Overview

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, produce an

evidence report to determine whether specific

factors or a combination of factors alone or in

addition to birth weight predict significant

developmental disability in former premature

infants and whether premature infants with such

factors have long-term developmental disabilities.

This evidence report is prepared to assist the SSA

in updating its Listing of Impairments, and revising

its disability policy, as may be appropriate. This

report does not provide or suggest a new listing of

impairments.

This report examines the evidence that Very

Low Birth Weight (VLBW) in infants (birth

weight <1,500 grams) with or without other

conditions is associated with long-term disabling

outcomes. The primary outcomes of interest

included in this report are cerebral palsy (CP),

mental retardation (MR), hearing/speech/

language/behavioral impairments, visual

impairments, adverse pulmonary function, and

disrupted growth.

The category of VLBW infants was chosen

because it is well recognized to represent a

population of infants, primarily premature infants,

at increased risk for acute and chronic

impairments related to their immaturity. VLBW is

often divided into subcategories of lower birth

weights, such as less than 1,250, less than 1,000,

and less than 750 grams, to facilitate analyses of

infants within different birth weight strata.

Extremely Low Birth Weight (ELBW) infants are

often defined as infants with birth weight less than

1000 grams, although this definition may vary

among studies by as much as 250 grams in either

direction. In general, the lower the birth weight,

the greater the degree of immaturity, and the

greater the risk for serious complications. 

Birth weight, however, is not a perfect measure

of immaturity since some infants may have birth

weights that are disproportionately large or small

for their gestational age. Many studies

appropriately and preferably use gestational age as

the marker of prematurity. Similar to birth weight,

gestational age categories of premature infants

often include groupings of premature infants less

than 32 weeks gestation, less than 30 weeks

gestation, less than 28 weeks gestation; or less than

26 weeks gestation. Less than 32 weeks gestational

age is considered by some authorities as “very

premature” and less than 28 weeks gestational age

as “extremely premature.”

Premature birth is an important public health

problem due to the number of premature births

each year, the serious acute complications of

prematurity, and the long-term sequelae directly

related to the vulnerability of VLBW infants.

Among the four million births in the United

States during the year 2000, about 58,000 (1.4%)

were VLBW (<1,500 grams). Although VLBW is

a relatively small proportion of total births in the

USA, this category of infants accounts for the

highest neonatal mortality and greatest morbidity

among newborns. The long-term complications

result in significantly increased tangible and

intangible lifelong costs to the family and society

for medical care as well as for ongoing ancillary

health and educational services.

Advances in neonatal/perinatal medicine have

improved the survival and the quality of survival

Evidence Report/Technology Assessment

Number 70

Criteria for Determining Disability in Infants and

Children: Low Birth Weight

Summary

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service

Agency for Healthcare Research and Quality
of premature infants. Despite advances in medical care, infants

born prematurely experience a disruption in the normal process

of growth and development. The degree of disruption in the

growth and development of each organ system is a reflection of

the degree of immaturity and physiologic derangement.

Survival is inversely proportional to the degree of prematurity.

Recent evidence indicates that approximately 95 percent of

infants with birth weights between 1,251 and 1,500 grams

survive in contrast to approximately 75 percent of infants with

birth weight less than 1,250 grams. For any adverse sequela

associated with premature birth, the incidence as well as the

severity of the complication is inversely proportional to the

gestational age. For instance, 12 percent of infants with birth

weight between 1,251 and 1,500 grams survived with at least

one major morbidity in contrast to 53 percent with birth

weight 501 to 1,250 grams.

Surviving premature infants often sustain multi-organ system

complications that may persist beyond the first few years of life

and frequently result in permanent impairments. Examples

include major neurodevelopmental impairments, such as CP,

MR, deafness and disorders of speech/language/

communication; perception, attention, behavior and learning

disorders; blindness or other visual impairments; chronic lung

disease; and growth retardation. Complications of even a single

organ system may have a profound impact upon other organ

systems. Biomedical determinants of disability in premature

infants are often compounded by adverse determinants of social

and psychological adaptation of these vulnerable children and

their families.

Reporting the Evidence

Key questions of interest

This review addresses the following key questions of interest

to SSA.

For infants with birth weight <1,200 grams and for infants

with birth weights between 1,200 grams and 1,500 grams:

1. What factors or combination of factors alone or in

addition to birth weight will predict significant

developmental impairment in former premature infants? 

2. Are such infants developmentally impaired at 1 year, 2

years, or beyond?

In order to identify the functional or physical outcomes

related to disability and the elements that predicted them, we

sought evidence that a specific factor was significantly

associated with a specific disability (e.g., very low birth weight

infants with bronchopulmonary dysplasia [BPD] have lower

receptive language scores; or the degree of immaturity

influences the risk of CP and neurodevelopmental disability in

VLBW infants). We looked for evidence of association of

VLBW with six outcome conditions: 

• CP and neurological impairments

• Abnormal cognitive development and MR

• Speech/language delay, hearing loss, behavioral disorders,

and learning disabilities

• Visual impairment (with or without other conditions)

• Pulmonary impairment (with or without other

conditions)

• Growth impairment

Methods

A systematic literature search was performed for journal

articles with original data. English language studies were

identified primarily through MEDLINE® searches conducted

between October 2000 and February 2001. We performed an

updated search in September 2001 and again in January 2002.

Supplemental searches were also performed in ERIC,

PsychINFO, HealthSTAR and E<BASE. Additional studies

were identified from reference lists, review and primary articles,

and from domain experts and reviewers.

Disability is not a specific medical condition that can be

readily searched for. Thus we had to look at many studies with

related concepts (i.e., medically definable impairments that are

related to disability) to identify potentially relevant studies.

Therefore, we developed a comprehensive list of predictors and

outcomes by organ system and those that are associated with

VLBW infants. The predictor and outcomes then formed the

basis of literature search terms.

We focused the literature review primarily on premature

infants born weighing less than 1,500 grams, including all

subcategories of birth weights (e.g., less than 1,250 grams, less

than 1,000 grams, and less than 750 grams). We also

incorporated literature that included infants with birth weight

less than 1,500 grams within a larger premature cohort and

literature on infants whose prematurity was defined by

gestational age, since many studies use gestational age and not

birth weight criteria.

We reviewed retrospective and prospective studies reporting

impairments in infants or children who weighed 2,000 grams

or less, whose gestational age was 35 weeks or less, or whose

birth weight or gestational age were below these thresholds.

Longitudinal data for a minimum of 6 months was preferred.

We identified and screened 16,614 abstracts from the

literature searches. These abstracts covered 13 categories: central

nervous system (2,930 abstracts), opthalmology (398),

audiology (80), pulmonary (1,833), nutrition and growth

(2,533), medication (dexamethasone) (183), perinatal factors

(875), illness acuity (56), infectious diseases (2,378),

gastrointestinal (477), bone/osteomalacia (10), health care

(466), and immune disorder (921). Approximately 1,693

potentially relevant articles were retrieved after screening the

abstracts.

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The very large number of articles precluded all of them from

being incorporated into the evidence report. We used the

following method to reduce the articles to a feasible number

and include the most relevant. We screened in articles that met

the minimum inclusion criteria for LBW, reported one or more

relevant clinical outcomes, had a followup duration greater than

or equal to 6 months, a study size greater than 10, and enrolled

patients born after 1980. We then established a hierarchy of

studies based on study size and birth year of the infants. Studies

with birth years from 1990 onward were given preference,

followed by studies with birth years between 1985 and 1989,

and then studies before 1985. Within each birth year cohort,

studies with more than 100 infants were selected first, followed

by studies with 50 to 100 infants and less than 50 infants.

Using this classification hierarchy, we worked through the most

relevant (recent) and strongest (largest study size) studies in

succession before older and smaller studies, until a complement

of 178 articles were reviewed.

We report the evidence organized by the six outcome

conditions listed under the key questions. We summarized the

evidence in three complementary forms. The evidence tables

provide detailed information about the features of study design

and results of all the studies reviewed. A narrative and a tabular

summary of the strength and quality of the evidence of each

study are provided for each outcome condition. The summary

tables describe the strength of the evidence according to four

dimensions: study size, applicability of the study population,

association of the factor of interest with impairments, and the

methodological quality of the study.

Findings

Evidence that VLBW With or Without Other

Conditions is Associated With Cerebral Palsy

(CP) and Neurologic Disability

The literature overwhelmingly supports evidence that the

risk of CP and major neurologic disability is increased among

VLBW infants compared to full-term infants. The literature is

consistent in demonstrating that risk of CP, major neurosensory

and/or neurologic disability is inversely proportional to the

degree of immaturity whether measured by gestational age or

by birth weight. The recently reported incidence of CP is

currently stable compared to the 1980s (7-10 percent VLBW

infants; 7-17 percent ELBW infants) or modestly decreased

despite improved survival of extremely immature infants. This

suggests that recent advances in neonatal care have had either

no or modest effect on further reduction in the incidence of

CP. Several studies demonstrated that the risk of major

neurosensory or neurologic disability may range from 12-50

percent among VLBW and ELBW infants. Despite the stable

risk of CP, the risk of disability, due primarily to visual

disabilities, has increased since the 1980s. Differences among

studies regarding the incidence of CP, neurologic, and

neurosensory disability may be accounted for by differences in

the criteria for neurologic/neurosensory disability, the era of

study, the degree of immaturity, and other characteristics or risk

factors of the patient population, neonatal care practices, as well

as length and completeness of followup.

Several articles in this review provide compelling evidence

that cerebral white matter damage (WMD), as manifested by

periventricular leukomalacia (PVL) (such as echodensities and

echolucencies), ventriculomegaly, posthemorrhagic cerebral

infarct, and severe intracranial hemorrhage are among the

strongest predictors of CP and other neurologic disabilities in

VLBW infants. Visual and ocular abnormalities are often

associated with neurodevelopmental abnormalities in VLBW

infants with cerebral white matter damage. The degree of visual

impairment correlates with the degree of neurodevelopmental

impairment. 

Increasing evidence indicates that antenatal events contribute

to the etiology and sequence of events leading to neurologic

impairment and CP in VLBW infants. Antenatal

inflammation, chorioamnionitis, subclinical infection, fetal

hypoxia/acidosis, and premature rupture of membranes (which

may be related to antenatal inflammation and infection) and

abruption appear to play an important role via stimulating a

fetal inflammatory response that injures the immature cerebral

white matter. 

Several studies documented that prolonged mechanical

ventilation and BPD are associated with increased adverse

neurodevelopmental outcome in premature infants compared

to infants without BPD or prolonged mechanical ventilation.

In addition, there is increasing evidence that the use of

postnatal systemic glucocorticoid therapy (specifically,

dexamethasone) for the prevention or treatment of neonatal

chronic lung disease may have an adverse effect on long-term

neurologic development and increase the risk of CP. The

evidence supports that BPD and systemic dexamethasone each

may be separate factors influencing the risk of CP and

neurologic impairment in VLBW infants. 

Studies also illustrate that VLBW infants with parenting,

social, and environmental risk factors are at increased risk for

neurodevelopmental disabilities. The relationship between

biological-medical risk factors and parenting-psychosocial risk

factors on subsequent neurodevelopmental outcome is

complex. The interaction of these factors may have synergistic

effects on an infant’s outcome. 

Evidence that VLBW With or Without Other

Conditions is Associated With Abnormal

Cognitive Development and Mental

Retardation (MR)

The evidence demonstrates that children who were born

VLBW have significantly higher rates of cognitive abnormality

in early childhood and a several-fold increased prevalence of IQ

<70 as adults compared with children or adults who were born

normal birth weight at term. Given current rates of birth and

3
VLBW in the USA, these results suggest that there may be

more than 3,500 new cases of MR in the United States each

year in former VLBW infants. There is evidence that even

children who were apparently “well” VLBW infants during

their neonatal course are also at significantly greater risk for

both moderate and severe delay compared to larger-birthweight groups.

Among children born as ELBW infants, the prevalence of

MR is even higher than in VLBW infants, who are larger than

ELBW infants. Approximately 40 percent of ELBW survivors

have Bayley Mental Development Index (MDI) <70, half of

ELBW survivors have at least one significant

neurodevelopmental impairment, and 20-35 percent of ELBW

survivors have two or more impairments. Evidence suggests

that the incidence of MR in ELBW infants is not changing

with time, despite recent increases in survival rates in this birth

weight category. Our search methods identified evidence that

birth weight is a useful factor in identifying VLBW infants at

especially high risk for MR. However, once the range of birth

weight and gestational age are narrowed to the most immature

infants, and stronger predictors of neurodevelopmental

outcome are taken into consideration, the evidence that birth

weight or gestational age is useful in identifying VLBW infants

at high risk for MR was mixed. 

Intraventricular hemorrhage (IVH), particularly severe (i.e.,

grade III or IV) IVH, PVL, and ventriculomegaly are also

among the strongest independent predictors of cognitive

impairment and MR in VLBW and ELBW infants. Infants

with a combined outcome IVH ≥ grade III or PVL are more

than twice as likely to have Bayley MDI <70 as those without

these findings, after adjusting for the effect of other clinical

factors. 

Recent studies strongly document a significant independent

relationship between BPD and abnormal neurodevelopment in

both VLBW and ELBW infants. This effect of BPD on long

term outcome is independent from the many co-morbid

conditions commonly seen concurrently in VLBW infants,

such as intraventricular hemorrhage, posthemorrhagic

hydrocephalus and periventicular leukomalacia. Evidence

strongly indicates that postnatal systemic steroid therapy

(dexamethasone) for the amelioration or prevention of BPD is

an independent determinant of abnormal cognitive

development in ELBW infants after adjusting for clinical

factors and associated with almost two-fold increased risk of

Bayley MDI <70. 

Our search methods identified many strong studies

documenting a significant independent association between

parenting-pychosocial risk factors and cognitive development in

VLBW infants even after accounting for the effects of

intraventricular hemorrhage and chronic lung disease. Methods

used to measure social risk are numerous, however, and the

identified evidence in the literature is not always sufficient to

distinguish the independent effects of various commonly

examined elements of social risk, such as race, economic status,

or level of maternal education. The quality of parent-infant

interactions may play an important role in cognitive

development of VLBW infants. The variability among studies

with respect to the association of parenting-pyschosocial risk

and cognitive outcome may be accounted for by differences

among studies with respect to population characteristics,

sample size, age of assessment, ascertainment of other potential

confounding factors, accuracy of methods/measures used to

determine social risk, parenting risk, and other socioeconomic

markers.

The identified evidence suggests that race may be an

independent predictor of cognitive development in VLBW

infants with black race among the social risk factors associated

with an approximately 50 percent increased risk of subnormal

Bayley MDI. 

The level of maternal education was identified as a

significant independent predictor of abnormal cognitive

development in VLBW and ELBW infants. One

methodologically strong study found that maternal education

less than high school graduate level increased risk of Bayley

MDI <70 almost two-fold. 

The identified evidence suggests that gender may be a

significant independent predictor of MR among ELBW

infants, but this relationship may be less significant in larger

birth weight categories. 

Evidence suggests that illness severity scoring systems may be

useful in identifying infants at risk for MR. Durations of

various therapies such as mechanical ventilation, intravenous

nutrition, etc. are markers of illness severity and may be tested

as independent predictors of outcome. 

The evidence identified by our search methods was equivocal

regarding the utility of antepartum and intrapartum factors as

independent predictors of MR. Strong studies suggested that

specific antepartum factors (e.g., use of antenatal steroids,

maternal hypertension, route of delivery, or inborn versus

outborn) do not provide a useful contribution to prediction of

MR in ELBW infants after accounting for other clinical factors. 

The identified evidence regarding intrauterine growth

retardation/small for gestational age (IUGR/SGA) as an

independent risk factor for MR was equivocal. One study

documented worse cognitive development in children who

were SGA VLBW infants compared with appropriate

gestational age (AGA) VLBW infants. Other studies that found

that SGA ELBW infants were not at increased risk for cognitive

delay compared with their AGA peers after adjusting for other

clinical factors. 

Our methods located no studies examining the relationship

between necrotizing enterocolitis (NEC) and subsequent

cognitive development in VLBW infants.

4
Our search methods identified studies that examined the

relationship between sepsis or meningitis and subsequent

cognitive development in VLBW infants. Two studies found

that neither sepsis nor meningitis was associated with cognitive

outcome in ELBW infants after adjusting for other clinical

factors. 

Evidence that VLBW is Associated With

Speech/Language Delay, Hearing Loss,

Behavioral Disorders, and Learning

Disabilities

VLBW infants are at high risk for developing cognitive,

neuromotor, and neurosensory disabilities including blindness

and hearing loss. These disabilities in turn may lead to other

disabilities in speech and language, behavior problems, and

learning disabilities affecting school performance. All of the

above problems have been identified in disproportionate

numbers in the VLBW infants.

The studies provided strong evidence of increased incidence

of speech and language delays in VLBW and extremely

premature infants, and identified clinical factors associated with

the increased incidence. One study emphasized higher

prevalence of functional limitations in most language domains

with children who were born ELBW. Children who were

ELBW have a higher utilization rate of speech therapists and

require more educational and health care services. Across all

measures of short-term memory and language outcomes,

preschool children who were born preterm performed at a

lower level than children who were full-term counterparts.

These deficits were independent of the general IQ. 

In overall communication skills, children who had BPD as

preterm neonates scored significantly lower than the other

comparison non-BPD groups. Even after controlling for lower

IQ, children who were VLBW infants with BPD have lower

receptive language scores. 

Data on the incidence of hearing loss in ELBW infants is

conflicting. Four excellent, recent studies report higher

incidence ranging from 9 to 14 percent and nine studies report

rates (~1-2 percent) similar to their full-term controls. This

variability may be due to differences in testing methods. 

There is good evidence that VLBW infants have increased

attention problems and more passive temperament. Intracranial

lesions, CP, impaired cognition, and urban socioeconomic

setting was associated with the increased incidence.

Available evidence suggests that VLBW and ELBW infants

are at higher risk for developing learning disabilities and have

difficulty in school. Studies of school learning problems at 6

years may be too early and may miss children with less grossly

obvious difficulties. 

One study provided evidence that even seemingly “healthy”

premature infants may have later sequelae needing special

assistance. The well-preterm group, compared to full-term

controls, had significantly higher than expected incidence of

minimal brain dysfunction including attention deficit disorder,

learning disabilities, language impairment, mild neurologic

impairment, and general school concerns. In fact, only 25

percent had no concerns by grade 5 compared to 57 percent in

term controls. The mother’s perception of their infants’

competence was a sensitive marker for disabilities. 

Evidence that VLBW With or Without Other

Conditions is Associated With Visual Disability

The evidence identified by this review clearly demonstrates

that children born as VLBW, with or without retinopathy of

prematurity (ROP), are at significantly increased risk of visual

impairments and disability compared to children born full

term. The risk of visual disability in VLBW infants varies

inversely with gestational age. The risk of having any

ophthalmic morbidity (e.g., significant reduction in visual

acuity tests or presence of strabismus, myopia, color vision

defect, or visual field defect) is two-fold greater in children born

VLBW infants and five-fold greater in children born ELBW

compared to children born at term. Ophthalmic morbidity

(i.e., greatest reduction in visual acuity or incidence of

strabismus, myopia, etc.) is highest in eyes with severe (Stage 3

or 4) ROP. No or regressed mild ROP, by itself, has no major

important long-term effect on visual acuity, although children

born prematurely with no or regressed mild ROP may have

statistically significantly reduced visual acuities compared with

full-term controls. 

The risk of blindness is higher in ELBW infants compared

to normal birth weight controls and is inversely related to birth

weight or gestational age. The reported incidence of blindness

in ELBW infants, the population at greatest risk for visual

disability, ranges from 1 to 4 percent in most studies identified

in this review. 

Retinal ablation with cryotherapy or laser therapy for severe

(i.e., threshold) ROP significantly reduces the incidence of

blindness and unfavorable outcome, especially in Zone 2

threshold eyes. Despite this benefit, infants successfully treated

with cryotherapy still had an unacceptably high risk of

unfavorable functional outcome (44.4 percent of treated eyes).

Unfavorable outcome was particularly true in eyes with Zone 1

(posterior pole) threshold ROP regardless of whether or not the

eye received cryotherapy (i.e., poor outcome in 75 percent of

Zone 1 treated eyes and 92 percent of not treated eyes).

Unfavorable outcome of successfully treated eyes is most likely

a reflection of the severity of the underlying retinal injury and

of the disruption in normal growth and development of the

retina. Retinal ablative therapy (cryotherapy or laser therapy)

for threshold ROP is cost effective therapy that can improve the

quality of life. Laser therapy can reduce the risk and/or severity

of myopia, which is a major complication of premature infants,

especially in premature infants with severe ROP. Any reduction

in myopia is important in terms of long-term visual benefit.

5
A 10-year followup of premature infants with threshold

ROP revealed that the rate of retinal detachment among

control (no cryotherapy) threshold eyes increased at 5.5 years

(38.6 percent) and again at 10 years of age (41.4 percent), after

having been “stable” during the first 3 years of followup. The

rate of retinal detachment remained stable in treated eyes (22.0

percent). Eyes with severe ROP and not treated, have smaller

visual fields compared to eyes that never had ROP. Eyes treated

with cryotherapy had a further reduction in the visual fields. At

the 10-year outcome, treated and control threshold eyes are

equally likely to have 20/40 visual acuity, but this is the

minority of threshold eyes.

VLBW infants are also at increased risk for non-retinal

ophthalmic diseases. Cortical visual impairment is visual

impairment due to central nervous system (CNS) damage.

Causes of cortical visual impairment in VLBW infants include

hypoxic-ischemic-hemorrhagic and /or inflammatory injury

(antenatal, perinatal, or postnatal) which may be manifested in

the neonatal period as periventricular leukomalacia,

ventriculomegaly, intracranial hemorrhage, and

posthemorrhagic hydrocephalus. Neuroimaging of VLBW

infants via cranial ultrasonography, cranial tomography, and

magnetic resonance imaging (MRI) techniques has provided

strong evidence that central nervous system injury, especially

periventricular leukomalacia, is associated with visual disability

and other neurodevelopmental abnormalities, including motor

and perceptual abnormalities. The strong association of visual

impairment with the extent of MRI evidence of cerebral white

matter damage and the concomitant occurrence of

neurodevelopmental disability in premature infants is well

documented. 

One study demonstrated that even healthy preterm children

with no detectable neurodevelopmental problems on screening

examinations, have evidence of visual-motor disabilities when

these functions are specifically tested.

There is long-standing evidence that the risk and degree of

myopia increases with the degree of prematurity, degree of ROP

severity, and with central nervous system injury. Myopia is the

most common ophthalmic sequela of premature infants and

requires optical correction. Other adverse ophthalmic

outcomes, such as astigmatism and anisometropia, were highly

correlated with severe myopia. Studies clearly illustrate the

significant and independent contributions of prematurity, ROP,

and central nervous system injury in the development of visual

disability in terms of myopia and strabismus.

There is a strong positive association between the occurrence

of strabismus and the degree of prematurity, the severity of

ROP, abnormal cranial ultrasounds, and neurodevelopmental

abnormality, especially CP. The presence of strabismus and

nystagmus implies a central nervous system component or

insult, which may or may not be independent of ROP. The

ocular misalignments may result from CNS injury and/or as a

direct result of retinal disease (e.g., ROP) and its treatment.

Strabismus may continue to increase in frequency through

second year. Among children with Grade III or IV IVH, 100

percent had strabismus (esotropia).

Ophthalmic examinations revealed that premature infants

with BPD and no detectable severe neonatal neurological

abnormalities and no ROP > Stage 2 had greater incidence of

strabismus and high refractive error and poorer recognition

acuity compared to premature infants with hyaline membrane

disease but no BPD and healthy preterm infants. Extremely

premature infants treated with systemic dexamethasone therapy

for BPD had significantly higher rates of blindness in addition

to significantly higher rates of CP and lower intelligence

quotients. Extreme prematurity, brain injury, ROP, BPD, and

glucocorticoid therapy individually and/or collectively have an

impact on visual disability.

Children who had ROP are at even greater risk for longterm ophthalmic sequelae in terms of anatomic and functional

problems, and thus need close ophthalmic evaluation and

interventions. The frequency of procedures to correct visual

disability increases with severity of ROP. Long-term costs of

both extreme prematurity and ROP include not only the initial

ablative therapy for ROP and individual/family/societal loss

due to vision impairment and blindness, but ongoing costs of

caring for eye problems in children who were VLBW. Expenses

include doctor’s office visits, time lost from work, eyeglasses,

surgery, and special education.

Evidence that VLBW With or Without Other

Conditions is Associated With Pulmonary

Disability

The studies reviewed indicate that VLBW infants with

bronchopulmonary dysplasia (BPD) are at increased risk for

long-term pulmonary disability. The greater the severity of

BPD, the greater the association with long-term pulmonary

impairment and need for re-hospitalization. Children who were

VLBW infants who had no BPD have comparable pulmonary

outcome to children who were born full term. Children who

were VLBW with more severe BPD may have persistent lung

disease during young childhood and continuing through to

their adolescent, and young adult years. Findings in five studies

indicate that BPD at 36 weeks corrected gestational age is

predictive of longer-term pulmonary disability through at least

1-2 years of age.

Preterm children with BPD have an increase in multiple

measures of pulmonary disability. The most frequently

described consequences of pulmonary disability are increased

respiratory symptoms and respiratory illnesses, the need for

respiratory medications, and re-admission to the hospital for

other medical and surgical reasons. Respiratory illnesses

frequently documented in children who had BPD include

chronic lung disease, recurrent bronchitis and pneumonia,

increased airway responsiveness and asthma. Asthma or

6
bronchial responsiveness actually appears to be increased in

VLBW premature children who did or did not have BDP. 

Rehospitalization of former VLBW infants is unfortunately a

common event especially during the first 2 years of life and is

even higher among VLBW infants with BPD. Most

hospitalizations are for respiratory conditions or failure to

thrive. 

Evidence that VLBW With or Without Other

Conditions is Associated With Growth

Impairment

VLBW infants, with or without other conditions, are at high

risk for poor growth during the first years of life due to acute

neonatal illnesses, developmental delays, and chronic illnesses

(e.g., BPD, gastroesophageal reflux, short-gut syndrome).

Understandably, the degree of prematurity and severity of the

illness/hospital course have great impact and influence growth.

Attaining appropriate growth and nutrition in VLBW infants

continues to be a challenge during the initial hospitalization

and after discharge from the neonatal unit. Long-term studies

demonstrated definitive problems with postnatal growth. There

is evidence that the weight and height of VLBW infants is

significantly behind that of normal birth weight infants

through 14 years of age, although the differences become less

over time.

It is well documented that VLBW infants with BPD are

smaller and have difficulty gaining weight while in the neonatal

intensive care unit. Recurrent illness and pulmonary

exacerbations of BPD, increased metabolic needs and

inadequate nutrient intakes all contribute to compromise

growth in VLBW infants with BPD. BPD infants with home

oxygen therapy had a three-fold increase in rehospitalization for

failure to thrive. The primary reasons for failure to thrive in the

BPD patients were related to poor feeding and gastroesophageal

reflux.

Future Research

We propose two prospective health service research

opportunities. The first proposal, “Evaluation of the

Application Process of SSA VLBW Disability Criteria,” involves

documentation of baseline risk factor data on all VLBW infants

born within participating regions, following surviving VLBW

infants over pre-specified time with respect to pre-specified

disabilities, documenting the proportion of VLBW who come

to the attention of SSA, relative to the entire regional cohort of

VLBW infants, and identifying barriers to referring infants to

SSA. This research proposal would help SSA assess the

application of SSA VLBW Disability Criteria. This would, in

turn, provide greater insight into reasons for successful

programmatic implementation and impediments of applying

the criteria. It would provide insight regarding the effectiveness

of identifying high-risk VLBW infants.

The second proposal, “Determining the Appropriateness of

the New VLBW Disability Criteria” proposed by SSA based on

the evidence of this report, is a natural next step linked to the

first research concept. The combination of these two concepts

affords the SSA the ability to know if the process and the

criteria are achieving the objectives established by the SSA. 

Refinement of predictors of disability or identification of

new predictors, and development of a robust, well-designed,

and carefully validated predictive models to be used at the time

of hospital discharge could create a “profile” of a VLBW infant

at risk for specific disabilities. A series of models predictive of

longer-term outcome could be developed and validated to

incorporate new factors and information noted during specified

times of followup. Refinement of risk factors invites a

systematic, collaborative effort to develop a series of predictive

models using large regional cohorts of VLBW infants, followed

by validation of the model in an independent group.

Availability of the Full Report

The full evidence report from which this summary was taken

was prepared for the Agency for Healthcare Research and

Quality (AHRQ) by Tufts New England Medical Center

Evidence-base Practice Center (EPC), Boston, MA, under

Contract No. 290-97-0019. It is expected to be available in

the winter 2003. At that time, printed copies maybe obtained

free of charge from the AHRQ Publications Clearinghouse by

calling 800-358-9295. Requesters should ask for Evidence

Report/Technology Assessment No. 70, Criteria for

Determining Disability in Infants and Children: Low Birth

Weight. In addition, Internet users will be able to access the

report and this summary online through AHRQ’s Web site at

www.ahrq.gov.

7
www.ahrq.gov

AHRQ Pub. No. 03-E008

December 2002

ISSN 1530-440X