scores.

h Children aged ≤ 7.5 years

i Children aged > 7.5 years

Eight papers evaluated ambulation and/or mobility of up to 345 children with short stature 

due to skeletal dysplasia (Table 12). All evaluated patients with osteogenesis imperfecta. 

Osteogenesis Imperfecta

Among eight studies, six reported the frequency of different ambulatory abilities. Two 

studies scored subjects on scales to estimate ambulation and mobility abilities. Four papers by 

the same authors are likely to have substantial overlap in subjects. Seven were prospective; one 

was retrospective. Three were longitudinal; five were cross-sectional. One study was of good 

quality; five were of fair quality; and two were of poor quality.

Engelbert and co-authors reported on ambulation ability on children with osteogenesis 

imperfecta in four papers with separate, but probably overlapping groups of children. The largest 

(Engelbert, Uiterwaal, Gulmans, et al., 2000) evaluated 70 children with either Type I, III, or IV 

osteogenesis imperfecta who had a mean age of 11 years old. Questionnaires were sent to parents 

of children with “definite” osteogenesis imperfecta in this prospective cross-sectional study. The 

study attempted to identify predictors of walking ability in the children. They categorized 

mobility using a nine-level classification of walking ranging from electric wheelchair bound to 

independent community walking without cane or crutches. By parent report, most children with 

Type I disease were community walkers without aides. All children were walkers, but a 

substantial percentage of children were restricted in their walking ability or required assistance 

for walking. Of children with Type III disease, almost half were wheelchair bound and all 

walkers required assistance. Of children with Type IV disease, about a quarter were community 

walkers without aids, half required assistance with walking, and about a quarter were nonwalkers. Using univariate analysis, they found that rolling over by age 8 months, sitting without 

support by 9 months, and getting to sitting or standing position without support by 12 months 
52

were all correlated with improved chances of walking. Multivariate analysis, however, showed 

that the most important predictor is the type of osteogenesis imperfecta, or severity of illness. 

Developmental milestones added little predictive value. The presence of intermedullary rods and 

dentinogenesis imperfecta were better indicators than development of worse prognosis for most 

types.

Daly, Wisbeach, Sanpera, Jr., et al. (1996) aimed to compare the ability of the two popularly 

used classifications of osteogenesis imperfecta to predict walking and general motor 

development of the child. Questionnaires were mailed to families of children with osteogenesis 

imperfecta in a prospective cross-sectional study. Questionnaires were returned for 51 children 

with a mean age of 7 years old. The children were classified into categories described by Shapiro 

based on radiographic appearance of bones and history of fractures (Congenita A, Congenita B, 

Tarda A, and Tarda B) and into categories described by Sillence (I, III, and IV). They correlated 

the classifications with ultimate progression to walking, either aided or independent. Not all 

categories had sufficient numbers of children for analysis. Substantial percentages of children 

with either Congenita B or Tarda A osteogenesis imperfecta, or with Type III or IV disease were 

either wheelchair bound or required assistance with walking. Only one child with Type I disease 

required assistance with walking. In addition they found that of those children who could sit by 

10 months, 76 percent became walkers. Of those who could not independently sit by 10 months, 

only 18 percent ultimately walked. They concluded that the Sillence classification, the Shapiro 

classification and the ability to sit independently by 10 months were all predictors of ultimate 

ability to walk in children with osteogenesis imperfecta. .

In a second report by Engelbert, Beemer, van der, et al. (1999), 42 children with a mean age 

of 7 years who had osteogenesis imperfecta were followed in a prospective, longitudinal study. 

Children who had had intramedullary fixation surgery within 6 months or who had any other 

disability or impairment were excluded. Level of ambulation was measured. At follow-up, half 

the children with Type I disease were community walkers. All attained at least some degree of 

walking. Of children with Type III disease, about 40 percent were household or exercise (therapy 

only) walkers. The rest of the children were wheelchair bound. Of children with Type IV disease, 

only 10 percent were community walkers. Most children had some walking limitation or required 

a wheelchair. For all groups of children, it was not clear how many of the children could walk 

unassisted. Of note, little progression in walking ability occurred over time, particularly in the 

more severely affected. 

In a prospective, cross- sectional study by Alston (1979), 40 children with osteogenesis 

imperfecta who ranged in age from 5 to 16 years old were evaluated. Type of mobility was 

examined in an attempt to correlate these with the subject’s type of school. Approximately onethird of the children were wheelchair bound. The ambulatory level of the walking children was 

not reported and the type and severity of osteogenesis imperfecta were not defined for these 

subjects.

The third study by Engelbert, Gulmans, Uiterwaal, et al. (2001) was a prospective, crosssectional study of 40 children with osteogenesis imperfecta who had a mean age of 12 years old. 

The study reported limited data on ambulation ability. Children were categorized by a nine-level 

classification of walking ability. The mean scores for children with each type of disease were 

reported. Type I patients had median level of 9 or independent walking. Type III patients had a 

median level of 2 or capable of at most therapy walking with the aid of crutches or canes. Type 

IV patients had a median level of 5 or capable of household walking without the use of crutches 

or canes. 
53

Norimatsu, Mayuzumi, and Takahashi (1982) published a retrospective longitudinal case 

series of 22 children with osteogenesis imperfecta who were followed for up to 20 years and 

were between 4 and 22 years at final examination. Walking ability were reported in these 

patients. Three of the eight children with osteogenesis imperfecta congenita were wheelcha ir 

bound; the remainder walked with assistance. Among children with osteogenesis imperfecta 

tarda, two of 14 were wheelchair bound; the remainder walked with assistance. The low rate of 

successful walking may have been related to a high prevalence of scoliosis in this sample of 

children.

In the fourth study by Engelbert, Custers, van der Net, et al. (1997), 61 children with 

osteogenesis imperfecta were evaluated in a prospective cross-sectional study. Children under 

age 7.5 years were evaluated separately from those who were between ages 7.5 and 18 years old. 

Mobility and self-care were evaluated by questionnaires administered to either the parents or 

children. Younger and older children with Type I osteogenesis imperfecta scored within 2 SD of 

the test’s normal median for mobility. All younger and older children with Type III disease and 

most with Type IV disease had mobility scores considerably below 2 SD from the median. 

Younger children with all types of disease and older children with Types I and IV disease scored 

within 2 SD of the test’s normal median for self-care. Only older children with Type III disease 

were likely to have self-care scores below 2 SD from the normal median.

A study by Bleck (1981) evaluated 24 children with varying degrees of severity of 

osteogenesis imperfecta who had a mean age of 13 years old at the end of the study. In this 

prospective longitudinal study children were managed with surgery as needed and orthotics 

aiming for early weight bearing in order to minimize osteoporosis thereby preventing refracture 

and deformity. Ambulation and mobility were measured using 5-point scales ranging from no 

function to no limitation. Those children with the most severe disease (osteogenesis imperfecta 

congenita) had limitations in activities of daily living, mobility efficiency, and independence and 

severe limitation in ambulation even after aggressive orthotic management. Those with the mild 

to moderate osteogenesis imperfecta tarda also had mild limitations in mobility and activities of 

daily living and moderate limitations in independence and ambulation. Despite the limitations, 

all 12 with osteogenesis imperfecta tarda attained complete independence in daily living, 

mobility and ambulation.

Skeletal Dysplasia and Ambulation/Mobility

The eight papers that evaluated mobility and ambulation in children with skeletal dysplasia 

all included only children with osteogenesis imperfecta. All found significant impairment in 

ambulation, with greater impairment, as expected, in the patients with more severe disease. 

Children with the less severe types of osteogenesis imperfecta (tarda, Type I, and Type IV) were 

more likely to attain some walking capability, but still with a significant amount of assistance. 

Few children with congenita or Type III disease had any walking ability without assistance. 

Orthopedic abnormalities such as scoliosis, decreased range of motion, decreased muscle 

strength and fracture were found to contribute to limitations of ambulation. Although all the 

studies are relatively small, they are reasonably sized given the rarity of the disorder. Information 

regarding ambulation and mobility in children with short stature due to other skeletal dysplasias 

was not found.
54

Association of Short Stature Due to Skeletal Dysplasia with Limb Range of Motion

Table 13. Limb Range of Motion in Children with Skeletal Dysplasia

Author Year Joint Scale Sample N

(Controls) Category Measure (Range) Quality a

Achondroplasia

0-2 years 11° (5°-25°)

Bailey, 1971 Elbow 3-12 years 19° (10°-40°) Angle from full 

extension 41

13-20 years 24° (0°-40°)

°

Osteogenesis Imperfecta

17 Type I 0.5

Arm 11 Type III 1.8

12 Type IV 1.3

17 Type I 0

11 Type III 3.3

Engelbert, 2001

Leg

0 = Normal

4 = Maximally 

decreased

12 Type IV 1.7

£

a See Methods, Summary Tables, Study Quality.

Two studies evaluated limb range of motion in children with short stature due to skeletal 

dysplasia (Table 13). One study evaluated children with achondroplasia. The other evaluated 

children with osteogenesis imperfecta.

Achondroplasia

One poor quality study evaluated joint range of motion in children with achondroplasia. In a 

small descriptive paper, Bailey (1971) retrospectively looked at a cross-section of 41 children 

with achondroplasia, describing upper limb bony abnormalities. The entire study included 

subjects up to 72 years old. Data are reported for infants to 20 year olds. Nine upper limb 

abnormalities evaluated. Only two were found frequently in the sample. Almost all children had 

lack of full elbow extension (93 percent) and some had limited elbow supination (34 percent). 

Other abnormalities were found infrequently. Degree of elbow flexion deformity worsened with 

age. Although these orthopedic abnormalities were found, functional limitations were not 

evaluated. However, “none of the patients volunteered disability from this problem.”

Osteogenesis Imperfecta

One fair quality study evaluated joint range of motion in children with osteogenesis 

imperfecta. Engelbert, Gulmans, Uiterwaal, et al. (2001), in a prospective, cross-sectional study, 

measured motor function, including joint range of motion (ROM) in 40 children with 

osteogenesis imperfecta who had a mean age of 12 years old. Using standard goniometry, the 

total ROM in the upper and lower extremities were measured. Measurements were evaluated 

using the Joint Alignment and Motion Scale, where a score of 0 is normal ROM and a score of 4 

is maximally decreased ROM. Subjects with Type I disease all had normal or nearly normal 

ROM in both arms and legs. Subjects with Type III disease had somewhat limited ROM in upper 

extremities and substantially limited ROM in lower extremities. Subjects with Type IV disease 
55

had somewhat limited ROM in upper and lower extremities. Of note, level of ambulation 

strongly correlated with joint ROM.

Skeletal Dysplasia and Joint Range of Motion

Two studies demonstrate upper and lower ROM abnormalities in children with 

achondroplasia and with various types of osteogenesis imperfecta. ROM limitation correlated 

with functional disability in children with osteogenesis imperfecta but not with achondroplasia.

Association of Short Stature Due to Skeletal Dysplasia with Spinal Curvature

Table 14. Spinal Curvature in Children with Skeletal Dysplasia

Author Scoliosis Kyphosis

Year

Sample N

(Controls) Population Cobb Angle % of Subjects Cobb Angle % of Subjects Quality a

Osteogenesis Imperfecta

10°-19° 19

20°-49° 14

Benson, 

1978 103 All

≥ 50° 22

£

17 Type I > 10° 12 < 10° or > 40° 12

16 Type III > 10° 63 < 10° or > 40° 75 Engelbert, 

1998 14 Type IV > 10° 71 < 10° or > 40° 29

£

5°-29° 13

8 Congenita 30°-50° 0

> 50° 87

5°-29° 62

30°-50° 15

Norimatsu

, 1982

14 Tarda

> 50° 23

°

Diastrophic Dysplasia

Poussa, 

1991 38 All > 15° 29 £

a See Methods, Summary Tables, Study Quality.

Four papers assess spinal deformities in 209 children with short stature due to skeletal 

dysplasia (Table 14). Three studied children with osteogenesis imperfecta; one studied children 

with diastrophic dysplasia.

Osteogenesis Imperfecta

Three studies evaluated spinal curvature in children with osteogenesis imperfecta. One was 

prospective studies; two were retrospective. Two were longitudinal; one was cross-sectional. 

Two studies were of fair quality; one was of poor quality.

Benson, Donaldson, and Millar (1978) evaluated children with osteogenesis imperfecta aged 

1 month to 16 years in a retrospective longitudinal study. Scoliosis was measured by 

roentgenographic measurement in 103 children. Different forms of osteogenesis imperfecta were 

not analyzed separately. Scoliosis of at least 10 degrees was found in 55 percent of the children. 

Of note, progression of curvature was common. Younger children had less curvature and older 
56

children had more. Furthermore, in patients for whom more than one radiograph was available, 

progression was almost always noted. 

Engelbert, Gerver, Breslau-Siderius, et al. (1998) reported a prospective cross-sectional study 

of 47 children with a mean age of 7 years who had osteogenesis imperfecta and were examined 

for the presence of spinal deformities. Scoliosis was defined as spinal curvature of greater than 

10 degrees. Pathologic kyphosis was defined as curvature of less than 10 degrees or more than 

40 degrees. Scoliosis was highly prevalent among children with Types III and IV disease and 

less prevalent in children with Type I disease. Kyphosis was highly prevalent in children with 

Type III disease; those with Types I and IV disease were less likely to have kyphosis. Of note, no 

significant association was found between age and presence of scoliosis or pathological 

kyphosis. Children with scoliosis were twice as likely to also have pathological kyphosis.

Norimatsu, Mayuzumi, and Takahashi (1982) published a retrospective longitudinal study of 

22 children with osteogenesis imperfecta followed over the course of 20 years. Evaluation of the 

scoliosis was performed by Cobb’s method on radiographic examinations. All children had some 

degree of scoliosis (at least 5 degrees). Most children with osteogenesis congenita had severe 

scoliosis, while most children with osteogenesis tarda had mild scoliosis. Progression of scoliosis 

was found with age, and rapid progression occurred once curvature exceeded 50 degrees. 

However, the data for these findings were not reported. Of note, multiple subjects reported were 

closely related.

Diastrophic Dysplasia

One study evaluated spinal scoliosis in children with diastrophic dysplasia. The study was 

prospective longitudinal in design and of fair quality. Poussa, Merikanto, Ryoppy, et al. (1991) 

evaluated 38 children with diastrophic dysplasia, 20 years old or younger. Scoliosis was 

measured using Cobb’s method, and was defined as curvature greater than 15 degrees. Among 

the whole group, almost a third had scoliosis. Progression of scoliosis was suggested because 

older subgroups had a higher incidence of scoliosis than younger groups. The mean magnitude 

of curvature of those with scoliosis was 39 degrees.

Skeletal Dysplasia and Spinal Curvature

Among the four studies reviewed, a high prevalence of scoliosis was found in children with 

both osteogenesis imperfecta and diastrophic dysplasia. One study also found high prevalence of 

pathologic kyphosis. None of the papers used control groups for comparison. Although two 

groups followed their patient longitudinally, progression of spinal deformity was only implied 

from comparing age groups, as paired measurements were not presented for the majority of 

subjects. All groups likely represent a selected, perhaps more severe, population of patients 

followed by academic medical centers.
57

Association of Short Stature Due to Skeletal Dysplasia with Hearing Loss

Table 15. Hearing Loss in Children with Short Stature Due to Skeletal Dysplasia

Author Year Sample N

(Controls) Population Definition Results Quality a

Achondroplasia % of Subjects

Brinkmann, 1993 27 (28, 27) b All Parental Report 63 (18, 19) c £

Ruiz-Garcia, 1997 32 All Abnormal BAER d 50% °

Osteogenesis Imperfecta % of Subjects

Kuurila, 2000 45 All Pure Tone < 20 dB

Conductive < 15 dB 7 £

Cox, 1982 15 All

Pure Tone: 

< 30 dB at < 1000 Hz

< 25 dB at > 2000 Hz

33 °

Stewart, 1987 13 All Pure Tone < 30 dB

Conductive < 15 dB 15 °

Skeletal Dysplasia Score

Achondroplasia Hearing HRQOL 95 e

Diastrophic 

Dysplasia Hearing HRQOL 93 e

Apasajalo, 1998 19 (239)

Cartilage-hair 

Hypoplasia Hearing HRQOL 85 e

£

BAER = Brainstem auditory evoked responses; HRQOL = Health Related Quality of Life

a See Methods, Summary Tables, Study Quality.

b Short controls and normal controls, respectively

c Subgroup of all 13 children with osteogenesis imperfecta

d Abnormal defined as deviation from population normals by at least 3 SD. 

e Score (where 100 is normal)

Six studies tested hearing in 151 children with skeletal dysplasia (Table 15). Two studies 

evaluated children with achondroplasia; three evaluated children with osteogenesis imperfecta; 

and one evaluated children with a variety of skeletal dysplasias.

Achondroplasia

Two prospective cross-sectional studies evaluated hearing loss in children with 

achondroplasia. One study was of fair quality; one was of poor quality.

Brinkmann, Schlitt, Zorowka, et al. (1993) evaluated 27 children with achondroplasia with a 

mean age of 9 years old in a prospective cross-sectional study. The children were compared with 

28 children with short stature not due to skeletal dysplasia and 27 normal controls. Controls were 

matched for age, sex, and socioeconomic status. Hearing deficits were present in 63% of children 

with achondroplasia as reported by their parents, compared to 18% of short stature controls and 

19% of normal controls. Statistical significance of this comparison was not reported. Hearing 

testing was performed in only some of these patients. Of those reported to have hearing deficits, 

many had middle ear disease, tympanotstomy tubes, and speech and language delay and 

difficulty.

Ruiz-Garcia, Tovar-Baudin, Castillo-Ruiz, et al. (1997) prospectively evaluated children with 

achondroplasia who had a mean age of 4 years old in a cross-sectional study. Children who had 

prior neurosurgery were excluded. In 32 children hearing was assessed with brainstem auditory 
58

evoked response (BAER) testing. Half of the subjects had abnormal BAER studies revealing 

hearing loss. It was reported that the children had middle ear lesions due to repetitive ear 

infections.

Osteogenesis Imperfecta

Three studies evaluated hearing deficits in children with osteogenesis imperfecta. All were 

prospective cross-sectional studies. One was of fair quality; two were of poor quality.

Kuurila, Grenman, Johansson, et al. (2000) evaluated 45 children with mild to severe 

osteogenesis imperfecta for hearing loss in a prospective, cross-sectional study. The children had 

a mean age of 10 years old. All subjects underwent audiometry. Only three of the 45 (7 percent) 

children were found to have hearing loss. Only two of the children, both with conductive hearing 

loss, were thought to have hearing loss related to osteogenesis imperfecta. One child had 

sensorineural deafness in the first year of life thought due to another etiology.

In Cox and Simmons (1982), a prospective, cross-sectional study, 15 children with a mean 

age of 9 years old with osteogenesis imperfecta had objective audiological evaluation. The 

children were all from five families. Five of the fifteen children (33 percent) had some degree of 

hearing loss using a standard definition. All five were characterized as mild conductive loss.

Stewart and O'Reilly (1989) reported on 13 children between 10 and 19 years old with 

osteogenesis imperfecta. Hearing was tested with audiometry. A prospective cross-sectional 

examination found that two of the children (15 percent) had hearing loss. One of these two had 

pure sensorineural hearing loss, which is not considered to be the typical hearing loss of 

osteogenesis imperfecta, but no other explanation could be found. Of the 11 with no hearing loss, 

three had abnormal tympanometry possibly suggestive of early conductive hearing loss.

Skeletal Dysplasias

One prospective cross-sectional study evaluated hearing deficits in children with a variety of 

skeletal dysplasias. The study was of fair quality. Apajasalo, Sintonen, Rautonen, et al. (1998) 

evaluated 19 adolescent patients (aged 12 to 15 years old) with either achondroplasia, diastrophic 

dysplasia, or cartilage-hair dysplasia. Hearing function was self-reported on a measure of Health 

Related Quality of Life, a validated questionnaire tool. They were compared with a large control 

group of age-matched area students who also completed the questionnaire. There was no 

difference children with skeletal dysplasias and controls in their self-report of the hearing 

dimension. No actual hearing testing was performed.

Skeletal Dysplasia and Hearing Loss

Six studies evaluated hearing loss in children with skeletal dysplasia. Only four performed 

objective hearing testing. One relied on parental reporting and one was a study of health related 

quality of life. A large proportion of children with achondroplasia were reported to have hearing 

problems, either by parental report or by BAER testing. The papers that reported on hearing 

testing in young patients with osteogenesis imperfeca all reported a sizable proportion with 

hearing loss, although the prevalence varied due to selection and small sample sizes. One study 

concluded that hearing quality of life was not different among children with a variety of skeletal 

dysplasias as normal controls.
59

Association of Short Stature Due to Skeletal Dysplasia with Respiratory 

Dysfunction

Sleep Apnea

Table 16. Sleep Apnea in Children with Short Stature Due to Skeletal Dysplasia

% with Sleep Apnea

Author Year Sample N

(Controls) Population Central 

Hypopnea

Central 

Apnea

Obstructive 

Apnea

Quality a

Achondroplasia

Waters, 1993 20 b All 75 £

Pauli, 1995 35 All 40 66 23 °

Reid, 1988 26 All 35 °

Hecht, 1991 13 All 7 c 15 °

a See Methods, Summary Tables, Study Quality.

b 15 children; 5 adults

c Hypoxemia and respiratory acidosis

Four studies evaluated sleep abnormalities in 94 children with short stature due to skeletal 

dysplasia. All evaluated patients with achondroplasia and reported the percentage of children 

with either hypopnea or apnea during sleep. All were prospective. Two were longitudinal; two 

were cross-sectional. One study was of fair quality; and three were of poor quality.

Achondroplasia

Waters, Everett, Sillence, et al. (1993) performed overnight sleep studies on 20 patients with 

achondroplasia to measure and characterize the types of apnea and other respiratory 

abnormalities in a prospective cross-sectional study. Fifteen of the subjects were aged 1 to 14 

years old; five were between 20 to 31 years old. All subjects had at least snoring, implying at 

least some degree of airway obstruction during sleep. Three-quarters had abnormal frequency of 

apnea. Of the 15 subjects with apnea, 12 had periodic breathing (called “cyclic apnea” in this 

paper) and 9 had obstructive apnea. Because the sleep apnea seen in achondroplasia is thought to 

be due to constriction of the brainstem because of abnormal shape and size of the skull base, they 

also performed a test of brainstem dysfunction, somatasensory evoked potentials (SEP) in 19. 

More than half the subjects had normal studies; abnormal results in were found in 42 percent. 

Abnormal SEP did not correlate with sleep abnormalities, and could not be used to predict the 

sleep respiratory abnormalities.

Pauli, Horton, Glinski, et al. (1995) evaluated 35 infants and young children with 

achondroplasia in a prospective longitudinal study. The children were followed for clinical 

problems attributable to cervicomedullary junction compression. Overnight polysomnography 

revealed frequent central apnea, central hypopnea, and/or obstructive apnea.

Reid, Pyeritz, Kopits, et al. (1988) conducted a prospective longitudinal evaluation of 26 

children under 7 years old with achondroplasia. Three-quarters of the children had been referred 

to the clinic for various undefined symptoms. History, physical examination, and respiratory 

evaluation including arterial blood gases, electrocardiogram, echocardiogram, chest radiograph, 
60

and multi-channel polysomnography were performed. By history 22 subjects (85 percent) had 

respiratory abnormality in the preceding 6 months, including pneumonia, loud snoring, cyanotic 

spells, or apnea. On testing, 85 percent of the subjects had respiratory abnormalities, such as 

hypoxemia, hypercapnea, pulmonary infiltrates, abnormal right systolic time intervals on 

echocardiography, right ventricular hypertrophy on electrocardiogram, and apnea. One-third of 

subjects had obstructive apnea. An unreported number of those with obstructive apnea also had 

central apnea. The subjects evaluated were highly selected patients, in that most were referred for 

respiratory and/or neurological symptoms, and the others were followed in a tertiary center.

In a prospective, cross-sectional study, Hecht, Thompson, Weir, et al. (1991) evaluated 13 

infants with achondroplasia. Four of the subjects had a history consistent with respiratory 

dysfunction, including one with tachypnea, two with obstructive apnea, and one with daytime 

apnea. Three of the infants were also found to have abnormal polysomnograms showing 

obstructive apnea or hypoxemia with respiratory acidosis. The subjects were a small, selected 

group, in that five of them were referred for symptoms of the complications they were studying.

Skeletal Dysplasia and Sleep Apnea

Of the four papers evaluating sleep and respiratory dysfunction in children with 

achondroplasia, all found a high incidence of abnormality, including central hypopnea, central 

apnea, and obstructive apnea. All four papers, however, reported on small groups; two of which 

were highly selected samples. 

Pulmonary Function

Table 17. Pulmonary Function in Children with Short Stature Due to Skeletal Dysplasia

Pulmonary Function

Author Year % Predicted or mm Hg Sample N

(Controls) Population

FVC RV FEV1 / FVC P O2 P CO2

Quality a

Achondroplasia

Stokes, 1988 24 All 72% b £

Osteogenesis Imperfecta

Falvo, 1973 10 All 85 c 119 c 99 88 35 £

FVC = Forced vital capacity; FEV1/FVC = Forced expiratory volume in 1 second divided by forced vital capacity; P O2 = 

Oxygen partial pressure; P CO2 = Carbon dioxide partial pressure; RV = Residual volume

a See Methods, Summary Tables, Study Quality.

b Significantly lower than population norms

c Reduction of FVC and increase in RV were found only in subjects with kyphoscoliosis

Two studies measured pulmonary function in children with skeletal dysplasias (Table 17). 

One study evaluated children with achondroplasia. The other evaluated children with 

osteogenesis imperfecta.
61

Achondroplasia

One study of fair quality evaluated pulmonary function in children with achondroplasia. 

Using a prospective, cross-sectional cohort design, Stokes, Pyeritz, Wise, et al. (1988) 

systematically measured pulmonary function tests in 24 children under age 18 years old with 

achondroplasia. Mean forced vital capacity for the group of children was significantly lower than 

predicted values for children with comparable sitting height. Although only a small number of 

children were included, the sample evaluated was relatively unselected, and probably is broadly 

representative of the average child with achondroplasia.

Osteogenesis Imperfecta

One study of fair quality evaluated pulmonary function in children with osteogenesis 

imperfecta. Falvo, Klain, Krauss, et al. (1973) performed pulmonary function testing on 10 

children between ages 4 and 19 years old with osteogenesis imperfecta of varying severity. 

While it was implied that the data were collected prospectively for a cross-section of patients, the 

study methodology is unclear. Results were compared with population norms. Vital capacity and 

residual volume were abnormal only in the four subjects who also had kyphoscoliosis. No patient 

had severe hypoxemia or hypercapnea. Other parameters of pulmonary function were within 

normal limits. The number of subjects is small, and no statistical comparisons were reported. 

Skeletal Dysplasia and Pulmonary Function

One study found abnormal pulmonary function in a small group of children with 

achondroplasia. A second study found no significant abnormality in a smaller group of children 

with osteogenesis imperfecta.

Association of Short Stature Due to Skeletal Dysplasia with Psychological 

Outcomes

Table 18. Psychological Outcomes in Children with Skeletal Dysplasia

Author, Year Sample N

(Controls) Population Measure Results a Quality b

Skeletal Dysplasia

BDI score (mean) 6.5 [6.4]

Moderate to severe depression (%) 7% [11%]

SSTAI score- State (mean) 27.6 [27.9]

Hunter, 1998 55 (37) Not defined

SSTAI score- Trait (mean) 32.5 [31.7]

£

BDI = Beck Depression Inventory; SSTAI = Spielberger State-Trait Anxiety Inventory Score

a Results of normal controls are in brackets.

b See Methods, Summary Tables, Study Quality.
62

Only one paper was found that adequately studied the association of short stature due to 

skeletal dysplasia with psychological outcomes (Table 18). It was a prospective cross-sectional 

study that was of fair quality. Hunter (1998) evaluated 55 children aged less than 15 years old 

with the diagnosis of primary skeletal dysplasia. Levels of depression and anxiety were assessed 

using the Beck Depression Inventory, childhood version, and the Spielberger State-Trait Anxiety 

Inventory, respectively. Average scores on the Beck inventory and percentage of children with 

moderate or severe depression were similar for children with skeletal dysplasia as their sibling 

controls. Likewise, Spielberger inventory scores for both state (current level of anxiety) and trait 

(proneness toward developing anxiety) were similar for children with skeletal dysplasia and 

controls. In fact, the trait anxiety scores for children were below (implying less anxiety) general 

population norms. 

The single study of depression and anxiety among children with skeletal dysplasias found no 

evidence for increased rates of depression or anxiety.

Question 3. What is the evidence that a sustained decrease in linear 

growth velocity can be used as a marker of severity of an underlying 

disease? Is such a process likely to be disabling? 

See Evidence Table 3.

We reviewed 53 articles that evaluated whether a sustained decrease in linear growth velocity 

can be used as a marker of the severity of 12 medical conditions and whether such a process is 

likely to be disabling. One study separately evaluated children with both asthma and congenital 

heart disease. The evidence from four conditions - congenital heart disease, Crohn’s disease, 

juvenile rheumatoid arthritis, and human immunodeficiency virus (HIV) infection - appear to 

indicate that a sustained decrease in linear growth velocity can be used as a marker of the 

severity of these underlying conditions. Evidence is less clear for asthma, diabetes, ßthalassemia, chronic kidney failure, and atopic dermatitis. There was only one study each for 

cerebral palsy, sickle cell anemia and congenital adrenal hyperplasia, so it is difficult to draw 

conclusions for these conditions. None of the studies addressed the question of whether the 

process of having a decreasing linear growth velocity was likely to be disabling. Detailed 

information on all 31 papers is reported in Evidence Table 3.
63

Association of Severity of Asthma with Decreased Growth Velocity

Table 19. Height Association with Severity of Asthma

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

Low potency 

medications

Neville 1996 ÇÇÇ 699 Asthmatic 

children High dose 

inhaled 

steroids

£

Mild - Severe Age 10 y Very severe

Mild - Severe Age 14 y Very severe Martin 1981 ÇÇÇ 315 d

Age 21 y Mild - Very 

severe

£

McNicol 1970 ÇÇÇ 226 Asthmatic 

children

Frequency of 

asthma 

episodes

£

Rona 1980 ÇÇÇ 102 Asthmatic 

children

Frequency of 

asthma 

episodes

 unadjusted

 adjusted e

 unadjusted

 adjusted e £

500 Class II-IV 

(Osváth)

CARA vs 

asthma vs 

asthma 

w/eczema

Hauspie 1979 ÇÇ 

607

Asthmatic 

boys

Steroid 

requirements

£

Sant’Anna 

1996 ÇÇ 514 Asthmatic children Mild - Severe £

Spock 1965 ÇÇ 200 Asthmatic 

children

Poor -

Excellent £

Ferguson 

1982 Ç 36

Short 

asthmatic 

children

Mild-Severe £

Cernelc 1975 ÇÇ 337 Asthmatic 

children

Pulmonary 

function °

Klein 1991 ÇÇ 176

Non-steroiddependent 

asthmatic 

MildModerate °

Balfour-Lynn 

1986 ÇÇ 66 Asthmatic children

Medications 

required

 initial 

height

 adult 

height

°

CARA = Chronic aspecific respiratory affection

a See Methods...
64

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe asthma associated with growth retardation (or no statistical analysis)

More severe asthma significantly associated with growth retardation

No association between asthma severity and growth retardation.

d Same children at different ages.

e Adjusted for parental height, socioeconomic status, and number of siblings.

Eleven studies evaluated the association between severity of asthma and height or height 

velocity in 3,778 children (Table 19). Only three of the studies measured height velocity; 10 

studies measured only the association of severity of disease with height. Each study used its own 

definitions of severity of disease classifications. Five used various scales to directly measure 

severity, two measured frequency of asthma episodes, two graded severity based on medication 

requirements, one measured pulmonary function, and one used a disease severity scale in one 

group of children and both disease subtypes and steroid requirements in a second group of 

children. Seven studies were prospective; four were retrospective. Six studies were longitudinal; 

five were cross-sectional. No study was of good quality; nine were of fair quality, and two were 

of poor quality.

In a secondary analysis of a prospective longitudinal cohort of 2,915 children with asthma, 

Neville, McCowan, Thomas, et al. (1996) evaluated height measurements in 699 children aged 3 

to 13 years old. Children were grouped based on their medication requirements over the previous 

year. Only children who required high dose inhaled steroids had a mild decrease in height in 

comparison to the general local population. Children who required less intense therapy were of 

equivalent height in comparison to the general local population. Height velocity was not 

measured.

Martin, Landau, and Phelan (1981) reported on a prospective longitudinal cohort study of 

315 children with asthma who were examined at 10, 14 and 21 years of age. Disease severity 

was based on the frequency and recency of wheezing episodes. Height percentile was compared 

to that of 62 non-asthmatic children evaluated at the same ages. Children with very severe 

asthma were significantly more likely to have height less than tenth percentile than nonasthmatic children at 10 and 14 years old, but by 21 years of age, there was no significant 

difference in the prevalence of height less than tenth percentile between groups. Height velocity 

was not measured.

Mcnicol, Williams, and Gillam (1970) reported on a prospective longitudinal cohort study of 

226 children with asthma and 94 controls at age 10 years. Asthmatic children were grouped as 

mild, moderate and severe based on number of episodes of asthma by age 10 years and 

symptoms within 12 months of examination. Children with asthma were evaluated for height and 

compared to non-asthmatic controls. There was no significant difference in height found between 

the control group and any group of asthmatic children regardless of degree of severity of asthma. 

Height velocity was not measured.

In a retrospective cross-sectional study of 102 5 to 11 year old children attending primary 

school in the United Kingdom, Rona and du (1980) reported on children identified with asthma 

based on parental report. Severity of disease was graded by number of asthma episodes a year. 

Height velocity, measured as centimeters gained in the previous 12 months, was lower for both 

boys and girls with more frequent asthma (3 or more asthma episodes per year) than for children 

with less frequent asthma, who also had lower height velocity than non-asthmatic controls. 

However, the difference in height velocities were not statistically significant in unadjusted 
65

models or models that adjusted for parental height, social class, and number of siblings. In both 

unadjusted and adjusted models, children with frequent asthma were significantly shorter (mean 

of –0.4 SDS) than controls. Children with less frequent asthma were of similar height as controls.

In a retrospective cross-sectional study, Hauspie, Gyenis, Alexander, et al. (1979) reported 

on two different samples of 3 to 16 year old boys with asthma (500 Hungarian boys in 

institutional setting and 607 Belgian boys who were a sub-sample of a longitudinal growth 

study). Among the Hungarian boys, severity of disease was based on Osvath (1976). Belgian 

boys were categorized as having either chronic aspecific respiratory affection, asthma alone, or 

asthma with eczema; steroid requirements were also measured. The study found similar results 

for both groups. Height was retarded in subjects with more severe disease and longer duration of 

corticotherapy. It is unclear if those with more severe disease had more steroid use. Height

velocity was not measured.

Sant'Anna, Sole, and Naspitz (1996) reported a retrospective cross-sectional case series of 

514 6 month to 16 year old children with various degrees of asthma. Children were measured 

upon admission to an asthma/allergy clinic. Asthma severity was based on the International 

Consensus Report on Diagnosis and Treatment of Asthma (International consensus report on 

diagnosis and treatment of asthma, 1992). Heights were compared to National Standards for age 

(National Center for Health Statistics standard) and the number of children with heights less than 

third percentile were noted. No significant increase in short stature was noted for the asthmatics 

in this study. Moreover, age, asthma severity, and steroid use had no statistically significant 

effect on heights of these asthmatic children. Height velocity was not measured.

Spock (1965) reported on a retrospective longitudinal cohort study of 200 children with 

asthma (initial age 4-12 years old) who had growth parameters followed for at least 4 years. 

Asthma severity was graded poor to excellent, although the scale was not defined. Height 

velocity was approximately normal in all groups of children. Children with excellent clinical 

status had height velocity 9 percent above normal values established by the Child Research 

Council of the University of Colorado. Children with good clinical status had height velocity 7 

percent above normal, those with fair clinical status had height velocity 2 percent above normal, 

and those with poor clinical status had height velocity 3 percent below normal. These differences 

were not statistically different. The study also found that appropriate asthma therapy did not 

result in a growth spurt, but that steroid therapy dosage and duration was associated with 

retarded growth in asthmatic children. 

Ferguson, Murray, and Tze (1982) evaluated 36 3 to 17 year old asthmatic children with 

short stature (height less than third percentile) in a prospective longitudinal study. Disease 

severity was based on wheezing frequency and duration, therapy requirements and duration. No 

significant association was found between height and severity of asthma. Height velocity was not 

measured.

Cernelc and Cernelc (1974) reported on a prospective cross-sectional study of 337 asthmatic 

children. The children’s ages were not reported. Asthma severity was based on normal versus 

abnormal pulmonary function tests. No significant difference in height was found between the 

two groups of children. Height velocity was not measured.

In a prospective cross-sectional study Klein, Dungy, and Galant (1991) evaluated 176 2 to 15 

year old children with non-steroid dependent asthma. Asthma severity was based on 

hospitalization and medication requirements over the previous year. No significant difference 

was found between the height and asthma severity. Height velocity was not measured.
66

Balfour-Lynn (1986) reported on a prospective longitudinal study of 66 2 to 12 year old 

children who were followed for height from entrance into a pediatric asthma clinic until they 

reached adult heights. Disease severity was based on medication requirements. No significant 

difference was found “growth retardation,” although this term was not defined. The proportion of 

children with height less than the tenth percentile was similar in all groups; no child had height 

below the third percentile. All children “grew along expected centile lines without appreciable 

deviation... until age 10 years, regardless of treatment required.”

Among the 11 reviewed studies, the evidence of the association between asthma severity and 

children’s heights were mixed. Four studies found a significant association between the severity 

of asthma and height; one found a non-significant trend toward an association; and five found no 

association between asthma severity and height. No study found an association between mild 

asthma and growth retardation. The three studies that examined the association of asthma 

severity and height velocity did not find a statistically significant association between the two, 

although two studies found a possible trend toward slower height velocity with more severe 

asthma.

Poorly defined samples, limited data and analysis, missing data and varying definitions of 

disease severity limited these studies. Asthma severity was commonly defined by medication 

requirements, including steroid treatment. The underlying question of how growth is affected by 

severity of asthma is not clearly answered by these studies in part due to lack of consistency in 

defining asthma severity between the studies as well as differences in the treatment of asthma in 

the studies.

Association of Severity of Congenital Heart Disease with Decreased Growth 

Velocity

Table 20. Growth Retardation Association with Severity of Congenital Heart Disease

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

Levy 1977 ÇÇ 777 Ventricular 

septal defect

Severity 

based on 

pressure and 

resistance

£

Cyanosis

Cardiac 

enlargement 181

Congenital 

heart 

disease, 

Age 0-2 y Congestive 

heart failure

Cyanosis

Cardiac 

enlargement

Strangway 

1976 ÇÇ 

387

Congenital 

heart 

disease, 

Age 2-11 y Congestive 

heart failure

£

Baum 1980 ÇÇ 26

Congenital 

heart 

disease

Congestive 

heart failure £
67

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

73

Aortic or 

pulmonary 

stenosis

Valvular 

gradient > 50 

mm Hg

83 Tetralogy of 

Fallot

Various 

including 

hemoglobin

Feldt 1969 ÇÇ 

155 Ventricular 

septal defect

Pulmonary 

vascular 

pressure

°

Cernelc 1975 ÇÇ 22

Congenital 

heart 

disease

Cyanosis °

White 1970 Ç 80

Congenital 

heart 

disease

Cyanosis °

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe cardiac disease associated with growth retardation (or no statistical analysis)

More severe cardiac disease significantly associated with growth retardation

No association between cardiac disease severity and growth retardation.

Six studies evaluated the association between severity of congenital heart diseases and height 

or height velocity in 1,784 children (Table 20). Only one study measured height velocity; the 

other five measured only the association of severity of disease with height. Each study used its 

own definitions of disease classifications. Multiple different heart defects were examined. Five 

studies were prospective; one was retrospective. Three studies were longitudinal; three were 

cross-sectional. No study was of good quality; three were of fair quality; and three were of poor 

quality.

Levy, Rosenthal, Miettinen, et al. (1978) evaluated 777 children with ventricular septal 

defect (VSD) with a mean age of 4 years old in a retrospective longitudinal study. Subjects were 

evaluated for growth and hemodynamic severity based on pulmonary artery pressure and 

systemic resistance ratio. The study found that children with VSD had subnormal height, 

regardless of the severity of the defect and that the more severe the hemodynamic disturbance, 

the shorter the children. Height velocity was not evaluated.

Strangway, Fowler, Cunningham, et al. (1976) evaluated two groups of children with a 

variety of congenital heart defects in a prospective longitudinal study. The study evaluated 181 

infants to age 2 years and 387 children between 2 and 11 years old. Children with additional 

major congenital lesions or who had undergone corrective cardiac surgery were excluded. The 

children were classified by the presence of cyanosis, cardiac enlargement, and congestive heart 

failure. Overall, short stature was uncommon and growth rates were close to normal for both 

infants and children. Among cyanotic infants, height velocities were significantly delayed 

compared to those infants without cyanosis. Cyanosis was not associated with height velocity in 

older children. Cardiac enlargement and congestive heart failure were not significantly 

associated with height velocity in either infants or children.

In a prospective cross-sectional study Baum, Beck, Kodama, et al. (1980) evaluated 26 

children with a variety of acyanotic congenital heart diseases and a mean age of 4 years. Disease 
68

severity was based on congestive heart failure (CHF), although this was not defined. The study 

found that children with acyanotic congenital heart disease with CHF had a significant reduction 

in height (by 5 to 9 cm) in comparison to children without CHF. Furthermore, half the children 

with CHF had height less than the fifth percentile, while none of the children without CHF did. 

Height velocity was not analyzed.

Feldt, Strickler, and Weidman (1969) reported on 311 children of all ages with a variety of 

congenital heart diseases in a prospective longitudinal study. For children with aortic or 

pulmonary stenosis, disease severity was based on valvular gradient. For children with tetralogy 

of Fallot, disease severity was based on cyanosis, hematocrit level, magnitude of shunt, and 

history of hypoxemia. For children with VSD, disease severity was based on pulmonary vascular 

pressure. Growth failure was based on both height and weight being more than 2 SD below the 

mean. Among the 73 children with valvular stenoses, those with pressure gradients above 50 mm 

Hg were more likely to have “severe growth failure.” Among the 83 children with tetralogy of 

Fallot, growth failure was not associated with any of the measures of defect severity. Among the 

155 children wit VSD, growth failure was not associated with pulmonary vascular pressure. 

However, no statistical analyses were explicitly reported. Height velocity was not analyzed.

Cernelc and Cernelc (1974) evaluated 22 children with congenital heart disease in a 

prospective cross-sectional study. The age of the children and the types of heart defects among 

the children were not reported. Disease severity was based on the presence of cyanosis. The 

study found that children with cyanotic congenital heart disease were significantly shorter than 

the general population while those without cyanosis were not significantly different in height 

than the general population. Height velocity was not analyzed.

White, Jr., Jordan, Fischer, et al. (1971) evaluated 80 12 to 18 year old children with a 

variety of congenital heart diseases in a prospective cross-sectional study. Children who had 

undergone total corrective surgery for tetralogy of Fallot were excluded. Disease severity was 

based on the presence of cyanosis. Of the children with cyanosis, 19 percent had height less than 

the second percentile compared to only 2 percent of the children without cyanosis. However, no 

statistical analysis was performed. Height velocity was not analyzed. 

Among the reviewed studies, there was general agreement that those children with more 

severe congenital heart disease were more likely to have growth retardation. One study, however, 

found no association between height and severity of either tetralogy of Fallot or VSD. Only one 

study evaluated height velocity and found that reduced height velocity was associated with 

cyanosis in infants; however, the association was not found in older children. They also found a 

trend toward reduced height velocity being associated with the presence of CHF. Many studies 

were limited by incomplete data and statistical analysis and some studies were limited because 

they excluded children with the most severe congenital heart defects.
69

Association of Severity of Insulin Dependent Diabetes Mellitus with Decreased 

Growth Velocity

Table 21. Growth Retardation Association with Control / Severity of Insulin Dependent Diabetes 

Mellitus

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

Wise 1992 ÇÇÇ 122 Type I DM Hgb A1c =

Soliman 1996 ÇÇÇ 45 Type I DM Hgb A1c > 10% =

Court 1982 ÇÇÇ 111 Diabetes Glucosuria £

Izumi 1995 ÇÇÇ 107 Type I DM Hgb A1c £

Salardi 1987 ÇÇÇ 79 Type I DM Hgb A1c £

Pitukcheewanont 1995 ÇÇ 82 Type I DM Hgb A1c

 unadjusted

 adjusted d

£

Arreola 1991 ÇÇÇ ~198 Type I DM Hgb A1c °

Rosenbloom 

1982 ÇÇ 142 Type I DM Limited joint mobility °

Jivani 1973 ÇÇ 104 Diabetes Poor or Good °

Herber 1988 ÇÇ 67 Type I DM Hgb A1c °

Vanelli 1992 Ç 42 Type I DM 

pubertal girls

Insulin 

requirement °

DM = Diabetes mellitus; Hgb A1c = Glycosylated hemoglobin

a See Methods...

b Univariate analysis, unless noted otherwise.

c More severe diabetes significantly associated with growth retardation

No association between diabetes severity and growth retardation.

d Multivariate analysis adjusting for age of diabetes onset and initial height

Eleven studies evaluated the association between severity of diabetes mellitus and height or 

height velocity in 1,099 children (Table 21). Nine of the studies clearly include only children 

with Type I diabetes; the remaining two only imply that they are evaluating insulin dependent 

diabetes. No study explicitly evaluates children with Type II diabetes. All but two of the studies 

measured height velocity. Six studies measured the association of severity of disease with height. 

Various definitions of severity of disease were used. Seven used glycosylated hemoglobin (i.e., 

hemoglobin A1c, Hgb A1c) levels to determine disease severity. The remaining studies use either 

glucosuria, limited joint mobility, insulin requirements, or a scale based on a variety of signs and 

symptoms. Five studies were prospective; six were retrospective. Ten studies were longitudinal; 

one was cross-sectional. Two studies were of good quality; four were of fair quality, and five 

were of poor quality.

Wise, Kolb, and Sauder (1992) evaluated 122 children with Type I diabetes in a prospective 

longitudinal study over a 5-year period. No data were reported on the age of the children. Height 

velocity and glycemic control, using Hgb A1c levels, were assessed. A significant linear 

relationship was seen between Hgb A1c and growth velocity. The most severe growth retardation 
70

occurred when Hgb A1c levels were greater than 16 percent. These children had average height 

velocity 0.07 SDS below the mean. In contrast, Hgb A1c levels less than 8 percent were 

associated with growth acceleration; average height velocity was 0.10 SDS above the mean. The 

level of Hgb A1c at which growth suppression occurred was dependent on pubertal status. 

Children who were prepubertal or in the early stages of puberty were most vulnerable to growth 

suppression. For these children growth suppression was seen with Hgb A1c greater than 8 

percent.

In a prospective longitudinal study Soliman, Ahmed, and Asfour (1996) evaluated 45 

children aged 2 to 12 years with Type I diabetes who had height velocity and glycemic control 

evaluated. Good glycemic control was defined as Hgb A1c less than 10 percent. Children with 

good glycemic control had significant higher growth velocity (mean +0.75 SDS) than those with 

poor glycemic control (mean –1.6 SDS).

Court, Parkin, Roberts, et al. (1982) evaluated 121 diabetic children with a mean age of 13 

years in a retrospective cross-sectional study. The study implied only that the subjects all had 

Type I diabetes. Diabetic control was measured by urinary glucose score or by 24-hour urinary 

glucose excretion. Children whose diabetes was under poor control had average height 

(–0.96 SDS) that was significantly lower than those under good control (–0.22 SDS). Likewise, 

average height velocity was significantly lower for children under poor control 

(–1.22 SDS) than those under good control (–0.61 SDS).

Izumi, Hoshi, Kuno, et al. (1995) evaluated 107 Type I diabetic children with a mean age of 

14 years old in a retrospective longitudinal study. Severity of diabetes was based on Hgb A1c 

levels and were graded mild (less than 10 percent), moderate (10 to 12 percent) and severe (more 

than 12 percent). The study found no height and diabetic control. Height velocity was not 

evaluated.

Salardi, Tonioli, Tassoni, et al. (1987) evaluated 79 children ranging in age from 1 to 15 

years with Type I diabetes in a prospective longitudinal study. Diabetics control was measured 

by Hgb A1c levels. Height and height velocity were not associated with diabetic control.

In a retrospective longitudinal cohort study Pitukcheewanont, Alemzadeh, Jacobs, et al. 

(1995) evaluated 82 children with Type I diabetes with a mean age of 11 years old over a 6-year 

period. Glycemic control was determined with Hgb A1c levels. There was no association between 

mean Hgb A1c and height in univariate or multivariate analyses. There was also no association 

between Hgb A1c and height velocity at any Tanner stage in univariate analysis.

Arreola, Junco, Partida-Hernandez, et al. (1991) reported on a retrospective longitudinal 

cohort study of about 198 children with Type I diabetes. The children’s medical records were 

examined yearly for five years. They were between 1 and 16 years old in the first year evaluated. 

The exact number of children included varied from year to year. Diabetic control was based on 

Hgb A1c levels. Children with poor control (Hgb A1c greater than 11 percent) had significantly 

lower height velocity (approximately 0.54 cm/month) compared to those with good control 

(approximately 0.22 cm/month). Overall, there was a significant correlation between Hgb A1c 

level and height velocity.

Rosenbloom, Silverstein, Lezotte, et al. (1982) performed a prospective longitudinal cohort 

study of 142 pre-pubertal children with diabetes who had had diabetes for at least 3 years. The 

study used joint mobility as an indication of severity of microvascular disease. Diabetic children 

with mild, moderate or severe limitations of joint mobility were significantly more likely to be 

below the 25th percentile for height than those without limited joint mobility. However, the 

correlation between Hgb A1c and joint mobility was poor. There were no data on height velocity
71

Jivani and Rayner (1973) evaluated 104 diabetic children aged between 9 months and 13 

years old in a retrospective longitudinal study. Diabetes control was measured good, fair or poor 

based on ketonuria, glycosuria, serum glucose, and hypoglycemic reactions. Data on subjects 

with “fair” control were not reported. Height and height velocity were not associated with 

severity of diabetes. 

Herber and Dunsmore (1988) evaluated 67 children with Type I diabetes who had an initial 

mean age of 11 years and were followed over 3 years in a retrospective longitudinal study. 

Disease severity was based on Hgb A1c levels. The study found no association between change in 

height and Hgb A1c. Height velocity was also similar to the general population. The range of 

diabetes severity was somewhat limited in that, in general, the study population was in good 

control.

Vanelli, de Fanti, Adinolfi, et al. (1992) evaluated 42 girls with Type I diabetes who became 

diabetic at the onset of puberty in a prospective longitudinal study. Diabetes severity was insulin 

requirements. It is likely that the children were stratified into high and low insulin requirement 

groups post hoc. The children treated with greater amounts of insulin had lower mean Hgb A1c (9 

percent) and significantly higher mean peak height velocity (8.5 cm per year) than those treated 

with less insulin (Hgb A1c 10 percent; peak height velocity 6.9 cm per year).

Among the reviewed studies, there were mixed results correlating severity of diabetes with 

height and height velocity. Five studies demonstrated a positive relationship between poor 

diabetes control/increased severity of disease and decreased growth velocity; four studies found 

no association. Two studies found an association between markers of severity of diabetes and 

height; three found no association. Several studies associated growth deceleration with 

peripubertal onset of illness. Some studies were limited because they did not use a well-defined, 

objective measure like Hgb A1c to assess severity/control. Some studies were limited by unclear 

statistical analysis, lack of specific data included or summary results.

Association of Severity of b -Thalassemia with Decreased Growth Velocity

Table 22. Growth Retardation Association with Hemoglobin Level / Severity of b-Thalassemia

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

Kattamis 1970 ÇÇÇ 74 β-thalassaemia Hemoglobin °

Madeddu 1978 ÇÇÇ 50 β-thalassaemia Hemoglobin °

β-thalassemia 

severity index d

Hemoglobin d

Constantoulakis 

1975 ÇÇ 171 β-thalassaemia

Total blood 

transfusion

d

°

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe β-thalassemia associated with growth retardation (or no statistical analysis)

More severe β-thalassemia significantly associated with growth retardation

No association between β-thalassemia severity and growth retardation.

d Linear regression model adjusting for age and other variables listed.
72

Three studies evaluated the association between severity of β-thalassemia and height in 295 

children (Table 22). None of the studies measured height velocity. All the studies used 

hemoglobin levels to grade severity of disease. One study also used a severity index and blood 

transfusion requirements to grade disease severity. Two were prospective cross-sectional studies; 

one was a retrospective longitudinal study. All studies were of poor quality.

In a prospective cross-sectional study, Kattamis, Touliatos, Haidas, et al. (1970) evaluated 74 

children aged 1 to 11 years old with homozygous β-thalassemia. Subjects height percentiles were 

compared in reference to the severity of their anemia. Severity of anemia was determined by pretransfusion hemoglobin (Hgb) concentration. Children were transfused either when Hgb was at 

levels greater than 8 mg/dL, between 6 and 8 mg/dL, or below than 6 mg/dL. Children with 

higher pre-transfusion Hgb were significantly taller (mean height of 56th percentile) than children 

with moderate Hgb levels (22nd percentile) and lower Hgb (7th percentile). However, the study 

may have confounded disease severity with treatment options. The children in the moderate 

anemia group were not followed as regularly and were either of low socioeconomic status or had 

to travel long distances for transfusion. The children in the severe anemia group mostly were 

allowed to have their Hgb levels fall below 5 mg/dL before transfusion. Height velocity was not 

evaluated.

Madeddu, Dore, Marongiu, et al. (1978) evaluated 50 children with homozygous βthalassemia ages 2 to 13 years old in a prospective cross-sectional study. Severity of disease was 

based on pre-transfusion Hgb levels. Children with height less than the 3rd percentile had 

somewhat lower mean Hgb (6.6 g/dL) than taller children (approximately 7.1 g/dL). There was 

no significant association between Hgb level and height. Height velocity was not evaluated.

In a retrospective longitudinal, Constantoulakis, Panagopoulos, and Augoustaki (1975) 

evaluated 171 patients aged 7 months to 28 years with homozygous β-thalassemia. A variety of 

measures were used to determine disease severity. These measures were included in a multiple 

regression analysis to determine the association between height and the measures. A “severity of 

disease index” was created that was based on the amount of blood transfused in the previous two 

years. The regression also included total blood transfused since birth, mean Hgb level of the 

previous two to four years, and age. Of note is that none of the variables included in the model 

are independent of other included variables. In the model there was a trend toward lower height 

percentiles being associated with low Hgb levels and severity of disease index; however, neither 

was statistically significant in a linear regression controlling for age. Total blood transfused since 

birth was not associated with height. Height velocity was not evaluated.

Among the three reviewed studies, the evidence of the association between β-thalassemia 

severity and children’s heights was inconclusive. One study found a significant association 

between pre-transfusion Hgb and height. However, the study may have confounded underlying 

severity of disease with treatment choices. Another study may have found some evidence of an 

association between disease severity and height, but the value of their finding is limited by the 

poor regression technique used. The third study found no association, although a trend may have 

been indicated.
73

Association of Severity of Inflammatory Bowel Disease with Decreased Growth 

Velocity

Table 23. Growth Retardation Association with Severity of Inflammatory Bowel Disease

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

29 UC 

Saha 1998 ÇÇÇ 

18 Crohn’s

Disease 

severity £

Frequency / 

Chronicity d

Griffiths 1993 ÇÇ 100 Crohn’s Disease 

location

£

Farmer 1979 ÇÇ 513 Crohn’s Disease 

location °

UC = Ulcerative colitis

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe inflammatory bowel disease associated with growth retardation (or no statistical 

analysis)

More severe inflammatory bowel disease significantly associated with growth retardation

No association between inflammatory bowel disease severity and growth retardation.

d Linear regression adjusting for corticosteroid use.

Three studies evaluated the association between severity of inflammatory bowel disease and 

height in 660 children (Table 23). Two of the studies measured height velocity. The studies used 

various measures to grade severity of disease, including disease location. All were retrospective 

longitudinal studies. Two studies were of fair quality; one was of poor quality.

Saha, Ruuska, Laippala, et al. (1998) evaluated 47 prepubertal children with a mean age of 7 

years old who had either ulcerative colitis or Crohn’s disease in a retrospective longitudinal 

study. The children were followed for the first four years after diagnosis or until they reached 

age 12 years old. Mean height and height velocity standard deviation scores were calculated at 

diagnosis and yearly after that. Disease severity was scored based on number of relapses, 

hospitalizations, surgeries and medications. For both children with ulcerative colitis and Crohn’s 

disease, disease severity was significantly associated with height velocity. Children with more 

severe disease were the shortest, but the difference in height among children with different 

disease severity was not statistically significant. Of note, no statistical difference in HVSDS in 

children receiving or not receiving Prednisone was found. 

In a retrospective longitudinal study, Griffiths, Nguyen, Smith, et al. (1993) evaluated 100 

prepubertal children with a mean age of 11 years old at initial diagnosis of Crohn’s disease who 

had been followed for at least two years. The study evaluated the relationship between growth 

velocity, defined as growth in cm/year, and severity of the Crohn’s disease, determined by 

gastrointestinal symptom frequency and chronicity, and disease location. The study found that 

the severity of gastrointestinal symptoms was the major factor influencing linear growth during 

the first two years after diagnosis. Height velocity decreased with increasing symptoms. No 

difference in mean linear growth velocities were found among patients stratified by anatomical 

localization of disease. Longer term follow-up found that those children who reached maturity by 
74

the end of the study achieved their expected height, regardless of disease severity or location. Of 

note, duration of corticosteroid administration was not a significant predictor of height velocity. 

Farmer and Michener (1979) performed a retrospective longitudinal case series study of 513 

patients younger than 20 years old who had Crohn’s disease. The mean duration of follow-up 

was almost 8 years. Growth retardation was defined as height less than third percentile on the 

growth curve for any given age. Short stature occurred at similar frequencies among children 

diagnosed with Crohn’s disease no matter what the pattern of disease: ileocolic (7 percent), colon 

(8 percent) and small intestine (6 percent). The study did not report whether those with short 

stature had different complication rates than taller children. Height velocity was not explicitly 

measured.

All three studies evaluating the relationship between growth retardation and the severity of 

inflammatory bowel disease included children with Crohn’s disease. One study also included 

children with ulcerative colitis. Severity of inflammatory bowel disease was found to correlate 

with loss of height velocity in two studies. Crohn’s disease location, however, did not correlate 

with either height or height velocity in two studies. There were no data presented to suggest that 

the process of growth failure is likely to be disabling. 

Association of Severity of Juvenile Rheumatoid Arthritis with Decreased Growth 

Velocity

Table 24. Growth Retardation Association with Subtypes / Severity of Juvenile Rheumatoid 

Arthritis

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

Bernstein 

1977 ÇÇÇ 31 JRA Systemic vs Other £

ÇÇ 58 JRA 

Systemic / 

Polyarticular vs 

Pauciarticular

Number of 

affected joints

Total disease 

flares

Polito 1997

Ç 37 Systemic or 

Polyarticular 

Functional 

class

£

Polyarticular vs

Systemic / 

Pauciarticular

d,e

 d,e

for 1st year Saha 1999 ÇÇ 64 JRA 

Severity Score d,f

 d,f

for 1st year

°

JRA = Juvenile rheumatoid arthritis

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe juvenile rheumatoid arthritis associated with growth retardation (or no statistical 

analysis)

More severe juvenile rheumatoid arthritis significantly associated with growth retardation

No association between juvenile rheumatoid arthritis severity and growth retardation.

d Statistical significance not explicitly reported. Implied significance.

e Adjusted for sex and duration of disease (implied).

f Adjusted for glucocorticoid use and duration of disease (implied).
75

Three studies evaluated the association between severity of juvenile rheumatoid arthritis 

(JRA) and height in 153 children (Table 24). All of the studies measured height velocity. The 

studies categorized patients by disease type. Two studies also used various measures to grade 

severity of disease. All were retrospective longitudinal studies. Two studies were of fair quality; 

one was of poor quality.

Bernstein, Stobie, Singsen, et al. (1977) performed a retrospective longitudinal cohort study 

of 31 children with JRA. At initial evaluation, the children were between 1 and 11 years old and 

were followed for a mean of 6.6 years. Children with JRA were classified into systemic, 

polyarticular, and pauciarticular groups according to the mode of onset of their disease. Children 

with systemic JRA (more severe disease) had significantly lower mean change in height in 

comparison to children with polyarticular and pauciarticular JRA. 

In a retrospective longitudinal study of 58 children with JRA who had a mean age of 6 years 

old at initial evaluation, Polito, Strano, Olivieri, et al. (1997) evaluated subjects for at least 1 

year. The study evaluated height velocity compared to a population standard and measured 

disease severity based on disease type in all subjects. In children with systemic or polyarticular 

disease, height velocity was also evaluated based on number of affected joints, the total duration 

of disease flares, and an undefined functional class. Children with more severe JRA (systemic or 

polyarticular) were significantly more likely to have a decreased growth velocity when followed 

over time in comparison to children with less severe JRA (pauciarticular). Among those with 

either systemic or polyarticular disease, decreased height velocity significantly correlated with 

duration of flares and with functional class, but not with the number of joints affected. 

Furthermore, the study concluded that decreased growth velocity was likely secondary to the 

JRA separate from steroid medication use. Of note, though, since steroid use was an exclusion 

criteria, those most seriously affected were likely excluded.

Saha, Verronen, Laippala, et al. (1999) conducted a retrospective longitudinal study of 64 

prepubertal children diagnosed with juvenile chronic arthritis who were followed from the time 

of diagnosis for 2 years or until they reached age 12. At initial evaluation, the children had a 

mean age of 4 years old. Children with the most severe disease were excluded. Disease severity 

was based on type of disease (pauciarticular, polyarticular, and systemic) and by a severity score 

based on medication requirements. The paper implied that associations with height and height 

velocity were adjusted in multivariate analyses. The study found that both height and height 

velocity were significantly decreased with increased severity of disease type or severity in the 

first year after diagnosis. However, height severity normalized after this.

All studies indicated an association between decreased growth velocity and increased 

severity of JRA. One of the studies, however, found that height velocity normalized after the first 

year of treatment. Two studies excluded children with the most severe disease There were no 

data reported to address the question of whether decreased growth velocity is in itself disabling.
76

Association of Severity of Chronic Kidney Disease with Decreased Growth 

Velocity

Table 25. Growth Retardation Association with Severity of Chronic Kidney Disease

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

GFR Schaefer 1996 d ÇÇÇ 321 CKD

GFR < 25

£

47 CKD, aged 9 

mo-2 y e

Karlberg 1996 d ÇÇ 

14 Infants with 

CKD

GFR

e

£

24 ARPKD girls GFR < 60 Konrad 1995 d Ç 34 ARPKD boys GFR < 60 £

Norman 2000 ÇÇÇ 60 CKD GFR 

categories £

Rizzoni 1984 ÇÇÇ 47 CKD GFR £

Tsau 1989 ÇÇ 52

Nephrotic 

syndrome

Relapsing vs 

non-relapsing 

disease

£

No CKI f

CKI ÇÇ 33 f

Prepubertal 

nephrotics

ESRD Schärer 1999 f

Ç 16

Steroid 

resistant 

nephrotics

Serum 

albumin / 

protein

£

Ismaili 2001 ÇÇ 11 Infants with 

CKD 

GFR < 15 at

6 months £

Claris-Appiani 

1989 ÇÇ 17 Predialysis CKD

Creatinine 

clearance g °

Tejani 1983 Ç 24

Focal 

segmental 

sclerosis

Steroid 

resistant vs 

sensitive

°

ARPKD = autosomal recessive polycystic kidney disease, CKD = chronic kidney disease, GFR = glomerular filtration rate.

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe juvenile rheumatoid arthritis associated with growth retardation (or no statistical 

analysis)

More severe juvenile rheumatoid arthritis significantly associated with growth retardation

No association between juvenile rheumatoid arthritis severity and growth retardation.

d Karlberg, Schaefer, Hennicke, et al. (1996), Schaefer, Wingen, Hennicke, et al. (1996) and Konrad, Zerres, Wuhl, et al. 

(1995) used subjects from same dataset.

e Multivariate analysis. No data on other variables in model.

f No CKI = Reached final height without kidney function deterioration (chronic kidney insufficiency).

CKI = Reached final height with serum creatinine > 1.2 mg/dL after age 13.6 years.

ESRD = Developed end stage renal disease before reaching final height.

g Adjusted for multiple variables including bone age, blood urea nitrogen, nutrition, and parathyroid hormone.
77

Ten studies evaluated the association between severity of chronic kidney disease (CKD) and 

height in up to 684 children (Table 25). Seven of the studies measured height velocity; six 

measured height. Most studies based disease severity on kidney function, although other 

measures were used. Six studies were prospective; four were retrospective. Eight studies were 

longitudinal; two were cross-sectional. Eight studies were of fair quality; two were of poor 

quality.

Three papers reported separate analyses on different sets of subjects from the same overall 

sample of patients (Karlberg, Schaefer, Hennicke, et al., 1996; Konrad, Zerres, Wuhl, et al., 

1995; Schaefer, Wingen, Hennicke, et al., 1996). The largest, by Schaefer, Wingen, Hennicke, et 

al. (1996) reported on a prospective longitudinal study of 321 children with CKD followed to age 

10 years old. Disease severity was based on a measure of kidney function, glomerular filtration 

rate (GFR). For children in most age groups evaluated, those with lower GFR had lower height 

velocities. Among children of all ages, those with GFR less than 25 mL/min had significantly 

lower heights and height velocities compared to children with greater kidney function.

In a subset of children reported in Schaefer, Wingen, Hennicke, et al. (1996), 61 children 

diagnosed with CKD prior to age 6 months and who were younger than 2 years old were 

evaluated by Karlberg, Schaefer, Hennicke, et al. (1996) in a prospective longitudinal analysis. 

In a multivariate analysis, kidney function, measured by GFR, was not associated with height 

velocity in either infants or young children.

In another subset of patients, Konrad, Zerres, Wuhl, et al. (1995) reported a prospective 

longitudinal study of 58 prepubertal children with autosomal recessive polycystic kidney disease 

(ARPKD) who were older than 1 year at initial evaluation. Severity of CKD was measured by 

GFR. Girls with ARPKD who had GFR less than 60 mL/min/1.73 m2 were significantly shorter 

than girls with greater kidney function. However, in boys, height was not associated with kidney 

function. Height velocity was not analyzed.

Norman, Coleman, Macdonald, et al. (2000) performed a prospective cross-sectional study of 

60 children with CKD aged 2 to 17 years old. Severity of CKD was defined as mild (GFR 50-75 

mL/min/1.73 m2), moderate (GFR 25-50 mL/min/1.73 m2) and severe (GFR less than 25 

mL/min/1.73 m2). The study found that those with more severe CKD (moderate and severe) were 

more likely to be significantly shorter than children with only mild CKD. Height velocity was 

not analyzed.

Rizzoni, Basso, and Setari (1984), in a retrospective longitudinal study, eva luated 47 children 

with CKD, from neonate to age 15 years old. CKD severity was measured with GFR. No 

relationship between GFR and growth velocity or height was found.

Tsau, Chen, and Lee (1989) performed a retrospective longitudinal analysis of 52 children 

with nephrotic syndrome, with a mean age of 5 years old. The children were categorized into two 

groups based on clinical course. Those with frequent relapsing, steroid-dependent and steroidresistant disease were classified as having a less favorable clinical course. Those with occasional 

relapsing disease or who had not had relapses were classified as having a more favorable course. 

Growth data were obtained and analyzed up to the age of 15 years old. The study found that 

children with more severe nephrotic disease had significantly decreased yearly growth velocity 

in comparison to children with more mild nephrotic syndrome. However, further analysis 

concluded that the duration of steroid administered per year was found to be the major 

determinant of growth suppression in nephrotic children.

Scharer, Essigmann, and Schaefer (1999) performed a prospective cross-sectional study of 33 

prepubertal children with nephrotic syndrome, who had a mean age of 4 years old. Children were 
78

followed for a minimum of 1.2 years. Children were classified by the degree of deterioration of 

their kidney function during follow-up. Nephrotic children with no or with moderate 

deterioration of kidney function did not experience reduction of height velocity compared to 

population norms. Those children who went on to develop end-stage renal disease had significant 

reduction of height velocity compared to population norms. In a subgroup of 16 children who 

had steroid resistant nephrotic syndrome, disease severity was determined by serum total protein 

and albumin levels. Height velocity correlated significantly with total protein and albumin levels, 

such that those with more severe nephrotic syndrome had lower height velocity.

Ismaili, Schurmans, Wissing, et al. (2001) performed a retrospective longitudinal study of 11 

infants with kidney dysplasia and CKD. The authors analyzed kidney function and growth from 

birth to 4 years of age. Disease severity was based on GFR at 6 months of age, using 15 mL/min 

as a threshold for severity. Infants with more severe CKD at 6 months had a significantly more 

severe delay in height compared to those children with less severe CKD.

Claris-Appiani, Bianchi, Bini, et al. (1989) performed a prospective longitudinal cohort study 

of 17 children with CKD who were aged 1 to 9 years old and were followed for 1 year. Severity 

of CKD was measured using creatinine clearance. Children with more severe CKD were 

significantly shorter. However, growth velocity did not correlate with creatinine clearance in 

multivariate analysis controlling for a variety of factors.

Tejani, Nicastri, Sen, et al. (1983) performed a retrospective longitudinal evaluation of 24 

children with nephrotic syndrome and focal segmental glomerular sclerosis (FSGS). The children 

were between 3 and 19 years old at follow-up. The children were classified based on whether 

their disease was steroid resistant or steroid sensitive. Sixty-nine percent of children with steroid 

resistant FSGS had short stature, compared to 12% of children with steroid sensitive disease. The 

growth retardation was less common in steroid sensitive FSGS despite increased exposure to 

steroids in these children. 

Among the reviewed studies, the majority found a positive relationship between increased 

severity of CKD and either decreased growth velocity or short stature. However, these findings 

were not universal. Single studies of sub-populations, such as children with ARPKD and very 

young children found conflicting evidence. Two studies commented on the use of steroids and 

how they related to growth. In one study of children with nephrotic syndrome, steroid use was 

associated with growth retardation. However, the second study, of children with focal segmental 

sclerosis, found that children whose disease was amenable to steroid use, and therefore received 

steroids, grew faster than children with steroid resistant disease. Some studies were limited by 

using a severity marker that was not GFR or by small sample sizes or limited data reporting. No 

data were available to assess if a decreased height velocity is in itself disabling
79

Association of Severity of Human Immunodeficiency Virus Infection with 

Decreased Growth Velocity

Table 26. Growth Retardation Association with Severity of Human Immunodeficiency Virus

Author Year Generalizability aSample N Population Disease Severity Height b, c Height 

Velocity b, c Quality a

Brettler 1990 ÇÇ 36

Hemophiliac 

boys with 

HIV

Progression to 

AIDS or ARC d £

Matarazzo 1994 ÇÇ 24 Perinatal 

HIV 

Clinical 

deterioration °

HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome; ARC = AIDS related complex

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe HIV disease associated with growth retardation (or no statistical analysis)

More severe HIV disease significantly associated with growth retardation

No association between HIV disease severity and growth retardation.

d Multivariate analysis. Included CD4 count and p24 antigenemia and possibly other variables not reported.

Two studies evaluated the association between severity of HIV infection and height in 60 

children (Table 26). Both studies measured height velocity; one also measured height. Various 

measures of disease severity were used. One study used both prospective and retrospective data; 

the other was prospective. Both studies were longitudinal. One study was of fair quality; one was 

of poor quality.

Brettler, Forsberg, Bolivar, et al. (1990) evaluated 36 boys with hemophilia A and HIV in a 

longitudinal study. Data were collected both retrospectively and prospectively. The boys had a 

median age of 8 years old and were younger than 12.5 years old. Growth failure was defined as a 

decrease in at least 15 percentile points in height or weight for age for two consecutive years. In 

a multivariate analysis that controlled for CD4 count and p24 antigenemia, growth failure was 

found to be the strongest prognostic variable for the progression to acquired immunodeficiency 

syndrome (AIDS) or AIDS-related complex (ARC). The authors conclude that “growth 

abnormalities in HIV-infected children without symptoms should be considered as an early sign 

of progression toward symptomatic disease.”

Matarazzo, Palomba, Lala, et al. (1994) performed a prospective longitudinal cohort study of 

24 children who were perinatally infected with HIV who were evaluated for 24 months. Disease 

severity was based on clinical deterioration; although this was not defined. At both 1 and 2 year 

follow-up, children who had clinical deterioration were substantially shorter and had 

substantially lower height velocity than children with stable clinical condition. At follow-up, 

most children with a stable clinical condition maintained normal growth whereas those with 

growth reduction showed progression in the severity of the disease. However, statistical analysis 

was not performed. 

Both studies that evaluated growth retardation in children with HIV found that linear growth 

retardation is a marker for progression to active disease in HIV positive children and that linear 

growth deceleration may precede the onset of symptoms of active disease. These studies were 

limited by incomplete reporting of data and poorly defined methods, predictors and outcomes. 

Despite the limitations, the studies seem to indicate that a sustained decrease in linear growth 
80

velocity is a marker for progression from seropositive status to active disease. No data were 

included that assess whether a decreased linear growth velocity is in itself likely to be disabling.

Association of Severity of Atopic Dermatitis with Decreased Growth Velocity

Table 27. Growth Retardation Association with Severity of Atopic Dermatitis / Eczema

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

% BSA 

affected

d

Massarano 

1993 ÇÇÇ 68 Eczema >50% vs 

<50% BSA 

affected

=

>50% vs 

<50% BSA 

Patel 1988 ÇÇÇ 80 affected Atopic 

dermatitis Asthma vs no 

asthma

°

BSA = body surface area

a See Methods...

b Univariate analysis, unless noted otherwise.

c More severe atopic dermatitis or eczema significantly associated with growth retardation

No association between atopic dermatitis or eczema severity and growth retardation.

d In multivariate analysis controlling for parental height, diet, duration of eczema, treatment and asthma.

Two studies evaluated the association between severity of eczema or atopic dermatitis and 

height in 148 children (Table 27). One study measured both height and height velocity; the other 

measured only height. Both studies used percentage of total skin affected; one study also 

considered the presence of asthma. Both studies were prospective. One study was longitudinal; 

one was cross-sectional. One study was of good quality; one was of poor quality.

Massarano, Hollis, Devlin, et al. (1993) performed a prospective cross-sectional analysis of 

68 children age 2 to 12 years old with atopic eczema. Disease severity was based on percentage 

of skin affected by eczema. All children had been treated with topical steroids; however those 

with more than 50% skin involvement were treated with more potent steroids. Both groups had 

similar asthma and asthma treatment scores. In a multivariate analysis, height was significantly 

associated with percent of skin affected by eczema. Furthermore, the mean height of those 

children with more than 50% skin involvement was significantly less those with less skin 

involvement. Children on systemic steroids were included in the study. There were no data on 

height velocity.

Patel, Clayton, Addison, et al. (1998) performed a prospective longitudinal study of 80 

prepubertal children with atopic dermatitis. The children had a mean age of 5 years old at initial 

evaluation and were followed over a 2-year period. In one analysis, height severity was based on 

percentage of skin involvement. Neither height velocity nor height differed between patients 
81

with less than 50% skin involvement and those with at least 50% skin involvement. In a 

secondary analysis, affected children with and without asthma had similar heights and height 

velocities. Of note, there were also no differences in height or height velocities between children 

treated with mild potency topical glucocorticoids and those treated with moderate potency ones. 

Children with systemic steroids were excluded from the study.

The two studies of growth in children with atopic dermatitis reported conflicting results. One 

study, which included children on systemic steroids, found a positive association between 

increased severity and decreased height. The other study, which excluded children on systemic 

steroids, found no association between increased severity and decreased height or height 

velocity. These studies do not clearly provide evidence that a sustained decrease in linear growth 

velocity is a marker for the severity of the underlying disease. Further prospective longitudinal 

studies that evaluate the severity of the dermatitis and the contribution of systemic and topical 

steroid use and coexisting conditions like asthma are needed to determine whether growth failure 

is related to severity of illness or to medication treatment or co-morbid medical illness. No data 

were provided that look at whether the process of a decreasing linear growth velocity is in itself 

disabling.

Association of Severity of Other Diseases with Decreased Growth Velocity

Table 28. Growth Retardation Association with Severity of Miscellaneous Chronic Diseases

Author Year Generalizability aSample N Population Disease 

Severity Height b, c Height Velocity b, c Quality a

81 Cognitive 

impairment

72 Nonambulatory

Samson-Fang 

1998 ÇÇ 

80

Cerebral 

palsy

Type of 

disease

=

Evliyaoglu 

1996 ÇÇ 24 Sickle cell anemia Severe vs Mild £

Rasat 1995 ÇÇ 9

Congenital 

adrenal 

hyperplasia 

Number of 

escapes from 

suppression

°

a See Methods...

b Univariate analysis, unless noted otherwise.

c Non-significant trend toward more severe chronic disease associated with growth retardation (or no statistical analysis)

More severe chronic disease significantly associated with growth retardation

No association between chronic disease severity and growth retardation.

The relationship between growth and the seve rity of three chronic diseases – cerebral palsy, 

sickle cell anemia, and congenital adrenal hyperplasia – were evaluated in one paper each.

The association of growth and severity of cerebral palsy was evaluated by Samson-Fang and 

Stevenson (1998) in a retrospective cross-sectional study of good quality. The study included 81 

children with cerebral palsy younger than 10 years old. Severity of disease was evaluated in three 

ways: presence of a cognitive impairment, ambulation ability, and type of cerebral palsy (spastic 
82

disease, extra-pyramidal disease, and mixed disease). Cognitive impairment and non-ambulatory 

status were independently associated with a lower height velocity. Height velocity, however, was 

not associated with disease type.

The association of growth and severity of sickle cell anemia was evaluated by Evliyaoglu, 

Kilinc, and Sargin (1996) in a prospective cross-sectional study of fair quality. The study 

included 24 children with homozygous SS sickle cell anemia with a mean age of 9 years old. 

Sickle cell patients were classified into two groups: a mild clinical course group who did not 

require blood transfusions and had no sickle crises; and a severe clinical course group who 

needed blood transfusions beginning early in life and had suffered from frequent sickle crises. 

The children with severe sickle cell anemia were significantly shorter than those with mild 

courses. Height velocity was not analyzed.

The association of growth and severity of congenital adrenal hyperplasia was evaluated by 

Rasat, Espiner, and Abbott (1995) in a retrospective longitudinal study of poor quality. The study 

analyzed 9 children with congenital adrenal hyperplasia who had a mean age at initial evaluation 

of 15 years old and were followed for a median of 14 years. All subjects had been treated with 

glucocorticoids. Disease severity was expressed as the frequency of biochemical escapes from 

adrenal suppression. There was no association between final height and number of suppression 

escapes. Height velocity was not evaluated.

In one study, height velocity was found to be associated with severity of impairments due to 

cerebral palsy, but not with type of disease. Height was associated with severity of course of 

sickle cell anemia in a single study. In a small study, no associa tion was found between final 

height and severity of congenital adrenal hyperplasia. Further studies disease are needed to 

confirm these results and to more clearly evaluate height velocity and severity of disease. No 

data were presented to answer the question about whether the process of having a decreasing 

linear growth velocity is in itself disabling in children with any of these diseases. 
83

Chapter 4. Conclusions

Overview

In this chapter, we discuss the conclusions resulting from our evaluation of the three 

questions asked by the Social Security Administration (SSA). We also describe the limitations of 

the existing studies related to disability and short stature as well as the relationship between 

chronic disease and decreased growth.

This report summarizes the scientific evidence in regard to three questions attempting to 

determine if children with short stature are disabled because of the ir short stature, if children 

with short stature secondary to a skeletal dysplasia are disabled and if decreased growth velocity 

can be related to severity of chronic disease. 

The results presented in Chapter 3 are based on the screening of 13,537 MEDLINE® 

citations and the review of 825 full articles. 

Question 1. Is short stature (height less than the 5th percentile) as a 

result of a medically determinable impairment associated with severe 

functional Limitations, according to, but not limited to, SSA’s

definition of disability?

There were 23 studies that provided information on functional abilities among children with 

short stature due to medically determinable impairments. Fifteen were prospective crosssectional studies; seven were prospective longitudinal studies; and one was a retrospective 

longitudinal study. Two were of good quality, eleven were of fair quality, and nine were of poor 

quality. One study was of fair quality in its analysis of intelligence, but of poor quality in its 

analysis of academic achievement.

Based on the reviewed articles, no severe functional limitations were found in children with 

short stature due to growth hormone deficiency, multi-hormone deficiency, Turner syndrome, 

Russell-Silver syndrome or isolated short stature. These specific causes of short stature were 

chosen because they allowed us to isolate the effect of short stature and thus enabled us to 

determine if there was an increased risk for disability-related problems due just to short stature. 

The articles focused on intelligence, academic achievement, behavior, visual-motor perception, 

and psychomotor development. In each of these categories, children with short stature either had 

testing that was not significantly different from the controls or from the population mean, or if 

the testing were significantly poorer it was still for the most part within 1 standard deviation 

(SD) of the population mean. 

Academic Achievement

Eleven studies evaluated the relationship between academic achievement and short stature. 

Five of the studies found that children with short stature had academic achievement scores at or 

above the population norm. The other six studies found scores below the population norm but the 

great majority of subjects were still within 1 SD of the mean. These results imply that children 
84

with short stature do not have enough difficulties with academic achievement to qualify as a 

disability. A major limitation in five of the studies was the exclusion of children with a low 

intelligence quotient (IQ). Further studies that look at academic achievement in a large 

unselected population of children with short stature and compares them to matched controls are 

needed to more clearly delineate this relationship.

Intelligence

Intelligence was evaluated in 21 studies of children with short stature. Fifteen studies found 

short stature children to have IQs at or above the population mean, while the remaining studies 

reported IQs for the most part less then 1 SD below the mean. Three of the studies that found IQs 

at or above the mean excluded children with low IQs. The studies were limited by the IQ 

exclusion and also by an absence of a control population in many of the studies. Future studies 

are needed to better delineate this question.

Visual-Motor Skills

 Only three studies could be found that evaluated visual-motor perception in children with 

short stature. All three found significantly lower visual-motor skills in the evaluated children. 

These studies, however, were limited by their reporting of the data. Furthermore, it is not clear 

how a decrease in visual-motor skill can be correlated with the SSA definition of disability. 

Future studies are needed to evaluate disabilities caused by functional limitations in visual-motor 

skills.

Developmental Skills

Only one study evaluated developmental skills in a group of children with short stature. 

These children, who had Russell-Silver syndrome, were found to have delays in meeting their 

developmental landmarks. However, the value of this finding in relation to disability is 

questionable since the children did eventually meet their developmental landmarks (e.g., 

walking). Future studies are needed to determine the significance of these findings.

Behavior

Teacher-based evaluation of behavior in children with short stature was reported in seven 

studies. In general, behavior in the children with short stature was not significantly different from 

the controls. Exceptions to this were increased hyperactivity reported in one study, increased 

locus of control in another study, and general increased behavior problems in a third study. It is 

difficult to extrapolate behavior in general from these studies since they tended to use different 

tests, and the test results do not always overlap. In addition, sub-group results were not given for 

each study. Furthermore, the value of behavioral impairments for determining a child’s level of 

disability is questionable. Further studies are needed that evaluate large groups of non-selected 

short stature children, use the same behavior based test, compare results to matched controls, and 

determine likelihood of disability.
85

Question 2. What is the evidence that short stature (height less than 

the 5th percentile) due to a skeletal dysplasia is disabling according 

to, but not limited to, SSA’s definition of disability? If so, are children 

disabled by virtue of their size or other features of their conditions?

There were 31 papers from 25 study groups that provided information on functional abilities 

among children with short stature due to skeletal dysplasia. Of the studies, 22 were prospective 

cross-sectional studies; five were prospective longitudinal studies; two were retrospective 

longitudinal; and two were retrospective cross-sectional. One was of good quality, 16 were of 

fair quality, and 12 were of poor quality. One study was of good quality in its analysis of 

academic achievement, but of fair quality in its analysis of ambulation and mobility. One study 

was of fair quality in its analysis of neuromuscular function and range of motion, but of poor 

quality in its analysis of ambulation and mobility.

Based on the articles reviewed, children with skeletal dysplasias were not at increased risk of 

having severe impairments in intelligence, academic achievement, or psychological outcome. 

There was an increased risk for delay in achievement of motor skills in children with 

achondroplasia and osteogenesis imperfecta, and decreased ambulation, range of motion and 

mobility in children with more severe forms of osteogenesis imperfecta. The results for hearing 

impairment, respiratory dysfunction and spinal curvature appear to indicate an increased risk for 

impairment in these three areas, but the studies were limited in the number of children evaluated 

and how the samples were selected, thus making it difficult to arrive at a definitive conclusion in 

these areas.

Academic Achievement

Three studies examined academic achievement among children with achondroplasia or 

osteogenesis imperfecta. In two studies, achondroplasia patients scored lower than control 

groups, yet remained in the normal range. Further studies on this issue are needed to evaluate a 

larger population of children with achondroplasia, osteogenesis imperfecta and other types of 

skeletal dysplasias.

Intelligence

Five studies evaluated intelligence in children with achondroplasia, osteogenesis imperfecta 

and other skeletal dysplasias. No evidence of significantly impaired intelligence was found in 

any of the skeletal dysplasias by intelligence testing with all scores either above the population 

norm or within 0.5 SD of the norm. These studies were generally small for the comparisons 

made. Further studies on this issue are needed to evaluate a larger population with skeletaldysplasias clearly defined by up-to-date standards.

Psychomotor Development

Six studies found generally delayed achievement of psychomotor abilities or development in 

children with achondroplasia and osteogenesis imperfecta. Each group evaluated was small, used 

different testing instruments, and had varying ages of subjects. Furthermore, none was followed 

longitudinally. Clinically useful conclusions about ultimate motor function in children with 
86

skeletal dysplasias cannot be made from these studies. Larger, longitudinal studies are needed 

that test psychomotor functional abilities.

Neuromuscular

From review of the available literature, children with short stature due to various skeletal 

dysplasias appear to be at risk for neuromuscular abnormalities. Six studies evaluated 

neuromuscular function in children with skeletal dysplasias. The four studies that looked solely 

at children with achondroplasia found varied abnormalities. The three that measured strength 

found substantial weakness and hypotonia. Asymmetry, sensory deficits, poor coordination, and 

seizures were found in frequencies higher than controls or than are expected in the healthy 

population. All studies highlighted the significant risk of often occult cervical cord compression 

in these young children. The one paper that evaluated osteogenesis imperfecta found substantial 

muscle weakness in children who are moderately to severely affected their disease. The one 

paper that reviewed other skeletal dysplasias found cervical cord complications in children with 

Morquio disease. Further studies of children with skeletal dysplasias, especially achondroplasia, 

are needed to better delineate the extent of neuromuscular impairment.

Ambulation and Mobility

Of the eight papers considering ambulation and mobility in children with short stature due to 

skeletal dysplasia, all considered children with osteogenesis imperfecta. All found significant 

impairment in ambulation, with greater impairment, as expected, in patients with more severe 

disease. Children with the less severe types of osteogenesis imperfecta (tarda, Type I, Type IV)

were more likely to attain some walking capability, although a substantial proportion of these 

children did require assistance. Orthopedic abnormalities such as scoliosis, decreased range of 

motion, decreased muscle strength and fracture contribute to limitations of ambulation. All of the 

studies were of small size; although given the rarity of osteogenesis imperfecta, the studies were 

of reasonable size. Definitions of levels of ambulation were consistent and fairly objective. 

Studies of ambulation and mobility disabilities are necessary for children with skeletal dysplasias 

other than osteogenesis imperfecta.

Limb Range of Motion

Two studies evaluated upper and lower range of motion (ROM) abnormalities in children 

with various types of osteogenesis imperfecta and with achondroplasia. Decreased ROM was 

found in children with osteogenesis imperfecta, but no such correlation was seen in children with 

achondroplasia. Decreased lower extremity ROM may impact on ability to independently 

ambulate. Decreased upper extremity ROM may limit an individual’s independence by reducing 

his or her ability to engage in self-care. Further studies are necessary to better delineate the 

connection between limb ROM and various skeletal dysplasias.

Spinal Curvature

Four papers assessed spinal deformities in children with short stature due to skeletal 

dysplasia. Three studied children with osteogenesis imperfecta, and one studied children with 
87

diastrophic dysplasia. A high prevalence of scoliosis was found in children with both conditions. 

One study also found a high prevalence of pathologic kyphosis. All studies, however, likely 

represent a selected, perhaps more severe, population of patients followed by academic medical 

centers. Thus to find prevalence in the general population of individuals with skeletal dysplasias, 

it will be necessary to evaluate scoliosis and kyphosis in a group of unselected individuals with 

skeletal dysplasias.

Hearing Loss

Of the six studies that reported on hearing loss in children with skeletal dysplasia, only three 

performed objective hearing testing. All papers that reported actual hearing testing in young 

osteogenesis imperfecta patients reported a sizable proportion with hearing loss, although the 

prevalences varied due to selection and cohort size differences. Subjective reports of hearing 

problems in achondroplasia patients were common. One study did not show a high level of selfreport of hearing in patients with a mix of skeletal dysplasias, including achondroplasia. The 

available literature supports that children with at least some skeletal dysplasias, specifically 

achondroplasia and osteogenesis imperfecta, are at risk for hearing problems. Further studies 

with a larger, unselected population of children with skeletal dysplasia are needed to better 

define the extent, severity and type of hearing loss. 

Sleep Apnea and Respiratory Dysfunction

Of the four papers evaluating sleep and respiratory dysfunction in children with 

achondroplasia, all found a high incidence of abnormality, including central hypopnea, central 

apnea, and obstructive apnea. All four papers, however, reported on small numbers of children. 

Two of the groups contained patients referred for their respiratory or neurologic symptoms, and 

therefore may not represent the general achondroplasia population. Further studies that look at 

larger groups of non-selected achondroplasia patients are needed to define the prevalence of 

apnea in this population.

Little information on pulmonary function in children with skeletal dysplasia was found. One 

group found abnormal pulmonary function in a small group of children with achondroplasia, and 

one found no significant abnormality in a smaller group of children with osteogenesis 

imperfecta. More data are required before meaningful conclusions can be drawn.

Psychology

Only one paper was found that adequately studied the association of short stature due to 

skeletal dysplasia with psychological outcomes. The study found no evidence for increased rates 

of depression or anxiety in children with skeletal dysplasia. Further studies that evaluate 

psychological problems such as depression and anxiety are needed to validate these results.
88

Question 3. What is the evidence that a sustained decrease in linear 

growth velocity can be used as a marker of severity of an underlying 

Disease? Is such a process likely to be disabling?

We reviewed 53 articles that evaluated whether a sustained decrease in linear growth velocity 

can be used as a marker of the severity of 12 medical conditions and whether such a process is 

likely to be disabling. Nineteen were prospective longitudinal studies, 19 were retrospective 

longitudinal studies, 10 were prospective cross-sectional studies, and five were retrospective 

cross-sectional studies. Four were of good quality, 29 were of fair quality, and 20 were of poor 

quality. The evidence from four conditions (congenital heart disease, juvenile rheumatoid 

arthritis, Crohn’s disease and (human immunodeficiency virus infection (HIV)) appear to 

indicate that a sustained decrease in linear growth velocity can be used as a marker of the 

severity of these underlying conditions. Evidence is less clear for asthma, atopic dermatitis, 

diabetes, ß-thalassemia, and chronic kidney failure. There was only one study for sickle cell 

disease, congenital adrenal hyperplasia and cerebral palsy so it is difficult to draw conclusions 

for these conditions. None of the studies addressed the question of whether the process of having 

a decreasing linear growth velocity was likely to be disabling.

Asthma

Eleven studies evaluated the relationship between the severity of asthma and growth 

retardation. Overall, the studies did not find a consistent result. Six of the studies found no 

association between severity of asthma and growth retardation. No study found an association 

between mild asthma and growth retardation.

Studies were limited by poorly defined samples, limited data and analysis, missing data and, 

frequently, by the fact that severity of disease was measured by steroid treatment. These studies 

do not clearly provide evidence that a sustained decrease in linear growth velocity can be used as 

a marker of severity of asthma or whether a decrease in growth velocity is likely to be disabling. 

Future well-designed studies are needed.

Congenital Heart Disease

There were six studies that evaluated the relationship between congenital heart disease and 

growth retardation. Many studies were limited by incomplete data and statistical analysis and 

some studies were limited because they excluded children with the most severe congenital 

cardiac defects. Given the limitations, the results do suggest that height and height velocity 

retardation is seen in children with severe congenital heart defects and may be a marker for more 

severe disease. Whether the decrease in height or height velocity in itself is disabling is not 

answered. 

Diabetes Mellitus

Eleven studies evaluated the relationship between growth retardation and control or severity 

of insulin dependent diabetes mellitus. Overall, the studies showed mixed results with five 

studies demonstrating a positive relationship between poor diabetes control or increased severity 

of disease and decreased growth velocity. Several studies associated growth deceleration with 
89

peripubertal onset of illness. Some studies were limited because they did not use a well-defined, 

objective measure, such as glycohemoglobin (Hgb A1c), to assess severity or control. Some 

studies were limited by unclear statistical analysis, lack of specific data included or summary 

results. These studies did not find clear evidence that a sustained decrease in linear growth 

velocity can be used as a marker of severity of diabetes or whether a decrease in linear growth 

velocity is in itself disabling. Further prospective, longitudinal studies of the linear growth of 

children with diabetes mellitus, using objective measure of control like Hgb A1c, are needed to 

clarify whether a decrease in linear growth velocity may be a marker for severity of disease. 

β-Thalassemia

There were three studies that evaluated the relationship between growth retardation and 

severity of anemia in ß-thalassemia. One study showed a relationship between increased severity 

of anemia and reduced height and one study showed a trend toward increased severity of disease 

and decreased growth. The studies were limited by incomplete data reporting and by inconsistent 

definitions of severity. These studies do not show clear evidence that a sustained decrease in 

linear growth velocity can be used as a marker of the severity of the disease. Prospective 

longitudinal cohort studies with clear definitions of severity (i.e. hemoglobin levels) and 

measurements of height velocity may answer the question. 

Inflammatory Bowel Disease

There were three studies evaluating the relationship between growth retardation and the 

severity of inflammatory bowel disease. Two studies included only children with Crohn’s 

disease. The other two studies included children with both Crohn’s disease and ulcerative colitis. 

Disease severity was associated with height velocity among children with both Crohn’s disease 

and ulcerative colitis; however, height was not significantly associated with disease severity in 

any study. There are no data presented to suggest that the process of growth failure is likely to be 

disabling. Further prospective longitudinal studies that include both larger numbers of patients 

with ulcerative colitis patients and Crohn’s disease and that compare both to population 

standards and to each other may clarify whether growth retardation is a marker associated with 

severity of all inflammatory bowel diseases, or is related to one in particular.

Juvenile Rheumatoid Arthritis

Three studies evaluated the relationship between growth retardation and the subtypes or 

severity of juvenile rheumatoid arthritis. All studies indicated an association between decreased 

growth velocity and increased severity of the disease. One study noted that height velocity 

normalized after the first year of treatment. The studies were limited in two cases by excluding 

children with the most severe disease, by incomplete statistical analyses in one, and by poorly 

defined outcomes in another. With these caveats, the studies suggest that a decrease in linear 

growth velocity is associated with more severe disease and may serve as a marker of severity of 

the underlying disease. There are no data reported addressing the question of whether decreased 

growth velocity is in itself disabling. Future well-designed studies with broad inclusion criteria 

are needed to clarify the issue.
90

Chronic Kidney Disease

Ten studies evaluated the relationship between growth retardation and severity of chronic 

kidney disease. Eight of the studies found a positive relationship between increased severity of 

kidney failure and decreased height or height velocity. Single studies of sub-populations of 

children with autosomal recessive polycystic kidney disease (ARPKD) and very young children 

with chronic kidney disease found no association of disease severity with height velocity. There 

was conflicting evidence about the role of steroid use in causing growth retardation. Some 

studies were limited by using a severity marker other than glomerular filtration rate, by small 

sample sizes, or by incomplete data reporting. Overall, the studies suggest that a decrease in 

linear growth velocity is associated with the severity of the underlying disease but this finding 

was not universal. No data were available to assess if a decreased height velocity is in itself 

disabling. Additional prospective, longitudinal studies that evaluate whether a decrease in linear 

growth velocity can be used as a marker of severity of underlying kidney disease are needed.

Human Immunodeficiency Virus Infection

There were two studies evaluating the relationship between growth retardation and 

progression to disease in HIV positive children. Both studies found that linear growth retardation 

is a marker for progression to active disease in HIV positive children and linear growth 

deceleration may precede the onset of symptoms of active disease. These studies were limited by 

incomplete data reporting and poorly defined methods, predictors and outcomes. Despite the 

limitations, the studies do indicate that a sustained decrease in linear growth velocity is a marker 

for progression from seropositive status to active disease. No data were included that assess 

whether a decreased linear growth velocity is in itself likely to be disabling. Larger, prospective, 

longitudinal studies of the relationship between decreasing linear growth velocity and 

progression of disease could confirm the usefulness of decreased linear growth velocity as a 

marker for increasing severity of disease.

Atopic Dermatitis

Two studies evaluated the relationship between growth retardation and severity of atopic 

dermatitis. The studies reported conflicting results with one study reporting a positive association 

between increased severity and decreased height and the other study showing no association 

between increased severity and decreased height or height velocity. In the first study the more 

severely affected group had higher steroid use and some used systemic steroids. In the second 

study, those using systemic glucocorticoids were excluded from analysis. This study was also 

limited by a failure to report complete results and a failure to report statistical analyses. These 

studies do not clearly provide evidence that a sustained decrease in linear growth velocity is a 

marker for the severity of the underlying disease. No data were provided that look at whether the 

process of a decreasing linear growth velocity is in itself disabling. Further prospective 

longitudinal studies are needed to clarify whether growth velocity is affected by the severity of 

atopic dermatitis, or whether the apparent effect is related to steroid treatment.
91

Cerebral Palsy

There was only one study with 81 subjects that looked at the relationship between growth 

retardation and cerebral palsy. The study did not find a significant association between the type 

of cerebral palsy and decreased growth velocity but cognitive impairment and non-ambulatory 

status were associated with decreased growth velocity. This suggests that those more severely 

affected by both motor and non-motor neurological deficits have decreased growth velocity. This 

study was limited by the exclusion criteria, which likely excluded the most severely affected 

children. No data were presented to answer the question about whether the process of having a 

decreasing linear growth velocity is in itself disabling. Further prospective longitudinal studies of 

children with varying severity of cerebral palsy are needed to confirm whether a decreasing 

linear growth velocity is a marker for the severity of the underlying disorder. 

Sickle Cell Disease

There was only one study with 24 subjects that evaluated the association of growth 

retardation with the severity of sickle cell disease. That study found a positive association 

between severe sickle cell disease (measured by need for transfusions and the number of crises) 

and decreased height percentile compared to controls. The study was small and did not explicitly 

compare less severe sickle cell disease to more severe disease. The study also did not look at 

height velocity as a predictor of more severe disease. Further prospective longitudinal studies 

that compare larger numbers of patients with mild, moderate and severe sickle cell disease are 

needed to determine if a decreasing linear growth velocity can serve as a marker for the severity 

of the underlying disease.

Congenital Adrenal Hyperplasia

There was only one study with 9 subjects that looked at the relationship between growth 

retardation and congenital adrenal hyperplasia. It did not find an association between number of 

escapes (more severe disease) and decreased growth velocity. The study was limited by its small 

size and by its reporting of results in graphic form only. There is not clear evidence that a 

decreasing linear growth velocity can be used as a marker for the underlying severity of 

congenital adrenal hyperplasia. No data were presented that look at whether the process of a 

decreasing linear growth velocity is in itself disabling. Further prospective longitudina l studies of 

larger numbers of patients with congenital adrenal hyperplasia are needed to answer the question 

of whether decreasing linear growth velocity can be used as a marker for severity of the 

underlying disease.

Limitations

There were several limitations encountered in evaluating Questions 1 and 2. Very few studies 

looked specifically at disability as defined by SSA. Most studies in fact were looking at 

functional ability such as IQ or academic achievement. Such areas are focused on in the 

published literature because they allow for acquisition of data that can be compared to published 

norms. Results from such studies have to be extrapolated to determine if the children evaluated 

meet the SSA definition of disability. For example, one SSA criterion of disability includes 
92

acquiring and using information. A significantly reduced IQ in a child may lead to such 

limitations, but there is not a clear relationship between IQ and difficulties in acquiring and using 

information. Even those studies that evaluated functional impairment, such as those that 

evaluated inability or limitation of walking, do not necessarily correlate directly with SSA’s 

definitions of disability. A further limitation to evaluation of intellectual function for Questions 1 

and 2 is that many relevant articles excluded children with limited IQ. Similar biases due to 

eligibility criteria and sample choices limit the generalizability of many of the studies.

One limitation to evaluating Question 3 relates to difficulties in trying to correlate the 

severity of disease with decreasing growth velocity. Frequently a report that details height in a 

specific disorder does not directly correlate this with severity of disease. Also the way in which 

severity of disease was reported may vary between reports discussing the same disease. The 

same problem was seen with the reporting of growth data, which is given in a variety of different 

formats (e.g., one-time height, growth velocity, and standard deviation from the mean). This 

makes it more difficult to determine the overall validity of the results. 
93

Chapter 5. Future Research

Questions 1 and 2

If the relationship between short stature and disability is to be elucidated, future research is 

needed. This is true for both short stature caused by medical conditions and skeletal dysplasia. 

Such research would be most beneficial if it focused on functional deficits (including disability, 

as defined by the Social Security Administration). Especially helpful would be studies that look 

at physical limitations related to short stature such as difficulties in using public restrooms due to 

the height of the toilet or difficulties in climbing stairs. Such studies may need to focus more on 

more extreme short stature (i.e. 5 to 7 standard deviations below the mean) to see a significant 

difference. Also studies on short children have tended to focus on functional ability and have not 

specifically evaluated functional deficits. For example, many studies evaluated intelligence in 

children with short stature but few have evaluated the proportion of short children who have 

mental retardation. 

Question 3

To properly answer the question of whether a decreasing growth velocity may indicate 

worsening severity of disease, prospective, longitudinal studies are needed. Studies should be 

prospective to minimize bias related to treatment, severity of disease and to allow accurate and 

consistent measurement of disease severity and growth. Longitudinal studies will allow accurate 

measurement of growth velocity and avoid using height as a proxy. Studies are also needed of 

children at various ages including puberty to account for different growth rates at different ages. 

The severity of disease in such studies needs to be clearly defined. In classifying children by 

severity of disease, researchers should clearly define the severity categories and use wellestablished definitions of severity. The severity definitions should not be confounded by 

treatment or management decisions. Finally other factors that affect height should be controlled 

for such as parental height, age and socioeconomic status. This is also why growth velocity is the 

best way to evaluate growth in an individual since it tends to remove the influence of some of 

these confounding factors, especially parental height. 
95

References and Bibliography

Online Mendelian Inheritance in Man. 

http://www.ncbi.nlm.nih.gov/Omim/ . 2002. 

Ref Type: Internet Communication

Disability evaluation under Social Security. Social 

Security Administration,Office of Disability; 1999

International consensus report on diagnosis and 

treatment of asthma. 92-3091. 1992. National Heart 

and Blood Institute, National Institutes of Health. 

Ref Type: Report

Instability of the upper cervical spine. Skeletal 

Dysplasia Group. Archives of Disease in Childhood 

1989 Feb;64(2):283-8.

Abbott D, Rotnem D, Genel M et al. Cognitive and 

emotional functioning in hypopituitary short-statured 

children. Schizophrenia Bulletin 1982;8(2):310-9.

Abrams SA. Chronic pulmonary insufficiency in 

children and its effects on growth and development. 

[Review] [40 refs]. Journal of Nutrition 2001 

Mar;131(3):938S-41S.

Alston J. Children with brittle bones. Special 

Education: Forward Trends 1979 Dec;6(4):18.

Angehrn V, Zachmann M, Prader A. Silver-Russell 

syndrome. Observations in 20 patients. Helvetica 

Paediatrica Acta 1979 Sep;34(4):297-308.

Apajasalo M, Sintonen H, Rautonen J et al. Healthrelated quality of life of patients with genetic skeletal 

dysplasias. European Journal of Pediatrics 1998 

Feb;157(2):114-21.

Arreola F, Junco E, Partida-Hernandez G et al. 

HbA1, height velocity and weight gain as indicators 

of metabolic control in type I diabetic children. A 5 

year survey. Archivos de Investigacion Medica 1991 

Jul;22(3-4):303-7.

Attie KM. Genetic studies in idiopathic short stature. 

[Review] [34 refs]. Current Opinion in Pediatrics 

2000 Aug;12(4):400-4.

Bacon GE, Spencer ML, Hopwood NJ et al. A 

practical approach to pediatric endocrinology. 3ed. 

Chicago, IL: Year Book Medical Publishers, Inc.; 

1990:62-77

Bailey JA. Elbow and other upper limb deformities in 

achondroplasia. Clinical Orthopaedics & Related 

Research 1971 Oct;80:75-8.

Balfour-Lynn L. Growth and childhood asthma. 

Archives of Disease in Childhood 1986 

Nov;61(11):1049-55.

Baum D, Beck R, Kodama A et al. Early heart failure 

as a cause of growth and tissue disorders in children 

with congenital heart disease. Circulation 1980 

Dec;62(6):1145-51.

Benson DR, Donaldson DH, Millar EA. The spine in 

osteogenesis imperfecta. Journal of Bone & Joint 

Surgery - American Volume 1978 Oct;60(7):925-9.

Bernstein BH, Stobie D, Singsen BH et al. Growth 

retardation in juvenile rheumatoid arthritis (JRA). 

Arthritis & Rheumatism 1977 Mar;20(2 Suppl):212-

6.

Bleck EE. Nonoperative treatment of osteogenesis 

imperfecta: orthotic and mobility management. 

Clinical Orthopaedics & Related Research 1981 

Sep;(159):111-22.

Brettler DB, Forsberg A, Bolivar E et al. Growth 

failure as a prognostic indicator for progression to 

acquired immunodeficiency syndrome in children 

with hemophilia. Journal of Pediatrics 1990 

Oct;117(4):584-8.

Brinkmann G, Schlitt H, Zorowka P et al. Cognitive 

skills in achondroplasia. American Journal of 

Medical Genetics 1993 Oct 1;47(5):800-4.

Cernelc D, Cernelc M. Comparative study of growth 

in asthmatic children and other children with chronic 

disease to a control group. Allergie und 

Immunologie 1974;20-21(1):7-13.

Claris-Appiani A, Bianchi ML, Bini P et al. Growth 

in young children with chronic renal failure. 

Pediatric Nephrology 1989 Jul;3(3):301-4.

Constantoulakis M, Panagopoulos G, Augoustaki O. 

Stature and longitudinal growth in thalassemia major. 

A study of 229 Greek patients. Clinical Pediatrics 

1975 Apr;14(4):355-8.
96

Court S, Parkin M, Roberts DF et al. HLA antigens 

and growth in diabetic children. Annals of Human 

Biology 1982 Jul;9(4):329-36.

Cox JR, Simmons CL. Osteogenesis imperfecta and 

associated hearing loss in five kindreds. Southern 

Medical Journal 1982 Oct;75(10):1222-6.

Daly K, Wisbeach A, Sanpera I, Jr. et al. The 

prognosis for walking in osteogenesis imperfecta [see 

comments]. Journal of Bone & Joint Surgery -

British Volume 1996 May;78(3):477-80.

Downie AB, Mulligan J, Stratford RJ et al. Are short 

normal children at a disadvantage? The Wessex 

growth study. BMJ 1997 Jan 11;314(7074):97-100.

Downie AB, Mulligan J, McCaughey ES et al. 

Psychological response to growth hormone treatment 

in short normal children. Archives of Disease in 

Childhood 1996 Jul;75(1):32-5.

Engelbert RH, Gulmans VA, Uiterwaal CS et al. 

Osteogenesis imperfecta in childhood: perceived 

competence in relation to impairment and disability. 

Archives of Physical Medicine & Rehabilitation 2001 

Jul;82(7):943-8.

Engelbert RH, Uiterwaal CS, Gulmans VA et al. 

Osteogenesis imperfecta in childhood: prognosis for 

walking. Journal of Pediatrics 2000 Sep;137(3):397-

402.

Engelbert RH, Beemer FA, van der GY et al. 

Osteogenesis imperfecta in childhood: impairment 

and disability--a follow-up study. Archives of 

Physical Medicine & Rehabilitation 1999 

Aug;80(8):896-903.

Engelbert RH, Gerver WJ, Breslau-Siderius LJ et al. 

Spinal complications in osteogenesis imperfecta: 47 

patients 1-16 years of age. Acta Orthopaedica 

Scandinavica 1998 Jun;69(3):283-6.

Engelbert RHH, Custers JWH, van der Net J et al. 

Functional outcome in osteogenesis imperfecta: 

disability profiles using the PEDI. Pediatr Phys Ther 

1997;9:18-22.

Evliyaoglu N, Kilinc Y, Sargin O. Thyroid functions 

in mild and severe forms of sickle cell anemia. Acta 

Paediatrica Japonica 1996 Oct;38(5):460-3.

Falvo KA, Klain DB, Krauss AN et al. Pulmonary 

function studies in osteogenesis imperfecta. 

American Review of Respiratory Disease 1973 

Nov;108(5):1258-60.

Farmer RG, Michener WM. Prognosis of Crohn's 

disease with onset in childhood or adolescence. 

Digestive Diseases & Sciences 1979 Oct;24(10):752-

7.

Feldt RH, Strickler GB, Weidman WH. Growth of 

children with congenital heart disease. American 

Journal of Diseases of Children 1969 

May;117(5):573-9.

Ferguson AC, Murray AB, Tze WJ. Short stature and 

delayed skeletal maturation in children with allergic 

disease. Journal of Allergy & Clinical Immunology 

1982 May;69(5):461-6.

Fowler ES, Glinski LP, Reiser CA et al. Biophysical 

bases for delayed and aberrant motor development in 

young children with achondroplasia. Journal of 

Developmental & Behavioral Pediatrics 1997 

Jun;18(3):143-50.

Frisch H, Hausler G, Lindenbauer S et al. 

Psychological aspects in children and adolescents 

with hypopituitarism. Acta Paediatrica Scandinavica 

1990 Jun;79(6-7):644-51.

Gilmour J, Skuse D. Short stature--the role of 

intelligence in psychosocial adjustment. Archives of 

Disease in Childhood 1996 Jul;75(1):25-31.

Gordon M, Post EM, Crouthamel C et al. Do children 

with constitutional delay really have more learning 

problems? Journal of Learning Disabilities 1984 

May;17(5):291-3.

Gordon M, Crouthamel C, Post EM et al. 

Psychosocial aspects of constitutional short stature: 

social competence, behavior problems, self-esteem, 

and family functioning. Journal of Pediatrics 1982 

Sep;101(3):477-80.

Griffiths AM, Nguyen P, Smith C et al. Growth and 

clinical course of children with Crohn's disease. Gut 

1993 Jul;34(7):939-43.

Hauspie RC, Gyenis G, Alexander F et al. Heights 

and weights of Hungarian and Belgian asthmatic 

boys. Human Biology 1979 Dec;51(4):507-21.
97

Hecht JT, Thompson NM, Weir T et al. Cognitive 

and motor skills in achondroplastic infants: 

neurologic and respiratory correlates. American 

Journal of Medical Genetics 1991 Nov 1;41(2):208-

11.

Herber SM, Dunsmore IR. Does control affect 

growth in diabetes mellitus? Acta Paediatrica 

Scandinavica 1988 Mar;77(2):303-5.

Holmes C.S, Karlsson JA, Thompson RG. 

Longitudinal evaluation of behavior patterns in 

children with short stature. In: Stabler B and 

Underwood LE, editors. Slow grows the child: 

Psychosocial aspects of growth delay. Hillsdale, NJ: 

Lawrence Erlbaum Associates; 1986. p. 1-12.

Holmes CS, Karlsson JA, Thompson RG. Social and 

school competencies in children with short stature: 

longitudinal patterns. Journal of Developmental & 

Behavioral Pediatrics 1985 Oct;6(5):263-7.

Hunter AG. Some psychosocial aspects of nonlethal 

chondrodysplasias: II. Depression and anxiety. 

American Journal of Medical Genetics 1998 Jun 

16;78(1):9-12.

Ismaili K, Schurmans T, Wissing KM et al. Early 

prognostic factors of infants with chronic renal 

failure caused by renal dysplasia. Pediatric 

Nephrology 2001 Mar;16(3):260-4.

Izumi K, Hoshi M, Kuno S et al. Glycemic control, 

growth and complications in children with insulindependent diabetes mellitus--a study of children 

enrolled in a Summer camp program for diabetics in 

Kinki district, Japan. Diabetes Research & Clinical 

Practice 1995 Jun;28(3):185-90.

Jivani SK, Rayner PH. Does control influence the 

growth of diabetic children? Archives of Disease in 

Childhood 1973 Feb;48(2):109-15.

Karlberg J, Schaefer F, Hennicke M et al. Early agedependent growth impairment in chronic renal 

failure. European Study Group for Nutritional 

Treatment of Chronic Renal Failure in Childhood. 

Pediatric Nephrology 1996 Jun;10(3):283-7.

Kattamis C, Touliatos N, Haidas S et al. Growth of 

children with thalassaemia: effect of different 

transfusion regimens. Archives of Disease in 

Childhood 1970 Aug;45(242):502-9.

Kelts DG, Grand RJ, Shen G et al. Nutritional basis 

of growth failure in children and adolescents with 

Crohn's disease. Gastroenterology 1979 

Apr;76(4):720-7.

Klein GL, Dungy CI, Galant SP. Growth and the 

nutritional status of nonsteroid-dependent asthmatic 

children. Annals of Allergy 1991 Jul;67(1):80-4.

Konrad M, Zerres K, Wuhl E et al. Body growth in 

children with polycystic kidney disease. 

Arbeitsgemeinschaft fur Padiatrische Nephrologie. 

Acta Paediatrica 1995 Nov;84(11):1227-32.

Kranzler JH, Rosenbloom AL, Proctor B et al. Is 

short stature a handicap? A comparison of the 

psychosocial functioning of referred and nonreferred 

children with normal short stature and children with 

normal stature [see comments]. Journal of Pediatrics 

2000 Jan;136(1):96-102.

Kuurila K, Grenman R, Johansson R et al. Hearing 

loss in children with osteogenesis imperfecta. 

European Journal of Pediatrics 2000 Jul;159(7):515-

9.

Lai KY, Skuse D, Stanhope R et al. Cognitive 

abilities associated with the Silver-Russell syndrome. 

Archives of Disease in Childhood 1994 

Dec;71(6):490-6.

Levy RJ, Rosenthal A, Miettinen OS et al. 

Determinants of growth in patients with ventricular 

septal defect. Circulation 1978 Apr;57(4):793-7.

Madeddu G, Dore A, Marongiu A et al. Growth 

retardation, skeletal maturation and thyroid function 

in children with homozygous beta-thalassaemia. 

Clinical Endocrinology 1978 May;8(5):359-65.

Mahoney CP. Evaluating the child with short stature. 

[Review] [91 refs]. Pediatric Clinics of North 

America 1987 Aug;34(4):825-49.

Martin AJ, Landau LI, Phelan PD. The effect on 

growth of childhood asthma. Acta Paediatrica 

Scandinavica 1981 Sep;70(5):683-8.

Massarano AA, Hollis S, Devlin J et al. Growth in 

atopic eczema. Archives of Disease in Childhood 

1993 May;68(5):677-9.
98

Matarazzo P, Palomba E, Lala R et al. Growth 

impairment, IGF I hyposecretion and thyroid 

dysfunction in children with perinatal HIV-1 

infection. Acta Paediatrica 1994 Oct;83(10):1029-

34.

McCauley E, Kay T, Ito J et al. The Turner 

syndrome: cognitive deficits, affective 

discrimination, and behavior problems. Child 

Development 1987 Apr;58(2):464-73.

McCauley E, Ito J, Kay T. Psychosocial functioning 

in girls with Turner's syndrome and short stature: 

social skills, behavior problems, and self-concept. 

Journal of the American Academy of Child 

Psychiatry 1986 Jan;25(1):105-12.

Mcnicol KN, Williams HE, Gillam GL. Chest 

deformity, residual airways obstruction and 

hyperinflation, and growth in children with asthma. I. 

Prevalence findings from an epidemiological study. 

Archives of Disease in Childhood 1970 

Dec;45(244):783-8.

Meyer-Bahlburg HF, Feinman JA, MacGillivray MH 

et al. Growth hormone deficiency, brain 

development, and intelligence. American Journal of 

Diseases of Children 1978 Jun;132(6):565-72.

Neville RG, McCowan C, Thomas G et al. Asthma 

and growth--cause for concern? Asthma & Growth in 

Tayside Children. Annals of Human Biology 1996 

Jul;23(4):323-31.

Norimatsu H, Mayuzumi T, Takahashi H. The 

development of the spinal deformities in osteogenesis 

imperfecta. Clinical Orthopaedics & Related 

Research 1982 Jan;(162):20-5.

Norman LJ, Coleman JE, Macdonald IA et al. 

Nutrition and growth in relation to severity of renal 

disease in children. Pediatric Nephrology 2000 

Dec;15(3-4):259-65.

Oliva MM, Lake AM. Nutritional considerations and 

management of the child with inflammatory bowel 

disease. [Review] [76 refs]. Nutrition 1996 

Mar;12(3):151-8.

Osvath P. Allergical and immunological diseases of 

childhood (In Hungarian). Budapest: Medicina; 1976

Patel L, Clayton PE, Addison GM et al. Linear 

growth in prepubertal children with atopic dermatitis. 

Archives of Disease in Childhood 1998 

Aug;79(2):169-72.

Pauli RM, Horton VK, Glinski LP et al. Prospective 

assessment of risks for cervicomedullary-junction 

compression in infants with achondroplasia. 

American Journal of Human Genetics 1995 

Mar;56(3):732-44.

Pitukcheewanont P, Alemzadeh R, Jacobs WR et al. 

Does glycemic control affect growth velocity in 

children with insulin-depende diabetes mellitus 

[published erratum appears in Acta Diabetol 1996 

Mar;33(1). Acta Diabetologica 1995 Oct;32(3):148-

52.

Plotnick LP. Growth, growth hormone, and pituitary 

disorders. In: Oski FA, DeAngelis CD, Feigin RDet 

al., editors. Principles and practice of pediatrics. 

Philadelphia: Lippincott & Co.; 1990. p. 1803-11.

Polito C, Strano CG, Olivieri AN et al. Growth 

retardation in non-steroid treated juvenile rheumatoid 

arthritis. Scandinavian Journal of Rheumatology 

1997;26(2):99-103.

Pollitt E, Money J. Studies in the psychology of 

dwarfism I. Intelligence quotient and school 

achievement. Journal of Pediatrics 1964;64:415-21.

Poussa M, Merikanto J, Ryoppy S et al. The spine in 

diastrophic dysplasia. Spine 1991 Aug;16(8):881-7.

Rasat R, Espiner EA, Abbott GD. Growth patterns 

and outcomes in congenital adrenal hyperplasia; 

effect of chronic treatment regimens. New Zealand 

Medical Journal 1995 Aug 11;108(1005):311-4.

Reid CS, Pyeritz RE, Kopits SE et al. 

Cervicomedullary cord compression in young 

children with achondroplasia: value of 

comprehensive neurologic and respiratory evaluation. 

Basic Life Sciences 1988;48:199-206.

Reite M, Davis K, Solomons C et al. Osteogenesis 

imperfecta: psychological function. American 

Journal of Psychiatry 1972 Jun;128(12):1540-6.

Rizzoni G, Basso T, Setari M. Growth in children 

with chronic renal failure on conservative treatment. 

Kidney International 1984 Jul;26(1):52-8.

Robinson A, Bender B, Borelli J et al. Sex 

chromosomal anomalies: Prospective studies in 

children. Behavior Genetics 1983;13.(4):321-9.

Rogers JG, Perry MA, Rosenberg LA. IQ 

measurement in children with skeletal dysplasia. 

Pediatrics 1979 Jun;63(6):894-7.
99

Rona RJ, du VF. National study of health and 

growth: respiratory symptoms and height in primary 

schoolchildren. International Journal of 

Epidemiology 1980 Mar; 9(1):35-43.

Rosenbloom AL, Silverstein JH, Lezotte DC et al. 

Limited joint mobility in diabetes mellitus of 

childhood: natural history and relationship to growth 

impairment. Journal of Pediatrics 1982 

Nov;101(5):874-8.

Ross JL, Feuillan P, Kushner H et al. Absence of 

growth hormone effects on cognitive function in girls 

with Turner syndrome [see comments]. Journal of 

Clinical Endocrinology & Metabolism 1997 

Jun;82(6):1814-7.

Ross JL, Stefanatos G, Roeltgen D et al. UllrichTurner syndrome: neurodevelopmental changes from 

childhood through adolescence. American Journal of 

Medical Genetics 1995 Jul 31;58(1):74-82.

Rovet, J. F., Netley, C., and MacLeod, V. Cognitive 

Function in Individuals with Atypical Pubertal 

Development. 1986. Toronto, Ontario Mental Health 

Foundation. 

Ref Type: Report

Ruiz-Garcia M, Tovar-Baudin A, Castillo-Ruiz V et 

al. Early detection of neurological manifestations in 

achondroplasia. Childs Nervous System 1997 

Apr;13(4):208-13.

Saha MT, Verronen P, Laippala P et al. Growth of 

prepubertal children with juvenile chronic arthritis. 

Acta Paediatrica 1999 Jul;88(7):724-8.

Saha MT, Ruuska T, Laippala P et al. Growth of 

prepubertal children with inflammatory bowel 

disease. Journal of Pediatric Gastroenterology & 

Nutrition 1998 Mar; 26(3):310-4.

Salardi S, Tonioli S, Tassoni P et al. Growth and 

growth factors in diabetes mellitus. Archives of 

Disease in Childhood 1987 Jan;62(1):57-62.

Samson-Fang L, Stevenson RD. Linear growth 

velocity in children with cerebral palsy. 

Developmental Medicine & Child Neurology 1998 

Oct;40(10):689-92.

Sant'Anna CA, Sole D, Naspitz CK. Short stature in 

children with respiratory allergy. Pediatric Allergy & 

Immunology 1996 Nov;7(4):187-92.

Schaefer F, Wingen AM, Hennicke M et al. Growth 

charts for prepubertal children with chronic renal 

failure due to congenital renal disorders. European 

Study Group for Nutritional Treatment of Chronic 

Renal Failure in Childhood. Pediatric Nephrology 

1996 Jun;10(3):288-93.

Scharer K, Essigmann HC, Schaefer F. Body growth 

of children with steroid-resistant nephrotic syndrome. 

Pediatric Nephrology 1999 Nov;13(9):828-34.

Shurka E, Laron Z. Adjustments and rehabilitation 

problems of children and adolescents with growth 

retardation. III. Bone diseases. Acta Med Auxiol 

1976;8:215-21.

Siegel PT, Clopper R, Stabler B. The psychological 

consequences of Turner syndrome and review of the 

National Cooperative Growth Study psychological 

substudy. Pediatrics 1998 Aug;102(2 Pt 3):488-91.

Siegel PT, Clopper RR, Stoppani C et al. The 

psychological adjustment of short normal children 

and normal controls. In: Stabler B and Underwood 

LE, editors. Growth, stature, and adaptation. Chapel 

Hill: University of North Carolina; 1994

Siegel PT, Hopwood NJ. The relationship of 

academic achievement and intellectual functioning 

and affective conditions of hypopituitary children. In: 

Stabler B and Underwood LE, editors. Slow grows 

the child: Psychosocial aspects of growth delay. 

Hillsdale, NJ: Lawrence Erlbaum Associates; 1986. 

p. 57-71.

Skuse D, Gilmour J. Quality of life of children with 

normal short stature. Clinical Pediatric 

Endocrinology 1997;6 (suppl 9):29-37.

Skuse D, Gilmour J, Tian CS et al. Psychosocial 

assessment of children with short stature: a 

preliminary report. Acta Paediatrica 1994 

Dec;Supplement. 406:11-6.

Soliman AT, Ahmed HI, Asfour MG. Growth 

parameters, growth hormone (GH) response to 

clonidine and circulating insulin-like growth factor-I 

(IGF-I), free thyroxine (FT4) and cortisol 

concentrations in relation to glycaemic control in 

children with insulin-depe diabetes mellitus. Journal 

of Tropical Pediatrics 1996 Aug;42(4):228-32.

Spock A. Growth patterns in 200 children with 

bronchial asthma. Annals of Allergy 1965 

Dec;23(12):608-15.
100

Stathis SL, O'Callaghan MJ, Williams GM et al. 

Behavioural and cognitive associations of short 

stature at 5 years. Journal of Paediatrics & Child 

Health 1999 Dec;35(6):562-7.

Steinhausen HC, Stahnke N. Psychoendocrinological 

studies in dwarfed children and adolescents. 

Archives of Disease in Childhood 1976 

Oct;51(10):778-83.

Stewart EJ, O'Reilly BF. A clinical and audiological 

investigation of osteogenesis imperfecta. Clinical 

Otolaryngology & Allied Sciences 1989 

Dec;14(6):509-14.

Stokes DC, Pyeritz RE, Wise RA et al. Spirometry 

and chest wall dimensions in achondroplasia. Chest 

1988 Feb;93(2):364-9.

Strangway A, Fowler R, Cunningham K et al. Diet 

and growth in congenital heart disease. Pediatrics 

1976 Jan;57(1):75-86.

Tanner JM, Lejarraga H, Cameron N. The natural 

history of the Silver-Russell syndrome: a longitudinal 

study of thirty-nine cases. Pediatric Research 1975 

Aug;9(8):611-23.

Taybi H, Lachman RS. Radiology of syndromes, 

metabolic disorders, and skeletal dysplasias. 4ed. St 

Louis, MO: Mosby-Year Book, Inc.; 1996:746-951

Tejani A, Nicastri AD, Sen D et al. Long-term 

evaluation of children with nephrotic syndrome and 

focal segmental glomerular sclerosis. Nephron 

1983;35(4):225-31.

Thompson NM, Hecht JT, Bohan TP et al. 

Neuroanatomic and neuropsychological outcome in 

school-age children with achondroplasia. American 

Journal of Medical Genetics 1999 Apr 16;88(2):145-

53.

Tolmie JL. Down syndrome and other autosomal 

trisomies. In: Rimoin DL, Connor JM, and Pyeritz 

RE, editors. Principles and Practice of Medical 

Genetics. New York: Churchill Livingstone; 1997. p. 

925-71.

Tsau YK, Chen CH, Lee PI. Growth in children with 

nephrotic syndrome. Taiwan I Hsueh Hui Tsa Chih -

Journal of the Formosan Medical Association 1989 

Sep;88(9):900-6.

US Census. Profiles of general demographic 

characteristics. 2000 Census of population and 

housing. 2001. 

Ref Type: Internet Communication

Vanelli M, de Fanti A, Adinolfi B et al. Clinical data 

regarding the growth of diabetic children. Hormone 

Research 1992;37 Suppl 3:65-9.

Voss LD, Mulligan J. The short normal child in 

school: sef-esteem, behavior, and attainment before 

puberty (The Wessex Growth Study). In: Stabler B 

and Underwood LC, editors. Growth, stature, and 

adaptation. Chapel Hill: University of North 

Carolina; 1994

Voss LD, Ba iley BJ, Mulligan J et al. Short stature 

and school performance--the Wessex Growth Study. 

Acta Paediatrica Scandinavica - Supplement 

1991;377:29-31.

Waters KA, Everett F, Sillence D et al. Breathing 

abnormalities in sleep in achondroplasia. Archives of 

Disease in Childhood 1993 Aug;69(2):191-6.

White RI, Jr., Jordan CE, Fischer KC et al. Delayed 

skeletal growth and maturation in adolescent 

congenital heart disease. Investigative Radiology 

1971 Sep;6(5):326-32.

Wilson DM, Duncan PM, Dornbusch SM et al. The 

effects of growth on intellectual function in children 

and adolescents. In: Stabler B and Underwood LE, 

editors. Slow grows the child: Psychosocial aspects 

of growth delay. Hillsdale, NJ: Lawrence Erlbaum 

Associates; 1986. p. 139-50.

Wise JE, Kolb EL, Sauder SE. Effect of glycemic 

control on growth velocity in children with IDDM. 

Diabetes Care 1992 Jul;15(7):826-30.

Young-Hyman D. Effects of short stature on social 

competence. In: Stabler B and Underwood LE, 

editors. Slow grows the child: Psychosocial aspects 

of growth delay. Hillsdale, NJ: Lawrence Erlbaum 

Associates; 1986. p. 27-45.
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

103

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Abbott

1982

82277019

Location: US

Setting: In-patient

Mean age: 11±3 y

Age range: 4-18 y

Mean height: ND

Height range: 81-132 cm

Male: 64%

Race: White 82%, Black 18%

Enrolled: ND

Evaluated: 11

Number of sites: 1

Short stature due to growth 

hormone deficiency and/or other 

pituitary hormone deficiency

None Isolated short stature Prospective crosssectional cohort

Angehrn

1979

80093987

Location: Switzerland

Setting: ND

Mean age: 4±2.2 y

Age range: ND

Mean height, SDS: –4.4±1.0

Male: 80%

Race: ND

Enrolled: ND

Evaluated: 20

Number of sites: 1

Russell-Silver syndrome:

Height < 2 SDS

Low normal growth velocity

Low birth weight

Moderate bone age retardation

Small triangular face and skull of 

large appearance

None RSS Prospective longitudinal 

cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

104

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Frisch

1990

90350511

Location: Austria

Setting: Clinic

Mean age: 12±3 y

Age range: 6.8-15.7 y

Mean height, SDS: –2.5±0.9

Height range, SDS: –4.5 to –0.9 

Male: 67%

Race: ND

Enrolled: ND

Evaluated: 23

Number of sites: 1

Isolated GH deficiency, or 

Multi-pituitary hormone deficiency

None GH deficiency Prospective crosssectional

Gordon

1984

84214634

Gordon

1982

82268405

Location: US

Setting: Pediatric endocrinology 

clinic

Mean age: 

Cases 10±2.2 y

Controls 10±2.1 y

Age range: 

Case 6-12 y

Control 6-12 y

Mean height, SDS: <5th percentile

Male: 83%

Race: ND

Mean SES: 3.5 (Hollinghead)

Enrolled: ND (23 controls)

Evaluated: 24 (23)

Number of sites: 1

Cases - Constitutional short stature < 

5

th percentile height

Skeletal maturation delayed > 13 

months 

Height velocity > 4 cm/y

Controls - Normal height

Matched for age, IQ, SES and 

sex

Cases - Abnormal GH 

studies

Psychiatric history

Controls - Psychiatric 

history

Isolated short stature Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

105

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Holmes

1986

Holmes

1985

86060101 

Location: US

Setting: Pediatric endocrinology 

clinic

Mean age, initial: 12 y

Mean age, follow-up: 15 y

Age range: ND

Mean height, SDS: < –2

Male: ND

Race: ND

SES: Middle class 21%

Enrolled: 76

Evaluated: 47

Number of sites: 1

Height < –2 SDS

Patients at pediatric endocrinology 

clinic

Additional medical 

diagnoses (e.g., IDDM)

Isolated short stature:

GH deficiency (17)

Constitutional delay 

(21)

Turner syndrome (9)

Prospective longitudinal 

cohort

(Mean 3.1 y

Range 2.2-4.0 y)

Kranzler

2000

20102780

Location: US

Setting: Region

Mean age: 10±1.4 y

Age range: 6-12 y

Mean height, SDS:

Referred –2.7±1.0

Non-referred –1.7±0.5

Controls +0.1±0.4

Height range, SDS:

Referred –4.5 to –1.3

Non-referred –3.2 to –1.3

Controls –0.7 to +0.7

Male: 51%

Race: ND

Enrolled: ND

Evaluated: 61 (29 controls)

Number of sites: 2

Referred Cases - Height < 5th

percentile

Pediatric endocrinology clinics

(n=27)

Non-referred - Identified in local 

public schools as shortest 10% of 

class

(n=34)

Controls - Height in middle 50%

At local public schools.

IQ < 75

Serious psychiatric or 

medical problem

English not primary 

language

Isolated short stature Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

106

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Lai

1994

95243689

Location: UK

Setting: Clinic

Mean age: 9±2 y

Age range: ND

Mean height, SDS: –2.2±1.5

Male: 80%

Race: White 95%; West Indian 5%

SES: 80% Middle-class or higher

Enrolled: 30

Evaluated: 25

Number of sites: 3

Russell-Silver Syndrome (met 3 of 5 

criteria)

Age 6-12 y

None RSS Prospective crosssectional

McCauley

1987

87161055

McCauley

1986

86141341

Location: US

Setting: Pediatric endocrinology 

clinic

Mean age: 

Turner 13±2.4 y

SS 13±2.8 y

Age range: ND

Mean height:

Turner 52±5.0 in

SS 53±4.5 in

Male: 0%

Race: White 94%, Black 6%

SES:41±16 (Hollingshead revised)

Enrolled: 23 (22 controls with SS)

Evaluated: 33 total

Number of sites: 1

Cases - Turner syndrome

Followed at Endocrine and 

Genetics Clinics

Controls - Girls with height < 5th

percentile from cause other than 

Turner syndrome

Followed at Endocrine and 

Genetics Clinics

Verbal IQ < 79-80 Turner syndrome (17)

Isolated short stature 

(16)

Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

107

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Meyer-Bahlburg

1978

78184456

Location: US

Setting: Pediatric endocrine clinic

Mean age:

GH def 12 y

Multi-hormone def 13 y

Age range:

GH def 4-18 y

Multi-hormone def 6-18 y

Mean height, SDS:

GH def –3.6

Multi-hormone def –3.9

Height range, SDS:

GH def –4.8 to –2.4

Multi-hormone def –6.0 to –1.9

Male: 73%

Race: ND

Enrolled: 29

Evaluated: 22 (age ≤ 18 y; 29 total)

Number of sites: 1

Isolated growth hormone deficiency, 

or

Multiple hormone deficiency

None Isolated growth 

hormone deficiency 

(9 total)

Multiple hormone 

deficiency (13 total)

Prospective crosssectional cohort

Pollitt

1964

Location: US

Setting: Endocrine clinic

Mean age: ND

Age range: 3-16 y

Mean height: ND

Height range: 70-126 cm

Male: 40%

Race: ND

Enrolled: ND

Evaluated: 15

Number of sites: 1

Significant short stature thought to be 

due to growth hormone deficiency 

– either pan-hypopituitary or 

isolated

Pediatricians thought were welladjusted psychologically and had 

cooperative parents

None Isolated short stature Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

108

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Robinson

1983

84052395

Location: US

Setting: Region

Mean age: ND

Age range: 7-15 y

Mean height: ND

Male: 0%

Race: ND

Enrolled: 9

Evaluated: 9

Number of sites: ND

Monosomy X karyotype (45, X) and 

partial monosomy X

None Turner Syndrome

Monosomy (6)

Partial monosomy 

(3)

Prospective crosssectional cohort

Ross

1997

97320537

Location: US

Setting: ND

Mean age: 9.5 y

Age range: ND

Mean height: ND

Male: 0%

Race: 87% White

SES: 47 (Hollingshead)

Enrolled: ND

Evaluated: 40

Number of sites: 2

Turner syndrome, confirmed by 

karyotyping

Age ≥5 and <12 y

Estrogen treatment

Androgen treatment

Turner syndrome Prospective crosssectional cohort 

(derived from RCT of 

GH treatment)

Rovet

1985

Location: Canada

Setting: Clinic

Mean age: 14±1 y

Age range: ND

Mean height: 139±9 cm

Male: 100%

Race: ND

Enrolled: 27

Evaluated: 25

Number of sites: 1

Height more than 2 SD below mean History of familial short 

stature

Isolated short stature Prospective crosssectional
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

109

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Siegel

1986

Location: US

Setting: Endocrinology clinic

Mean age: 12±2.3 y

Age range: 6-16 y

Mean height, SDS: < –2

Male: 71%

Race: ND

SES, Social position: High 5%, High 

average 21%, Average 31%, 

Low average 33%(14), Low 

10%

Enrolled: 53

Evaluated: 42

Number of sites: 2

Idiopathic hypopituitarism Deprivation dwarfism

Craniopharyngioma

Age < 6 y

IQ < 30

Isolated short stature

GH def (28)

Multiple hormone def 

(14)

Prospective crosssectional cohort

Siegel

1994

Location: US

Setting: Endocrinology clinic

Mean age: 

GHD 11±2.7 y

ISS 11±2.6 y

Control 11±2.8 y+

Age range: ND

Mean height, SDS:

GHD –2.7±0.6

ISS –2.8±0.6

Control +0.1±0.9

Male: 75%

Race: White 91%

Enrolled: 177 (90 controls)

Evaluated: 177 (90)

Number of sites: 27

Cases - Height < 3rd percentile

Controls - Normal height

Known mental impairment

Severe psychiatric

Chronic medical illness

Non-English speaking

Short stature secondary to 

systemic disease, tumor, 

or genetic abnormalities

Isolated short stature

GH Def (87)

Idiopathic SS (90)

Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

110

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Siegel

1998

98356098 

Location: US

Setting: Clinic

Initial mean age: 10 y

Control 11 y

Initial mean height:

TS 120±13 cm

GHD/ISS 125±12 cm

Control 145±17 cm

Male: 0%

Race: ND

Enrolled: 88 (Controls 67)

Evaluated: 47 (25)

Number of sites: ~27

Cases - Girls with Turner 

syndrome, GH deficiency, or 

idiopathic short stature

Controls - Matched for age and 

socioeconomic status

Did not follow through with 3 

y of GH therapy

Turner syndrome (22)

GH deficiency (13)

Idiopathic short stature 

(12)

Prospective longitudinal 

cohort 

(3 y)

Skuse

1997

Gilmour

1996

96408881

Skuse

1994

95252652

Location: UK

Setting: Growth clinics

Mean age:

Case 8±1.5 y

Control 9±1.4 y

Age range:

Case 6-11 y

Control 2-11 y

Mean height, SDS :

Case –2.5±0.3

Control –0.3±1.1

Male: 72%

Race: ND

SES (Parent profession): 59% 

advantaged/professional ; 14% 

clerical/craft; 14% manual

Enrolled: 31 (25 controls)

Evaluated: 22 (22)

Number of sites: 2

Cases - Height < 5th percentile

(< –2 SDS)

Height velocity over the last year 

above –1.5 SDS

Age 6-11 y

Prepubertal

Controls - From each case’s school 

class, matched for age, sex, and 

SES

Cases - Bone age delayed 

> 2 y

Medical treatment for growth 

retardation

Russell-Silver children 

who had IQ < 72

Isolated short stature 

(15)

Russell-Silver 

syndrome (7)

Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

111

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Stathis

1999

20099119

Location: Australia

Setting: Region

Mean age: 5.5 y

Age range: 4-6 y

Mean height: <3rd percentile

Male: 53%

Race: ND

Enrolled: ND

Evaluated: 113 (3,178 controls)

Number of sites: 1

Cases - Height < 3rd percentile

Age 4-6 y

Controls - Height between 10th and 

90th percentile

Age 4-6 y

PPVT-R score < 50

Cerebral palsy

Other serious neurological 

disorder

Isolated short stature Prospective crosssectional cohort

Steinhausen

1976

77086274

Location: Germany

Setting: Inpatient

Mean age:

SS 14±2.7 y

Control 14±2.6 y

Age range: 

SS 9-18 y

Control 9-18 y

Mean height, SDS: <3rd percentile

Male: 81%

Race: ND

SES: Lower class 59%, Middle 

class 41%

Enrolled: ND

Evaluated: 32 (32 controls)

Number of sites: 1

Cases - Height < 3rd percentile

Controls - Age and sex matched 

from local schools with “normal” 

stature

None Isolated short stature

GH deficiency (16)

Constitutional delay 

(16)

Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

112

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Tanner

1975

75217260

Location: UK

Setting: Growth disorder clinic

Mean age: ND

Age range: 1.4-10 y

Mean height, SDS: –3.6

Height range, SDS: –6.3 to –2.2

Male: 56%

Race: ND

Enrolled: 39

Evaluated: 39

Number of sites: 1

Russell-Silver syndrome

Height < –2 SDS

Adjusted birth weight ≥ 2 SD below 

the mean of the Tanner-Thomson 

standard

None RSS Unclear

Voss

1994

Voss

1991

92151680

Downie

1997

97159125 

Downie

1996

96408882

Location: UK

Setting: Region

Mean age: ND

Age range: Data at ages 5-6 y, 7-9 

y, 11-13 y, mean 13 y (see 

comments)

Mean height (age 5-6 y), SDS:

Case –2.3±0.3

Control +0.1±0.6

Mean height (mean age 13, No 

GH): Case 139 cm

Control 155 cm

Male: 54%

Race: ND

SES: Class I/II 20%; Class III 49%; 

Class IV/V 31%; 25% 

unemployed fathers

Enrolled: 140 (140 controls)

Evaluated: 140 (140)

(See comments)

Number of sites: 1

Cases - Height <3rd percentile, 

starting school between 1985 and 

1986

Controls - From same school class

Height between 10th and 90th 

percentile

Matched for age, sex and school 

class

Cases - Organic disease 

(e.g., Turner syndrome 

or celiac disease); 

Immigrant parents

Controls - None

Isolated short stature Prospective longitudinal 

cohort

(up to 9 y)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part I

113

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease/Condition 

Type (N)

Study Design

(Duration)

Wilson

1986

Location: US

Setting: ND

Mean age: ND

Age range: 6-17 y

Mean height, SDS: ND

Male: ND

Race: ND

Enrolled: ND

Evaluated: 6,768-7,119 (all heights)

Number of sites: ND

National Health Examination Survey 

(NHES):

1963-1965: 7,119 children

6-11 y

1966-1970: 6,768 adolescents

12-17 y

None Isolated short stature Prospective crosssectional cohort

Young-Hyman

1986

Location: US

Setting: Endocrine clinic

Mean age: 12 y

Age range: ND

Mean height, SDS: ND

Male: 78%

Race: ND

SES: Upper middle class

Enrolled: 27

Evaluated: 27

Number of sites: 1

Children with SS who presented to 

endocrine clinics for evaluation

Chronic health problem

Mental disability

Isolated short stature Prospective crosssectional cohort
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part II

114

Author, Year Predictors Predictor Measures Outcomes Outcome Measures

Abbott

1982

82277019

Isolated short stature ND Cognitive/Academic IQ (WISC)

Academic achievement (WRAT)

Visual-motor skills (Developmental Test of 

Visual-Motor Integration)

Angehrn Cognitive/Academic IQ (ND)

1979

80093987

Russell-Silver syndrome Height < –2 SDS, low normal growth 

velocity, low birth weight for 

gestational age, moderate bone age 

retardation, ty pical small triangular 

face, and large skull

Psychomotor Psychomotor development (Denver 

developmental screening test)

Cognitive/Academic IQ (HAWIK & HAWIE, German version of 

Wechsler IQ test)

Academic performance (Repetition of 

grade)

Frisch

1990

90350511

Isolated short stature/GH 

deficiency

Hypopituitary GH deficiency

GH peak < 5 ng/ml in 2 stimulation tests

Behavioral/Psychological Personality structure tests (Freiburger 

Personality Questionnaire, Giessen 

Test)

Sociability, Social activity, Neuroticism 

(Hamburger Neuroticism-Extroversion 

Scales)

Cognitive IQ (WISC-R)

Math, reading, comprehension (PIAT)

Gordon

1984

84214634

Gordon

1982

82268405

Isolated short stature Height < 5th percentile

Behavioral School adjustment, Internalization (CBCL 

– Teacher)

Isolated short stature:

CGD (21)

Retarded bone age, growth velocity 

within 2 SD of normal for age, 

projected adult height normal

Holmes

1986

Holmes GHD (17) Maximum GH ≤ 7 ng/ml on 9 samples

Cognitive/Academic IQ (WISC-R)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part II

115

Author, Year Predictors Predictor Measures Outcomes Outcome Measures

1985

86060101 

TS (9) ND

Cognitive/Academic Verbal and non-verbal intelligence (KBIT)

Educational achievement (KTEA brief 

form)

Kranzler

2000

20102780

Isolated short stature Referred: Height < 5th percentile

Non-referred: Height < 10th percentile 

of class

Behavioral Adaptive and problem behaviors (BASC 

– Teacher)

Lai

1994

95243689

Isolated short stature Russell-Silver syndrome Cognitive/Academic IQ (WISC)

Reading comprehension (Neale Analysis 

of Reading Ability)

Arithmetic comprehension (ND)

Cognitive processing (Matching Familiar 

Figure Test)

Special educational needs

Turner syndrome Karyotype showing absence of all or Cognitive IQ (WISC)

part of an X chromosome Behavioral Behavior factor (Piers-Harris Scale –

Children self-report)

McCauley

1987

87161055

McCauley

1986

86141341

Isolated short stature Height < 5th percentile Psychological Depression (Children’s Depression 

Inventory)

Meyer-Bahlburg

1978

78184456

Isolated growth hormone 

deficiency, and multiple 

hormone deficiency

GH deficient or panhypopituitary Cognitive IQ (WISC)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part II

116

Author, Year Predictors Predictor Measures Outcomes Outcome Measures

Pollitt

1964

Hypopituitary short stature Panhypopituitary 

Isolated GH deficiency

Turner syndrome

Primordial

Undiagnosed

Cognitive IQ (WISC Scale for Children – age > 5 y)

Cognitive IQ (Wechsler Preschool and Primary 

Scale of Intelligence)

Language development (“A 

comprehensive speech and language 

evaluation”)

Robinson

1983

84052395

Turner Syndrome 45, X monosomy or partial monosomy 

on karyotype from chromosomal 

exam of amniotic membrane

Physical Development Neuromuscular maturation (BruininksOseretsky Test of Motor Proficiency)

Ross

1997

97320537

Turner syndrome Karyotype 45,X Cognitive/Academic IQ (WISC-R)

Academic achievement (WART - reading)

Rovet

1985

Isolated short stature SD from mean Cognitive IQ (WISC)

Siegel

1986

Hypopituitary isolated short stature GH secretion < 7 ng/dL, delayed bone 

age, growth < 4 cm in past year, 

height < –2 SDS or below the 3rd

percentile

Cognitive/Academic IQ (WISC-R)

Academic achievement (WRAT)

Visual-motor integration skills (Bender 

Visual-Motor Gestalt Test: a significant 

visual-motor integration deficit was 

defined as if the developmental score 

was < 16th percentile, and four or 

more errors were significant indicators 

of brain injury)

Siegel

1994

Isolated short stature

GH deficient

Idiopathic short stature

Height < 3rd percentile Cognitive/Academic IQ (Slosson Intelligence Test)

Academic achievement (WRAT - revised)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part II

117

Author, Year Predictors Predictor Measures Outcomes Outcome Measures

Siegel

1998

98356098 

Isolated short stature Turner syndrome

GHD/ISS

Cognitive/Academic IQ (Slosson Intelligence Test)

Academic achievement (WRAT - revised)

Skuse Cognitive IQ (WISC for children – version III)

1997

Gilmour

1996

96408881

Skuse

1994

95252652

Isolated short stature and RussellSilver syndromeHeight < –2 SDS

Behavioral Competence and self-concept (Harter Self 

Perception Profile for Children, Harter 

Pictorial Scale of Perceived 

Competence and Social Acceptance 

for Young Children, CHIPS)

Stathis

1999

20099119

Isolated short stature Height < 3rd percentile Cognitive Receptive vocabulary (PPVT-R, which 

correlates closely with intellectual 

ability)

Cognitive/Academic Primary mental abilities (LPS)

IQ (WISC)

Academic performance (Grade level for 

age)

School achievement (ND)

Steinhausen

1976

77086274

Isolated short stature Height < 3rd percentile

GH deficiency or no endocrine 

disease

Behavior Extraversion and Neuroticism (Hamburg 

Neuroticism Extraversion Scale)

Tanner

1975

75217260

Russell-Silver syndrome Height < –2 SDS, adjusted birth 

weight< –2 SDS, no other obvious 

cause of short stature

Cognitive/Academic IQ (ND)

Academic achievement (Grade repetition)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part II

118

Author, Year Predictors Predictor Measures Outcomes Outcome Measures

Cognitive/Academic IQ (Short form IQ scale of the British Ability 

Scales)

Attainment (Word reading and basic 

number skills scales of British Ability 

Scales)

Voss

1994

Voss

1991

92151680

Downie

1997

97159125 

Downie

1996

96408882

Isolated short stature Height < 3rd percentile

Behavioral Behavioral problems (Rutter’s Behavior 

Questionnaire – Teacher)

Locus of control (Nowicki and Strickland 

scale )

Wilson

1986

Isolated short stature Height < 5th percentile Cognitive/Academic IQ (WISC)

Academic achievement (WRAT)

Young-Hyman

1986

Isolated short stature ND Cognitive IQ (WISC-R)

Visual-motor integration skills (Bender 

Visual-Motor Gestalt Test)
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

119

Author, Year Associations found Potential Biases Comments

Abbott

1982

82277019

Mean (SD) IQ of children with SS due to pituitary hormone deficiency (n=11) was 

Full Scale = 88 (17), Verbal = 89 (20), Performance = 89 (16), Reading = 88 

(17), Spelling = 85 (14), and Arithmetic = 83 (15)

Mean (SD) WRAT scores for children with SS (n=11) were Reading = 88 (17), 

Spelling = 85 (14), and Math = 83 (15)

Visual-Motor Integration skills were significantly below average among children 

with SS

Compared to population norms Study was government and 

hospital funded

Angehrn

1979

80093987

Mean (range) IQ for children with SS due to RSS (n=9) was 91 (38 to 110); 3 

subjects had low IQs of 85, 83, and 38; an additional 5 subjects were 

“probably of normal intelligence”

Of subjects with RSS, 3 of these children had microcephaly; 3 children had subnormal IQ, 2 of whom had microcephaly

More than half of the psychomotor activities on the Denver developmental 

screening test occurred at an age > 90th percentile in subjects with RSS 

(n=14)

Incomplete testing

IQ test used not reported

Incomplete and unclear reporting

Small sample size for IQ data

No data on funding source

Frisch

1990

90350511

The median (range) IQ of children with GHD (n=23) were Full Scale = 115 (68-

131), Performance = 114 (61-136), Verbal = 104 (72-128); full score and 

performance IQ were significantly higher than population norms; verbal IQ 

was similar to population norms

Performance Behavior (zeal and school aversion) was similar in children with 

GHD (n=20) compared to population norms

Sociability in children with GHD (n=20) than population norms; Social activity in 

children with GHD was similar to population norms (No further data)

Emotional Stability (including mood, control, depression) in children with GHD was 

similar to population norms (No further data)

Delayed Schooling was more common in children with multiple pituitary hormone 

deficiencies and SS (33%) than normal population (2.1%)

Compared to population norms

Reporting incomplete

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

120

Author, Year Associations found Potential Biases Comments

Gordon

1984

84214634

Gordon

1982

82268405

Mean (SD) IQ for children with SS due to constitutional delay (n=24) were total 

108 (14), verbal 107 (16), and performance 108 (14).

Mean (SD) scores on PIAT for children with SS (n=24) were math 103 (16), 

reading recognition 102 (11), and comprehension 102 (11); these were, 

similar to scores among children with normal stature who were matched by IQ 

(n=23): 103 (9.6), 102 (7.5), and 103 (10), respectively

Mean (SD) teacher CBCL scores for children with SS (n=24) were total 31.2 

(26.5) and for controls (n=23) 27.5 (27.6); conduct problem scores were 

22.6 (4.3) and 24.1 (6.8), respectively; inattentive/passive 12.7 (4.8) and 

12.1 (4.8), respectively; hyperactive 13.7 (5.9) and 11.9 (4.3), respectively; 

and socialization 14.7 (2.5) and 14.3 (3.0), respectively

Comparisons of cognitive function between short 

children and controls of questionable value 

since controls were matched for overall IQ

No outline of the statistical analyses used in the 

paper; therefore, it is hard to evaluate the 

significance

Study was government and 

private funded

There is no evidence that 

these behavior 

problems constitute a 

disability

The subjects and controls 

were matched for IQ 

and had equal school 

performance

Holmes

1986

Holmes

1985

86060101 

Mean (SD) Verbal IQ in children with isolated SS (n=47) was 102 (13); among 

these children, those with GH deficiency (n=17) verbal IQ was 97 (13), those 

with constitutional delay (n=21), 104 (14) and those with TS (n=9), 103 (14); 

these were all similar to population norms

40% non-participation rate

Those declining participation more likely to have 

constitutional delay and to have received 

optimal treatment benefits

Study presented only partial data, focusing on 

significant results

IQ compared only to population norms

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

121

Author, Year Associations found Potential Biases Comments

Kranzler

2000

20102780

Mean (SD) IQ scores of referred children with SS (n=27) were Verbal = 101 

(16), Matrices = 106 (14), and Composite = 103 (14); of non-referred children 

with SS (n=34) were Verbal = 104 (15), Matrices = 105 (14), and Composite 

= 105 (14); and of normal controls (n=29) were verbal = 110 (12), matrices = 

110 (17), and composite = 112 (13);

Post hoc analysis found that referred short children had significantly lower 

Verbal IQ than normal controls; other comparisons were statistically similar

Mean (SD) composite and spelling Educational Achievement (KTEA) scores were 

similar for referred short children, 106 (18) and 105 (15), non-referred short 

children, 107 (19) and 104 (19); and, controls, 114 (17) and 102 (17).

Mean (SD) mathematics and reading KTEA scores were lower for referred short 

children, 107 (21) and 104 (15) and for non-referred short children, 105 (19) 

and 106 (18) than for controls, 121 (20) and 115 (18).

Teacher ratings on BASC for Externalizing behavior, Internalizing behavior, 

School Problems composite, Behavior symptoms index and Adaptive Skills 

composite were each similar among referred short children, non-referred short 

children and normal controls

Study of cognitive skills excluded children with 

low IQ

Definition of non-referred short children sample 

vague

Predominantly post hoc analyses

Study was government, 

privately and 

pharmaceutical funded

Lai

1994

95243689

The mean (SD) IQ of children with RSS (n=25) were Full Scale = 86 (24), range 

46-130, Verbal = 89 (23), range 52-141, and Performance = 84 (24), range 

47-127; these were significantly lower than population norm, 100 (15)

In children with RSS, larger Head Circumference was significantly associated with 

higher IQ (r=0.5-0.6)

Reading Comprehension in children with RSS was delayed by a mean of 15.4 

months; Arithmetic Competence was delayed by a mean of 7 months

Cognitive Processing, measured by reaction time and error scores in children with 

RSS (n=22) was similar to normal controls from an earlier study (n=90)

Special Education needs were necessary in 9 (36%) children with RSS, primarily 

in reading and language skills; 12 (48%) children received speech therapy

Compared to population norms and controls 

from prior study

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

122

Author, Year Associations found Potential Biases Comments

McCauley

1987

87161055

McCauley

1986

86141341

Mean verbal and performance IQ (SD) for girls with TS (n=17) were 95 (11) and 

91 (10), respectively; those IQ (SD) scores for girls with SS not due to TS 

(n=16) were 100 (12) and 108 (14), respectively.

The difference in performance IQ between the groups was significant; 

however, both groups had verbal and performance IQ scores within 1 SD of 

the mean

Girls with TS had significantly lower performance on arithmetic, digit span, picture 

completion, object assembly, and coding subscales than girls with SS; 

performance on other subscales were similar for the two groups

Self-reported Piers-Harris behavior factor and Children’s Depression Inventory 

scores were similar in girls with TS and girls with SS;

“Although the TS children indicated low self-concept they did not endorse 

features of clinical depression.”

Excluded children with low IQ Study was hospital funded

Meyer-Bahlburg

1978

78184456

Mean IQ of children with isolated GHD (n=13) was 101, and of children with 

multiple hormone deficiency (n=9) was 102

Patients with multiple hormone deficiencies have somewhat lower IQs than patients 

with isolated GHD, after controlling for SES

Compared to population norms No data on funding source

Pollitt

1964

Mean (SD) IQ for children over age 5 with SS (n=13) were total 103 (16), verbal 

103 (15), and performance 102 (16);

These IQ scores were not significantly different than normal IQ

Compared to population norms No data on funding source

Descriptive study

Robinson

1983

84052395

Mean (SD) IQ of girls with TS (n=9) were Full Scale = 87 (20), Verbal = 93 (25), 

and Performance = 83 (12). Siblings (n=17) had significantly higher Full Scale 

IQ = 111 (15) and Performance IQ = 107 (14), but similar Verbal IQ =113 

(15).

The TS girls were at non-significantly greater risk of developing Language 

Disorders than their unaffected siblings

Small sample

Handwriting problems not defined

Methods and results not fully reported

Most analyses were done for all subjects (girls 

and boys with various sex chromosomal 

anomalies) together

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

123

Author, Year Associations found Potential Biases Comments

Ross

1997

97320537

Mean (SD) Full scale IQ in girls with TS with GH treatment (n=20) was 98 (14) 

and without GH (n=20) was 99 (15)

Mean (SD) Academic Achievement (WART) reading score in girls with TS with 

GH treatment (n=20) was 100 (14) and without GH treatment (n=20) was 97 

(17), similar to population norms

Indirectly compared to population norms Study was government 

funded

Rovet

1985

The mean IQ of boys with SS (n=25) were Verbal = 98, Performance = 102, and 

Full Scale = 101

Compared to population norms Study was hospital funded

Siegel

1986

Mean (SD) IQ for children with hypopituitary SS (n=42) were verbal 94 (18), 

range 52 to 127, and performance 94 (16), range 49-123;

Both the verbal and performance IQ were significantly below normal IQ

Mean (SD) WRAT scores for children with hypopituitary SS (n=42) were reading 

96 (16.9), range 52 to 131, and math 85 (13.9), range 52-126;

The WRAT reading score was in normal range, but the WRAT math score 

was significantly below the normal score (100)

Significant visual-motor integration deficits occurred in 11 (26%) of children with 

hypopituitary SS (n=42), indicating “a significant number of hypopituitary 

youngsters have visual-motor integration problems.”

Compared to population norms

Excluded children with severe mental 

retardation

Study was hospital funded

Siegel

1994

Mean (SD) IQ for children with GHD (n=87) was 110 (16) for children with ISS 

(n=90) was 107 (19); compared to 116 (15) for control children (n=90);

Significantly more GHD children (9%) and ISS children (18%) had IQs < 90, 

than control children (3%)

Mean (SD) WRAT scores for children with GHD (n=87) were reading 103 (18), 

spelling 98 (17), and math 99 (17); for children with ISS (n=90) were reading 

102 (18), spelling 98 (17), and math 96 (21); and for control children (n=90) 

were reading 105 (14), spelling 103 (14), and math 105 (16)

Significantly more ISS children (22%) had a skill deficit in math (score < 80) 

compared to GHD (10%) and normal children (7%)

Excluded children with “known mental 

impairment”

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

124

Author, Year Associations found Potential Biases Comments

Siegel

1998

98356098 

The mean IQ of girls with TS (n=22) was 102 (11), and with GHD/ISS (n=25) 

was 105 (15); these were not significantly different than controls (n=25) with 

109 (17).

Mean (SD) WRAT scores for children with TS (n=22) were reading 98 (15), 

spelling 95 (19), and math 90 (16); for children with GHD/ISS (n=25) were 

reading 105 (18), spelling 99 (21), and math 102 (22); and for control children 

(n=25) were reading 98 (16), spelling 100 (15), and math 99 (20). No 

significant differences among groups.

CBCL completed by parent, typically mother Study was pharmaceutical 

company funded

Skuse

1997

Gilmour

1996

96408881

Skuse

1994

95252652

Mean (SD) IQ of children with SS (n=22) were Full Scale = 96 (19), Verbal = 95 

(20), and Performance = 97 (17); for normal children (n=22), Full Scale = 

107 (17), Verbal = 105 (17), and Performance = 108 (17);

Children with SS had statistically lower Full Scale IQ and Performance IQ than 

controls, but statistically similar Verbal IQ

Conduct, Global, Physical, Athletic, Social, and Scholastic competencies measured 

by Teacher CBCL were similar among SS children (n=17) and controls

Excluded Russell-Silver Syndrome children 

who had low IQ

Incomplete reporting of results.

Teacher CBCL completed only on subset of 

subjects

Study was pharmaceutical 

funded 

Stathis

1999

20099119

Mean receptive vocabulary score on PPVT-R test for boys with SS (n=60) was 

92, which was significantly lower for normal height boys, 98 (n=1,660)

Mean receptive vocabulary score on PPVT-R test for girls with SS (n=53) was 

92, which was significantly lower for normal height girls, 95 (n=1,508)

Study of correlation of PPVT-R score to height 

excluded those with score < 50

No data on funding source

PPVT-R score was 

adjusted for maternal 

age, education, nonEnglish speaking 

background, age at 

evaluation, maternal 

depression at birth and 

maternal height
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

125

Author, Year Associations found Potential Biases Comments

Steinhausen

1976

77086274

Mean IQ for children with SS (n=32) were total 103, verbal 102, and performance 

103.

Primary mental abilities on LPS intelligence test were significantly different among 

children with SS (n=32) and controls (n=32) for only 2 of 14 measures of 

intelligence; Spatial orientation was 4.7 for SS children and 6.2 for controls; 

Speed of closure was 4.4 for SS children and 5.3 for controls

Grade level was appropriate in 59% of children with SS (n=17); Academic 

achievement was adequate in 48% of SS children

Among children with short stature (n=32) mean extraversion and neuroticism 

scores on HANES were 11.4 and 12.9, respectively. These were similar to 

controls (11.6 and 15.6, respectively).

Not all of the psychological tests are published 

and validated; the one well-known test 

(WISC) was used without data in control 

group

Many comparisons with some statistical 

significance but questionable clinical 

significance; the intelligence (LPS) and 

personality (CPQ) variables are not well 

defined

No statistical comparison was done for social 

and coping behavior; and, school 

performance; Average scores only

No outline of how the subset 17 kids were 

selected

School achievement not defined

No data on funding source

Tanner

1975

75217260

Mean (SD) IQ for children with SS due to RSS (n=11) was 103 (21), range 70-

130

Of subjects with RSS and head circumference < 3rd percentile (n=18), 83% were 

at “normal” schools, 17% were at schools for educationally subnormal children 

(“usually IQ < 80”);

Of subjects with head circumference > 3rd percentile (n=19), all were at normal 

schools

IQ test not described and performed in only a 

sub-sample

No data on funding source
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

126

Author, Year Associations found Potential Biases Comments

Voss

1994

Voss

1991

92151680

Downie

1997

97159125 

Downie

1996

96408882

Mean (SD) IQ in children aged 7-9 y with SS (n=140)was 102 (15.2) and for 

controls with normal height (n=140), IQ was 104 (14.1); there was no 

significant difference between the two groups; there was also no significant 

difference in Verbal scales, Non-verbal scales, Speed of Information 

Processing, or Reading or Number Attainment, after controlling for SES

Behavior Disturbance (total Teacher RBQ score > 9) occurred in 29% of 

children aged 7-9 y with SS (n=132), and in 21% of control children (n=132); 

the difference was not significant;

Hyperactivity (Activity subscale score ≥ 3) occurred in 16% of SS children 

compared to 8% of control children (p=0.003);

Mean (SD) Total Behavior scale score for children with SS was 6.2 (6.2), 

compared to 5.1 (6.5) for control children (NS)

Conduct subscale score was 1.2 (2.3) for children with SS, compared to 1.0 

(2.1) for control children (NS)

Emotional subscale score was 1.2 (1.4) for children with SS, compared to 1.2 

(1.7) for control children (NS)

Activity subscale score was 1.7 (2.1)for children with SS, compared to 1.1 

(1.6) for control children (NS after controlling for SES)

Mean (SD) IQ in children aged 13 y with SS, not treated with GH, (n=84-106 for 

different tests) and controls (n=93-119), were 103 (17) and 109 (16), 

respectively (p=0.005);

Reading Attainment of 44.3 (8.8) and 47.9 (8.5), respectively (p=0.002);

Math Attainment of 40.2 (7.2) and 43.5 (9.2), respectively (p=0.003);

Locus of Control score of 16.6 (5.0) and 14.3 (5.1), respectively (p=0.001),

Behavior score of 6.8 (7.5) and 5.3 (6.8), respectively (NS);

The statistical significance of these differences were reduced, but remained 

significant, after controlling for SES

None noted Studies were hospital and 

pharmaceutical funded

Downie studies included 

subsets of subjects in 

Voss studies; one 

examined subjects 

treated with GH; one 

examined untreated 

subjects

Different sized subsets of 

subjects, at different 

ages, analyzed in 

different articles
Evidence Table 1. Studies Evaluating Short Stature Secondary to Medical Impairment

Part III

127

Author, Year Associations found Potential Biases Comments

Wilson

1986

Mean IQ (WISC) for children with SS, aged 12-17 (N~350) was 92

Mean IQ (WRAT) for children with SS, aged 12-17 (N~350) was 91

Among children of all heights, aged 6-11 (n=7,119), both WISC and WRAT 

scores showed a significant but small correlation with height (r=0.18, WISC; 

r=0.17, WRAT)

Among children of all heights, aged 12-17 (n=6,768), both WISC and WRAT 

scores showed a significant but small correlation with height (r=0.20, WISC; 

r=0.19, WRAT)

“The association between height and IQ scores is less among the subjects with a 

high family income”

Prevalence and correlation data only

Incomplete reporting

Study was government 

funded

Young-Hyman

1986

Mean (SD) IQ for children with SS (n=27) was 110 (16), range was 85 to 142

Mean (SD) perceptual-motor skill for children with SS (n=27) was significantly 

delayed at 9.2 y (1.2 y), compared to chronological age 11.8 y

How significance was defined for perceptualmotor skill test was not outlined in the paperNo data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

129

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Alston

1983

Location: UK

Setting: Brittle Bone Society, 

Health Authorities

Mean age: ND

Age range: 5-16 y

Mean height: ND

Male: ND

Race: ND

Enrolled: 40 (40 controls)

Evaluated: 40 (40)

Number of sites: ND

Cases - Osteogenesis 

imperfecta

Controls - Same school class 

or neighborhood as cases, 

matched for age, sex and 

social class

None reported Osteogenesis imperfecta Prospective cross-sectional 

cohort

Apajasalo

1998

98163312

Location: Finland

Setting: Clinic

Mean age: ND

Age range: 12-15 y

Mean height: ND

Male: 42%

Race: ND

Enrolled: 21 (239 controls)

Evaluated: 19 (239)

Number of sites: 1

Cases - Diagnosis of skeletal 

dysplasia

Age 12-15 y

Controls – Age-matched 

Helsinki elementary school 

pupils who completed the 

HRQOL questionnaire

Age 12-15 y

Cases – Incomplete 

questionnaires

Skeletal dysplasia

Achondroplasia

Cartilage hair hypoplasia

Diastrophic dysplasia

Prospective cross-sectional
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

130

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Bailey

1971

72080259

Location: US

Setting: Clinic

Mean age: ND

Age range: 3 days - 72 y

Mean height: ND

Male: 51%

Race: ND

Enrolled: ND

Evaluated: 41 (no data on 

number < 21 y)

Number of sites: 1

Diagnosis of achondroplasia None reported Achondroplasia Retrospective cross-sectional

Benson

1978

79027354

Location: US

Setting: Shriner’s Hospital

Mean age: ND

Initial age range: 1 mo - 16 y

Mean height: ND

Male: 44%

Race: White 94%; Black 6%

Enrolled: 143

Evaluated: 126

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta from 1924 to 

1974

Spine X-ray films not available Osteogenesis imperfecta Retrospective longitudinal 

case series

(Mean [Range] 5 [0-17] y)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

131

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Bleck

1981

82026195

Location: US

Setting: ND

Initial mean age: 9y

Follow-up mean age: 13 y

Initial age range: 3 mo - 21 y

Follow-up age range: 4-26 y

Mean height: ND

Male: ND

Race: ND

Enrolled: 30

Evaluated: 24

Number of sites: ND

Diagnosis of osteogenesis 

imperfecta: congenita or 

tarda

Death

Too young to enable a 

satisfactory follow-up

Moved out of the state

Osteogenesis imperfecta Prospective longitudinal cohort 

(Mean [Range] 4 [1-15] y)

Brinkmann

1993

94091382

Location: Germany

Setting: Clinic

Mean age: 9 y

Age range: ND

Mean height: ND

Male: 47%%

Race: ND

SES: Primarily middle-class

Enrolled: 30 (90 controls)

Evaluated: 30 (90)

Number of sites: 1

Cases - Clinical and 

radiographic diagnosis of 

achondroplasia

Controls - Closest sibling; 

Other causes of short 

stature

Matched for age, sex and 

SES

Normal height children, 

matched for age, sex and 

SES

None reported Achondroplasia Prospective cross-sectional
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

132

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Cox

1982

83016754

Location: US

Setting: Dept of Communicative 

Disorders

Mean age: 10 y

Age range: 4-17 y

Mean height: ND

Male: 53%

Race: ND

Enrolled: 30

Evaluated: 30 (15 met criteria for 

current review)

Number of sites: 1

Medically diagnosed 

osteogenesis imperfecta, 

types I, III or IV

History of head injury

Prior surgery

Treatment for ear disease

Noise exposure

(For current review, excluded 

those age ≥ 18 y)

Osteogenesis imperfecta Prospective cross-sectional 

cohort

Daly

1996

96219608

Location: UK

Setting: Osteogenesis imperfecta 

clinic

Mean age: 7.4 y

Age range: 3.5-16.3 y

Mean height: ND

Male: 49%

Race: ND

Enrolled: 59

Evaluated: 51

Number of sites: 1

Patients registered at OI clinic 

who had been recently 

seen

No reply to the questionnaire Osteogenesis imperfecta Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

133

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Engelbert

1997

Possible 

overlap with 

Engelbert 

1998, 

Engelbert 

1999

Engelbert

2000

Engelbert 

2001

Location: Netherlands

Setting: Children’s hospital

Mean age:

Type I OI: 7.3±3.5 y

Type III OI: 6.5±2.9 y

Type IV OI: 9.1±5.0 y

Age range:

Type I OI: 2-16 y

Type III OI: 2-12 y

Type IV OI: 1-17 y

Mean height: ND

Male: 54%

Race: ND

Enrolled: 68

Evaluated: 61

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

Visit source hospital = 1 per 

year

Parents declined to participate Osteogenesis imperfecta Prospective cross-sectional 

cohort

Engelbert

1998

98366964

Possible 

overlap with 

Engelbert 

1997, 

Engelbert 

1999

Engelbert

2000

Engelbert 

2001

Location: Netherlands

Setting: Children’s hospital

Mean age: 8 y

Age range: 1-15 y

Mean height, SDS:

Type I OI –1.6±1.3

Type III OI –8.0±2.0

Type IV OI –2.8±1.7

Male: 47%

Race: ND

Enrolled: 47

Evaluated: 47

Number of sites: 1

Children with osteogenesis 

imperfecta who regularly 

attended a referral center

None reported Osteogenesis imperfecta Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

134

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Engelbert

1999

99381568

Possible 

overlap with 

Engelbert 

1997, 

Engelbert 

1998

Engelbert

2000

Engelbert 

2001

Location: Netherlands

Setting: Children’s hospital

Mean age:

Initial: 7.3±3.8 y

Follow-up: 9.4±3.6 y

Age range:

Initial: 1-15 y

Follow-up: 3-17 y

Mean height: ND

Male: 50%

Race: ND

Enrolled: 54

Evaluated: 44

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

Intramedullary fixation surgery 

within 6 months

Any other disability or 

impairment

Parents’ refusal in follow-up

Unable to be reached

Surgical interventions in the 

last half year of the study

Osteogenesis imperfecta Prospective longitudinal cohort

(Mean [Range] 1.2 [0.7-1.8] 

y)

Engelbert

2000

20429012

Possible 

overlap with 

Engelbert 

1997, 

Engelbert 

1998

Engelbert

1999

Engelbert 

2001

Location: Netherlands

Setting: Children’s hospital

Mean age: 11.2±5.2 y

Type I OI: 10.8±5.8 y

Type III OI: 9.4±2.9 y

Type IV OI: 13±4.6 y

Age range: 1-28 y

Type I OI: 1-28 y

Type III OI: 5-15 y

Type IV OI: 4-20 y

Mean height: ND

Male: 45%

Race: ND

Enrolled: 98

Evaluated: 70

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

Completed questionnaire

Too young to expect walking Osteogenesis imperfecta Retrospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

135

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Engelbert

2001

21334060

Possible 

overlap with 

Engelbert 

1997, 

Engelbert 

1998

Engelbert

1999

Engelbert 

2000

Location: Netherlands

Setting: Hospital

Mean age: 12.6±3.2 y

Age range: 8-16 y

Mean height: ND

Male: 50%

Race: ND

Enrolled: 40

Evaluated: 40

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

None reported Osteogenesis imperfecta Prospective cross-sectional 

cohort

Falvo

1973

74013834

Location: US

Setting: ND

Mean age: 13.5 y

Age range: 4-34 y

Mean height: ND

Male: 27%

Race: ND

Enrolled: ND

Evaluated: 11

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

None reported Osteogenesis imperfecta Unclear
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

136

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Fowler

1997

97356792 

Possible 

overlap with 

Pauli 1995

Location: US

Setting: Bone dysplasia clinic

Mean age: ND

Age range: 1-60 months

Mean height: ND

Male: 48%

Race: White 88%, Black 2%, 

Hispanic 3%, 

Korean/Asian/Indian 5%

Enrolled: 93

Evaluated: 37

Number of sites: 1

Diagnosis of achondroplasia None reported Achondroplasia Prospective cross-sectional

Pauli

1995

95193803

Possible 

overlap with 

Fowler 1997

Location: US

Setting: Bone clinic

Mean age: ND

Age range: Infants, young 

children

Mean height: ND

Male: 52%

Race: White 85%; Black 3%; 

Hispanic 4%; Korean 7%; 

Asian Indian 1%

Enrolled: 75

Evaluated: 75

Number of sites: 1

Clinical diagnosis of 

achondroplasia

None reported Achondroplasia Prospective longitudinal (N = 

53) and cross-sectional (N 

= 22) cohorts

(To age > 1 y)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

137

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Hecht

1991

92152267

Location: US

Setting: Clinic

Mean age: 15±5 mo

Age range: 8.5-26 mo

Mean height: ND

Male: 46%

Race: ND

Enrolled: 13

Evaluated: 13

Number of sites: ND

Infants with clinical diagnosis of 

achondroplasia

None reported Achondroplasia Prospective cross-sectional 

cohort

Hunter

1998

98299528

Location: Multinational

Setting: Clinic

Mean age: ND

Age range: ND

Mean height: ND

Male: 49%

Race: White 100%

Enrolled: 55 (37 controls)

Evaluated: 55 (37)

Number of sites: 6

Cases - Diagnosis of primary 

skeletal dysplasia

Age < 16-18 y old (by site)

Controls - Unaffected siblings

None reported Skeletal dysplasia Prospective cross-sectional

Kuurila

2000

20379515

Location: Finland

Setting: Dept of clinical genetics

Mean age: 10 y

Age range: 4-16 y

Mean height: ND

Male: 42%

Race: White

Enrolled: 60

Evaluated: 45

Number of sites: 1

Diagnosis of osteogenesis 

imperfecta

Age 4-16 y

Insufficient cooperation 

No audiometry performed

Moderate mental retardation.

Osteogenesis imperfecta Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

138

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Norimatsu

1982

82163323

Location: Japan

Setting: Children’s Hospital

Initial mean age: ND

Follow-up mean age: 15.5 y

Initial age range: 12 d - 14 y

Follow-up age range: 4-28 y

Mean height: ND

Male: 68%

Race: (Japanese)

Enrolled: 30

Evaluated: 22

Number of sites: 1

Osteogenesis imperfecta

Treated from 1959 to 1980

Followed by spinal x-ray

None reported Osteogenesis imperfecta 

(congenita and tarda)

Retrospective longitudinal 

case series

(Mean [Range] 7.6 [1-20] y)

Poussa

1991

92054945

Location: Finland

Setting: Genetics and bone 

clinics

Mean age: ND

Age range: 6-20 y

Mean height: ND

Male: ND

Race: White

Enrolled: 101

Evaluated: 38

Number of sites: 2

Diagnoses of diastrophic 

dysplasia

Age ≤ 20 y

None reported Diastrophic dysplasia Prospective longitudinal cohort 

13.5 y
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

139

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Reid

1988

89193370

Possible 

overlap with 

Stokes 1988

Location: US

Setting: Genetics clinic

Mean age: ND

Age range: < 7 y

Mean height: ND

Male: ND

Race: ND

Enrolled: 62

Evaluated: 26

Number of sites: 1

Achondroplasia

Age < 7 y

Seen in genetics clinic

Seen only in orthopedics clinic 

(not in genetics clinic)

Achondroplasia Prospective longitudinal cohort

20-45 mo

Stokes

1988

88110722

Possible 

overlap with 

Reid 1988

Location: US

Setting: Hospital, genetics clinic, 

LPA convention

Mean age: ND

Age range: ND

Mean height: ND

Male: 50%

Race: ND

Enrolled: 102 (including adults)

Evaluated: 24 children

Number of sites: 1

Achondroplasia Acute medical or surgical 

problems

Hypochondroplasia

Technically unsatisfactory 

spirometry

Too young to cooperate with 

spirometry

Achondroplasia Prospective cross-sectional 

cohort

Reite

1972

72182015

Location: US

Setting: Clinic

Mean age: ND

Age range: 6-17 y

Mean height: ND

Male: ND

Race: ND

Enrolled: ND

Evaluated: 12

Number of sites: 2

Children with “severe” 

osteogenesis imperfecta

None reported Osteogenesis imperfecta Retrospective cross-sectional
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

140

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Rogers

1979

79200737

Location: US

Setting: Pediatric clinic research 

unit

Mean age: ND

Age range: 5 mo – 15 y

Mean height: ND

Male: ND

Race: ND

Enrolled: 68

Evaluated: 68

Number of sites: 1

Diagnosis of skeletal dysplasia 

leading to short stature

Syndromes of low-birth-weight 

dwarfism

Multiple malformations

Mucolipidosis or 

mucopolysaccharidosis

Cardiac arrest

Skeletal dysplasia and 

achondroplasia

Prospective cross-sectional 

cohort

Ruiz-Garcia

1997

97346439

Location: Mexico

Setting: Genetics clinic

Mean age: 4.5 y

Age range: 3 mo - 17 y

Mean height: ND

Male: 49%

Race: ND

Enrolled: 39

Evaluated: 39

Number of sites: 1

“Classical” achondroplasia 

diagnosed in Genetics 

Department

History of neurosurgical 

procedures

Achondroplasia Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

141

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Shurka

1976

Location: Israel

Setting: Pediatric endocrinology 

clinic

Mean age: 15 y

Age range: 9-17 y

Mean height: 134 cm

Height range: 104-157 cm

Male: 46%

Race: ND

SES: Primarily average or high

Enrolled: 12

Evaluated: 11 (7 met criteria for 

current review)

Number of sites: 1

Dwarfism due to bone disease (For current review, age ≥ 18 

y)

Bone disease

(External chondromatosis, 

Achondroplasia, 

Undefined)

Prospective cross-sectional 

cohort

Skeletal 

Dysplasia 

Group

1989

89192477

Location: UK

Setting: Workgroup’s registers

Mean age: ND

Age range: 1-15 y

Mean height: ND

Male: 49%

Race: ND

Enrolled: 182

Evaluated: 15 (children with 

Morquio disease)

Number of sites: ND

Diagnosis of skeletal dysplasia

Adequate cervical spine films

(Morquio disease: other 

disease sub-groups did not 

meet criteria for current 

review)

Osteogenesis imperfecta

Sclerosing bone dysplasias or 

tumor-like disorders

Malformation syndromes

Morquio disease Retrospective cross-sectional 

case series
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

142

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Stewart

1989

90125184

Location: Scotland

Setting: Dep. Of medical genetics

Mean age: ND

Age range: 10-19 y

Mean height: ND

Male: 43% for the larger group

Race: ND

Enrolled: 56

Evaluated: 56 (13 met criteria for 

current review)

Number of sites: ND

Diagnosed based on their 

history of spontaneous 

fractures.

Contacted via Brittle Bon 

Society.

For current review, only 

children aged 10-19 were 

included

None reported Osteogenesis imperfecta Prospective cross-sectional 

cohort

Thompson

1999

99221075

Location: US

Setting: Genetics clinic

Mean age:

Cases: 89 mo

Premature: 107 mo

Controls: 111 mo

Age range: ND

Mean height: ND

Male: 52%

Race: White 74%, Black 6%, 

Hispanic 13%, Other 7%

SES: Low 31%, Middle 19%, 

High 50%

Enrolled: 16 (21 premature, 17 

controls)

Evaluated: 16 (21, 17)

Number of sites: 1

Cases - clinical and 

radiographic diagnosis of 

ACH

Premature controls- premature 

infants with hydrocephalus

Normal controls - normally 

developing children of 

average stature

All - IQ>69

Severe psychiatric disorder

Uncontrolled seizure

Other neurological disorder

Child abuse

Sensory deficit

Unable to speak English

Achondroplasia Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part I

143

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Disease / Condition

Type

Study Design

Mean Duration (Range)

Waters

1993

94029092

Location: Australia

Setting: Sleep lab and clinic

Mean age: ND

Age range: 1-31 y

Mean height: ND

Male: 50%

Race: ND

Enrolled: 20

Evaluated: 20

Number of sites: 1

Patients with dysplasia 

(implied)

Refusal to participate Achondroplasia Prospective cross-sectional 

cohort
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

144

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Cognitive/Academic Non-verbal intelligence (Raven’s Matrices)

Reading (Primary Reading Test, Wide Span 

Reading Test, or Gapadol Reading 

Test)

Spelling (Graded Word Spelling Test)

Writing speed (Number of words written in 5 

minutes)

Alston

1983

Osteogenesis imperfecta ND

Motor function Mobility (Walk vs wheelchair)

Achondroplasia Disproportionate short limbed short 

stature, characteristic facial features 

and joint and spine disorders

Cartilage-hair hypoplasia Congenital disproportionate shortlimbed short stature, thin/sparse hair, 

defective immunity

Apajasalo

1998

98163312

Diastrophic Dysplasia Severe physical handicap due to shortlimbed short stature, progressive joint 

limitations, kyphoscoliosis, foot 

deformities

Physical development Overall quality of life (Health related quality 

of life, 16 dimensions)

Mobility dimension

Vision dimension

Hearing dimension

Bailey

1971

72080259

Achondroplasia ND Motor function Elbow flexion (Angle, Self-reported 

disability)

Osteogenesis imperfecta, mild Thicker cortical bone with visible 

trabeculae, not severe osteoporosis 

of vertebrae

Osteogenesis imperfecta, 

moderate

ND

Benson

1978

79027354

Osteogenesis imperfecta, severe Thin osteoporotic long bones and 

severe osteoporosis of vertebrae

Motor function Walking ability (Independent walkers, 

Walked with appliance, Sitter)

Scoliosis (spinal curvature on spine 

radiography)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

145

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Osteogenesis imperfecta 

congenita

Bleck Severe type

1981

82026195 Osteogenesis imperfecta tarda ND

Physical development/Motor function Independence (0 = No achievement 

possible

1 = Complete dependence

2 = Partial dependence

3 = Independence through technical help

4 = Completely independent, but not 

normal in timing, effort expenditure, or 

external appearance

5 = Normal activity)

Mobility efficiency (0 = None

1 = Mobility not functional enough to be 

used

2 = Moves about immediate 

surroundings

3 = Travels in the community

4 = Travel beyond the community

Activities of daily living (ADL: 0 = No ADL 

possible

1 = Meets own essential needs

2 = Completes personal care

3 = Household activity possible

4 = Normal ADL)

Ambulation (0 = None

1 = Walking possible but not functional 

enough to be useful

2 = Household walker

3 = Walk outside home but limited to 

neighborhood

4 = Community walker)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

146

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Cognitive Cognitive Abilities Test, German version

Verbal component

Arithmetic component

Reasoning component

Physical development Motor development (Months to sit, stand, 

walk alone)

Delayed speech (parental report)

Sensory Hearing deficit (parental report)

Brinkmann

1993

94091382

Achondroplasia Short limbs and characteristic skull 

changes with macrocephaly

Pain Limb, joint, back pain

Cox

1982

83016754

Osteogenesis imperfecta Idiopathic bone fragility, blue sclerae, 

hearing impairment

Sensory Hearing loss (Pure tone thresholds > 30 dB 

hearing loss at 250-1,000 Hz and/or > 

25 db hearing loss at 2,000-6,000 Hz)

Daly

1996

96219608

Osteogenesis imperfecta

Shapiro classification:

Congenita A

Fractures at birth, bones 

radiographically abnormal

Physical development/Motor function Mobility (Wheelchair, Aided walker, 

Independent)

Patterns of development (Abnormal 

arrested, Delayed arrested, Normal 

arrested, Delayed, Normal)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

147

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Congenita B Fractures at birth, bones 

radiographically normal

Tarda A First fracture by walking stage, bones 

narrow, osteopenic

Tarda B First fracture after walking, bones 

radiographically normal

Osteogenesis imperfecta

Sillence classification:

I A

Autosomal dominant, normal stature, 

blue sclerae

I B IA plus dentinogenesis imperfecta

III Autosomal recessive, multiple fractures 

at birth, progressively deforming

IV A Autosomal dominant, bone fragility, 

normal sclerae

IV B IV A plus dentinogenesis imperfecta

Engelbert

1997

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Motor function Self-care (Pediatric Evaluation of Disability 

Inventory, PEDI, range 0-100, median 

50. Score scaled for children older than 

7.5 years such that normal score=100)

Mobility (PEDI)

Engelbert

1998

98366964

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Motor function Scoliosis (Cobb angle > 40°)

Kyphosis (Cobb angle < 10° or > 40°)

Engelbert

1999

99381568

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Motor function Level of ambulation (Bleck classification)

Engelbert

2000

20429012

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Motor function Level of ambulation (Bleck classification)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

148

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Motor function Self-care (Pediatric Evaluation of Disability 

Inventory, PEDI, range 0-100. Score 

scaled for children older than 7.5 years 

such that normal score=100)

Mobility (PEDI)

Level of ambulation (Bleck classification)

Engelbert

2001

21334060

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Motor function Joint range of motion: arms, legs (0=normal, 

4=maximally decreased)

Muscle strength: arms, legs (0=no muscle 

activity, 5=normal muscle strength)

Osteogenesis imperfecta Generalized osteoporosis, blue 

sclerae, dentinogenesis imperfecta, 

history of fracture

Mild No noticeable deformity of long bones

Moderate Bowing of lower extremity long bones 

only

Falvo

1973

74013834

Severe Bowing of all long bones

Pulmonary Pulmonary function tests (Vital capacity (VC), 

Residual volume (RV), 1-second forced 

expiratory volume divided by forced vital 

capacity (FEV1/FVC))

Arterial blood analysis (Oxygen partial 

pressure, carbon dioxide partial 

pressure)

Fowler

1997

97356792 

Achondroplasia ND Physical development Motor development (Denver Developmental 

Screening Test: Months to sit, stand, 

walk alone)

Neurological Neurological examination (Truncal tone, 

Limb tone, Arm strength, Leg strength)

Neurological history (Developmental delays, 

Asymmetry, Weakness, Sensory 

abnormality, Arching / opisthotonus, 

Clonus, Seizure, Apnea)

Pauli

1995

95193803

Achondroplasia ND

Pulmonary Polysomnography (Central apnea, Central 

hypopnea, Obstructive apnea)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

149

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Cognitive Mental development index (Bayley Scales of 

Infant Development)

Psychomotor development index (Bayley)

Hecht

1991

92152267

Achondroplasia ND

Pulmonary Sleep apnea

Hunter

1998

98299528

Chondrodysplasia ND Psychological Depression (Beck Depression Inventories)

Anxiety (Speilberger State-Trait Anxiety 

Inventories)

Kuurila

2000

20379515

Osteogenesis imperfecta

I, III and IV

Classified according to Sillence method 

(see Daly 1996, above)

Sensory Hearing loss (Pure tone < 20 dB, 

Conductive < 15 dB)

Norimatsu

1982

82163323

Osteogenesis imperfecta

Mild, Moderate, Severe

Per Falvo 1973 (see above) Motor function Walking ability (Wheelchair bound, 

ambulates with assistance)

Scoliosis (Mild <30°; Moderate 30°-50°; 

Severe > 50°, by Cobb’s method)

Poussa

1991

92054945

Diastrophic dysplasia Short-limbed short stature, joint 

limitations, spinal and foot deformities, 

dysmorphic earlobes, cleft palate

Motor function Scoliosis (>10° by Cobb’s method)

Pulmonary Obstructive sleep apnea (>5 obstructive or 

>2 central apneas per hour)

Reid

1988

89193370

Achondroplasia ND

Neurological Paresis (not defined)

Stokes

1988

88110722

Achondroplasia Rhizomelia, macrocephaly with 

midfacial hypoplasia, spinal canal 

narrowing

Pulmonary Forced vital capacity

Reite

1972

72182015

Osteogenesis imperfecta ND Cognitive IQ (WISC)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

150

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Rogers Achondroplasia ND

1979

79200737

Other skeletal dysplasia Multiple diagnoses

Cognitive IQ (Age< 2 y: Bayley Scales of Infant 

Development; Age 2-6 y: Stanford-Binet 

Intelligence Scale; Age 6-15 y: WISC)

Neurological Neurological examination (Quadriparesis, 

Weakness, Sensory deficit)

Compressive neural syndrome 

(craniocervical compression, lumbar 

compression)

Ruiz-Garcia

1997

97346439

Achondroplasia Autosomal dominant, abnormally short 

stature, macrocephaly, rhizomelia

Hearing Loss Brainstem auditory evoked response

Shurka

1976

Skeletal dysplasia External chondromatosis,

achondroplasia, or undefined

Cognitive IQ (WISC)

Skeletal 

Dysplasia Group

1989

89192477

Morquio disease ND Neurological Neurological complications (ND)

Stewart

1989

90125184

Osteogenesis imperfecta ND Sensory Hearing loss (Pure tone < 30 dB, conductive 

< 15 dB)

Cognitive IQ (WISC-R)

Academic achievement (WRAT-R)

Thompson

1999

99221075

Achondroplasia ND

Motor function Gross motor arm and leg coordination 

(McCarthy Scales)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part II

151

Author,

Year Predictors Predictor Measures / Definitions Outcomes Outcome Measures

Visual-motor skills Motor-based design copying task (Beery 

Test of Visual Motor Integration)

Motor-free spatial matching task (Judgment 

of Line Orientation)

Fine motor skills

Waters

1993

94029092

Achondroplasia ND Pulmonary Sleep apnea (> 5 apneic episodes per 

hour)
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

152

Author,

Year Associations found Potential Biases Comments

Alston

1983

In children with osteogenesis imperfecta (n=40) mean non-verbal intelligence 

(104), reading ability (100) and spelling ability (102) were similar to control 

children (n=40, 105, 102, 104, respectively). Writing speed was 

significantly slower (51 words in 5 minutes) compared to controls (61 

words).

Of children with osteogenesis imperfecta (n=40), 38% required wheelchair 

use.

None noted Study was privately funded

Apajasalo

1998

98163312

Among adolescents with skeletal dysplasia (n=19), overall quality of life 

(HRQOL=92) was significantly lower than in controls (n=239, 95) in 

univariate and multivariate analyses.

Among adolescents with skeletal dysplasias (n=19), the quality of life 

dimension mobility was significantly lower than for normal children. 

Children with diastrophic dysplasia and achondroplasia had mean scores 

of ~81 (from graph); those with cartilage-hair hypoplasia had a mean 

score of 100.

Those with skeletal dysplasia had similar scores to normal children for vision 

and hearing. Children with diastrophic dysplasia had mean scores of 94 

for vision and 93 for hearing; those with achondroplasia had mean scores 

of 96 and 95, respectively; those with cartilage-hair hypoplasia had mean 

scores of 96 and 85, respectively.

In the analysis of 16 dimensions of quality of life, there were no statistically 

significant differences among the different groups of children with skeletal 

dysplasia.

Few definitions of outcome measures

Reporting of analyses incomplete

No data on funding source

Bailey

1971

72080259

Infants with achondroplasia, aged 0-2 years, had mean elbow flexion 

deformity of 11°, ranging from 5°-25°; Children, aged 3-12 years, had 

mean elbow flexion of 19°, ranging from 10°-40°; adolescents, aged 13-

20 years, had mean elbow flexion of 23.5°, ranging from 0°-40°.

No data on actual disability due to 

limited joint movement specifically in 

children.

Unknown number of subjects in 

relevant age ranges. 

No data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

153

Author,

Year Associations found Potential Biases Comments

Benson

1978

79027354

Among children with osteogenesis imperfecta (n=126) 48% were wheelchair 

bound (sitters), 25% walked with appliances, and 28% were independent 

walkers.

Among those children with osteogenesis imperfecta who had spine 

radiography performed (n=103), 38% had straight spines, 7% had 

scoliosis between 0°-9°, 19% had scoliosis between 10°-19°, 14% had 

scoliosis between 20°-49°, 14% had scoliosis between 50°-79°, and 9% ≥

80°.

Incomplete data available.

Incomplete reporting

No data on funding source

Bleck

1981

82026195

Among children with osteogenesis imperfecta congenita, severe type (n=12), 

mean independence, mobility, activities of daily living, and ambulation 

scores after orthotic and mobility management were 2.6 (partial 

dependence-independence through technical help), 3.0 (travels in 

community ), 2.5 (completes personal care-household activity possible), 

and 0.7 (no ambulation-walking possible but not functional), respectively.

Among children with osteogenesis imperfecta tarda (n=12), mean 

independence, mobility, activities of daily living, and ambulation scores 

after orthotic and mobility management were 3.4 (independence through 

technical help-completely independent but not normal), 3.8 (almost travel 

beyond community), 3.7 (almost normal activities of daily living), and 2.8 

(almost walk outside home but limited to neighborhood), respectively.

No statistical analysis. No data on funding source.

No statistical comparison.
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

154

Author,

Year Associations found Potential Biases Comments

Brinkmann

1993

94091382

Among children with achondroplasia (n=30), mean Cognitive Abilities Scores 

were Total 48, Verbal 46, Arithmetic 49, and Reasoning 51. Compared to 

normal controls (n=30), Total (56), Verbal (54) and Arithmetic (55), 

children with achondroplasia had significantly lower scores; Reasoning 

scores (control 55) were not significantly different. Overall comparisons to 

siblings (n=30) and other short children (n=30) were similar.

Children with achondroplasia (n=30) were able to sit alone at a median of 12 

months (compared to 7 months for normal controls, n=30), according to 

parental reports, to stand alone at 14 months (10 months), and to walk 

alone at 18 months (12 months). Siblings (n=30) and short controls (n=30) 

had motor development similar to other controls. No statistical analysis 

reported.

Among children with achondroplasia (n=27) 63% were reported by their 

parents to have hearing deficits, compared to 18% of short controls (n=28) 

and 19% of normal controls (n=27).

Among children with achondroplasia (n=27) 41% were reported by their 

parents to have delayed speech development, compared to 14% of short 

controls (n=28) and 7% of normal controls (n=27).

Among children with achondroplasia (n=30) limb, joint or back pain was 

present by parental report in 80%, compared to 43% of short controls 

(n=30) and 10% of normal controls (n=30).

Limited statistical analyses. 

No data on sibling controls for factors 

that were reported by parents.

Study was government funded

Cox

1982

83016754

Of children with osteogenesis imperfecta (n=15) 33% had hearing loss All subjects from 5 families with history 

of osteogenesis imperfecta.

Limited data on hearing function

Study was university funded
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

155

Author,

Year Associations found Potential Biases Comments

Daly

1996

96219608

Among children with osteogenesis imperfecta classified by Shapiro as 

congenita B (n=31) 19% had abnormal arrested development, 19% had 

delayed arrested development, 29% had normal arrested development, 

29% had delayed development, and 3% had normal development. 

Among these children, 87% were wheelchair bound and 13% were 

independent walkers.

Among children with osteogenesis imperfecta tarda A (n=15) none had 

abnormal arrested development, 27% had delayed arrested 

development, 7% had normal arrested development, 20% had delayed 

development, and 47% had normal development. Among these children, 

27% were wheelchair bound, 13% were aided walkers, and 60% were 

independent walkers.

Too few children had osteogenesis congenita A (n=1) or tarda B (n=4) for 

analysis.

Among (the same sample of) children with osteogenesis imperfecta classified 

by Sillence as Type I (n=15) none had abnormal arrested or delayed 

arrested development, 7% had normal arrested development, 27% had 

delayed development, and 67% had normal development. Among these 

children, 7% were aided walkers and 93% were independent walkers.

Among children with osteogenesis imperfecta Type III (n=29) 21% had 

abnormal arrested development, 34% had delayed arrested 

development, 28% had normal arrested development, 17% had delayed 

development, and none had normal development. Among these children, 

97% were wheelchair bound and 3% were independent walkers.

Among children with osteogenesis imperfecta Type IV (n=7) none had 

abnormal arrested development, 14% had delayed arrested 

development, 14% had normal arrested development, 43% had delayed 

development, and 29 had normal development. Among these children, 

57% were wheelchair bound, 14% were aided walkers and 29% were 

independent walkers.

Only a parental questionnaire

No statistical analysis.

Definitions of development unclear

No data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

156

Author,

Year Associations found Potential Biases Comments

Engelbert

1997

Among children aged ≤ 7.5 years with osteogenesis imperfecta Type I (n=16) 

mean Self-care Functional Skills score on PEDI (normal median 50) was 

39 and mean Mobility score was 31. Among children with Type III (n=8) 

mean Self-care score was 31 and Mobility score was 5. Among children 

with Type IV (n=6) mean Self-care score was 37 and Mobility was 48.

Among children aged > 7.5 years with osteogenesis imperfecta Type I (n=16) 

mean Self-care Functional Skills score on PEDI (normal = 100) was 100 

and mean Mobility score was 100. Among children with Type III (n=6) 

mean Self-care score was 70 and mean Mobility was 41. Among children 

with Type IV (n=9) mean Self-care score was 93 and Mobility was 62.

Interpretation of scales difficult due to 

different norms used and unclear 

description of scales

No explicit comparison to normal 

children

Unclear how much overlap in sample 

with other Engelbert papers.

No data on funding source

Engelbert

1998

98366964

Among children with osteogenesis imperfecta scoliosis > 10° was present in 

12% of those with Type I (n=17), 63% with Type III (n=16), and 71% 

with Type IV (n=14).

Among children with osteogenesis imperfecta kyphosis < 10° was present in 

6% of those with Type I (n=17), 38% with Type III (n=16), and 14% with

Type IV (n=14).

Among children with osteogenesis imperfecta kyphosis > 40° was present in 

6% of those with Type I (n=17), 38% with Type III (n=16), and 14% with 

Type IV (n=14).

No comparison with normal controls

Unclear how much overlap in sample 

with other Engelbert papers.

No data on funding source

Engelbert

1999

99381568

At follow-up, of children with osteogenesis imperfecta Type I (n=19) 53% 

were community walkers, 26% were neighborhood walkers, 16% were 

household walkers, and 5% were exercise walkers.

Of children with Type III (n=13) 31% were household walkers, 8% were 

exercise walkers, 38% were bottom shufflers, 15% could sit unsupported, 

and 8% could only sit supported.

Of children with Type IV (n=10) 10% were community walkers, 10% were 

neighborhood walkers, 10% were household walkers, 40% were 

exercise walkers, 20% could weight bear on feet, and 10% were bottom 

shufflers.

No children with recent intramedullary 

fixation surgery or other disability or 

impairments.

PEDI scale scores reported for small to 

very small samples of children. 

Appears to be earlier subset of data 

reported earlier in Engelbert 1997. 

Not analyzed here.

Unclear how much overlap in sample 

with other Engelbert papers.

No data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

157

Author,

Year Associations found Potential Biases Comments

Engelbert

2000

20429012

At follow-up, of children with osteogenesis imperfecta Type I (n=41) 59% 

were community walkers without aides, 5% were community walkers with 

aides, 10% were neighborhood walkers without aides, 12% were 

household walkers without aides, 7% were household walkers with aides, 

and 7% were therapy walkers with aides.

Of children with Type III (n=11) 9% were neighborhood walkers with aides, 

27% were household walkers with aides, 19% were therapy walkers with 

aides, and 45% were non-walkers.

Of children with Type IV (n=18) 28% were community walkers without aides, 

11% were community walkers with aides, 6% were neighborhood 

walkers with aides, 11% were household walkers with aides, 22% were 

therapy walkers with aides, and 22% were non-walkers.

Unclear how much overlap in sample 

with other Engelbert papers.

No comparison with normal children

No data on funding source.
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

158

Author,

Year Associations found Potential Biases Comments

Engelbert

2001

21334060

Among children aged > 8 years with osteogenesis imperfecta Type I (n=17) 

mean Self-care Functional Skills score on PEDI (normal = 100) was 100 

and mean Mobility score was 92. Among children with Type III (n=11) 

mean Self-care score was 81 and mean Mobility was 55. Among children 

with Type IV (n=12) mean Self-care score was 100 and Mobility was 67.

Among children with osteogenesis imperfecta Type I (n=17) the average child 

was a community walker without aides. Among children with Type III 

(n=11) the average child was a therapy walker with aides. Among 

children with Type IV (n=12) the average child was a household walker 

without aides.

Among children with osteogenesis imperfecta Type I (n=17), the average joint 

range of motion on a scale of 0 (normal) to 4 (maximally decreased) was 

0.5 for arms and 0 for legs. Among children with Type III (n=11) the 

average arm range of motion was 1.8 and leg range of motion was 3.3. 

Among children with Type IV (n=12) the average arm range of motion 

was 1.3 and leg range of motion was 1.7.

Among children with osteogenesis imperfecta Type I (n=17), the average 

muscle strength on a scale of 0 (no muscle activity) to 5 (normal muscle 

strength) was 4.5 for arms and 4.8 for legs. Among children with Type III 

(n=11) the average arm strength was 3.5 and leg strength was 3.6. 

Among children with Type IV (n=12) the average arm strength was 4.5 

and leg strength was 3.8.

Unclear how much overlap in sample 

with other Engelbert papers, 

especially those with PEDI 

analyses (1997 and 1999)

No comparison to normal children.

Meaning of scales unclear.

No data on funding source.

Falvo

1973

74013834

Among children with osteogenesis imperfecta mean pulmonary vital capacity 

was 85% of predicted normal (n=10), mean residual volume was 119% of 

predicted normal (n=10), mean FEV1/FVC was 99% of predicted normal 

(n=10), mean arterial oxygen partial pressure was 88 mm Hg (n=8), and 

mean arterial carbon dioxide partial pressure was 35 mm Hg (n=8).

“No patient had severe hypoxemia or hypercapnea. Reduction of VC and 

increase in RV were found only in patients with kyphoscoliosis. Other 

parameters of pulmonary function were within normal limits.”

Limited analyses Study was government and privately 

funded.
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

159

Author,

Year Associations found Potential Biases Comments

Fowler

1997

97356792 

Among children with achondroplasia, by parental report, the mean age of 

sitting unsupported was 12 months (n=37), the mean age of standing alone 

was 19 months (n=21), and the mean age of walking alone was 18 months 

(n=24). “Virtually all fine motor skills were delayed when compared with 

children without achondroplasia.”

Includes subjects in Pauli 1995

Data on motor development from few 

subjects enrolled in study

No data on funding source

Pauli

1995

95193803

Among children with achondroplasia, 72% had decreased truncal tone 

(n=39), 70% had decreased limb tone (n=44), 32% had abnormal arm 

strength (n=40), and 50% had abnormal leg strength (n=40). No child had 

marked abnormalities in neurological examination.

Among children with achondroplasia (n=52) 42% had an abnormality by 

neurological history. These included disproportionate developmental 

delays (10%), asymmetries (21%), weakness (14%), sensory 

abnormalities (4%), arching/opisthotonos (10%), clonus (8%), seizures 

(8%), and apnea (27%).

Among children with achondroplasia (n=35) by polysomnography 40% had 

mild to severe central apnea, 66% had mild to severe central hypopnea, 

and 23% had mild obstructive apnea

Earlier subset of subjects in Fowler 

1997

Study was hospital funded

Hecht

1991

92152267

Among infants with achondroplasia (n=13) mean BSID Mental Development 

Index score was 97 (1 or 2 infants had scores <70, text and table 

disagree) and mean Psychomotor Development Index score was 63 

(62% scored <50).

Among infants with achondroplasia (n=13) 77% had normal 

polysomnography. Two infants (15%) had obstructive apnea, 1 had 

hypoxemia and respiratory acidosis.

5 of 13 patients were initially seen (and 

thus included) for apnea, motor 

delay or neurological complication

Reporting errors

Study was government funded
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

160

Author,

Year Associations found Potential Biases Comments

Hunter

1998

98299528

Among children with chondroplasias (n=55) 7% had moderate or severe 

depression per the Beck Depression Inventories, which was not 

significantly different than among normal siblings (11%, n=35).

Among children with chondroplasias (n=55) the mean Speilberger Child State 

Anxiety score was 28.4 and Trait Anxiety score was 32.5, which were 

significantly lower (implying less anxiety) than general population means 

for boys (31.0 and 36.7, respectively) and girls (30.7 and 38.0, 

respectively).

None noted No data on funding source

Kuurila

2000

20379515

Among children with osteogenesis imperfecta (n=45), 7% had hearing loss: 2 

children had conductive hearing loss and 1 had sensorineural deafness.

Descriptive study only No data on funding source.

Norimatsu

1982

82163323

Among children with osteogenesis imperfecta congenita (n=8) 38% were 

wheelchair bound; the remainder walked with assistance. Among children 

with osteogenesis imperfecta tarda (n=14) 14% were wheelchair bound; 

the remainder walked with assistance.

Among children with osteogenesis imperfecta congenita (n=8) 88% had 

severe scoliosis (59°-139°; one had mild scoliosis (17°). Among children 

with osteogenesis imperfecta tarda (n=14) 21% had severe scoliosis (55°-

125°), 14% had moderate scoliosis (32° & 33°), 64% had mild scoliosis 

(5°-28°).

Multiple subjects were closely related.

Descriptive study only

No data on funding source

Poussa

1991

92054945

Among children with diastrophic dysplasia (n=38) 29% had scoliosis. Of those 

≤ 10 years (n=17) 6% had scoliosis; of those between 11 and 20 years 

(n=21) 48% had scoliosis. Those with scoliosis (n=11) had a mean 

magnitude of curvature of 39° (range 15°-80°).

Descriptive analysis only No data on funding source.

Subjects are part of the study. 

Descriptive data only.

Reid

1988

89193370

Among children with achondroplasia (n=26) 85% had a history of respiratory 

abnormalities including pneumonia, loud snoring, cyanotic spells or apnea 

in the preceding 6 months; 35% had obstructive sleep apnea.

Among children with achondroplasia (n=26) 42% had paresis.

Descriptive study only

No specific definitions of conditions 

reported

Appears to be subgroup of subjects 

included in Stokes 1988

No data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

161

Author,

Year Associations found Potential Biases Comments

Stokes

1988

88110722

Among children with achondroplasia (n=24) mean forced vital capacity was 

72% of predicted, significantly lower than population norms.

Limited details of pediatric sub-sample.

Appears to include subjects in Reid 

1988

Study funded by government, hospital 

and private sources

Reite

1972

72182015

Among children with osteogenesis imperfecta (n=12) the mean IQ was 107, 

ranging from 78-133.

Only children with “severe” 

osteogenesis imperfecta

Incomplete data reported

Study was government and privately 

funded.

Rogers

1979

79200737

Among school aged children with achondroplasia (n=19) mean Full scale IQ 

was 96, Verbal IQ was 95, and Performance IQ was 100; 5% had IQ<70.

Among preschool aged children with achondroplasia (n=15) mean Full scale 

IQ was 97; 13% had IQ<70.

Among school aged children with other skeletal dysplasias (n=22) mean Full 

scale IQ was 104, Verbal IQ was 104, and Performance IQ was 103; 

none had IQ<70.

Among preschool aged children with other skeletal dysplasias (n=12) mean 

Full scale IQ was 100; none had IQ<70.

Descriptive study only Study was government funded

Ruiz-Garcia

1997

97346439

According to summary table, among children with achondroplasia (n=39) 59% 

had hypotonia, 15% had quadriparesis, 31% had weakness, and 10% 

had a sensory deficit.

According to text, 49% had hypotonia, 13% had quadriparesis, 26% had 

weakness, and 5% had sensory deficit. In additon, 31% had compressive 

neural syndromes (18% craniocervical, 13% lumbar).

According to the text, among children with achondroplasia (n=32), 50% had 

abnormal hearing as tested by brainstem auditory evoked response.

No definitions of outcomes

Results reported in text differ from 

results reported in table

Descriptive study only.

No data on funding source

Shurka

1976

Among children with skeletal dysplasias (n=7) mean Full scale IQ was 102, 

Verbal IQ was 103, and Performance IQ was 99.

Very small sample size.

Multiple, poorly defined causes of 

dwarfism.

No data on funding source
Evidence Table 2. Studies Evaluating Short Stature Secondary to Skeletal Dysplasia

Part III

162

Author,

Year Associations found Potential Biases Comments

Skeletal 

Dysplasia Group

1989

89192477

Among children with Morquio disease (n=15) 33% had “known neurological 

complications.”

Limited data reported

Conditions and outcomes not defined

Only subset met criteria for inclusion in 

SSA report

No data on funding source

Stewart

1989

90125184

Among children with osteogenesis imperfecta (n=13), 15% had hearing loss. Incomplete reporting

Descriptive only

Study was private funded

Thompson

1999

99221075

Among children with achondroplasia mean WISC-R Verbal IQ was 94 (n=16), 

Performance IQ was 101 (n=16), WRAT-R Spelling score was 88 (n=14), 

Arithmetic was 89 (n=15), and Sentence writing was 80 (n=12). These 

scores were all statistically similar to normal controls (IQ ND, Spelling 97, 

Arithmetic 96, Sentence writing 95, n=17).

Among children with achondroplasia (n=13) Gross Motor Arm Coordination 

score on McCarthy Scales was 73 and Leg Coordination was 79, 

significantly lower than normal controls (93, 104, respectively; n=13).

Among children with achondroplasia (n=13) visual motor skills were 

significantly lower (Beery 82, JLO 85) than among normal controls (Beery 

92, JLO 100, n=12). Various measures of fine motor skills were similar 

between the two groups.

Biased sample as some children 

dropped who were unable to 

complete the testing for many 

measures and excluded children 

with IQ<69.

Study was government funded.

Subjects were recruited as part of larger 

previous study of hydrocephalus

Waters

1993

94029092

Among children with achondroplasia (n=20) 75% had > 5 apneic episodes 

per hour of sleep.

Descriptive study only No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

163

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Balfour-Lynn

1986

87074993

Location: UK

Setting: Pediatric asthma clinic

Initial mean age: 7.5 y

Initial age range: 2-12 y

Follow-up mean age: 21 y

Follow -up age range: 13-26 y

Mean height: ND

Male: 68%

Race: ND

SES: ND

Enrolled: 66

Evaluated: 66

Number of sites: 1

Chronic perennial asthma None reported Asthma Prospective longitudinal 

cohort

(Mean 8.9 y)

Cernelc

1975

76016195

[Also in cardiac section]

Location: Yugoslavia

Setting: Clinic

Mean age: ND

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: ND

Evaluated: 337

Number of sites: ND

Asthmatic children with normal 

or pathological lung function 

tests

None reported Asthma Prospective cross-sectional
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

164

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Ferguson

1982

82190765

Location: Canada

Setting: Regional

Mean age: ND

Age range: ~3-17 y

Mean height: ND

Male: 89%

Race: ND

SES: ND

Enrolled: 36

Evaluated: 36

Number of sites: 1

Children with a diagnosis of 

asthma and short stature 

(height < 3rd percentile)

None reported Asthma Preliminary study of a 

prospective longitudinal 

study

Hauspie

1979

80114229

Location: Belgium and Hungary

Setting: Sanatorium; Asthma clinic

Mean age: ND

Age range: 3-16 y

Mean height: ND

Male: 100%

Race: ND

SES: ND

Enrolled: 1107

Evaluated: 1107

Number of sites: 2

Hungary : asthmatic boys 

residing in the National 

Sanatorium for Children

Belgium: boys with chronic 

aspecific respiratory affection, 

asthma or asthma and 

eczema.

None reported Asthma /Respiratory 

disease

Retrospective crosssectional cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

165

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Klein

1991

91314975

Location: US

Setting: Clinic

Mean age: 8.5 y

Age range: 2-15 y

Mean height: ND

Male: ~ 69%

Race: ND

SES: ND

Enrolled: 176

Evaluated: 176

Number of sites: 4

Children with moderately 

severe, non-steroiddependent asthma

> 6 short courses of 

steroids during 

previous year

Asthma Prospective cross-sectional

Martin

1981

82110081

Location: Australia

Setting: Region

Initial age: 7 y

Follow-up ages: 10 y, 14 y, 21 y

Mean height: ND

Male: 63%

Race: ND

SES: ND

Enrolled: 375

Evaluated: 315

Number of sites: 1

Asthmatic children

Aged 7 y in 1964

None reported Asthma Prospective longitudinal 

cohort

(14 y follow-up)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

166

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

McNicol

1970

71076839

Location: Australia

Setting: Unclear

Ages: 7 and 10 y

Mean heights: 123 cm (age 7 y); 

138 cm (age 10)

Male: ND

Race: ND

SES: ND

Enrolled: 226

Evaluated: 226

Number of sites: ND

Asthmatic children None reported Asthma Prospective longitudinal 

cohort

(Ages 7 and 10)

Neville

1996

96427603

Location: UK

Setting: Pediatric practices

Mean age: ND

Age range: 3.5-13 y

Mean height: ND

Male: 57%

Race: ND

SES: “Broad range”

Enrolled: 2915

Evaluated: 699

Number of sites: 12

Tayside Childhood Asthma 

Project (1990-92)

Possible asthma, based on 

medication prescriptions, from 

chart review

Age 3.5-13 y

Height and weight 

measurements available

Loss to follow-up Asthma Secondary analysis of 

prospective longitudinal 

cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

167

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Rona

1980

81025712

Location: UK

Setting: Schools

Mean age: ND

Age range: 5-11 y

Mean height: ND

Male: 68%

Race: ND

SES: Proportionally more lower SES 

areas

Enrolled: 102

Evaluated: 102

Number of sites: 28

Parental reporting of asthma in 

last 12 months

None reported Asthma Retrospective crosssectional cohort

Sant’Anna

1996

97295750

Location: Brazil

Setting: Pediatric immunology clinic

Mean age: ND

Age range: 6 mo - 16 y

Mean height: ND

Male: 58%

Race: ND

SES: ND

Enrolled: 514

Evaluated: 514

Number of sites: 1

Children with asthma followed 

in Division of Allergy, Clinical 

Immunology and 

Rheumatology

Phenotypical deviations

Clear changes in body 

proportions

Other chronic diseases

Rash and/or atopic 

dermatitis

Asthma Retrospective crosssectional case series
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part I

168

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Spock

1965

Location: US

Setting: Pediatrics department

Mean age: 7 y

Age range: 4-12 y

Mean height: ND

Male: 65%

Race: White

SES: ND

Enrolled: 200

Evaluated: 200

Number of sites: 1

Children with bronchial asthma 

Age > 4 y at the first visit

Followed for minimum of 3 y

Concomitant chronic 

illness

Cyproheptadine use

Asthma Retrospective longitudinal 

cohort 

(19 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part II

169

Author, Year Severity of Illness Groups Outcomes

Balfour-Lynn

1986

87074993

Treatment required to control asthma 

• Bronchodilators alone or children whose asthma resolved before puberty

• Sodium cromoglycate and bronchodilators in children whose asthma did not improve at 

puberty

• Steroids and bronchodilators 

Initial growth retardation (not defined)

Growth along centile lines

Final adult height

Percentile, based on Tanner and Whitehouse 

growth chart

Cernelc

1975

76016195

Pulmonary function tests

• Normal

• Pathological (not defined)

Height by age (linear regression)

Compared to normal values for Slovenian children

Ferguson

1982

82190765

Asthma symptom score, based on frequency of wheezing in past year, duration of wheezing, level 

of therapy required, and bronchodilator medication days in past year (16 point scale)

• Mild: score 1-7

• Moderate: score 8-12

• Severe: score 13-16

Height

Percent average height for age

Hauspie

1979

80114229

Hungarian sample: Ovsáth’s system, based on based on frequency of attacks, seriousness of 

dyspnea, duration of dyspnea, and number of symptom-days per year

• Class II: Less severe

• Class III: More severe

• Class IV: Most severe

Belgian sample: Disease diagnosis

• Chronic aspecific respiratory affection

• Asthma

• Asthma and eczema

Belgian sample: Treatment required to control asthma:

• No corticotherapy

• Interrupted corticotherapy

• Continuous corticotherapy for at least 6 months

Height Z-scores

Klein

1991

91314975

Asthma severity score (by event), based on hospitalization and medication requirements in 

previous year (score: 0-60)

• Mild: score < 25

• Moderate/severe ≥ 25

Height

Height percentile

Based on National Center for Health Statistics 

Growth Chart
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part II

170

Author, Year Severity of Illness Groups Outcomes

Martin

1981

82110081

Asthma grade, based on frequency and recency of wheezing

• Grade A: ≤ 5 episodes of wheezing

• Grade B: > 5 episodes of wheezing but no wheezing within 12 months of exam

• Grade C: Episodic asthma over a number of years and wheezing within 12 mo of exam

• Grade D: Very frequent or chronic unremitting asthma

Percentage of subjects <10th percentile

Based on Australian Department of Health 

Anthropometric tables

At ages 10, 14, and 21 y

McNicol

1970

71076839

Asthma grade, based on frequency and recentness of asthma episodes

• Grade I: ≤ 5 episodes of asthma

• Grade II: ≤ 20 episodes of asthma or no asthma within 12 mo of exam

• Grade III: >20 episodes and still having asthma within 12 mo of exam

Height

Neville

1996

96427603

Asthma severity (British Thoracic Society treatment steps), based on medication requirements

• Step 1: Beta-agonist only in past year

• Step 2: Beta-agonist and cromoglycate

• Step 3: Beta-agonist and low dose inhaled steroid

• Step 4: Beta-agonist and > 400 μg/day inhaled steroid

Height 

SDS, based on control group within study

Rona

1980

81025712

Frequency of asthma episodes

• ≤ 2 episodes in the past year

• ≥ 3 episodes in the past year

Hospitalization for asthma

Height SDS, based on Scottish and English norms

• Unadjusted

• Adjusted for parents’ height, social class, number 

of siblings 

Height gain, cm/year

• Unadjusted

• Adjusted

Sant’Anna

1996

97295750

Asthma severity, based on the International Consensus Report on Diagnosis and Treatment of 

Asthma

• Mild

• Moderate

• Severe

Percentage with short stature 

< 3rd percentile, based on National Center of Health 

Statistics, US, 1977
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part II

171

Author, Year Severity of Illness Groups Outcomes

Spock

1965

Clinical status (not defined)

• Poor

• Fair

• Good

• Excellent

Linear growth rate

Percentage of normal, based on Stuart and Wetzel’s 

anthropometic charts
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part III

172

Author, Year Associations found Potential Biases Comments

Balfour-Lynn

1986

87074993

Comparing children whose asthma was controlled with bronchodilators alone or had 

resolved at puberty (n=18, Group I) with those whose asthma required sodium 

cromoglycate and had not resolved at puberty (n=19, Group II), and with those 

whose asthma required treatment with steroids (n=29, Group III), there was no 

statistical difference in growth retardation at the start of the study. However, 

“growth retardation” was not defined. Of children in Group I, 2 of 18 (11%) had 

initial height < 10th percentile. Of children in Group II, 1 of 19 (5%) had initial height 

< 10th percentile. Of children in Group III, 3 or 29 (10%) had initial height < 10th

percentile. No child had height < 3rd percentile.

All children “grew along expected centile lines without appreciable deviation, from 

initial age (mean 7.5 y) until age 10 y, regardless of treatment required. 30 of 66 

(45%) children had “physiological decelerating growth velocity pattern of delayed 

puberty.” No data are reported regarding association with asthma severity.

Comparing the three groups of asthmatic children, based on treatment requirements, 

no statistical difference was found in final adult height. Possible minor trend toward 

taller adult height from Group I to II to III seen in graph.

Severity of asthma based on 

treatment used, not objective 

measures

Reported data incomplete

Study sample poorly defined

6 subjects lost to follow up prior to 

obtaining final adult height but 

were followed for mean 8.3 

years (6.3-14.6 y)

No data on funding source

Cernelc

1975

76016195

Asthmatic children with normal pulmonary function tests (n=225) were not significantly 

different in height for age compared to asthmatic children pathological pulmonary 

function tests (n=112).

No data on growth velocity.

Limited data and analysis

Study sample poorly defined

No data on funding source

Data on asthmatic children with 

bronchiectasis (n=22) not 

included because children 

reported to be both 

significantly and not 

significantly more likely to 

have growth retardation

Ferguson

1982

82190765

The percentages of average normal height for age (50th percentile) of short children 

whose asthma was mild (n=19, 90.7%), moderate (n=13, 90.2%) and severe 

(n=4, 88.5%) were not significantly different among the three groups.

No significant correlation was found between symptom score and percentage of 

average normal height for age of individual subjects (r=0.20).

No data on growth velocity

Study limited to children with 

height < 3rd percentile, 

however results reported as 

percentage of average normal 

height

Study was government and 

private funded.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part III

173

Author, Year Associations found Potential Biases Comments

Hauspie

1979

80114229

Mean height of Class II (relatively mild) Hungarian asthmatic boys (n=222) is normal 

(~ 0 SDS, from graph). The mean height of Class III asthmatic boys (n=253) was 

significantly lower (~ –0.3 SDS) and that of Class IV asthmatic boys (n=25) was 

even lower (~ –0.9 SDS). “A gradually increasing degree of growth retardation in 

relation to the seriousness of the disease can be observed.”

In a separate sample of Belgian asthmatic boys, those with chronic aspecific 

respiratory affection (n=204) had normal mean height (~ –0.1 SDS, from graph). 

Those with asthma (n=323) were statistically significantly but minimally shorter (~ –

0.2 SDS) and those with asthma and eczema (n=80) were even shorter (~ –0.4 

SDS).

Belgian asthmatic boys requiring no corticotherapy (n=245) and requiring interrupted 

corticotherapy (n=130) had normal mean height (~ –0.1 SDS, from graph). Those 

who required continuous corticotherapy (n=16) were statistically shorter (~ –0.5 

SDS). 

No data on growth velocity.

Chronic aspecific respiratory 

affection includes illnesses 

other than asthma.

Data reported mostly in graphical 

format only

Study limited to boys

No data on funding source.

Klein

1991

91314975

Children (n=176 total) with mild asthma (ND on n) had mean ± SD height of 145±10 

cm; those with moderate asthma were on average 148±10 cm. The height 

difference was not significantly different. No data reported on children with severe 

asthma. 

“There was no relationship between the severity of asthma (as assessed by a clinical 

and medications score) and the height percentile.” Reported data are incomplete.

No data on growth velocity

Reported data very incomplete.

Mean heights reported as 44.8 cm 

and 47.8 cm. We understood 

this to mean 144.8 cm and 

147.8 cm, however, reported 

numbers may refer to 

percentiles.

Children requiring > 6 short 

courses of steroids within 

previous year excluded.

No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part III

174

Author, Year Associations found Potential Biases Comments

Martin

1981

82110081

The prevalence rates of height < 10th percentile in 10 years old children whose 

asthma was rated Grade A (mild, n=64), Grade B (moderate, n=88), Grade C 

(severe, n=106), and Grade D (very severe, n=57) were 9%, 8%, 8%, and 

15% respectively. Only children with very severe asthma had significant higher 

prevalence of height < 10th percentile at age 10 y compared to non-asthmatic 

children (n=62, 4%).

The prevalence of short stature in the asthmatic children when they were 14 years old 

was similar to when they were 10 years old. Height < 10th percentile in Grade A 

asthmatics was 6%, Grade B 5%, Grade C 5%, and Grade D 17%. Only 

children with very severe asthma had significant higher prevalence of height < 

10th percentile at 14 years of age compared to non-asthmatic children (1%).

At age 21 years, the prevalence of short stature was similar among all asthma grades. 

Height < 10th percentile Grade A asthmatics was 15%, Grade B 15%, Grade C 

9%, and Grade D 19%. There was no difference in the prevalence of height < 

10th percentile at 21 years of age, between the 4 groups and non-asthmatic 

children (12%).

No direct data on growth velocity

None noted. No data on funding source

McNicol

1970

71076839

The mean heights of children at both ages 7 and 10 years were the same (123-124 

cm at age 7 years; 137-139 cm at age 10 years) regardless of frequency of 

asthmatic episodes among 276 asthmatic children and 94 non-asthmatic controls. 

No significant difference was found between controls and any degree of asthma 

severity.

No data on growth velocity

None noted No data on funding source

Neville

1996

96427603

Asthmatic children who used only beta agonists (n=537) had a mean height of +0.04 

SDS. Those who used beta agonists and cromoglycate (n=64) had a mean height 

of +0.04 SDS. Those who used beta agonists and low dose inhaled steroids 

(n=39) had a mean height of +0.08. Those who used beta agonists and > 400 

μg/day inhaled steroids (n=59) had a mean height of –0.38. Only those on high 

dose inhaled steroids were significantly shorter than normal.

No data on growth velocity.

Large number of potential subjects 

excluded due to missing height 

data

Statistical analysis implied only

Asthma severity based on 

medication use

Study was government, 

privately, and 

pharmaceutical funded
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Asthma – Part III

175

Author, Year Associations found Potential Biases Comments

Rona

1980

81025712

Among children with asthma episodes, those with ≤ 2 episodes in previous year 

(n=33) were not significantly shorter (–0.1 SDS, – 0.2 SDS, respectively) than 

controls (n=4334) in both unadjusted model and model adjusted for parental 

height, social class, and number of siblings. Those with ≥ 3 asthma episodes in 

previous year (n=69) were significantly shorter (–0.4 SDS) than controls in both 

models. Overall, “there was a highly significant negative relationship between 

unadjusted [and adjusted] height and number of [asthma] episodes. 

“Hospitalization for asthma was more closely associated with shorter stature for boys 

than for girls, but the number of children hospitalized was too small for useful 

analysis.”

In adjusted model, height velocity was non-significantly lower in boys with ≤ 2 asthma 

episodes per year (n=22, 5.34 cm/y) and with ≥ 3 episodes per year (n=41, 5.57 

cm/y) than non-asthmatic boys (n=1873, 5.72 cm/y), and in girls with ≤2 episodes 

per year (n=9, 5.67 cm/y) and with ≥ 3 episodes per year (n=16, 5.50 cm/y) than 

non-asthmatic girls (n=1552, 5.93 cm/y).

Retrospective survey of parents 

(for medical history) and 

school records

Logic of adjusting for number of 

siblings unclear.

Study was government funded.

Sant’Anna

1996

97295750

The prevalence of short stature (< 3rd %tile) in children with mild asthma (n=211, 6%) 

was non-significantly lower than those with moderate asthma (n=154, 11%) and 

severe asthma (n=149, 11%).

No data on growth velocity

Multiple height-related exclusion 

criteria

No data on funding source

Spock

1965

The mean linear growth rate in percentage of normal was 109% for asthmatic patients

with excellent clinical status (n=68), 107% for asthmatic patients with good clinical 

status (n=86), 102% for asthmatic patients with fair clinical status (n=30), and 97% 

for asthmatic patients with poor clinical status (n=16). The correlation between 

severity of clinical status and the linear growth rate in percentage of normal was 

not statistically significant.

“No statistically significant correlation was found between the duration and/or severity 

of asthmatic symptoms and growth impairment for height or weight.”

Degree of clinical status not 

defined

The percentage of children 

requiring steroids was 

unusually low at 12%

No data on funding source.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part I

176

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Baum

1980

81065058

Location: US

Setting: Clinic

Mean age: 3.8±1.0 y

Age range: ND

Mean height: 99 cm

Male: 77%

Race: ND

SES: ND

Enrolled: 26

Evaluated: 26

Number of sites: 1

Diagnosis of acyanotic 

congenital heart disease

Age 2 to 6 y

None reported Congenital heart disease:

Patent ductus arteriosus

Ventricular septal defect

Atrial septal defect

Pulmonic stenosis

Aortic stenosis

Atrioventricular canal

Pulmonary artery band

Right ventricular band

Mitral stenosis

Mitral insufficiency

Prospective crosssectional cohort

Cernelc

1975

76016195

[Also in asthma section]

Location: Yugoslavia

Setting: Clinic

Mean age: ND

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: ND

Evaluated: 22

Number of sites: ND

Children with congenital heart 

disease with or without 

cyanosis

None reported Congenital heart disease:

Not defined

Prospective crosssectional
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part I

177

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Feldt

1969

69176079

Location: US

Setting: Clinic

Mean age: ND

Age range: 1 wk - 17 y

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 463

Evaluated: 311

Number of sites: 1

Diagnosis of congenital heart 

disease

Trisomy 21

Gonadal dysgenesis

Clinically recognized 

maternal rubella 

syndrome

Congenital heart disease:

Ventricular septal defect

Tetralogy of Fallot

Aortic stenosis

Pulmonary stenosis

Prospective longitudinal 

cohort

(5 mo)

Levy

1977

78125814

Location: US

Setting: Cardiology clinic

Mean age: ND

Age range: ND

Mean height: ND

Male: 50%

Race: ND

SES: ND

Enrolled: 1,210

Evaluated: 777

Number of sites: ND

Diagnosis of ventricular septal 

defect

None reported Ventricular septal defect Retrospective 

longitudinal cohort 

(mean[range] 6.4 [4-8] 

y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part I

178

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Strangway

1976

76101945

Location: Canada

Setting: Cardiology clinic

Mean age: ND

Age range: < 2-11 y

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 568

Evaluated: 568

Number of sites: 1

Diagnosis of congenital heart 

disease

Additional major 

congenital lesion

Mental retardation

Undergone corrective 

surgery

Acute or chronic 

intercurrent illness

Congenital heart disease:

Tetralogy of Fallot

Ventricular septal defect

Atrial septal defect

Pulmonary stenosis

Aortic stenosis

Coarctation of aorta

Patent ductus arteriosus

Arterioventricular canal

MIscellaneous

Retrospective 

longitudinal cohort

(5 y)

White

1970

72024496

Location: US

Setting: Adolescent cardiac clinic

Mean age: ND

Age range: 12-18 y

Mean height: ND

Male: ND

Race: White 96%

SES: Generally middle class

Enrolled: 80

Evaluated: 80

Number of sites: 1

Diagnosis of congenital heart 

disease

Age < 19 y

Tetralogy of Fallot with 

total corrective 

surgery

Congenital heart disease:

Ventricular septal defect

Atrial septal defect

Patent ductus arteriosus

Pulmonary stenosis

Aortic stenosis

Coarctation of aorta

Aortic insufficiency

Undiagnosed acyanotic

Prospective crosssectional 
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part II

179

Author, Year Predictors (N) Outcomes

Baum

1980

81065058

Heart Failure (not defined) Height by age (linear regression)

Height percentile

Based on National Center for Health Statistics growth 

charts

Cernelc

1975

76016195

[Also in asthma section]

Cyanosis Height by age (linear regression)

Compared to normal values for Slovenian children

Feldt

1969

69176079

Pulmonic valve pressure gradient

Aortic valve pressure gradient

Tetralogy of Fallot lesion severity

• Hematocrit

• Oxygen saturation (cyanosis)

• Magnitude of right to left shunt

• History of hypoxemia

Ventricular septal defect shunt severity

• Pulmonary vascular disease (pressure)

Growth failure

preoperative height (and weight) ≤ –2 SDS

Height SDS

based on Reed and Stuart, 1959

Levy

1977

78125814

Ventricular septal defect severity

• I: Trivial to mild, pulmonary artery mean pressure < 20 mm Hg

• II: pulmonary artery mean pressure ≥ 20 mm Hg and pulmonary to systemic resistance ratio 

< 0.20

• III-IV: Severe: pulmonary artery mean pressure ≥ 20 mm Hg and pulmonary to systemic 

resistance ratio ≥ 0.20

Height SDS

Strangway

1976

76101945

Cardiac problems

• Cyanosis

• Cardiac enlargement (cardiothoracic ratio > 59% age < 2 y, > 55% age >2 y)

• Congestive heart failure

Height velocity

fraction of the normal mean for the same age and 

sex
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part II

180

Author, Year Predictors (N) Outcomes

White

1970

72024496

Cyanosis Short stature, height < 2nd percentile
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part III

181

Author, Year Associations found Potential Biases Comments

Baum

1980

81065058

Children with congenital heart disease with early heart failure (n=12) were significantly 

shorter for age than asymptomatic children (n=14). On average, children age 2-6 

years with heart failure were 5-9 cm shorter than those without. The differences in 

height were greater with older age.

Six (50%) of the 12 children with early heart failure had height below the 5th

percentile, while none of the 14 asymptomatic children had height below the 10th

percentile.

No data on growth velocity.

None noted No data on funding source.

Cernelc

1975

76016195

[Also in asthma section]

Children with congenital heart disease and cyanosis (n=11) were significantly more 

likely to be short for age than normal population, as opposed to children with 

congenital heart disease without cyanosis (n=11) who were not significantly 

different in height for age than normal population.

Limited data and analysis

Study sample poorly defined

No data on funding source

Feldt

1969

69176079

Among children with aortic or pulmonary stenosis (n=73), those “with mild pressure 

gradients (< 50 mm Hg) across either the pulmonic or the aortic valve usually 

were of normal weight and height. In contrast, patients with severe valvular 

gradients were more likely to have severe growth failure.”

The severity of growth failure of children with Tetralogy of Fallot (n=83) “was not 

related to any criteria for seveity of the lesion such as hemaglobin value, oxygen 

saturation..., magnitude of right to left shunt, or history of hypoxemic spells.” 

Specifically height SDS was not associated with hemoglobin level.

Among children with ventricular septal defect (n=155) “there was no correlation 

between the extent of growth failure and the degree of pulmonary vascular 

disease assessed either at cardiac catheterization of from pressure measurements 

taken at the time of operation.”

No data correlated height velocity to severity of disease.

No statistical analyses

Growth retardation included both 

short stature and low weight

Study was government funded.

Levy

1977

78125814

For children with ventricular septal defect, the mean initial height SDS for those with 

mild disease (n=492) was –0.23 SDS, for those with moderate disease (n=170) –

0.63 SDS, and for those with severe disease (n=115) –0.86. The height of 

children in each category was statistically significantly lower than normal children. 

The statistical significance of the association between height and severity of 

disease is implied only.

Reporting of statistical analyses 

unclear and incomplete

Study was government funded.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Cardiac Disease – Part III

182

Author, Year Associations found Potential Biases Comments

No data on growth velocity

Strangway

1976

76101945

Among children aged 0 to 2 years with congenital heart disease (n=181), height 

velocity percentile was significantly lower in children with cyanosis (–14%) than 

those without cyanosis (+7%), was similar in children with cardiac enlargement 

(+2%) as without cardiac enlargement (+1%), and was non-significantly lower in 

children with congestive heart failure (–20%) than without congestive heart failure 

(+2%).

Among children aged 2 to 11 years with congenital heart disease (n=387), height 

velocity percentile was similar in children with cyanosis (+10%) as those without 

cyanosis (+7%), was similar in children with cardiac enlargement (+15%) as 

without cardiac enlargement (+6%), and was non-significantly lower in children 

with congestive heart failure (–13%) than without congestive heart failure (+7%).

Because of the calculation of 

height velocity, some subjects 

missing follow-up measures of 

height were excluded from 

analyses.

Study was government funded.

White

1970

72024496

Among children with congenital heart disease, height < 2nd percentile was more 

common among those with cyanosis (n=27, 19%) than those without cyanosis 

(n=53, 2%)

No statistical analyses performed

Reporting of data unclear

Study was partial government 

funded.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

183

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Arreola

1991

93191566

Location: Mexico

Setting: Outpatient diabetes clinic

Mean age: ND

Age range: 1-16 y

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 198±8 each year (1984-

1988)

Evaluated: 198±8 each year

Number of sites: 1

Patients with type I diabetes 

seen at outpatient diabetes 

clinic from 1984 to 1998

Age 1-16 y

None reported Insulin dependent 

diabetes

Retrospective longitudinal 

cohort

(4-5 y)

Court

1982

83021090

Location: UK

Setting: Region

Mean age: 13±3.7 y

Age range: ND

Mean height, SDS: –0.69

Male: 54%

Race: ND

SES: ND

Enrolled: 121

Evaluated: 111

Number of sites: ND

Children with diabetes attending 

clinics in the Newcastle 

region

None reported Diabetes (implied insulin 

dependent)

Retrospective crosssectional cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

184

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Herber

1988

88180314

Location: UK

Setting: Pediatric diabetic clinic

Initial mean age: 10 y

Follow-up mean age: 13 y

Age range: ND

Initial height, SDS: –0.24±1.16

Follow-up height, SDS: –0.20±1.08

Male: 64%

Race: ND

SES: ND

Enrolled: 67

Evaluated: 67

Number of sites: 1

Patients with Type I diabetes 

who have attended the 

pediatric diabetic clinic for at 

least 3 years

None reported Insulin dependent 

diabetes

Retrospective longitudinal 

cohort

(3 y)

Izumi

1995

96105591

Location: Japan

Setting: Summer camp

Initial mean age: ND

Follow-up mean age: 14 y

Age range: ND

Mean height: ND

Male: 40%

Race: ND

SES: ND

Enrolled: 385

Evaluated: 107

Number of sites: ND

Children participated in 

Summer camp program

More than 3 determinations of 

HgbA1c 

Age < 18 y at final examination.

None reported Insulin dependent 

diabetes mellitus

Retrospective longitudinal 

cohort

(18 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

185

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Jivani

1973

73134278

Location: UK

Setting: Children’s hospital

Mean age: ND

Age range: 9 mo - 13 y

Mean height: ND

Male: 46%

Race: ND

SES: ND

Enrolled: 116

Evaluated: 104

Number of sites: 1

Children with diabetes

> 3 y follow-up

Other condition which 

might have affected 

growth

(12 subjects with fair 

control were not 

analyzed)

Diabetes (implied insulin 

dependent)

Retrospective longitudinal 

cohort

(mean [range] 7 [3-13] y)

Pitukcheewanont

1995

96136504

Location: US

Setting: Clinic

Mean age: 11.5±3.8 y

Age range: ND

Mean height: ND

Male: 49%

Race: White 100%

SES: ND

Enrolled: 82

Evaluated: 82

Number of sites: 1

Type I diabetes < 3 visits during study

Other problems that 

might affect growth 

(thyroid disease, 

cerebral palsy, foster 

care placement, 

methylphenidate 

therapy)

Precocious or delayed 

puberty

Insulin dependent 

diabetes

Retrospective longitudinal 

cohort 

(6 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

186

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Rosenbloom

1982

83032889

Location: US

Setting: Clinic

Mean age: ND

Age range: ND

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 309

Evaluated: 142

Number of sites:8

Children with Type I diabetes

Pre-puberty

Duration of DM >3 y

None reported Insulin dependent 

diabetes mellitus

Prospective longitudinal 

cohort

(ND)

Salardi

1987

87127000

Location: Italy

Setting: Pediatric clinic

Mean age: 7.4±3.6 y

Age range: 0.7-15 y

Mean height: ND

Male: 44%

Race: ND

SES: ND

Enrolled: 79

Evaluated: 79

Number of sites: 1

Children with Type I diabetes None reported Insulin dependent 

diabetes mellitus

Prospective longitudinal 

cohort

(Mean [Range] 4.5 [1-10.7] 

y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

187

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Soliman

1996

96412723

Location: Oman

Setting: Diabetes clinic

Mean age: 9 y

Age range: 2-12 y

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 47

Evaluated: 45

Number of sites: 1

Prepubertal children with 

diagnosis of Type I diabetes 

mellitus

Intra-uterine growth 

retardation

Systemic or endocrine 

disease

Dysmorphic trait

Central nervous system 

irradiation

Hypothyroid

Insulin dependent 

diabetes mellitus

Prospective longitudinal 

cohort

(1 y)

Vanelli

1992

93052062

Location: Italy

Setting: Diabetes unit

Mean age: ND

Age range: 1.5-21 y

Mean height: ND

Male: 0% (analyzed)

Race: ND

SES: ND

Enrolled: 204

Evaluated: 42

Number of sites: 1

Diabetic children referred to 

diabetes clinic at diagnosis

Treated with daily insulin

Subset analysis of girls who 

became diabetic at onset of 

puberty

Endocrinological 

disease affecting 

linear growth

Insulin dependent 

diabetes mellitus

Prospective longitudinal 

cohort

(ND)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part I

188

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Wise

1992

92387067

Location: US

Setting: Pediatric diabetes clinic

Mean age: ND

Age range: ND

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 122

Evaluated: 122

Number of sites: 1

Children and adolescents with 

diabetes

Other problems that 

might affect growth 

(thyroid disease, 

cerebral palsy, foster 

care placement, 

methylphenidate 

therapy, or 

precocious or 

delayed onset of 

puberty)

Insulin dependent 

diabetes mellitus

Prospective longitudinal 

cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part II

189

Author, Year Severity of Illness Groups Outcomes

Arreola

1991

93191566

Diabetes control

• HgbA1c

• Poor control: HgbA1c > 11%

• Good control: HgbA1c < 11%

Height velocity

cm/month

Court

1982

83021090

Diabetes control (text unclear)

• Poor control: Glucosuria (>2%) frequency >75% or 24 hour urine glucose > 50 g

• Good control: Glucosuria frequency < 10% or 24 urine glucose < 20 g

Height SDS, based on Tanner 1976

Growth velocity SDS

Herber

1988

88180314

HgbA1c Change in height SDS

Izumi

1995

96105591

HgbA1c category

• <10.0%

• 10.0-12.4%

• ≥12.0% (unclear why overlap)

Height SDS, based on Japanese Ministry of Education 

statistics

Jivani

1973

73134278

Diabetes control

• Poor: Ketonuria, glycosuria up to 5% at clinic, BS > 250 mg/dL, severe or frequent 

hypoglycemic reactions

• Good: No ketonuia, ≤ 1% glycosuria at clinic, blood sugar < 150 mg/dL, rare mild 

hypoglycemic reactions

Height percentile, based on Tanner, 1966

Pitukcheewanont

1995

96136504

HgbA1c Height SDS, based on National Center for Health 

Statistics

Height velocity, SDS

Rosenbloom

1982

83032889

Limited joint mobility (“associat[ed with] early microvascular complications)

• None

• Mild: Involving 1 or 2 interphalangeal joints, 1 large joint, or only the metacarpophalangeal 

joints bilaterally

• Moderate/Severe: Involving 3 or more interphalangeal joints or 1 finger joint and 1 large 

joint bilaterally or cervical spine involvement or obvious hand deformity at rest

Height percentile, based on National Center for Health 

Statistics

< 25%
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part II

190

Author, Year Severity of Illness Groups Outcomes

Salardi

1987

87127000

HgbA1c Height SDS, based on Tanner’s centiles

Height velocity SDS, based on Tanner’s centiles

Soliman

1996

96412723

Diabetes control

• HgbA1c < 10%

• HgbA1c > 10%

Height velocity SDS, based on age-matched population

Vanelli

1992

93052062

Diabetes severity (apparently post hoc grouping)

• Lower insulin requirement: Mean ± SD insulin 37±1.5 U/m2/day; HgbA1c 10±1.8%

• Higher insulin requirement: Insulin 42±0.5 U/m2/day; HgbA1c 9±2.4%

Peak height velocity (during pubertal growth)

cm/year

Wise

1992

92387067

HgbA1c level categories

• 6.0-7.9

• 8.0-9.9

• 10.0-11.9

• 12.0-13.9

• 14.0-15.9

• 16.0-21.9

Height velocity 

Change in SDS, based on National Center for 

Health Statistics
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part III

191

Author, Year Associations found Potential Biases Comments

Arreola

1991

93191566

Children with diabetes with HgbA1c > 11% (no data on number of subjects) had 

significantly lower height velocity (0.54 cm/month, from graph) compared to those 

with HgbA1c < 11% (0.22 cm/month). There was a significant correlation between 

HbA1c level and height velocity.

True number of subjects included 

not reported.

No data on funding source

Court

1982

83021090

For children with diabetes that was under poor control (n=57) mean height (–0.96 

SDS) was significantly lower than those under good control (n=54, –0.22 SDS).

Mean height velocity was significantly lower for children under poor control (–1.22 

SDS) than those under good control (–0.61 SDS).

Determination of diabetes control 

based on glucosuria 

frequency and 24 hour urine 

glucose instead of HgbA1c

No data on funding source.

Herber

1988

88180314

In children with diabetes (n=67), “no significant effect on [change in height] was 

apparent with differing levels of HgbA1c.”

Specific data on height SDS in 

relation to HbA1c levels was 

not given.

Overall good control (mean 

HbA1c levels at 

commencement 10.2%; mean 

HbA1c levels at end 9.9%.

No data on funding source.

Izumi

1995

96105591

Among children with diabetes, mean height of those with HgbA1c < 10% (n=28) was 

–0.54 SDS, of those with HgbA1c of 10-12.4% (n=53) was –0.76, and of those 

with HgbA1c ≥ 12% (n=26) was –0.75. Height was not significantly associated to 

HgbA1c level.

No data on height velocity.

Categories of severity of diabetes 

overlapping. 

Unclear if statistical analysis based 

on groups or on individual 

HgbA1c levels

No data on funding source.

Jivani

1973

73134278

The mean height percentile among girls with diabetes with poor control (n=22) was 

38% and among those with good control (n=34) was 40%. There was no 

significant difference between the two groups.

The mean height percentile among boys with diabetes with poor control (n=19) was 

35% and among those with good control (n=29) was 29%. There was no 

significant difference between the two groups.

Among both boys and girls with diabetes, height velocity was not associated with level 

of diabetes control

Eligibility criteria unclear.

Age of children at time of follow-up 

analysis unclear.

Statistical analysis unclear.

Determination of diabetes control 

based on factors other than 

HgbA1c

No data on funding source.

The text and table of the criteria 

for assessment of diabetic 

control were not 

concordant.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Insulin Dependent Diabetes Mellitus – Part III

192

Author, Year Associations found Potential Biases Comments

Pitukcheewanont

1995

96136504

Among children with type I diabetes (n=82), there was no association between mean 

HgbA1c and mean height SDS in univariate analysis. In multivariate analysis, 

controlling for age of diabetes onset and initial height, there remained no 

association between HgbA1c and height.

There was no association between mean HgbA1c and mean height velocity at any 

Tanner stage in univariate analysis.

Retrospective analysis No data on funding source.

Rosenbloom

1982

83032889

Diabetic children with mild (n=31), moderate (n=19) or severe (n=24) limited joint 

mobility were significantly more likely to be below the 25th percentile for height 

(~75%, from graph) than those without limited joint mobility (n=68, ~37%)). 

However, the correlation between HgbA1c and joint mobility was poor.

No data on height velocity

Joint mobility is a poor proxy for 

severity of diabetes.

Only looked at quartiles of height.

Study hospital funded

Salardi

1987

87127000

In children with insulin dependent diabetes (n=79), height SDS and height velocity 

SDS were not significantly correlated with HgbA1c.

Only summary of results reported. Study was government funded

Soliman

1996

96412723

Children with diabetes whose HbA1c < 10% (n=30) had significant higher growth 

velocity (+0.75 SDS) than DM subject HbA1c > 10% (n=15, –1.6 SDS).

None noted No data on funding source.

Vanelli

1992

93052062

In a subset of girls who became diabetic at onset of puberty (n=42), the 23 treated with 

greater amounts of insulin (mean 41.5 U/m2/d) and who had lower mean HgbA1c 

(8.9%) had significantly higher mean peak growth velocity (8.5 cm/y) than the 19 

treated with less insulin (37.3 U/m2/d and higher HgbA1c (10.1%), at 6.9 cm/y.

Study poorly defined.

Unclear a priori hypotheses

Definitions of sample groups 

poorly defined

Single analysis of subgroup only

No data on funding source

Wise

1992

92387067

Among children with diabetes (n=122) a significant linear relationship was seen 

between HgbA1c and growth velocity. HgbA1c < 8% was associated with growth 

acceleration (+0.10 SDS); the most severe growth retardation occurred when 

HgbA1c levels were > 16% (–0.07 SDS).

None noted No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

ß-thalassemia – Part I

193

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Constantoulakis

1975

75129833

Location: Greece

Setting: Outpatients

Mean age: ND

Age range: 7 months – 28 y

Mean height: ND

Male: 58%

Race: ND

SES: ND

Enrolled: 229

Evaluated: 171

Number of sites: 1

Diagnosis of homozygous ßthalassemiaNone reported ß thalassemia major Retrospective longitudinal 

cohort

(Range 4-7 y)

Kattamis

1970

71003038

Location: Greece

Setting: Clinic

Mean age: ND

Age range: 1-11 y

Mean height: ND

Male: 53%

Race: ND

SES: ND

Enrolled: 74

Evaluated: 74

Number of sites: 1

Diagnosis of homozygous βthalassemiaClinical picture of 

thalassemia 

intermedia and 

hemoglobin between 

7-10 g/dL

Age > 11 y

ß thalassemia major Prospective cross-sectional 

cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

ß-thalassemia – Part I

194

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Madeddu

1978

78167848

Location: Italy

Setting: Clinic

Mean age: ND

Age range: 2-13 y

Mean height: ND

Male: 46%

Race: ND

SES: ND

Enrolled: 50

Evaluated: 50

Number of sites: 1

Homozygous ß thalassemia None reported ß thalassemia major Prospective cross-sectional
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

ß-thalassemia – Part II

195

Author, Year Severity of Illness Groups Outcomes

Constantoulakis

1975

75129833

Multiple linear regression including

• Mean hemoglobin level over previous 2-4 years

• Total blood transfused since birth

• “Index of severity of disease” based on amount of blood transfused during previous 2 years

• (Age)

Height percentiles, based on various Greek sources

Kattamis

1970

71003038

β-thalassaemia severity

• Group I: Pre-transfusion hemoglobin > 8 g/dL, frequent transfusions

• Group II: Unable to follow regularly, pre-transfusion hemoglobin 6-8 g/dL, either very low 

SES or had to travel “very long distance” for transfusion

• Group III: Transfused only when hemoglobin < 6 g/dL, usually < 5 g/dL

Height percentile, based on Children’s Medical Center, 

Boston growth chart

Madeddu

1978

78167848

Hemoglobin concentration between two transfusions Height percentile, based on Tanner, 1962
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

ß-thalassemia – Part III

196

Author, Year Associations found Potential Biases Comments

Constantoulakis

1975

75129833

Among children with ß-thalassemia major (n=171) there was a trend toward lower 

height percentiles being associated with low hemoglobin levels and severity of 

disease; however, neither was statistically significant in a linear regression 

controlling for age. Total blood transfused since birth was not associated with 

height.

No data on height velocity.

No data on hemoglobin levels, 

total blood transfused since 

birth, and index of severity of 

disease. Provides only the 

regression results.

Definition of the severity of the 

disease unclear.

Large numbers of subjects were 

not included in analyses. No 

explanation.

Model adjusted for nonindependent variables.

No data on funding source

Kattamis

1970

71003038

Children with mild ß-thalassemia major (n=38) had significantly higher mean height 

percentile (56%) than children with moderate (n=14, 22%) and severe (n=22, 

7%) disease.

No data on height velocity.

Thalassemia severity based on 

how low hemoglobin allowed 

to fall before transfusion

No data on funding source

Madeddu

1978

78167848

Children with ß thalassemia major who were < 3rd percentile for height (n=18) had 

mean hemoglobin of 6.6 g/dL, which was not significantly lower than those whose 

height was 3rd-25th percentile (n=12, 7.2 g/dL) and whose height was 25th-75th

percentile (n=19, 7.0 g/dL) (One child had height above 75th percentile).

No data on height velocity.

Cross-sectional study cannot 

evaluate previous degree of 

anemia

No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Inflammatory Bowel Disease – Part I

197

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Farmer

1979

80023814

Location: US

Setting: Clinic

Mean age: ND (41% < 16 y)

Age range: < 20 y

Mean height: ND

Male: ND

Race: ND

SES: ND

Enrolled: 522

Evaluated: 522

Number of sites:1

Crohn's disease established by 

clinical, radiographic and/or 

histological means

Age < 20 y

Diagnosis made form 1955-

1974

Unable to obtain followup dataCrohn’s disease Retrospective longitudinal 

case series

(Mean 7.7 y)

Griffiths

1993

93345883

Location: Canada

Setting: Clinic

Mean age: 11±2.3 y

Age range: 5 - 17 y

Mean height, SDS: –1.1±1.3

Male: 66%

Race: ND

SES: ND

Enrolled: 100

Evaluated: 100

Number of sites: 1

Diagnosis of Crohn's disease

Tanner stage 1 or 2 

Transferred after initial 

diagnosis and 

referred for 

consultation only

Crohn’s disease Retrospective longitudinal 

case series

(≥ 2 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Inflammatory Bowel Disease – Part I

198

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Saha

1998

98182041

Location: Finland

Setting: Pediatrics department

Mean age: 7 y

Age range: ND

Mean height: ND

Male: 43%

Race: ND

SES: ND

Enrolled: 47

Evaluated: 47

Number of sites: 1

Diagnosis of inflammatory 

bowel disease 

None reported Inflammatory bowel 

disease:

Ulcerative colitis

Crohn’s disease

Retrospective longitudinal 

cohort 

(13 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Inflammatory Bowel Disease – Part II

199

Author, Year Severity of Illness Groups Outcomes

Farmer

1979

80023814

Location of Crohn’s disease

• Ileocolic pattern

• Colon pattern

• Small intestine pattern

• Anorectal pattern

Short stature

Height < 3rd percentile, based on growth charts

Griffiths

1993

93345883

Severity of gastrointestinal symptoms over given year

• Quiescent: No symptoms, normal complete blood count and sedimentation rate

• Mild: Some symptoms, no prednisone treatment needed

• Moderate: Intermittent exacerbations requiring prednisone or nutritional support

• Severe: Chronic unremitting symptoms requiring prednisone or alternate treatment

Location of Crohn’s disease

• Small bowel

• Ileocecal

• Ileocolic

• Colon

Height velocity

cm/year

Percent with growth retardation

< 4 cm/year

Height SDS, based on National Center for Health 

Statistics

Change in height SDS

Saha

1998

98182041

Severity of Crohn’s disease/ulcerative colitis

12 point scale based on number of relapses, exacerbations, medications and need for surgery 

(correct scoring mechanism not clear)

• Mild: 1-3 points

• Moderate: 4-6 points

• Severe: ≥ 7 points

Height SDS, based on Finnish population mean

Height velocity SDS
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Inflammatory Bowel Disease – Part III

200

Author, Year Associations found Potential Biases Comments

Farmer

1979

80023814

Among children with Crohn’s disease likelihood of short (< 3rd height percentile) was 

not related to location of disease. Of those with ileocolic disease (n=175) 7% were 

short; of those with colonic disease (n=162) 8% were short; of those with small 

intestine disease (n=151) 6% were short; of those with anorectal disease (n=34) 

9% were short.

No data on height velocity

No statistical analyses.

“Severity” based on location of 

disease

No data on funding source

Griffiths

1993

93345883

Among children with Crohn’s disease, “severity of gastrointestinal symptoms was the 

major factor influencing linear growth during the first two years [after diagnosis]. 

Height velocity significantly decreased with increasing gastrointestinal symptoms 

during both year and year two, after adjusting for corticosteroid use. During year 

one, height velocity of children with quiescent disease (n=14) was ~5.7 cm/year 

(from graph), with mild disease (n=54) was ~4.6 cm/year, with moderate disease 

(n=23) was ~3 cm/year, and with severe disease (n=9) was ~2.7 cm/year. 

During year two, height velocity of children with quiescent disease (n=23) was 

~7.3 cm/year, with mild disease (n=44) was ~4.5 cm/year, with moderate disease 

(n=24) was ~4 cm/year, and with severe disease (n=8) was ~4.1 cm/year.

Among children with Crohn’s disease who were followed to maturity, initial and ultimate 

height were not associated with disease severity. Initial and ultimate height severity 

were –0.88 and –0.43 SDS for those with mild disease (n=26), –1.17 and –1.15 

SDS for those with moderate disease (n=15), –1.48 and –0.70 SDS for those with 

moderate or severe disease with sustained remission (n=14), and –1.12 and –

1.37 SDS for those with chronically severe disease (n=12).

Among children with Crohn’s disease who were followed to maturity, change in height 

was significantly associated with disease severity. Change in height was 0.58 SDS 

for those with mild disease (n=26), 0.03 SDS for those with moderate disease 

(n=15), 0.68 SDS for those with moderate or severe disease with sustained 

remission (n=14), and –0.11 SDS for those with chronic severe disease (n=12).

Among children with Crohn’s disease, at year two (n=100), disease location was not 

significantly associated with height velocity (cm/year) or percentage with height 

velocity < 4 cm/year. Among those with long-term follow-up (n=65), disease 

location was not associated with initial height SDS, ultimate height SDS, or change 

in height SDS.

Retrospective No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Inflammatory Bowel Disease – Part III

201

Author, Year Associations found Potential Biases Comments

Saha

1998

98182041

Among children with ulcerative colitis (n=29), mean overall change in height over 4 

years was –0.16 SDS for those with mild disease, –1.09 SDS for those with 

moderate disease, and –1.74 SDS for those with severe disease. This trend did 

not reach statistical significance. The overall change in height velocity was 

significantly greater in those with mild disease (+1.14 SDS) than those with 

moderate disease (+0.39 SDS) and those with severe disease (+0.12 SDS).

Among children with Crohn’s disease (n=18), mean overall change in height over 4 

years was +0.51 SDS for those with mild disease, –0.27 SDS for those with 

moderate disease, and –0.11 SDS for those with severe disease. This trend did 

not reach statistical significance. The overall change in height velocity was 

significantly greater in those with mild disease (+0.42 SDS) than those with 

moderate disease (+0.09 SDS) and those with severe disease (–1.09 SDS).

Height outcomes are difficult to 

interpret.

Numbers of subjects in each 

category not reported.

Study was hospital and 

privately funded.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Juvenile Rheumatoid Arthritis – Part I

202

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Bernstein

1977

87026009

Location: US

Setting: Clinic

Mean age: ND

Initial age range: 1-12 y

Mean height: ND

Male: 24%

Race: ND

SES: ND

Enrolled: 31

Evaluated: 31

Number of sites: 1

Children with diagnosis of 

juvenile rheumatoid arthritis

None reported Juvenile rheumatoid 

arthritis

Retrospective longitudinal 

cohort (mean [range] 

6.6[2.3-11] y, up to age 

of 15)

Polito

1997

97283189

Location: Italy

Setting: Pediatric clinic

Initial mean age: 7 y

Follow-up mean age: 12 y

Age range: ND

Initial mean height, SDS: +0.34

Follow-up mean height, SDS: –0.05

Male: 26%

Race: ND

SES: ND

Enrolled: 58

Evaluated: 58

Number of sites:1

Children with active juvenile 

rheumatoid arthritis for ≥ 1 y

Follow-up for ≥ 1 y

Steroid use

Growth hormone 

therapy

Juvenile rheumatoid 

arthritis:

Pauciarticular onset

Systemic onset

Polyarticular onset

Retrospective longitudinal 

case series

(≥ 1 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Juvenile Rheumatoid Arthritis – Part I

203

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Saha

1999

99374796

Location: Finland

Setting: Hospital based clinic

Mean age: 4 y

Age range: 0.9-11 y

Mean height: ND

Male: 36%

Race: ND

SES: ND

Enrolled: 64

Evaluated: 64

Number of sites: 1

Children with mild to moderate 

juvenile onset chronic 

arthritis

Prepuberty

Followed for ≥ 1 y

Ullrich-Turner 

syndrome

Juvenile rheumatoid 

arthritis:

Pauciarticular onset

Systemic onset

Polyarticular onset

Retrospective longitudinal 

case series

(1-11 y, until age 12 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Juvenile Rheumatoid Arthritis – Part II

204

Author, Year Severity of Illness Groups Outcomes

Bernstein

1977

87026009

Mode of onset of juvenile rheumatoid arthritis

• Systemic

• Polyarticular

• Pauciarticular

Mean percent change in height per year

Polito

1997

97283189

Type of juvenile rheumatoid arthritis

• Systemic

• Polyarticular

• Pauciarticular

Number of joints affected (systemic or polyarticular only)

Sum of periods of time with disease flares (systemic or polyarticular only)

joint swelling, tenderness, functional impairment, ESR > 25 mm/hr)

Functional class, not defined (systemic or polyarticular only)

Change in height SDS, based on Tanner 1976

Change in height SDS per year

Saha

1999

99374796

Severity of juvenile chronic arthritis score

6 point scale based on local anti-inflammatory administrations and number of systemic 

antirheumatics

• Mild: Score 1-3

• Moderate: Score ≥ 4

Type of disease

• Pauciarticular

• Polyarticular

• Systemic

• Iridocyclitis

Height velocity SDS, based on Tanner 1966

Height SDS
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Juvenile Rheumatoid Arthritis – Part III

205

Author, Year Associations found Potential Biases Comments

Bernstein

1977

87026009

Among children with juvenile rheumatoid arthritis, those with systemic disease (n=13) 

had significantly greater mean change in height per year (–0.85%) than those 

with polyarticular disease (n=9, +0.04%) and those with pauciarticular disease 

(n=9, –0.01%).

Definition of outcome measure 

(percent change in height per 

year) not well defined

Study was privately funded.

Polito

1997

97283189

Among children with juvenile rheumatoid arthritis, those with pauciarticular disease 

(n=21) were less likely to lose > 1 height SDS between first and last visits (0%) 

than those with systemic disease (n=19, 26%) or those with polyarticular disease 

(n=18, 28%). No statistical analysis was performed.

Among children with either systemic or polyarticular disease (n=37), change in height 

SDS per year was not associated with number of affected joints but was associated 

with the sum of the periods of disease flares. Children in functional class I (not 

defined) had significantly smaller change in height SDS per year 

(–0.01 SDS) than those in functional class II (–0.06 SDS)

Retrospective analysis

Inclusion criteria was no steroids, 

thus children with most severe 

disease, were excluded.

Functional class not defined.

No data on funding source

Saha

1999

99374796

Among children with juvenile rheumatoid arthritis (n=64), by multivariate analysis of 

covariance “the most obvious decrease in [height] velocity was seen in children 

with polyarthritis and growth velocity was affected slightly more in children with 

moderate than mild disease,” adjusting for sex and duration of disease.

“Heights were more affected in children with polyarthritis and the severity of the 

disease had an additive effect,” adjusting for glucocorticoid use and duration of 

disease.

Exclusion criteria unclear.

No children with severe arthritis.

Limited reporting of data.

Statistical significance of relevant 

findings not reported.

Study hospital and privately 

funded
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part I

206

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Claris-Appiani

1989

91002131

Location: Italy

Setting: ND

Mean age: 1.6-9 y

Age range: ND

Mean height: ND

Male: 65%

Race: ND

SES: ND

Enrolled: 17

Evaluated: 17

Number of sites: ND

Children with chronic kidney 

disease

Pre-dialysis

Stable

Acute obstruction

Pyelonephritis

Hypertension

Hyposthenuria

Salt wasting

Steroid treatment

Chronic kidney disease

Stage 3

Stage 4

Prospective 

longitudinal cohort

Ismaili

2001

21219717

Location: Belgium

Setting: Pediatric nephrology

Initial mean age: 6 mo

Follow-up mean age: 4 y

Age range: ND

Mean height: ND

Male: 55%

Race: ND

SES: ND

Enrolled: 11

Evaluated: 11

Number of sites: 1

Infants with kidney dysplasia 

and chronic kidney disease

Obstructive renal 

dysplasia

Chronic kidney disease

Kidney dysplasia

Stage 4

Stage 5

Retrospective 

longitudinal cohort

(4 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part I

207

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Karlberg

1996

96384503

Location: Europe

Setting: Pediatric nephrology clinics

Mean age: ND

Age range: 0-5 y

Mean heights (various ages), SDS: –

1.05 to –3.09

Male: 70%

Race: ND

SES: ND

Enrolled: 73

Evaluated: 61

Number of sites: 22

Onset of chronic kidney 

disease age < 6 mo

GFR < 3 SD below mean for 

age

≥ 2 height measurements 

before age 1 y and followed 

until at least age 3 y

Primary 

glomerulonephropathy

Systemic metabolic 

disorder

Chronic kidney disease

Stage 4

Stage 5

Prospective longitudinal 

case series

(Mean [Range] 7.3 [3-

16] y)

Konrad

1995

96162281

Location: Europe

Setting: Pediatric nephrology clinics

Initial mean age: 1.7 y

Initial age range: 1-8 y

Follow-up man age: 5.6 y

Follow-up age range: 2-9 y

Mean height: ND

Male: 59%

Race: ND

SES: ND

Enrolled: 67

Evaluated: 58

Number of sites: 22

Autosomal recessive 

polycystic kidney disease

Prepuberty

Girls ≤ 9 y old

Boys ≤ 10 y old

Age ≥ 1 y at first assessment

≥ 1 y follow-up

Subset of Karlberg, 1996 

[#226] and Schaefer, 1996 

[#3001]

Single growth 

measurement only

Autosomal recessive 

polycystic kidney 

disease

Stage 1

Stage 2

Stage 3

Stage 4

Prospective longitudinal 

case series

(≥ 1 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part I

208

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Schaefer

1996

96384504

Location: Europe

Setting: Pediatric nephrology clinics

Initial median age: 2.6 y

Initial age range: 0-8 y

Follow-up age: ~ 10 y

Height range, SDS: –4.2 to +4.1

Male: ND

Race: White 96%, Arab or Asian 4%

SES: ND

Enrolled: 500

Evaluated:321

Number of sites: 22

Born between 1970 and 1992

Marked reduction in functional 

kidney mass

Primary 

glomerulonephropathy

Systemic metabolic 

disorder

Chronic kidney disease

Stage 4

Stage 5

Prospective longitudinal 

case series

(Median [Range] 3.3 

[0.5-10] y)

Norman

2000

21024968

Location: UK

Setting: Clinic

Mean age: ND

Age range: 2-17 y

Mean height: ND

Male: 63%

Race: ND

SES: ND

Enrolled: 95

Evaluated: 95

Number of sites: 1

Children scheduled for GFR 

measurements

Congenital growth 

abnormalities

Receiving dialysis

Chronic kidney disease

Stage 1

Stage 2

Stage 3

Stage 4

Prospective crosssectional cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part I

209

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Rizzoni

1984

85010647

Location: Italy

Setting: Pediatric clinic

Mean age: 6 y

Age range: < 6 mo - 15 y

Initial mean height, SDS: –1.6

Follow-up mean height, SDS: –1.5

Male: 69%

Race: ND

SES: ND

Enrolled: 47

Evaluated: 47

Number of sites: 1

Children with GFR < 70 

ml/min/1.73 m2

≥ 1 bone age determined

Follow-up for ≥ 1 y

Proteinuria

Nephrotic syndrome

Steroid treatment

Chronic kidney disease

Stage 2

Stage 3

Stage 4

Stage 5

Retrospective 

longitudinal case 

series

(Mean [Range] 4.3 [1-

12] y)

Schärer

1999

20068988

Location: US

Setting: Clinic

Mean age: 4.5 y

Age range: 1.2-10 y

Mean height: ND

Male: 67%

Race: ND

SES: ND

Enrolled: 45

Evaluated: 38

Number of sites: ND

Prepubertal children with 

idiopathic nephrotic 

syndrome

Chronic kidney failure Idiopathic nephrotic 

syndrome

Prospective longitudinal 

cohort

(Mean [Range] 9.0 [2-

19] y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part I

210

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Tejani

1983

84068349

Location: US

Setting: Pediatric nephrology clinic

Mean age at onset:

Steroid resistant 7.7±3.7 y; Steroid 

sensitive, 3.5±2.5 y

Age range at onset: 10 mo - 15 y

Mean height: ND

Male: 42%

Race: White 16%, Black 50%, 

Hispanic 33%

SES: ND

Enrolled: 25

Evaluated: 24

Number of sites: 1

Nephrotic syndrome

Biopsy-proven focal 

segmental sclerosis

Biopsy performed because of 

lack of response to steroids 

or relapse after treatment 

with steroids

Diffuse increase in 

mesangial cells or with 

mesangial deposition of 

immunoglobulin

Focal segmental 

sclerosis

Retrospective 

longitudinal case 

series

(Steroid resistant: 7±5 y; 

Steroid sensitive: 13±8 

y))

Tsau

1989

90155156

Location: Taiwan

Setting: Hospital

Mean age of onset: 5 y

Age range: ND

Mean height: ND

Male: 83%

Race: Chinese

SES: ND

Enrolled: 52

Evaluated: 52

Number of sites: 1

Nephrotic syndrome 

beginning before age 15 y

Followed up for at least 2 y

Development of chronic 

kidney insufficiency

Nephrotic syndrome Retrospective 

longitudinal cohort 

(5.5±2.8 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part II

211

Author, Year Severity of Illness Groups Outcomes

Claris-Appiani

1989

91002131

GFR, Schwartz formula estimate Height SDS, based on Tanner 1976

Growth velocity per year SDS

Ismaili

2001

21219717

Chronic kidney disease severity, Schwartz formula estimate and direct measurement

• GFR < 15 mL/min/1.73 m2

• GFR > 15 mL/min/1.73 m2

Height SDS, based on Tanner 1966

Karlberg

1996

96384503

GFR, age-specific Schwartz formulae estimates Height SDS, based on normal Swedish children

Konrad

1995

96162281

GFR, Schwartz formula estimate

Chronic kidney disease severity

• GFR < 60 mL/min/1.73 m2

• GFR > 260 mL/min/1.73 m2

Height SDS, based on First Zurich Longitudinal Growth 

Study

Schaefer

1996

96384504

GFR, age-specific Schwartz formulae estimates

Chronic kidney disease severity

• GFR < 25 mL/min/1.73 m2

• GFR > 25 mL/min/1.73 m2

Height SDS

Height velocity SDS

Norman

2000

21024968

Chronic kidney disease severity, based on GFR direct measurements

• Normal: GFR > 75 mL/min/1.73 m2

• Mild: GFR 50-75 mL/min/1.73 m2

• Moderate: GFR 25-50 mL/min/1.73 m2

• Severe: GFR < 25 mL/min/1.73 m2

Height SDS, based on normal UK population

Rizzoni

1984

85010647

GFR, estimate or direct measurement Height SDS, based on Tanner 1976

Height velocity, cm/year
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part II

212

Author, Year Severity of Illness Groups Outcomes

Schärer

1999

20068988

Final kidney status

• Reached final height in absence of kidney function deterioration or ESRD

• Reached final height with serum creatinine > 1.2 mg/dL after age 13.6 years

• (Lost to follow-up before kidney function deterioration -- not evaluated in this report)

• Developed ESRD before reaching adult height

Idiopathic nephrotic syndrome severity (mean serum albumin level and serum protein level)

Height SDS

Change in height SDS

Tejani

1983

84068349

Responsiveness (improvement of proteinuria) of focal segmental sclerosis to steroids 

• Steroid responsive: Complete remission within 8 wk of prednisone, persisting for 2 mo after 

cessation of treatment

• Steroid resistant: No remission after 8 wk of treatment

Growth retardation

Height for age < 5th percentile at follow-up

Tsau

1989

90155156

Nephrotic syndrome severity

• Less favorable clinical courses, including frequent relapsing, steroid-dependent, and steroidresistant nephrotic syndromes 

• Had responded to steroid therapy initially with occasional or no relapse

Change in Height SDS, based on Department of Health, 

Taiwan

Growth velocity index

Ratio of actual growth velocity to normal growth 

velocity for age (% of expected growth)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part III

213

Author, Year Associations found Potential Biases Comments

Claris-Appiani

1989

91002131

Among children with pre-dialysis chronic kidney disease (n=17) there was a 

significant positive correlation between height SDS and creatinine clearance.

In multivariate analysis, height velocity was not associated with creatinine clearance, 

controlling for bone age, BUN, change in BUN, PTH, calcitriol, caloric and protein 

intake. 

Univariate analysis only was 

performed for height.

No univariate analysis for height 

velocity and creatinine 

clearance. Creatinine 

clearance not independent of 

other variables.

Far too few subjects for 

multivariate analysis

No data on funding source

Ismaili

2001

21219717

Among infants with chronic kidney disease with GFR < 15 mL/min/1.73 m2 at age 6 

months (n=5) mean height did not improve between age 6 months (–2.6 SDS) 

and 4 years (–2.3 SDS). Among those with GFR > 15 mL/min/1.73 m2 (n=6) 

mean height increased from age 6 months (–2.6 SDS) to 4 years (–1.4 SDS).

Small sample size No data on funding source.

Karlberg

1996

96384503

Among children with chronic kidney disease (n=47) change in height SDS between 9 

months and 2 years was not associated with GFR in a multiple linear regression.

Among infants with chronic kidney disease (n=14) change in height SDS during the 

“first postnatal months of life” were not associated with GFR. 

No data on variables in model.

Many children not included in all 

analyses

Study was pharmaceutical 

funded.

Same dataset as Schaefer 

1996

Konrad

1995

96162281

Among girls with autosomal recessive polycystic kidney disease, those with GFR < 60 

mL/min/1.73 m2 (n=9) had mean height of –2.1 SDS; those with higher GFR 

(n=15) had mean height of –0.3 SDS. Boys with GFR < 60 mL/min/1.73 m2

(n=10) had mean height of –1.5 SDS; those with higher GFR (n=24) had mean 

height of –0.5 SDS. There was a significant correlation between GFR and height 

SDS among girls but not among boys.

No data on height velocity.

None noted No data on funding source.

Subset of Karlberg, 1996 

[#226] and Schaefer, 1996 

[#3001]
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part III

214

Author, Year Associations found Potential Biases Comments

Schaefer

1996

96384504

Among children with chronic kidney disease (n=321) height velocity was positively 

correlated with GFR among 6 year olds and among children of 4 other age 

groups (of 9 age groups total).

Children with GFR > 25 mL/min/1.73 m2 had consistently higher annual height 

velocities than children with lower GFR.

Children with GFR > 25 mL/min/1.73 m2 were taller (mean height –1.65 SDS) than 

those with lower GFR (–2.79 SDS).

Numbers of children analyzed 

with GFR > 25 mL/min/1.73 m2

and with lower GFR not 

reported

Results for specific age groups not 

reported

Study was pharmaceutical 

funded.

Same dataset as Karlberg 1996

Norman

2000

21024968

Among children with chronic kidney disease, those with GFR > 75 mL/min/1.73 m2

(n=35) had mean height of +0.40 SDS, those with GFR 50-75 mL/min/1.73 m2

(n=23) had mean height of –0.34 SDS, those with GFR 25-50 mL/min/1.73 m2

(n=19) had mean height of –0.58 SDS, those with GFR < 25 mL/min/1.73 m2

(n=18) had mean height of –1.52. Those with moderate and severe chronic 

kidney disease had significantly lower height than those with normal GFR.

No data on height velocity

None noted No data on funding source.

Rizzoni

1984

85010647

Among children with chronic kidney disease (n=47) there was no association between 

GFR and growth velocity. or height SDS.

Limited data reported No data on funding source

Schärer

1999

20068988

Children with nephrotic syndrome who reached final height without deterioration of 

kidney function (n=16) had a mean change in height SDS from onset of kidney 

disease to final height of +0.27 SDS; those who developed serum creatinine > 1.2 

mg/dL before reaching final height (n=8) had a mean change in height SDS of –

0.08 SDS; those who developed ESRD before reaching final height (n=9) had a 

mean change in height of –1.35 SDS. Children who developed ESRD had a 

significant decrease in their height SDS compared to other groups.

Among children with steroid resistant nephrotic syndrome in whom steroid therapy 

was stopped before puberty (n=16) change in prepubertal height SDS and height 

velocity SDS correlated positively and significantly with total protein and albumin 

levels.

Analyses performed on only 

subgroups of subjects

Categorization of children by 

severity of disease is 

retrospective. Categorized 

only after reaching final height.

Serum albumin and protein are 

poor markers of disability -

related severity of disease

No data on funding source.
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Chronic Kidney Disease / Kidney Failure – Part III

215

Author, Year Associations found Potential Biases Comments

Tejani

1983

84068349

In children with focal segmental sclerosis, those with steroid responsive disease 

(n=10) were significantly less likely to have short stature (< 5th percentile) than 

those with steroid resistant disease (n=14) despite greater steroid doses among 

the former.

No data on growth velocity

Detailed results not reported. No data on funding source

Tsau

1989

90155156

Among children with nephrotic syndrome, those with relapsing disease (n=29) had 

significantly lower height velocity (80% of normal) and change in height SDS

(–0.63 SDS) than those without relapsing disease (n=23, 104%, +0.19 SDS). 

This association was true for up to 7 years of follow-up

Cannot distinguish the effect of 

steroid use from severity of 

disease. Those with relapsing 

disease required significantly 

longer duration of steroid use 

(8 months) than those without 

relapsing disease (4 months).

No data on funding source
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Human Immunodeficiency Virus – Part I

216

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Brettler

1990

91011887

Location: US

Setting: Hemophilia clinic

Median age: 8 y

Age range: 2.5-15 y

Mean height: ND

Male: 100%

Race: ND

SES: ND

Enrolled: 36

Evaluated: 36

Number of sites: 1

Hemophilia

HIV infection

2 y of growth data before HIV 

diagnosis

Age ≤ 12.5 y in 1980

None reported HIV (with hemophilia) Prospective and 

retrospective longitudinal 

cohort

(ND)

Matarazzo

1994

95143841

Location: Italy

Setting: Pediatric clinic

Median age: 2.6 y

Age range: 0-8 y

Mean height: ND

Male: 49%

Race: ND

SES: ND

Enrolled: 24

Evaluated: 24

Number of sites: 1

Perinatal HIV infection None reported HIV Prospective longitudinal 

cohort

(24 mo)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Human Immunodeficiency Virus – Part II

217

Author, Year Severity of Illness Groups Outcomes

Brettler

1990

91011887

Progression to AIDS or ARC (not defined) Growth failure

Decrease in ≥ 15 percentile points in height or 

weight for age for 2 consecutive years

Matarazzo

1994

95143841

Clinical condition

• Stable: not defined

• Clinical deterioration: not defined

Height SDS, based on Tanner 1966

Height velocity SDS
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Human Immunodeficiency Virus – Part III

218

Author, Year Associations found Potential Biases Comments

Brettler

1990

91011887

Among boys with hemophilia and HIV infection “progression to AIDS or [AIDS related 

complex]” was more common in those with “growth failure” over 2 years (n=9, 

55%) than those with normal growth (n=27, 7%). In multivariate analysis, “growth 

failure was the strongest prognostic variable” for progression to AIDS or AIDS 

related complex, adjusted for CD4, p24 antigenemia, and possibly other variables.

Methods, predictors and outcomes 

poorly defined

Variables included in multivariate 

analysis not reported

Definition of growth failure includes 

weight

No data on funding source

Matarazzo

1994

95143841

Among children with perinatal HIV infection (n=24), those with stable disease courses 

(n=14) had mean height at 1 year follow-up of –0.7 SDS, mean height at 2 year 

follow-up of –0.7 SDS, mean height velocity at 1 year follow-up of +1.2 SDS, and 

mean height at 2 year follow-up of +0.4 SDS. Children with unstable disease 

courses (n=10) had lower heights and height velocities. Mean height at 1-year 

follow-up was –2.0 SDS, mean height at 2 year follow-up of 

–2.6 SDS, mean height velocity at 1 year follow-up of –2.6 SDS, and mean height 

at 2 year follow-up of –3.0 SDS.

“At follow-up [after 2 years], most children with normal growth maintained a stable 

clinical condition, whereas those with growth reduction showed progression in the 

severity of the disease....Growth failure was a simple, sensitive predictor of clinical 

course [stable condition vs clinical deterioration].”

Direct comparison of children with 

stable and unstable disease 

had to be calculated from 

reported raw data.

Clinical condition not defined.

No statistical analysis.

Study was government and 

privately funded
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Atopic Dermatitis / Eczema – Part I

219

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Massarano

1993

93312068

Location: UK

Setting: Pediatric clinic

Mean age: 6 y

Age range: 2.3-12 y

Mean height: ND

Male: 68%

Race: ND

SES: ND

Enrolled: 68

Evaluated: 68

Number of sites: 1

Diagnosis of eczema

Prepubertal

Chronic non-atopic 

disease which would 

limit growth

Atopic eczema Prospective cross-sectional 

cohort

Patel

1988

99014336

Location: UK

Setting: Pediatric clinic

Mean age: 5.5±0.3 (SEM)

Age range: 2-10 y

Mean height, initial, SDS: +0.1±0.1 

(SEM)

Mean height, follow-up, SDS: –

0.1±0.2 (SEM)

Male: 55%

Race: ND

SES: ND

Enrolled: 80

Evaluated: 80

Number of sites:1

Atopic dermatitis that began 

before age 1 y

Prepubertal, age 2-11 y

Referred by pediatrician or 

dermatologist because of 

severity of disease

Systemic steroids Atopic dermatitis Prospective longitudinal 

cohort

(2 y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Atopic Dermatitis / Eczema – Part II

220

Author, Year Severity of Illness Groups Outcomes

Massarano

1993

93312068

Maximum percentage of skin surface area affected by atopic eczema (erythema, vesicle, and 

crusts)

Subgroups by percentage of skin surface area affected

• < 50% 

• > 50% 

Height SDS, based on Tanner 1966

Patel

1988

99014336

Percentage body surface area affected by atopic dermatitis

• < 50% 

• > 50% 

Coexistence of disease

• With asthma

• Without asthma

Height SDS, based on Tanner 1966

Height velocity SDS
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Atopic Dermatitis / Eczema – Part III

221

Author, Year Associations found Potential Biases Comments

Massarano

1993

93312068

Among children with atopic eczema (n=68), in a multivariate regression analysis, 

height SDS was correlated with surface area of eczema, controlling for parental 

height, diet, duration of eczema, treatment and asthma.

Those children with < 50% of skin affected (n=41) had mean height of +0.11 SDS; 

those with 50% of skin affected (n=27) had significantly shorter mean height of –

0.83 SDS.

No height velocity data.

None noted No data on funding source

Patel

1988

99014336

Among children with atopic dermatitis height SDS and height velocity SDS “did not 

differ between patients with < 50% body surface area (n=43) involvement and 

those with ≥ 50% body surface area involvement (n=37)...and between patients 

without asthma (n=36) and those with asthma (n=44).”

Complete results not reported.

No statistical analyses reported.

No data on funding
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Miscellaneous Diseases – Part I

222

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Evliyaoglu

1996

97097381

Location: Turkey

Setting: Pediatric hematology clinic

Mean age: 10 y

Age range: 5.5-15 y

Mean height, percentile: 20±22%

Height range, percentile: 3-75%

Male: ND

Race: ND

SES: ND

Enrolled: 24

Evaluated: 24

Number of sites: 1

Homozygote sickle cell anemia None reported Homozygous sickle cell 

anemia

Prospective cross-sectional 

cohort

Rasat

1995

95372015

Location: New Zealand

Setting: ND

Median age: 15 y

Age range: 2-31 y

Mean height: ND

Male: 50%

Race: ND

SES: ND

Enrolled: 16

Evaluated: 9

Number of sites: 1

Congenital adrenal hyperplasia 

diagnosed and treated at one 

hospital between 1962 and 

1993

None reported Congenital adrenal 

hyperplasia

Retrospective longitudinal 

case series

(Median [Range] 14 [2-31] 

y)
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Miscellaneous Diseases – Part I

223

Author, Year Demographics Inclusion Criteria Exclusion Criteria

Types of Diseases / 

Conditions

Study Design

(Duration)

Samson-Fang

1998

99066563

Location: US

Setting: Rehabilitation center

Mean age: 4.5 y

Age range: 1-12 y

Mean height, SDS: -1.2±1.5

Male: 53%

Race: White 80%, Black 20%

SES: ND

Enrolled: 175

Evaluated: 81

Number of sites: 1

Children with cerebral palsy

Age < 10 years old at the midpoint of assessing growth 

interval

Minimum time interval of 

measurements of 0.8 years

Genetic disorders

Complicating medical 

issues 

Cerebral Palsy Retrospective crosssectional cohort
Evidence Table 3. Association of Decreased Growth Velocity with Severity of Disease

Miscellaneous Diseases – Part II

224

Author, Year Severity of Illness Groups Outcomes

Evliyaoglu

1996

97097381

Severity of sickle cell anemia

• Mild: No blood transfusion or crises

• Severe: Blood transfusion needed early in life, frequent crises

Height percentile (not defined)

Rasat

1995

95372015

Number of episodes of biochemical escape from congenital adrenal hyperplasia suppression 

(morning 17-OH Progesterone > 60 nmol/L)

• < 3 episodes over at least 2 years

• > 3 episodes

Height SDS. based on Tanner 1966

Samson-Fang

1998

99066563

Cerebral palsy cognitive impairment

• Cognitive impairment: Learning disability, or delay in problem solving or receptive language 

skills

• No cognitive impairment

Type of cerebral palsy

• Spastic

• Extrapyramidal

• Mixed

Ambulatory status

• Ambulatory: Functionally ambulated with or without aids at home

• Non-ambulatory

Growth velocity SDS, based on Rikken 1992
Association of Decreased Growth Velocity with Severity of Disease

Abbreviations

225

Author, Year Associations found Potential Biases Comments

Evliyaoglu

1996

97097381

Among children with sickle cell anemia, those with mild disease (n=12) had significantly 

greater mean height percentile (22.5%) than those with severe disease (n=12, 

17.3%).

No data on height velocity

Only mild and severe sickle cell.

Height measurement (percentile) 

not clear.

Unclear why all children had low 

height percentile

No data on funding source

Rasat

1995

95372015

Among children with congenital adrenal hyperplasia there was no significant difference 

in final height SDS in those with < 3 biochemical escape episodes (n=4) and those 

with > 3 episodes (n=5).

No data on height velocity.

Very small numbers

Results shown only graphically.

No data on funding source

Samson-Fang

1998

99066563

Among children with cerebral palsy those with cognitive impairment (n=62) had 

significantly lower mean growth velocity (–1.25 SDS) than those with no cognitive 

impairment (n=19, –1.25 SDS)) 

Those age ≥ 2 years who were non-ambulatory (n=35) had significantly lower mean 

growth velocity (–1.20 SDS) than those who were ambulatory (n=37, 

–0.35 SDS).

There was no significant difference in mean height velocity among those with spastic 

disease (n=22, mean height velocity = –0.69 SDS), those with extrapyramidal 

disease (n=36, –0.86 SDS), and those with mixed disease (n=22, –1.50 SDS)

Exclusion criteria limit most severe 

impairments due to cerebral 

palsy

Study was privately funded.
229

Appendix A. Table 1. Main search performed in 

MEDLINE®

# Search History Results Summary

1 disab$.af. 66184

2 Limitation$.af. 45673

3 Handicap$.af. 13104

4 Impair$.af. 152795

5 1 or 2 or 3 or 4 263105

Disability

6 exp bone diseases, developmental/ 36107

7 exp growth disorders/ 16301

8 exp body height/ 18639

9 short stature.tw. 3374

10 6 or 7 or 8 or 9 68793

Height, growth 

disorders and short 

stature

11 5 and 10 3203 Questions 1 & 2

12 exp *bone diseases, developmental/ 27528

13 (short stature or skeletal dysplasia).tw. 3798

14 Growth velocity.tw. 1257

15 Growth retardation.tw. 8452

16 Growth delay.tw. 1306

17 Growth restriction.tw. 725

18 Height retardation.tw. 16

19 (height adj6 restrict$).tw. 54

20 linear velocity.tw. 160

21 (height adj6 delay).tw. 89

22 Length delay.tw. 106

23 (length adj6 retardation).tw. 145

24 exp growth disorders/ 16301

25 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 51939

Linear growth and 

linear growth delay

26 *fetal development/ 6938

27 *pregnancy/ 21154

28 *facial bones/ 3492

29 *facies/ 103

30 *failure to thrive/ 443

31 *thanatophoric dysplasia/ 122

32 *fetal growth retardation/ 3897

33 exp basal cell nevus syndrome/ 536

34 exp craniofacial dysostosis/ 3267

35 exp klippel-feil syndrome/ 469

36 exp synostosis/ 4073

37 exp funnel chest/ 828

38 exp gigantism/ 823

39 exp leg length inequality/ 1670

40 exp marfan syndrome/ 2697

41 exp fibrous dysplasia of bone/ 2313

42 exp hyperostosis, cortical, congenital/ 353

43 exp hyperostosis frontalis interna/ 241

44 exp exostoses, multiple hereditary/ 601

45 exp osteopetrosis/ 1419

46 exp osteopoikilosis/ 209

47 exp acquired hyperostosis syndrome/ 37

48 exp platybasia/ 278

Excluded 

diseases/conditions
230

49 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 

or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48 54379

50 25 not 49 32177 Question 3

51 11 or 50 36731 Questions 1, 2 & 3

52 Case Report/ 964105

53 51 not 52 22559 Exclude case reports

54 limit 53 to human 18613

55 limit 54 to English language 14258

Limit to humans and 

English language

56

limit 55 to (newborn infant <birth to 1 month> or infant <1 to 23 

months> or preschool child <2 to 5 years> or child <6 to 12 years> or 

adolescence <13 to 18 years>)

9857

57 55 not 56 4401

58 limit 57 to (adult <19 to 44 years> or middle age <45 to 64 years> or 

"aged <65 and over>" or "aged, <80 and over>") 900

59 55 not 58 13358

60

limit 59 to (addresses or bibliography or biography or comment or 

dictionary or directory or editorial or festschrift or interview or letter or 

news or periodical index)

714

61 59 not 60 12644

Limit to children

Table 2. Supplemental searches performed in 

MEDLINE®

# Search History Results Summary

1 exp growth 203509

2 exp growth disorders 16301

3 1 or 2 215194

Growth /

Growth disorders

4 exp Heart diseases 445916

5 3 and 4 9467

6 limit 5 to human, English, and children; Exclude main search results 667

Growth &

Heart diseases

7 exp Arthritis, rheumatoid 44173

8 3 and 6 184

9 limit 8 to human, English, and children; Exclude main search results 47

Growth &

Arthritis

10 exp Asthma 52692

11 2 and 8 618

12 limit 11 to human, English, and children; Exclude main search results 169

Growth &

Asthma

13 6 or 9 or 12 883 Total
231

Appendix B. Acronyms and Abbreviations

AAP American Academy of Pediatrics

ACH Achondroplasia

ADL Activities of daily living

AHRQ Agency for Healthcare Research and Quality

AIDS Acquired immunodeficiency syndrome

ARC AIDS-related complex

ARPKD Autosomal recessive polycystic kidney disease

BAER Brainstem auditory evoked responses

BAS British Ability Scales

BASC Behavior Assessment System for Children

BDI Beck Depression Inventory

BSA Body surface area

BSID Bayley Scales of Infant Development

CARA Chronic aspecific respiratory affection

CAS Cognitive abilities score

CBCL Child Behavior Checklist

CBPC Child Behavior Problem Checklist

CGD Constitutional growth delay

CHD Congenital heart disease

CHF Congestive heart failure

CHIPS Children’s Interpersonal Problem Solving Scale

CKD Chronic kidney disease

CKF Chronic kidney failure

CP Cerebral palsy

CPQ Children’s Personality Questionnaire

DDST Denver developmental screening test

Dept Department

DM Diabetes mellitus

EPC Evidence-based Practice Center

ESRD End-stage renal disease

FEV1/FVC Forced expiratory volume in 1 second divided by forced vital capacity

FRNS Focal relapsing nephrotic syndrome

FSGS Focal segmental glomerular sclerosis

FSS Familial short stature

FVC Forced vital capacity

GFR Glomerular filtration rate

GH Growth hormone

GHb Glycohemoglobin

GHD Growth hormone deficiency
232

Acronyms and Abbreviations, continued

GVI Growth velocity index

HANES Hamburg Neuroticism Extraversion Scale

Hgb Hemoglobin

Hgb A1c Hemoglobin A1c (Glycosylated hemoglobin)

HIV Human immunodeficiency virus

HRQOL Health-related quality of life

IBD Inflammatory bowel disease

IQ Intelligence quotient

ISS Isolated short stature

IUGR Intrauterine growth retardation

JLO judgment of line orientation

JRA Juvenile rheumatoid arthritis

K-BIT Kaufman-Brief Intelligence Test

KTEA Kaufman Test of Educational Achievement

LPA Little People of America

LPS Structural Intelligence Test, in German

MES Marburg Scales of Perceived Parental Behavior

MHD Multiple hormone deficiency

min Minutes

N&S Nowicki and Strickland Locus of control scale

NCHS National Center for Health Statistics

Neale Neale analysis of reading ability, British edition

NS Non-significant

OI Osteogenesis imperfecta

ORNS Occasional or no relapsing nephrotic syndrome

P CO2 Carbon dioxide partial pressure

P O2 Oxygen partial pressure

PEDI Pediatric Evaluation of Disability Inventory

PIAT Peabody Individual Achievement Test

PKD Polycystic kidney disease

PPVT-R Peabody Picture Vocabulary Test-Revised

RBQ Rutter’s Behavior Questionnaire

ROM Range of motion

RR Relative Risk

RSS Russell-Silver Syndrome

RV Residual volume

SB Stanford-Binet Intelligence Scale

SD Standard deviation

SDNS Steroid dependent nephrotic syndrome
233

Acronyms and Abbreviations, continued

SDS Standard deviation score

SEP Somatosensory evoked potentials

SES Socioeconomic status

SIT Slosson Intelligence Test

SRNS Steroid-resistant nephrotic syndrome

SSA Social Security Administration

SSTAI Spielberger State-Trait Anxiety Inventory Score

TS Turner Syndrome

UC Ulcerative colitis

VMI Visual motor integration

VSD Ventricular septal defect

WISC Wechsler Intelligence Scale for Children

WRAT Wide Range Achievement Test
235

Appendix C. Acknowledgments

The Evidence-based Practice Center staff acknowledges the collaboration of the clinical experts 

who served on the EPC Technical Expert Panel. The EPC also acknowledges the contributions 

by those who acted as peer reviewers for the evidence report.

New England Medical Center EPC Project Staff

Joseph Lau, MD; EPC/Project Director

Ethan Balk, MD, MPH, Assistant Project Director and Project Leader, Short Stature

Cynthia Cole, MD, MPH, Coordinating Team Leader

Deirdre DeVine, M Litt, Project Manager

Priscilla Chew, MPH, Project Leader, Failure to Thrive

Kimberly Miller, BA, Research Assistant

Chenchen Wang, MD, MSc, Project Leader, Low Birth Weight

Technical Expert Panel

Evidence Review Teams, Tufts New England Medical Center

Very Low Birth Weight 

Dr. Cynthia Cole, Project Coordinator and Team Leader

Drs. Geoffrey Binney, John Fiascone, James Hagadorn, and Chiwan Kim

 Patricia Casey, NNP

Short Stature

Dr. Patricia Wheeler, Team Leader

Drs. Barbara Shephard and Karen Bresnahan

Failure To Thrive

Dr. Ellen Perrin, Team Leader

Drs. Stephan Glicken, Nicholas Guerina, Kevin Petit, Robert Sege, MaryAnn Volpe, and 

Deborah Frank 

 James Perrin, MD, Pediatric Consultant to the EPC 

Social Security Administration (SSA):

Science Partner: Dr. Paul Burgan, MD, PhD; Regina Connell, MS 

Agency for Healthcare Research and Quality (AHRQ)

Marian James, PhD, Task Order Officer 
236

American Academy of Pediatrics 

Marilee Allen, MD (Very Low Birth Weight)

Professor

Neonatology, Department of Pediatrics

Johns Hopkins University 

Baltimore, Maryland

Joseph Hersh, MD (Short Stature)

Louisville, Kentucky

Michael Farrell, MD (Failure to Thrive)

Chief of Staff

Childrens’ Hospital Medical Center

Cincinnati, Ohio

Carla Herrerias, BS, MPH

Senior Health Policy Analyst

Department of Practice and Research

American Academy of Pediatrics

Elk Grove Village, Illinois

Disability Law Center, Inc.

Linda Landry, Esq.

Peer Reviewers

American Academy of Pediatrics

Very Low Birth Weight

Deborah Campbell, MD

Hartsdale, New York 

Warren N. Rosenfeld, MD

Department of Pediatrics

Winthrop University Hospital

Mineola, New York

Short Stature

Susan Rose, MD

Department of Endocrinology

Childrens’ Hospital Medical Center of Cincinnati

Cincinnati, Ohio
237

Failure to Thrive

William Cochran, MD

Department of Pediatric GI/Nutrition

Geisinger Health System

Danville, Pennsylvania

American Association of Clinical Endocrinologists

A. Jay Cohen, MD

The Endocrine Clinic, PC

Memphis, Tennessee

Lawson Wilkins Pediatric Endocrine Society

David M. Brown, MD

Professor of Pediatrics

University of Minnesota

Minneapolis, Minnesota

National Institute of Child Health and Human Development

Gilman Grave, MD

Chief, Endocrinology, Nutrition and Growth Branch 

Center for Research for Mothers and Children 

Bethesda, Maryland

Catherine Y. Spong, MD (for VLBW and Failure to Thrive)

Chief, Pregnancy and Perinatology Branch

Center for Research for Mothers and Children

Bethesda, Maryland

Tonse Raju, MD (for VLBW and Failure to Thrive)

Pregnancy and Perinatology Branch

Center for Research for Mothers and Children

Bethesda, Maryland

Society for Developmental and Behavioral Pediatrics

Denis Drotar, MD

Professor and Chief

Division of Behavioral Pediatrics and Psychology

Rainbow Babies and Childrens’ Hospital

Cleveland, Ohio

Daniel Kessler, MD

Phoenix, Arizona