## Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention

Report of the

Advisory Committee on Childhood Lead Poisoning Prevention

of the Centers for Disease Control and Prevention

January 4, 2012

Disclaimer This document was solely produced by the Advisory Committee for Childhood Lead Poisoning Prevention. The posting of this document to our website in no way authorizes approval or adoption of the recommendations by CDC. Following the committee vote on January 4, 2012 to approve these recommendations, HHS and CDC will begin an internal review process to determine whether to accept all or some of the recommendations and how to implement any accepted recommendations.ii 

### TABLE OF CONTENTS Abbreviations

...................................................................................................................... iii ACCLPP and Blood Lead Level Work Group Rosters

........................................................... iv Executive Summary

............................................................................................................ ix Introduction

......................................................................................................................... 1 I. Scientific Rationale for Eliminating the CDC’s 10 g/dL Blood Lead Level of Concern

.... 3 II. Putting Primary Prevention First

................................................................................... 16 III. Health Management for Primary Prevention of Lead Exposure

.................................. 18 IV. Achieving Lead-Safe Housing

........................................................................................ 32 V. Environmental Interventions

......................................................................................... 39 VI. Research Needs

............................................................................................................ 44 VII. References

................................................................................................................... 49iii 

### Abbreviations

AAP

– American Academy of Pediatrics ACCLPP

– Advisory Committee on Childhood Lead Poisoning Prevention BLL

– Blood Lead Level CDC

– Centers for Disease Control and Prevention NHANES

–

National Health and Nutrition Examination Survey RRP

-- Renovation, Repair and Painting Ruleiv 

### ACCLPP and Blood Lead Level Work Group Rosters

ACCLPP Roster, 2011-2012

Chair George G. Rhoads, MD, MPH School of Public Health, Associate Dean University of Medicine and Dentistry of New Jersey Piscataway, New Jersey

Designated Federal Official Mary Jean Brown, ScD, RN Centers for Disease Control and Prevention, Branch Chief National Center for Environmental Health Lead Poisoning Prevention Branch Atlanta, Georgia

Deborah A. Cory-Slechta, PhD University of Rochester School of Medicine, Professor Department of Environmental Medicine Rochester, New York

Kim Dietrich, PhD, MA School of Environmental Health, Professor University of Cincinnati Cincinnati, Ohio

Sher Lynn Gardner, MD, FAAP Department of Pediatrics, Assistant Professor Emory University Atlanta, Georgia

Perry Gottesfeld, MPH Occupational Knowledge International, Executive Director San Francisco, CA

Kimberly Hansen, MD Pediatric Medical Director Peoples Community Health Clinic Waterloo, Iowav

ACCLPP Roster (continued)

Michael Kosnett, MD, MPH Medical Toxicologist University of Colorado Health Sciences Center Denver, Colorado

David McCormick Indiana Lead and Healthy Homes Program, Director Indiana State Department of Health Indianapolis, Indiana

Elizabeth McKee-Huger Greensboro Housing Coalition, Executive Director Greensboro, North Carolina

Patrick Parsons PhD Division of Environmental Disease Prevention, Deputy Director Laboratory of Inorganic and Nuclear Chemistry, Chief New York State Department of Health Albany, New York

Brenda Reyes, MD, MPH Community and Children's Environmental Health Bureau, Chief City of Houston Health and Human Services Houston, Texas

Megan Sandel, MD, MPH Assistant Professor of Pediatrics Boston Medical Center Boston, Massachusetts

Dana Williams Parent Decatur, Georgiavi



### ACCLPP Blood Lead Level Work Group Roster 2011- 2012

Co -Chairs

Deborah A. Cory-Slechta, PhD, Co-Chair University of Rochester School of Medicine, Professor Department of Environmental Medicine Rochester, New York

Perry Gottesfeld, MPH, Co-Chair Occupational Knowledge International, Executive Director San Francisco, CA

Members

Walter Alarcon MD , MSc Senior Service Fellow National institute for Occupational Safety & Health (CDC) Cincinnati, Ohio

David Bellinger PhD Children's Hospital 300 Longwood Avenue Boston, Massachusetts

Elizabeth Colon Director of Training & Outreach Childhood Lead Action Project, Director Providence, Rhode Island

Kim N. Dietrich, PhD, MA Professor of Environmental Health The University of Cincinnati College of Medicine Cincinnati, Ohiovii

BLL Workgroup Roster (continued)

Kimberly Hansen, MD Pediatric Medical Director Peoples Community Health Clinic Waterloo, Iowa

Jeff Havlena Wisconsin Childhood Lead Poisoning Prevention Program Department of Health Services (DHS) Madison, Wisconsin

Linda Kite Executive Director Healthy Homes Collaborative Los Angeles, California

Jane Malone National Center for Healthy Housing, Policy Director Columbia, Maryland

David McCormick Indiana Childhood Lead Poisoning, Director Indiana State Department of Health Indianapolis, Indiana

Kimberly Neumann, MD Pediatric Medical Director Peoples Community Health Clinic Waterloo, Iowa

Walter Rogan, MD Epidemiology Branch National Institute of Environmental Health Science Research Triangle Park, North Carolinaviii

BLL Workgroup Roster (continued)

Anne Wengrovitz Healthy Housing Solution Arlington, Virginia

CDC Staff Members

Mary Jean Brown ScD, RN Centers for Disease Control and Prevention, Branch Chief National Center for Environmental Health Lead Poisoning Prevention Branch Atlanta, Georgia

Tiffany Turner PhD Healthy Homes/Lead Poisoning Prevention Branch Centers for Disease Control & Prevention, National Center for Environmental Health Atlanta, Georgiaix 

### Executive Summary

Based on a growing body of studies concluding that blood lead levels (BLLs) <10 μg/dL harm

children, the Centers for Disease Control and Prevention (CDC) Advisory Committee on Childhood

Lead Poisoning Prevention (ACCLPP) recommends elimination of the use of the term “blood lead level

of concern”. This recommendation is based on the weight of evidence that includes studies with a

large number and diverse group of children with low BLLs and associated IQ deficits. Effects at BLLs <

10 μg/dL are also reported for other behavioral domains, particularly attention -related behaviors and

academic achievement. New findings suggest that the adverse health effects of BLLs less than 10

μg/dL in children extend beyond cognitive function to include cardiovascular, immunological, and

endocrine effects. Additionally, such effects do not appear to be confined to lower socioeconomic

status populations. Therefore, the absence of an identified BLL without deleterious effects combined

with the evidence that these effects, in the absence of other interventions, appear to be irreversible,

underscores the critical importance of primary prevention.

Primary prevention is a strategy that emphasizes the prevention of lead exposure, rather than

a response to exposure after it has taken place. Primary prevention is necessary because the effects

of lead appear to be irreversible. In the U.S., this strategy will largely require that children not live in

older housing with lead-based paint hazards. Screening children for elevated BLLs and dealing with

their housing only when their BLL is already elevated should no longer be acceptable practice.

The purpose of this report is to recommend to the CDC how to shift priorities to implement

primary prevention strategies and how to best provide guidance to respond to children with BLLs <10

μg/dL. This report also makes recommendations to other local, state and federal agencies, and thex

ACCLPP recommends that CDC work cooperatively with these other stakeholders to provide advice

and guidance on the suggested actions.

This report recommends that a reference value based on the 97.5 th percentile of the NHANESgenerated BLL distribution in children 1- 5 years old (currently 5 μg/dL) be used to identify children

with elevated BLL. There are approximately 450,000 U.S. children with BLLs above this cut-off value

that should trigger lead education, environmental investigations, and additional medical monitoring.

In the pediatric primary care office, primary prevention must start with counseling

– even

prenatally when possible. This includes recommending environmental assessments for children

PRIOR to screening BLLs in children at risk for lead exposure. After confirmatory testing, children at

or above the reference value of 5 μg/dL must undergo ongoing monitoring of BLLs

. These children

should also be assessed for iron deficiency and general nutrition ( e.g. calcium and vitamin C levels),

consistent with American Academy of Pediatrics ( AAP ) guidelines. Iron-deficient children should be

provided with iron supplements. All BLL test results should be communicated to families in a timely

and appropriate manner. Children with elevated BLLs will need to be followed over time until the

environmental investigations and subsequent responses are complete.

Despite significant progress in reducing geometric mean BLLs in recent decades, racial and

income disparities persist. These observed differences can be traced to differences in housing quality,

environmental conditions, nutrition, and other factors. The goal of primary prevention is to ensure

that all homes become lead-safe and do not contribute to childhood lead exposure. Prevention

requires that we reduce environmental exposures from soil, dust, paint and water, before children

are exposed to these hazards. Efforts to increase awareness of lead hazards and ameliorative

nutritional interventions are also key components of a successful prevention policy.xi

Historical information on where children with elevated BLLs reside, and other housing data

can be used to direct resources for environmental testing and evaluation to homes where lead

hazards are more likely to be found. Because lead-based paint hazards are the primary source of

childhood exposure to lead in the U.S, and because lead-paint is present in one- third of the nation’s

dwellings, additional investment is needed to reduce lead hazards in older homes. Housing policies to

protect children against lead exposure must target the highest risk properties for priority action,

ensure that lead-safe practices are followed during renovation, repair and painting of pre-1978

homes, and to prohibit lead-based paint hazards, including deteriorated paint, in pre-1978 homes.

Local and state government must facilitate data-sharing between health and housing

agencies, enact and enforce preventive lead-safe housing standards for rental and owner-occupied

housing, help identify financing for lead hazard remediation, and provide families with the

information needed to protect their children from hazards in the home.

Additional research is needed to develop and evaluate interventions that effectively maintain

BLLs below the reference value in children who reside in pre-1978 housing. Other research priorities

should include efforts to improve the use of data from screening programs, develop next-generation

point- of -care lead analyzers, and improve the understanding of epigenetic mechanisms of lead

action.1 

### Introduction 1 2 The Lead Contamination Control Act of 1988 authorized the Centers for Disease Control and 3

Prevention (CDC) to initiate efforts to eliminate childhood lead poisoning in the U.S. As a result, the 4

CDC Childhood Lead Poisoning Prevention Program was created, with primary responsibility to: 1) 5

develop programs and policies to prevent childhood lead poisoning; 2) educate the public and health6

care providers about childhood lead poisoning; 3) provide funding to state and local health 7

departments to determine the extent of childhood lead poisoning by screening children for elevated 8

blood lead levels (BLLs), helping to ensure that lead-poisoned infants and children receive medical 9

and environmental follow-up and developing neighborhood-based efforts to prevent childhood lead 10

poisoning; and 4) support research to determine the effectiveness of prevention efforts at federal, 11

state, and local levels. 12

Furthermore, CDCs Healthy People 2010 initiative set forth as one of its 10-year goals the 13

elimination of childhood lead poisoning. Therefore, CDC, the Department of Housing and Urban 14

Development, the Environmental Protection Agency, and other agencies have developed a federal 15

interagency strategy to achieve this goal by 2010. The key elements of this interagency strategy 16

include: identification and control of lead paint hazards, identification and care for children with 17

elevated blood lead levels, surveillance of elevated BLLs in children to monitor progress; and research 18

to further improve childhood lead poisoning prevention methods. 19

Advisory Committee On Childhood Lead Poisoning Prevention (ACCLPP) 20

The Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP) was established by 21

the CDC to advise and guide the CDC regarding new scientific knowledge and technical advances and 22

their practical implications for childhood lead poisoning prevention efforts. The overall goal of the 23

ACCLPP is to provide advice that will assist the nation in reducing the incidence and prevalence of 242

childhood lead poisoning. ACCLPP is charged with evaluating information about the health effects of 1

lead exposure in children, the epidemiology of childhood lead poisoning, implementation issues, and 2

other factors. Furthermore, according to its charter, ACCLPP: 3

reviews and reports regularly on childhood lead poisoning prevention practices; 4

recommends improvement in national childhood lead poisoning prevention efforts; 5

develops written recommendations for the prevention and control of childhood lead poisoning. 6

7

Blood Lead Level of Concern Work Group Charge 8

In keeping with this assignment, ACCLPP established the Blood Lead Leve l Work Group in 9

November 2010 to recommend a new approach, terminology, and strategy for responding to and 10

preventing elevated BLLs in children. The charge of this working group was to: 11

Recommend how to best replace the ‘level of concern’ in relation to a ccumulating scientific 12

evidence of adverse effects of BLLs <10 μg/dL in children. 13

Consider laboratory capability for measuring BLLs in establishing new guidance on childhood BLLs. 14

Advise CDC on how to communicate advisories to groups impacted by policy changes concerning: 15

1) interpretation of childhood BLLs and trends in childhood BLLs over time; 2) screening and re16

screening intervals; 3) requirements and procedures for notifying relevant family members 17

concerning BLL test results; and 4) interventions known to reduce lead exposure. 18

Make recommendations for future research on lead-exposure prevention and intervention 19

strategies. 20

213 1 

### I. Scientific Rationale for Eliminating the CDCs 10 g/dL Blood Lead Level of Concern 2 3 KEY POINTS/RECOMMENDATIONS 4 **Based on the scientific evidence, the ACCLPP recommends that the term “level of concern” be** 5 **eliminated from all future agency policies, guidance documents, and other CDC publications, and** 6 **that current recommendations based on the “level of concern” be updated according to the** 7 **recommendations contained in this report.** 8 9 **CDC should use a childhood BLL reference value based on the 97.5 th**  **percentile of the population** 10 **BLL in children ages 1-5 (currently 5 μg/dL) to identify children and environments associated with** 11 **lead**

**-exposure hazards. The reference value should be updated by CDC every four years based on** 12 **the most recent population based blood lead surveys among children.** 13 14

15

Prior ACCLPP Guidance 16

The adverse health effects associated with elevated BLLs have been widely studied and 17

documented (http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=158823#Download). In the past, 18

the CDC responded to the accumulated evidence of adverse effects of elevated BLLs by lowering the 19

level requiring intervention or what is now deemed the “b lood lead level of concern. ” Over the 20

period from 1960 to 1990, the designated BLL of concern was lowered incrementally from 60 to 25 21

g/dL. In 1991, the CDC recommended lowering the BLL for individual intervention to 15 g/dL, and 22

implementing community-wide primary lead-poisoning prevention activities in areas where many 23

children had BLLs > 10 g/dL ( [ 1 ] (http://www.cdc.gov/nceh/lead/publications/>). 24

In 2005, the ACCLPP again considered the BLL of concern and evaluated new studies that had 25

been published through 2003 relating toxic effects, especially cognitive impairment in children, to 26

BLLs < 10 g/dL. Based on that evaluation, the CDC issued a statement in 2005[ 2 ] 27

( http://www.cdc.gov/nceh/lead/publications/PrevLeadPoisoning.pdf ) citing several reasons not to 28

lower the BLL level of concern. These reasons included: 1) the absence of effective clinical or public 29

health interventions identified that could reliably and consistently lower BLLs that were already <10 304

g/dL, 2) the assessment that data on IQ in association with BLLs <10 g/dL relied on fewer than 200 1

children, 3) the fact that because poor housing, poverty, lead exposure, and cognitive impairment 2

often occurred together especially in the U.S., the role of any specific component in influencing IQ, 3

was difficult to isolate with certainty, and, 4) uncertainties of BLL classification related to laboratory 4

testing precision. The 2005 document also strongly endorsed primary prevention and incorporated 5

these strategies into CDC-funded programs, as well as recommended to other agencies that they act 6

accordingly to carry out primary prevention. In addition, the 2010 Guidelines for the Identification 7

and Management of Lead Exposure in Pregnant and Lactating Women [ 3 ] 8

( htt p://www.cdc.gov/nceh/lead/publications/leadandpregnancy2010.pdf ) gave the level of 5 g/dL 9

as the level at which to take action by healthcare and public health providers. 10

11

New Evidence and Updating Guidance 12

However, for multiple reasons, the reliance on both the 10 g/dL BLL, as well as the concept 13

of a “level of concern” has been increasingly questioned. Since 2003, additional reports of 14

associations between BLLs <10 g/dL in children with adverse cognitive, and increasingly with other 15

physiological consequences, have been published. Additionally, data from earlier cross-sectional 16

studies of IQ in older children, not considered central to the argument in 2003, have since been re17

interpreted as highly relevant, based on reanalysis of prospective data focusing specifically on the 18

time course of associations between blood lead and IQ. The process for setting a “level of concern” 19

for lead has always failed to include consideration of uncertainty or the inclusion of a margin of 20

safety. Although initially intended as a designation of a population-based action level, the level of 21

concern has been widely treated as an individual toxicity threshold. At this time, other countries and 22

even individual U.S. states, have abandoned both 10 g/dL and the “level of concern

. ” 235

Consequently, ACCLPP convened a Work Group in 2010 to reconsider the approach, 1

terminology and strategy for elevated BLLs in children. After careful consideration of the current 2

scientific literature, the ACCLPP recommends discontinuation of a designated ‘level of concern’ for 3

elevated BLL in children. Because no measureable level of blood lead is known to be without 4

deleterious effects, and because once engendered, the effects appear to be irreversible in the 5

absence of any other interventions, public health, environmental and housing policies should 6

encourage prevention of all exposures to lead. Correspondingly, this document emphasizes 7

prevention of exposure rather than responses to specific BLLs, a strategy deemed ‘primary 8

prevention.’ Public health goa ls must target the reduction of the disparities in children's BLLs that 9

occur as a result of housing conditions, environmental contamination, race/ethnicity, and 10

socioeconomic status. 11

As stated in reports from the State of California [ 5 ] and Healey et al [ 4 ] and, a biological 12

“threshold” or “effect level” BLL is not synonymous with a BLL at which intervention is required or 13

effective. Correspondingly, the ACCLPP recognizes that the selection of any BLL as a trigger for 14

action or inaction at an individual or community level will be primarily dependent upon the 15

availability of effective remediation approaches and financial means to accomplish them and, to 16

some degree, related analytical considerations

. Given those facts, recommendations in the later 17

sections of the document refer to the use of reference values. 18

A statistically derived reference value characterizes the upper margin of the distribution of the 19

laboratory measurement of a given analyte in a given population. A reference value is useful to 20

characterize individual results as “elevated” or “not elevated” in comparison to the population 21

average or mean value. These values have also been used to set health policy goals and to interpret 22

results from measures of chemical exposure by CDC, the World Health Organization and other 236

government bodies. The German Federal Environmental Agency has recently applied the use of 1

reference values to define “precautionary action values” for exposures to lead among children and 2

adults [ 6 ]

. 3

A reference value* is derived from the distribution of concentrations of a specific compound 4

or element in a body fluid of a reference population (often the 97.5 th percentile)

. Therefore, thes e 5

levels only apply to a specific population at a specific time. In the context of childhood BLLs in the 6

U.S., NHANES data provides an appropriate source for characterizing a reference value for BLLs in 7

children 1-5 years old. We propose that the 97.5 th percentile derived from the combination of the 8

two most recent cycles of NHANES data be used to identify individuals with increased exposure and 9

set public health goals. The current reference value (approximately 5 μg/dL ) for children’s BLLs 10

should be re -considered by the CDC every four years to ensure that changes in this population are 11

adequately assessed. 12

* The term “reference value” used in this document should be distinguished from the term “reference 13 dose” used by U.S. EPA, which refers to “ An estimate (with uncertainty spanning perhaps an order of 14 magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is 15 likely to be without an appreciable risk of deleterious effects during a lifetime “, or to U.S. EPA’s 16 defin ition of “Reference value (RfV) as “ An estimate of an exposure for a given duration to the human 17 population (including susceptible subgroups) that is likely to be without an appreciable risk of adverse 18 health effects over a lifetime” [cf: http://www.epa.go v/iris/help_gloss.htm#r ] [accessed 19 11/09/2011]. 20 21

Focus on the Weight of Evidence 22

Section I of this document describes the scientific rationale for the recommendation to 23

eliminate the term “blood lead level of concern.” This document is not intended as a r isk assessment 24

for lead, nor as a comprehensive review of the current scientific literature. Indeed, the scientific 25

rationale presented here builds upon risk assessments carried out by other regulatory and policy 26

bodies, including the German Human Biomonitoring Commission [ 6 ], the State of California [ 5 ], and 277

the literature reviewed in the 2005 CDC statement [ 2 ]. Advice on clinical, public health, housing and 1

environmental interventions in relation to BLLs will be described in later sections. 2

Recognizing that any individual study may have shortcomings, the BLL Work Group based its 3

conclusions on the overall weight- of -the-evidence from epidemiological studies of BLLs <10 μg/dL 4

and the consistency of outcomes. In addition, it considered supporting biological plausibility evidence 5

from animal studies. 6

7

Additional Evidence Relating Increasing BLLs with Reductions in IQ 8

The recommendation of the ACCLPP arises from several considerations. In 2003, Canfield et al. 9

reported decrements in school age IQ among 213 children whose peak BLLs had never exceeded 10 10

g/dL [ 7 ]. Similarly, Bellinger and Needleman, in a re-analysis of data from 48 children from the 11

Boston cohort study whose BLLs never exceeded 10 g/dL, reported a similar association [ 8 ]. ACCLPP 12

reviewed these and other data, and stated in 2005 that these associations, more likely than not, were 13

causal. There are now additional compelling studies in the scientific literature, reporting associations 14

between BLLs <10 g/dL and adverse effects in children, forming a more substantive body of 15

evidence than was available at the time of the 2005 CDC statement. Collectively, these new studies 16

and re-interpretation of past studies have demonstrated that it is not possible to determine a 17

threshold below which BLL is not inversely related to IQ. 18

Healey et al. [ 4 ], citing Lanphear et al. [ 9 ] as the critical study in its toxicological assessment, 19

asserted that that there is a negative slope relating BLL and IQ down to concurrent BLLs of 1 g/ dL. 20

An increase in concurrent BLL from 1.0 to 4.0 g/dL is associated with a change in mean IQ of 21

approximately -2.3 to -5.2 IQ points, with a best estimate of -3.7 IQ points. The German Human 228

Biomonitoring Commission [ 6 ] concluded that it is not possible to identify a threshold BLL below 1

which there are no cognitive deficits. 2

3

Evidence for Reductions in Academic Achievement and Specific Areas of Cognitive Dysfunction 4

Studies have also now extended the effects of low BLLs, and suggest the involvement of 5

specific areas of cognitive dysfunction. These include measures of academic achievement such as 6

reading and writing, as well as attention deficits, specifically impulsivity. For example, Chandramouli 7

et al. [ 10 ] reported that BLLs in the range 5- 10 g/dL in 30 month-old children were associated with 8

reductions in reading and writing scores in 7-8 year old children from the Avon Longitudinal Study. In 9

a case-control study of children 6-17 years old [ 11 ], where the mean BLL was 0.73 and maximum BLL 10

was 2.2 g/dL, higher BLLs was associated with parent-reported combined-type attention deficit 11

hyperactivity disorder and hyperactivity-impulsivity after controlling for IQ and prenatal smoking. 12

13

Significance of the Impact of BLLs on Intelligence 14

Although only 1

– 4% of the variance in cognitive ability in prospective cohort studies is 15

attributable to lead, the public health impact of low level lead-exposure on the distribution of 16

intelligence in society is considerable. Because exposure to lead is still widespread, it may be 17

responsible for a general reduction in the mean IQ of children. A small change in mean IQ of even 3- 5 18

points associated with BLLs between 1 and 10 g/dL can shift the entire population IQ distribution, 19

thereby reducing the number of high achieving individuals with IQs above 130, and increasing the 20

number of children with IQ scores below 70, many of whom would need substantial remedial 21

education services [ 12 ]. 22

239

Critical Role of Concurrent BLLs and Intelligence 1

Studies published since 2005 have also established the importance of concurrent BLLs to IQ 2

reductions. In the U.S., BLLs peak at approximately 2 years of age, after which they decline to lower 3

levels in the absence of specific intervention. Bellinger et al. [ 13 ] reported that BLLs measured at 24 4

months of age, but not at 6, 12, 18 or 57 months of age, were associated with decrements in IQ when 5

measured at 10 years of age in children from the Boston cohort [ 14 ]

. These findings had cast doubt 6

on any study that did not include data on early childhood BLL s, suggesting that any relationship 7

between BLLs and IQ reductions in large surveys of school age children, such as NHANES, were not 8

causal associations, but rather residual effects of higher BLLs that went unmeasured in early 9

childhood. However, other studies noted that the findings from the Boston cohort appeared to be an 10

exception, as most prospective studies showed stronger associations between concurrent BLLs and IQ 11

reductions at school age, even though the average BLL at that age was much lower [ 15 , 16 ]. In 2005, 12

Chen et al. studied 780 children who qualified for a clinical trial by virtue of having BLLs in the range 13

20

- 44 μg/dL when they were “toddlers,” and found that lower IQ at age 7 was strongly associated 14

with concurrent BLL, but not asso ci at ed with peak BLL at 2 years of age [ 17 ]. Similar findings were 15

reported in a pooled analysis of major prospective cohort studies of IQ and BLLs, which involved 16

children with and without such high BLLs [ 9 ]. Thus, since 2003, data from a much larger number and 17

more diverse group of children with low BLLs and associated IQ deficits have informed consideration 18

of the effect levels. The associations of concurrent BLLs with reduced IQ in this age group suggests a 19

window of developmental vulnerability extending to older children, or perhaps the consequences of 20

protracted exposure during childhood. 21

Low BLL Effects in Children Extend to Other Organs/Systems 2210

Some recent studies have suggested that the adverse health effects of childhood BLLs < 10 1

μg/dL extend beyond cognitive function to include cardiovascular, immunological, endocr in e, and 2

behavioral effects [ 18

- 22 ]

. While the data on these outcomes are less extensive than th e data 3

characterizing the impact of lead on neurocognitive development, and therefore merit further 4

investigation, they nevertheless raise the possibility that BLLs <10 μg/dL might be associated with 5

broader public health consequences. 6

7

Elevated BLL Effects in Children are not Restricted to Low Socioeconomic Status Communities 8

The conclusions of the 2005 Working Group included concerns for residual confounding by 9

socioeconomic status. It is noteworthy that several studies report associations in populations of 10

relatively “advantaged” socioeconomic status. For example, the analyses from the Boston cohort 11

study, including assessment of children whose BLLs never exceeded 10 g/dL, was carried out in a 12

“socioeconomically

- advantaged population” [ 8 , 13 ]. Moreover, the BLL-associated reductions in IQ in 13

the Yugoslavian prospective study were seen in Mitrovica, where BLLs were elevated by the local 14

smelter, even though the town also had higher HOME scores and higher maternal IQ scores than the 15

comparison town, Pristina [ 23 ]. A s pointed out in Healey et al.’s review of 12 longitudinal studies of 16

BLLs and IQ ([ 4 ] p. xix), “The pattern of results does not appear to be dependent on cohort 17

demographics, such as SES [socioeconomic status], nor do they appear to be dependent on exposure 18

range –

significant associations have been reported among both relatively low and relatively high 19

socioeconomic strata....” 20

21

Expectations of Lower BLLs and Changes in IQ and Achievement 2211

It has been argu ed that even though BLL s have declined, measures on standardized indices 1

such as reading and IQ scores have not correspondingly increased in the U.S., which contradicts the 2

proposed negative association be tween these measures. As far as the ACCLPP is aware, there are no 3

published data that support this conclusion. Numerous studies have actually reported significant 4

increases in IQ scores over the past century, a phenomenon dubbed the Flynn effect, which has been 5

attributed both to characteristics of the IQ tests themselves and to cultural biases [ 24 , 25 ]. While this 6

does not demonstrate that lowering BLL is accompanied by higher IQ, it is not incompatible with that 7

possibility. U.S reading scores have increased 8

(http://nces.ed.gov/nationsreportcard/pdf/main2011/2012457.pdf) , although to a lesser extent; 9

changes over time are difficult to evaluate given changes in assessment format during this period 10

(National Assessment of Education Progress (NAEP): 11

http://nationsreportcard.gov/ltt_2008/ltt0003.asp and 12

http://nationsreportcard.gov/ltt_2008/ltt0002.asp ). (Note however the recent analysis suggesting 13

that the reduction in childhood BLLs in Massachusetts underlies a modest but statistically significant 14

improvement in scores on standardized English and mathematics tests 15

( http://www.bos.frb.org/econoomic/wp/index.htm ). Over the same time period, many other 16

significant changes have occurred that could reduce any gains in these cognitive measures, as such 17

functions clearly have multifactorial determinants

. For example, the poverty rate has continued to 18

increase (http://www.census.gov/hhes/www/poverty/data/incpovhlth/2010/tables.html) , the rates 19

of childhood obesity ( http://www.cdc.gov/obesity/data/trends.html#State ) and diabetes 20

( http://www.diabetesandenvironment.org/home/incidence/historical ) have increased dramatically, 21

and have been associated with cognitive dysfunction [ 26 , 27 ], and nutritional status has also changed. 22

It is also clear that the U.S. has lost ground in terms of prenatal mortality 2312

( http://www.cdc.gov/omhd/amh/factsheets/infant.htm#1)

. Moreover, as noted by Healey et al. 1

([ 4 ] p. xxxix): ”While the magnitude of the slope of the recommended relationship between mean 2

population IQ and concurrent blood lead in children is undoubtedly influenced to some unknown 3

degree by confounding, it is also likely attenuated by over-control. ” Other outcomes, such as high 4

school graduation, delinquency, violent crime, or incarceration have a less clear relationship with BLL 5

and perhaps a variable latency. A comprehensive examination of such outcomes might be of interest; 6

however, for reasons of multifactorial determination noted above, it seems unlikely that such effort 7

would yield a consistent interpretation, nor that it would inform judgment about the toxicity of lead 8

at a given BLL. 9

10

Shape of the BLL Curve and Outcomes 11

Other arguments also weigh in this decision. Recognizing the potential for residual 12

confounding, the CDC’s 2005 st atement ( [ 28 ] ; 13

http://www.cdc.gov/nceh/lead/publications/PrevLeadPoisoning.pdf ) explored the question of the 14

steeper dose response at lower BLLs, and evaluated how the interactions among lower dust lead, 15

hand to mouth activity, IQ and BLL might artifactually produce the steeper curve. The document 16

concluded that “Though this hypothetical example cannot demonstrate that residual confounding 17

underlies the steep blood lead-IQ slopes observed at low levels, it does support the need for caution 18

in interpretin g the absolute value of the estimated effect sizes.” However, it also did not state that 19

the existence of a steeper slope in some data was evidence against any role for lead in cognitive 20

impairment. As such, the specific shape of the curve above vs. below 10 μg/dL is not actually relevant 21

to the question of an association of BLLs with effects below 10 μg/dL. Additionally, for other outcome 2213

measures, effects below 10 μg/dL are found without reports of these effects being of greater 1

magnitude than those abov e 10 μg/dL. 2

3

Uncertainties Regarding the Ability to Reverse Lead Effects in Children 4

While trials involving chelating agents did not result in improved IQ or behavioral outcomes 5

relative to placebo [ 29 ], both human and animal studies have suggested that developmental effects 6

arising from lead exposure could be at least partially ameliorated by opportunities for environmental 7

‘enrichment’ [ 30

- 33 ]. The extent to which the developmental impacts of lead-exposure in children 8

can be fully reversed by such strategies as yet remains uncertain. The fact that significant stores of 9

lead are present in bone with a half-life of decades, coupled with the fact that lead can be mobilized 10

from bone back into the bloodstream to maintain equilibrium, if external lead exposure is reduced, 11

makes it difficult to directly test this possibility. Moreover, the prospect that some environmental 12

conditions or host factors (nutritional status, psychosocial stress, etc.) may aggravate the impact of 13

developmental lead exposure has yet to be considered. In general, non-specific interventions that 14

wo rk in Head Start and other enrichment programs might be expected to produce similar results in 15

children with and without a history of elevated BLLs. Tactics aimed solely at lowering BLLs with the 16

expectation of reversing effects, however are unlikely to produce a benefit. 17

18

Biological Plausibility Support from Experimental Animal and In Vitro Studies 19

Finally, the effects reported in children are supported by biological plausibility, i.e., 20

experimental animal studies. Rodent studies have revealed adverse consequences of BLLs of 7-11 21

g/dL on cognitive domains comparable to those associated with elevated BLLs in children; these 22

studies have not yet systematically attempted to define clear BLL threshold effects [ 34 , 35 ]

. 2314

Moreover, the alterations in the stress response of children in relation to low BLLs [ 19 ], particularly 1

the delay in glucocorticoid negative feedback, actually replicates findings in animal models [ 34 , 36 ]. 2

Animal and in vitro studies have identified mechanisms of lead toxicity that could explain the 3

observed greater magnitude of adverse outcomes at lower BLLs for some outcome measures. 4

Reports of non-linear dose effect relationships between BLLs and multiple outcomes, both in human 5

and experimental animal studies, are well established as first detailed by Davis and Svenndsgaard in 6

1990 [ 37 ]. A recent study found a greater delay in post-stress challenge reduction in corticosterone 7

(the rodent version of cortisol) in rats with lower BLLs (maternal exposure yielding peak BLLs of 15- 20 8

g/dL) than at higher BLLs (30-35 g/dL ) [ 36 ]. 9

Furthermore, with respect to the mechanisms of lead effects and possible differential effects 10

at lower rather than higher BLLs, the work of Audesirk and colleagues [ 38 , 39 ] is highly instructive. 11

Based on a general belief that many effects of lead exposure arise from its ability to substitute for 12

calcium, a metal which is essential to a substantive number of biochemical reactions and 13

physiological processes, this group examined the effects of lead alone or lead plus calcium on the 14

activity of Ca 2+ /calmodulin-dependent calcineurin. This study demonstrated that lead had the 15

potential, depending upon free concentration of Pb 2+ , to either stimulate or inhibit Ca 2+ /calmodulin16

dependent calcineurin, with lower lead concentrations increasing and higher lead concentrations 17

decreasing activation of calcineurin. 18

19

Summary of Scientific Rationale 20

In summary, many of the uncertainties associated with effects of BLLs <10 g/dL cited by the 21

CDC in 2005 [

2 ] have been minimized by more recently published studies. As a result, a BLL without 22

deleterious effects can not be identified at present, and thus the term ‘level of concern’, or any 2315

suggestion of the existence of a BLL threshold, should be discarded from CDC guidance policies and 1

replaced by new policies and terminology that offer scientifically-based and practical guidance for 2

application in the clinical, laboratory, and public health contexts. Consequently, public health and 3

environmental policies should encourage actions to reduce all lead exposure, to the extent feasible 4

[ 40 ], and, should specifically focus on minimizing disparities in childhood BLL s as demonstrated by 5

NHANES-documented disparities in housing conditions, environmental contamination, race/ethnicity, 6

and socioeconomic status. Even though the most recent NHANES survey (2007 - 20 08) demonstrates 7

considerable progress in lowering BLLs in the U.S., it also confirms that higher BLLs persist in non8

Hispanic black children. Similar disparities were noted when BLLs were stratified by poverty-income 9

ratio [ 41 ]. 10

11

A Renewed Call for Primary Prevention 12

The above arguments as well as those that follow all underscore the critical importance of 13

primary prevention. Using a strategy of identifying lead poisoning or elevated BLL relies on detection 14

in the child, relegating the child to the function of a sensing device for poor/contaminated housing, 15

contaminated water and/or tainted consumer products. Thus, the child can be considered the 16

proverbial ‘canary in the coal mine.’ The current strategy, which relies on the identifying extant 17

elevated BLLs), while still warranted to some extent, does not prevent the damage already incurred. 18

Moreover, while agents such as chelators can be used to treat overt lead poisoning and possibly 19

reduce the case fatality rate, these agents have been demonstrated not to improve IQ or behavioral 20

consequences of lead exposure. Therefore, primary prevention is the most important and significant 21

strategy. 22

2316 

### II. Putting Primary Prevention First 1 2 KEY POINTS/RECOMMENDATIONS 3

**CDC should develop and help implement a nationwide primary prevention polic y**  **to ensure that no** 4 **children in the U.S. live or spend significant time in homes, buildings or other environments with** 5 **lead**

**-exposure hazards.** 6 7

8 Despite the overall reduction in BLLs, each year thousands of children are exposed to lead at 9

levels now associated with negative consequences, including lower academic and life achievement. 10

Th e evidence supporting this conclusion, some of which is cited in this document, demonstrates that 11

no safe childhood BLL threshold can be identified. 12

In the past, CDC emphasized primary prevention ([ 2 ] ; 13

< http://www.cdc.gov/nceh/lead/publications/PrevLeadPoisoning.pdf >), but also recommended 14

screening BLLs in children, to alert policymakers and others to potential lead contamination in 15

communities. Generally, sources of lead exposure were only identified and remediated after a child 16

was identified with an elevated BLL. This strategy should now be considered unacceptable, given that 17

there is no evidence to demonstrate that remediation prevents damage from prior lead exposure 18

[ 42 ]. 19

The estimated economic cost of reducing or eliminating lead exposure as well as the predicted 20

associated health benefits are well studied. In most of these analyses, the cost of removing lead 21

contamination was compared to the cost of medical care, special education, and lost productivity; 22

however, more recent analyses often include the benefit of decreased violent crime [ 43 ] [ 44 ] [ 45 ] 23

[ 46 ]. 24

The success of regulatory policies that control or eliminate sources of lead in the 25

environment, the lack of proven methods to reverse harm in children with an elevated BLL, and the 2617

lack of a BLL threshold reinforce the need for a primary prevention strategy. CDC defines primary 1

prevention as interventions that reduce or eliminate exposure or risk factors before the onset of 2

disease. They include measures that restrict the use of lead or that remove lead from the 3

environment before exposure occurs. These ideas are not new. In 1970, Dr. Julian Chisolm testified 4

before Congress th at ‘elimination of the environmental hazard offers the only current practical 5

approach to the prevention of lead poisoning in young children .’ [ 47 ]. Th is call for primary prevention 6

to eliminate adverse health effects caused by childhood lead exposure was reiterated by the CDC, in 7

similar language, in multiple documents released after 1975 including guidance documents published 8

in 1991 [ 48 ] 2004 [ 49 ] and 2005 [ 2 ]. 9

Indeed, the success in lowering BLLs reduces the need for programs that chiefly focus on 10

strategies that identity individual lead-exposed children and manage their care, and instead, allows 11

resources to be re-directed to studies of evidenced-based primary prevention strategies. The 12

infrastructure needed to implement an effective primary prevention program is already in place. 13

Over the last 22 years , federal and state agencies have adopted requirements for lead-safe work 14

practices and developed a trained and visible workforce that can safely eliminate lead paint in 15

housing. State and local health and housing programs have used local data to identify geographic 16

areas and sub-populations at high risk for elevated BLLs, as well as specific properties in which many 17

children have been exposed to lead hazards. These data can and should be used to direct lead paint 18

hazard control resources; identify new sources of lead such as traditional pottery or medicines in 19

newly arrived populations; and [anticipate] increased lead exposure, resulting from environmental 20

changes (i.e., alterations in water chemistry that may enhance lead solubility in water). 21

In summary, the ACCLPP, in concert with elimination of the term “level of concern” for BLLs, 22

recommends that a primary prevention strateg y, first proposed in 1970 [ 47 ],be implemented to 2318

reduce all environmental exposure to lead. The following sections of this report outline strategies and 1

interventions recommended for achieving this goal. 2



### III. Health Management for Primary Prevention of Lead Exposure 3 4 KEY POINTS/RECOMME NDATIONS 5

**Clinicians should be a reliable source of information on lead hazards and take the primary role in** 6 **educating families about preventing lead exposures. This includes recommending environmental** 7 **assessments PRIOR to blood lead screening of children at risk for lead exposure.** 8 9 **Clinicians should monitor the health status of all children with a confirmed BLL ≥5 μg/dL for** 10 **subsequent increase or decrease in BLL until all recommended environmental investigations and** 11 **mitigation strategies are complete, and should notify the family of all affected children of BLL test** 12 **results in a timely and appropriate manner.** 13 14 **Clinicians should ensure that BLL values at or above the reference value are reported to local and** 15 **state health and/or housing departments if no mandatory reporting exists and collaborate with** 16 **these agencies in providing the appropriate services and resources to children and their families.** 17 18

19 Clinicians will play a crucial role in preventing lead exposure and responding to BLLs <10 μg/dL 20

in children, as they are often the primary source of nutritional and lead risk education received by 21

parents. In addition, medical offices are the most common site of childhood BLL testing. Most 22

practicing clinicians have been trained on how to respond to BLLs >10 μg/dL, but with a renewed call 23

for primary prevention and the observed effects of lower BLLs, this section presents a new health 24

management algorithm for children. 25

Clinicians must be reminded that they have an important role in preventing lead exposure and in 26

managing lead-exposed children. This role should include: 27

1. Screening questions, outreach and education to minimize exposures prior to blood lead 28

testing; 29

2. Emphasizing healthy nutrition and/or dietary supplements to reduce absorption; 3019

3. Blood lead testing to promptly identify exposed children, for whom primary prevention has 1

failed; 2

4. Intervening appropriately when clinically indicated; 3

5. Overseeing ongoing monitoring of children with elevated BLLs, defined as levels above the 4

reference value; 5

6. Coordinating efforts with parents and local and state authorities to minimize risks to 6

individual children and to assist communities in their primary prevention efforts. 7

8

Exposure Prevention; Role of the Clinician 9

Clinicians should be a consistent and reliable source of information, and take a primary role in 10

educating families about the risks of lead-exposure. If appropriately educated, all families will be 11

better equipped to make sound housing decisions based on an understanding of the risks associated 12

with lead hazards. Anticipatory guidance for parents should cover a number of lead risk topics, 13

including: in-home exposures; unsafe renovation practices; and potential lead-exposures associated 14

with parental occupations and hobbies. Parents should receive information on identifying lead 15

hazards and safe/reliable methods to minimize exposures, as well as contact information for 16

additional local lead-related resources. In addition, the clinician has a role in recognizing risks from 17

potential lead exposures specific to immigrant communities, refugees and children adopted from 18

foreign countries, whose previous and/or ongoing lead exposure may include folk/home remedies, 19

medications, toys, cosmetics, food, ceramic ware, and other less common items. 20

Personal Lead Risk Assessment Questionnaires 21

The effectiveness of personal risk assessment questionnaires for identifying children with 22

elevated BLLs has been documented [ 50 ]. However, no studies have evaluated the performance of 2320

these questionnaires at BLLS <10 μ g/dL or their effectiveness in directing counseling or in identifying 1

lead hazards in the home. When applied in consecutive samples of patients in clinical settings, the 2

ability of such questionnaires to identify children with BLLs ≥ 10 μ g/dL varies considerably by 3

population [ 50 ]. In certain studies, sensitivity was better for higher BLLs [ 51 ] or when questionnaires 4

were developed for specific populations [ 52 ] [ 53 ]. In general, to identify approximately 80% of 5

children with BLLs ≥ 10 μ g/dL, a blood test was required in 50% of those assessed using a 6

questionnaire. Multiple studies in populations with low [ 52 ] or high [ 54 , 55 ] prevalence of elevated 7

BLLs concluded that risk assessment questionnaires were not effective in a clinical setting. When 8

screening, it is important to keep in mind that exposure may begin in utero ; thus, potential exposures 9

during pregnancy should be considered (Table 1)

. In addition, it should be noted that young children 10

may be expos ed to lead through contact with paint, water, dust, and soil [ 56 ]. 11

12

Minimizing Absorption 13

In their role as advocates for children ’ s health and as educators of parents, clinicians routinely 14

provide nutritional guidance. A well-balanced diet is essential to meeting the child ’ s recommended 15

daily allowance of essential vitamins and minerals and to provide adequate calories for growth. 16

Certain vitamins and minerals, especially calcium, iron and vitamin C, play a specific role in minimizing 17

lead absorption. Regular assessment of the child ’ s nutritional status during well-child care can 18

identify children with inadequate intake of these and other nutrients, and allow the clinician to 19

proactively recommend supplementation. Note that the Committee on Nutrition of the American 20

Academy of Pediatrics recently published a comprehensive review of the diagnosis and prevention of 21

iron-deficiency and anemia ([ 57 ] ; 22

< http://pediatrics.aappublications.org/content/126/5/1040.full.html >)

. 2321

For the potentially lead-exposed child, adequate intake of iron, calcium and vitamin C, beyond 1

their requirement for overall good nutrition, can specifically minimiz e absorption of ingested lead. 2

For children with BLLs above the reference value, it is imperative to further reinforce healthy eating 3

habits and reinforce nutritional education. It is reasonably well-established that iron deficiency is 4

associated with increased BLLs, and that some effects, such as lower IQ, can result from both 5

conditions. Thus, children at high risk oflead exposure should be tested for iron deficiency and iron6

deficiency anemia and treated according to current AAP guidelines. 7

Specific assessment of bodily iron stores can be an essential part of treating lead-exposed 8

patients, because iron-deficiency anemia results in increased intestinal absorption of ingested lead 9

[ 58 , 59 ]. 10

1122 1 Table 1. Risk Factors for Lead Exposure in Pregnant an d Lactating Women 2 3 Recent immigration from or residency in areas where ambient lead contamination is high. 4 Women from countries where leaded gasoline is still being used (or was recently phased-out) 5 or where industrial emissions are not well-controlled. 6 Living near a point source of lead , such as lead mines, smelters, or battery recycling plants 7 (even if the establishment is closed). 8 Working with lead or living with someone who does . Women who work in or who have 9 family members who work in lead-industry (take home exposures). 10 Using lead-glazed ceramic pottery . Women who cook, store, or serve food in lead-glazed 11 ceramic pottery made in a traditional process and usually imported by individuals outside the 12 normal commercial channels. 13 Eating non-food substances (pica) . Women who eat or mouth non-food items that may be 14 contaminated with lead (such as soil or lead-glazed ceramic pottery) 15 Using alternative or complementary medicines, herbs, or therapies . Women who use 16 imported home remedies or certain traditional herbs that may be contaminated with lead 17 Using imported cosmetics or certain food products . Women who use imported cosmetics, 18 such as kohl or surma, or certain imported foods or spices that may be contaminated with 19 lead. 20 Engaging in certain high-risk hobbies or recreational activities . Women who engage in high21 risk activities or have family members who do. 22 Renovating or remodeling older homes without lead hazard controls in place . Women who 23 have been disturbing lead paint and/or creating lead dust, or spending time in such a home 24 environment. 25 Consumption of lead-contaminated drinking water . Women whose homes have leaded 26 pipes or source lines with lead. 27 Having a history of previous lead exposure or evidence of elevated body burden of lead

. 28 Women who may have high body burdens of lead from past exposures, particularly those who 29 are deficient in certain key nutrients (calcium, iron). 30 Living with someone identified with an elevated lead level . Women who may have 31 exposures in common with a child, close friend, or other relative living in same environment. 32

33

34

Formerly, hemoglobin (Hgb) screening was recommended, however Hgb alone is only 35

sufficient to diagnose anemia (by definition), and does not specifically rule out iron deficiency. Iron 36

deficiency, defined as inadequate bodily iron stores to preserve function, may be present without 37

anemia. In order to sufficiently assess iron status, iron levels, total i ron binding capacity (TIBC) or 38

serum ferritin (SF) can be used

. An abnormal value on any test can be diagnostic of iron deficiency. 39

Children identified as iron deficient should be treated with an appropriately dosed iron supplement, 4023

and reassessed periodically during treatment. Clinicians must keep in mind the risk of toxicity 1

associated with excess iron intake [ 57 ]and counsel parents accordingly. 2

3 Evaluation and Treatment of Lead Exposure - Identifying Exposed Children 4 5 A national surveillance program is crucial to gauge the success of our public health programs, 6

identifying subpopulations with higher exposure, and determining the reference value. In addition, 7

clinical testing for lead exposure must continue for the foreseeable future in order to identify those 8

children for whom primary prevention measures have failed. 9

BLL testing is currently required at 12 and 24 months for all Medicaid-enrolled children, 10

regardless of known lead-exposure risk. Testing will often occur during routine well-child care as 11

recommended by the American Academy of Family Physicians and the AAP. In addition, children ≤ 72 12

months who missed recommended screening at a younger age should be screened at presentation. 13

Screening at 12 and 24 months satisfies the Healthcare Effectiveness Data and Information Set 14

(HEDIS) measures. However, it is important to perform at least one BLL in all children between the 15

ages of 12-24 months, regardless of insurance status, to obtain accurate measurements of population 16

BLL. 17

In 1991, CDC recommended universal BLL testing for all children, with different screening 18

requirements for ≥6 mo nth old children at low and high risk of lead-exposure [ 48 ]. In 1997, the CDC 19

recommended that state and/or local agencies formulate their own lead screening recommendations 20

based on local data, because of the wide variability in lead-exposure in different urban and rural U.S. 21

communities [ 60 ]. In particular, the CDC recommended universal lead screening for communities 22

with a ≥ 27% pre-1950 housing or ≥12% prevalence of ≥ 10 μg/dL blood lead in children 12 -36 months 23

old. They further, recommend ed targeted screening for specific groups with higher risk factors in 24

communities with lower prevalence of elevated BLLs. In the absence of a statewide or local plan, 2524

universal BLL testing according to the 1991 CDC guidance is recommend ed . Based on the prevalence 1

of elevated BLLs, local health departments or other relevant agencies may implement different 2

testing guidelines, such as screening more frequently or at different ages. However, CDC and 3

Medicaid are currently negotiating the criteria for local exemptions. In general, information about 4

CDC-approved local screening programs can be found at: 5

http://www.cdc.gov/HealthyHomes/programs.html

. 6

A 2005 guidance statement from the AAP summarized the history of lead screening and 7

suggested that pediatricians screen according to local and state guidelines where they apply, but 8

screen all non-Medicaid children in their absence, and also screen all immigrant, refugee and 9

internationally-adopted children when they arrive in the U.S., due to their increased risk [ 61 ]. The 10

numerous reports of children with high blood lead levels, including fatalities, in many countries, as 11

well as lead exposure from imported products support the screening of foreign-born children [ 62

- 65 ] 12

[ 66 ]

. The CDC also recommends initial and follow- up screening of pregnant and lactating women [ 3 ], 13

as well as for neonates and infants of women with BLLs ≥ 5 μg/dL

. 14

ACCLPP recommends that health care providers follow local and state lead screening 15

guidelines, screen children coming from other countries when they arrive in the United States, and 16

screen neonates and infants born to women with lead exposure during pregnancy and lactation per 17

earlier CDC guidance. It recommends that children be screened according to guidelines for Medicaid18

enrolled children and the 1997 CDC guidelines for jurisdictions (screen at ages 12 and 24 months, and 19

once between 36 to 72 months of age in those without prior screening) in jurisdictions without 20

formal recommendations until those recommendations are issued. (See reference [ 40 ] for more 21

detail.) 2225

Some communities may provide screening outside of the child’s medical home (such as 1

through the WIC program). It is not necessary for the clinician to duplicate those efforts, but he/she 2

should confirm that the screening was performed elsewhere before testing is deferred during the 3

office visit. 4

5 Evaluation and Intervention Strategies for Children with BLLs above the Reference Value 6

With the move away from a designated “l evel of concern, ” a new algorithm is needed to 7

provide clinicians with guidance on responding appropriately to the lower range of BLLs. It is now 8

clear that there is no known threshold below which adverse effects of lead are absent . Management 9

strategies for children whose blood levels are equal to or greater than the reference value include 10

nutritional education and intervention, if indicated, educational intervention, ongoing monitoring, 11

and coordination with other organizations (Table 2). 12

Coordination of care with the local authorities and organizations, including local Childhood 13

Lead Poisoning Prevention programs is essential to initiate prompt investigation for the source of lead 14

exposure and potentially plan a response strategy. Although these services are typically outside of 15

the clinician’s role, medical and environmental interventions should be implemented simultaneously 16

to best protect the child. In addition, families with children whose BLLs are above the reference value 17

should be given access to services that provide : 18

1. Education about existing codes, lead-safe housing rules, disclosure requirements, landlord 19

responsibilities, risk factors for lead exposure in the home and at work, and steps for 20

maintaining a lead safe home (lead hazard identification and repair, lead dust testing, EPA and 21

state Renovation, Repair and Painting ( RRP ) requirements, and do- it -yourself precautions) 2226

2. Home visits by CLPPP staff, community health workers, Maternal and Child Health home 1

visiting programs, and other systems to assess the home, advise occupants, report 2

observations and lead test results, and make referrals in response to identified lead hazards. 3

3. Assistance and guidance regarding landlord violations of RRP, other lead rules, and housing 4

codes, including legal services for egregious situations like evictions and serial offender 5

property owners and referrals to code enforcement. 6

4. Educational needs of children with BLLs above the reference value are being addressed in a 7

separate publication from the ACCLPP. 8

9

Communicati

ng BLL Test Results 10

Effective screening policies and practices should ensure that the children of high-risk families 11

(i.e., families on Medicaid), are screened, and that lead-exposed children or children with elevated 12

BLLs receive key environmental interventions and case management services. Funding to sustain 13

these activities is an essential building block. Interactions with affected families must be performed in 14

a culturally-sensitive, same-language, and streamlined manner. The medical home, laboratory, and 15

other providers should offer simple information about the meaning of elevated BLL test results and 16

relevant, culturally-sensitive messages about relative impact should be conveyed

. Specialized terms 17

such as detectable level or elevated BLL should be defined. Pediatricians and other providers shall 18

integrate BLL test results into the “basic” report of indicators like weight, height, and developmental 19

percentiles. Pediatricians commonly present data in the form of percentiles, and a similar conventio n 20

could help physicians explain elevated BLLs to parents. (See reference [ 40 ] for more information, and 21

[ 67 ] for patient handouts). Test results should not be mysterious or difficult to obtain ; parents should 2227

have continuous access to BLL test results via internet and telephone retrieval systems until the child 1

reaches the age of twelve. 2

Pediatricians shoul d explain the uncertainty of all quantitative medical tests and BLL testing. 3

In particular, testing capillary blood for lead may be affected by residual lead contamination ingrained 4

on children's fingers, and that can be very difficult to remove. Thus, a capillary blood lead test above 5

the reference value should be repeated using a venous blood sample. Even in the best laboratories, 6

variations in test results of ± 2 μ g/dL are normal and are well within the acceptable lab error. Multiple 7

BLL tests are neede d over time to examine true trends in actual blood lead levels

. (See reference [ 40 ] 8

for more detailed discussion). 9

Given the challenges involved in measuring BLLs as low as 5 μg/dL, quality assurance practices 10

will need to be updated with the goal of improving accuracy and repeatability of BLL testing. ACCLPP 11

previously recommended that the federal Centers for Medicare & Medicaid Services, which is 12

responsible for regulating clinical laboratory testing through the Clinical Laboratory Improvement 13

Amendments 1988 [ 68 , 69 ], move as soon as possible to revise current regulations for allowable 14

laboratory error permitted in blood lead proficiency testing programs from ±4 μg/dL to ±2 μg/dL for 15

BLLs ≤ 20 μg/dL. Additional adjustments to internal laboratory quality assurance procedures may be 16

warranted, especially at BLLs <10 μg/dL. Laboratory practices and associated recommendations are 17

being addressed in a separate publication. 18

19

Confirmatory Testing of Children with BLLs above the Reference Value 20 21 Given the uncertainty of individual blood lead test results, it is important to do confirmatory 22

testing, especially for capillary blood samples that might be elevated due to residual lead on the skin 2328

at the puncture site. The recommended schedule for confirmatory testing is summarized in Table 3 1

and includes: 2

1) All capillary and venous BLL results greater than or equal to the reference value must be 3

confirmed within 1-3 months; 4

2) Children with BLLs ≥ 45 μg/dL or with symptoms of lead poisoning should have an immediate 5

(within 48 hr) confirmatory test; 6

3) Response actions should be initiated only after elevated BLLs are confirmed. 7

8

Management of Children with BLLs above the Reference Value 9

No changes are recommended to the existing CDC guidelines for the evaluation and treatment of 10

children requiring chelation (those with BLLs ≥ 45 μg/dL ) [ 70 ]. Unless the clinician is intimately 11

familiar with treatment protocols, he/she should consult with a medical toxicologist and/or regional 12

Pediatric Environmental Specialty Health Unit (PESHU), or a clinician experienced in treating children 13

with elevated BLLs. Contact information for regional PESHUs can be obtained at 14

http://aoec.org/PEHSU/serviceareas.html http://aoec.org/PEHSU/serviceareas.html ; local or regional 15

poison control contact information is available at 16

http://npic.orst.edu/health/poison.htm

. http://npic.orst.edu/health/poison.htm . The CDC’s Lead 17

Poisoning Branch is another resource available to clinicians at 18

http://www.cdc.gov/nceh/lead/about/program.htm

. http://www.cdc.gov/nceh/lead/about/program. 19

htm

. Children who undergo chelation should be monitored at least monthly, if not more often, for 20

potential side effects. 21

Of note, there are numerous touted interventions that are, at best, unnecessary and dangerous, 22

and, at worst, can be fatal. Non-medically managed chelation therapy has been widely promoted in 2329

lay literature and on the internet as a cure for a variety of diseases and disorders. These claims are 1

not scientifically-based, and families should be counseled proactively against becoming a victim of 2

these unproven and sometimes dangerous treatments. There is no medical foundation for relying on 3

the following methods to diagnose over-exposure to lead: gingival lead lines, testing of 4

neuro phy siologic function; evaluation of renal function (except during chelation with EDTA); testing 5

of hair, teeth, packed red cells, saliva or fingernails for lead; radiographic imaging of long bones (see 6

reference [ 70 ], Chapter 3) nor is provocative chelation prior to measurement of lead in urine testing 7

recommended. The widely accepted sequelae of BLLs < 45 μ g/dL are cognitive and behavioral 8

impairment. Chelation of children with BLLs ≥ 20 and ≤ 45 μ g/d L has not been shown to offer 9

therapeutic benefit for these outcomes [ 29 ]

. 10

11

Ongoing Monitoring For Lead-Exposed Children 12

For the child identified with a BLL results greater than or equal to the reference value, ongoing 13

monitoring of BLL is indicated during and after appropriate medical, educational and environmental 14

interventions (See Table 4). BLLs that rise may be indicative of an unrecognized source of exposure, 15

inappropriate abatement activities, failure to mitigate the identified hazard, or the redistribution of 16

lead stores within the child’s body. For the child with a rising BLL, additional medical and 17

environmental evaluation and interventions may be necessary, along with ongoing coordination of 18

care with the local CLPP. This monitoring is essential to identify a given source of lead, help 19

determine if there is any ongoing exposure, and to verify the decline in BLL after lead sources have 20

been reduced or eliminated. Ongoing monitoring is also essential for children undergoing chelation 21

[ 61 , 70 , 71 ]. 22

2330

Table 2: Recommended actions based on BLL 1 <Ref erence

Value ≥ Ref erence Value ≤45 ≥45 ≤69 ≥70

Lead education

- Dietary

- Environmental

Environ mental assessment* for pre

- 1978 housing

Follow

- up blood lead monitoring (see page s 23

- 24 ) Lead education

- Dietary

- Environmental

Follow

- up blood lead mon itoring

Complete history and physical exam

Lab work:

- Iron status Consider Hemoglobin

or hematocrit

Environmental investigation Lead hazard reduction

Neurodevelopmental monitoring

- Abdominal X

- ray (if particulate lead ingestion is suspected) with bowel decontamination if indicated Lead education

- Dietary

- Environmental

Follow

- up blood lead monitoring

Complete history and physical

exam

Lab work:

- Hemoglobin

or hematocrit

- Iron status

- Free erythrocyte protoporphyrin

Enviro nmental investigation Lead hazard reduction

Neurodevelopmental monitoring

Abdominal X

- ray with bowel decontamination if indicated

Oral Chelation therapy Consider hospitalization if lead

- safe environment cannot be assured Hospitalize and

commence chelat ion therapy (following confirmatory venous blood lead test) in conjunction with consultation from a medical toxicologist or a pediatric environmental health specialty unit

Proceed according to actions for 45

- 69 μ g/dL

2 * The scope of an "environmental assessment" will vary based on local resources and site conditions. However, this would include at a 3 minimum a visual assessment of paint and housing conditions, but may also include testing of paint, soil, dust, and water and other 4 lead sources discussed previously, e.g., [56]. This may also include looking for exposure from imported cosmetics, folk remedies, 5 pottery, food, toys, etc. which may be more important with low level lead exposure. See Section V for further clarification. 6 731 1 Table 3. Recommended Schedule for Obtaining a Confirmatory Venous Sample 2

3 Blood μg/dl Time to confirmation testing

≥ Reference Value

- 9 1

- 3 months

10

- 4 4 1 week

– 1 month *

45

- 59 48 hours

60

- 69 24 hours

≥70 Urgently as emergency test

* The higher the BLL on the screening test, the more urgent the need for confirmatory testing. 4 (Adapted from: Screening Young Children for Lead Poisoning: Guidance for State and Local Public Health Officials. Atlanta: 5 CDC; 1997.) 6 7 8 Table 4. Schedule for Follow-Up Blood Lead Testing a 9 10 Venous Blood lead level μg/dl Early follow up testing

(2

- 4 tests after identification) Later follow u p testing after blood lead level declining

≥ Reference Value

– 9 3 months * 6

- 9 months

10

- 19 1

- 3 months * 3

- 6 months

20

- 24 1

- 3 months * 1

- 3 months

25

- 44 2 weeks

- 1 month 1 months

≥45 As soon as possible As soon as possible

a Seasonal variation of BLLs exists and may be more apparent in colder climate areas. Greater exposure 11 in the summer months may necessitate more frequent follow ups. 12

* Some case managers or PCPs may choose to repeat blood lead tests on all new patients within a month to 13 ensure that their BLL level is not rising more quickly than anticipated. 1432

Children Deserving Special Attention 1

Numerous publications highlight the lead exposure risks to children from some immigrant 2

communities arising from a wide range of ongoing exposure sources or from exposures in their 3

country of origin. These children are at greater risk of having a BLL above the reference value outside 4

of the typical age range targeted for testing. Therefore, it is recommended that all immigrant 5

children, including international adoptees, be tested for lead exposure, with home evaluation to 6

identify sources if indicated. 7

Developmentally-delayed children with hand- to -mouth behavior persisting beyond the typical 8

age range should also be considered candidates for continued monitoring. In addition, healthcare 9

providers should consider blood lead testing for siblings of children with BLLs above the reference 10

value given the potential for lead exposure. 11



### IV. Achieving Lead-Safe Housing 12 13 KEY POINTS/RECOMMENDATIONS 14 **Educate families, service providers, advocates, and public officials on primary prevention of lead** 15 **exposure in homes and other child-occupied facilities, so that lead hazards are eliminated before** 16 **children are exposed.** 17 18 **CDC should encourage local, state, and other federal agencies to: 1) facilitate data-sharing between** 19 **health and housing agencies; 2) develop and enforce preventive lead-safe housing standards for** 20 **rental and owner-occupied housing; 3) identify financing for lead hazard remediation; and 4)** 21 **provide families with the information needed to protect their children from hazards in the home.** 22 23

24 ACCLPP has stated previously that the recommended approach to prevent lead poisoning is to reduce 25

exposures to lead-based paint hazards and to make and keep the U.S. housing stock "lead-safe". The 26

most common sources of exposure among children with BLLs above the reference value are lead 27

hazards in and around older housing, including deteriorated lead-based paint, lead-contaminated 28

dust, and accessible lead contaminated soil. Approximately 35% of all U.S. housing units have some 2933

lead-based paint, and 22% have significant lead-based paint hazards [ 72 ]. Low income households are 1

more likely to live in a home with lead-based paint hazards (29%) than higher income households 2

(18%) [ 72 ]. 3

4

Controlling and Preventing Lead Based Paint Hazards 5

Property owners can correct deteriorated paint and other lead hazards in the home 6

environment. Some local and state laws require abatement in a home where a child has been lead7

poisoned; this specialized work must be done by a certified abatement contractor. Abatement 8

involves permanent elimination of hazards through methods, such as enclosure, encapsulation, and 9

paint removal proven to last at least for 20 years. Interim controls and other lead-safe paint repairs 10

do not “permanently” eliminate hazards , because the paint is still present, but are effective in 11

arresting paint deterioration, if the underlying cause is addressed. 12

Uncontrolled renovation and painting that disturbs painted surfaces and generates leaded 13

dust and debris is a common route of child exposure to lead in the home. The events can occur 14

wherever there is lead-based paint, regardless of the condition of the buildin g’s painted surfaces. In 15

some communities, one-third to one-half of childhood lead poisonings have been reportedly derived 16

from renovation work. EPAs RRP rule now requires the use of trained, certified renovators for 17

activities that disturb painted surfaces in pre-1978 homes and child-occupied facilities. Twelve States 18

are authorized by EPA to conduct RRP in their jurisdictions. These states and EPA have certified 19

600,000 trained renovators. Maintaining paint in intact condition is the key strategy for preventi ng 20

deteriorated paint; fixing leaks can be an important means to this end. Although peeling paint is a 21

violation of most local and state housing codes, some officials are not aware of the importance of 22

citing the problem. 2334 1

Policies to Advance Lead Safe Housing 2

Primary prevention strategies focused on housing must be calibrated to address geographic 3

variation in the risk for lead exposure and to suit local circumstances, needs, and assets. Communities 4

and homes at highest risk should receive the greatest attention and resources. Collaboration among 5

housing, community development, and code enforcement agencies, property owners, and 6

community-based organizations is essential, in order to prioritize housing where occupants are likely 7

to be at greatest risk

. 8

Effective implementation of primary prevention requires access to a continuum of different 9

strategies for improving lead safety in various niches of the housing stock, with the goal of zero 10

tolerance for lead hazards. Key agencies must understand their roles and opportunities to stop lead 11

poisoning, particularly in code enforcement and repair financing. Lead-safe housing laws and 12

ordinances and housing or sanitary codes provide objective standards against which landlords can 13

demonstrate compliance. Property owners must ensure that deteriorated paint is repaired and not 14

create new hazards in the process . Renovators must comply with RRP and be held accountable to “do 15

no harm” throughout the repair and painting process

. Ideally, code agencies should be authorized to 16

cite non-compliance with RRP. Every effort should be made to integrate lead safety into other 17

housing activities, and to train and educate families, service providers, advocates, and public officials 18

to advance primary prevention by addressing lead exposure before a child is poisoned. 19

Because peeling paint and building materials in disrepair are already code violations in many 20

jurisdictions, enforcing these requirements is the basic minimum lead-safe housing policy. Federal 21

and state RRP mandates that paint repair activities in pre-1978 homes adhere to lead-safe work 22

practices designed to contain, control, and cleanup lead dust and debris. Because lead dust is 2335

invisible, clearance dust testing should be required after ordered repairs and in high-risk situations to 1

be certain that lead-contaminated dust does not remain behind to poison a child. 2

3

Recommendations for Local and State Government 4

Elected officials and the leaders of health, housing, and code agencies can help to protect 5

their jurisdicti ons’ children from lead in their homes through many activities [ 28 , 73 , 74 ] including 6

these six strategic approaches: 7

A. Target actions in pre-1978 properties according to known risk factors since the extent of risk 8

varies from property to property. Jurisdictions can have policies for designating higher risk 9

properties and specifying safeguards such as priority enforcement, environmental testing 10

requirements, more protective interventions such as abatement and interim controls, and higher 11

penalties for violations and non-compliance in response to risk. Multiple criteria can be combined 12

to best meet local needs. The key risk factors that should trigger additional requirements and 13

priority enforcement include real estate transactions (property sale, re-rental, or remodeling), 14

housing age (i.e. built before 1940/1950/1960), poor property condition, housing code or 15

environmental violations, and reported presence of lead hazards. Of course units and properties 16

occupied by children with blood test results above the CDC’s reference value should be targeted 17

if not reached by other environmental intervention policies. Neighborhood-level risk factors 18

include socioeconomic factors such as household income level, race/ethnicity and other 19

neighborhood demographics, concentrations of code violations, and other issues that can be 20

tracked using census or local agency data

. 21

B. Establish institutional linkages between public health programs and housing code enforcement 22

agencies to prioritize rental properties based on previous code violations and reported blood 2336

lead levels above the reference value

. These agencies must share data to uncover lead hazards 1

and confront housing violations of mutual concern, while independently fulfilling their respective 2

responsibilities for taking action. 3

C. Enact preventive housing standards and policies for rental housing (multifamily and single4

family) that mandate: 5

1. Property owner maintenance of painted surfaces and for other building components and 6

systems, and verification with an annual visual inspection for signs of water damage, moisture 7

problems, and deteriorated paint. Such inspections should also be mandated at unit turnover. 8

2. Proactive and routine code inspections that enable the code official to check all rental 9

dwellings for problems. 10

3. Priority enforcement of code requirements for intact paint in pre-1978 homes. To ensure no 11

lead dust hazards remain after ordered repairs, the property owner should obtain clearance 12

testing, and the agency that ordered repairs should confirm that the repairs were completed. 13

4. Attention to lead hazards at unit turnover since the convenience of current occupants is not of 14

concern in a vacant unit. 15

5. Clearance testing and a visual inspection to ensure that the home is lead-safe prior to renting 16

to new tenants and after other real estate transactions affecting rentals such as property sale, 17

lease renewal and refinancing. 18

6. Visual inspection and clearance dust testing after RRP jobs to ensure no lead dust hazards 19

remain. 20

7. Disclosure to other occupants, environmental testing, and building-wide repair if one unit in a 21

multifamily property has exposed a child to too much lead or contains lead hazards, since 22

there is a significant likelihood that similar hazards are present in other units in the building, 2337

due to the common construction, painting, and maintenance history. Other units’ tenants can 1

take steps to protect their children from lead exposure and have their children screened for 2

lead if they receive this information

. 3

D. Enact preventive housing standards and policies for owner-occupied housing

. While 4

enforcement opportunities for preventive housing standards and policies in these properties are 5

more limited, jurisdictions can mandate the following : 6

1. Priority enforcement of maintenance standards for painted surfaces and other building 7

components and systems on the exterior of an owner-occupied property. Citation of these 8

conditions can be reasonable cause for an interior inspection if there are indications of other 9

risk factors. To ensure no lead dust hazards remain after ordered repairs, the owner-occupant 10

should obtain clearance dust testing, and the agency that ordered repairs should confirm that 11

the repairs were completed. 12

2. Property owner performance of a visual inspection for signs of water damage, moisture 13

problems, and deteriorated paint prior to sale. 14

3. Disclosure to other multifamily occupant s if a child with a BLL above reference val ue is 15

identified in any unit, since there is a significant likelihood that similar hazards are present in 16

other units in the building or complex, due to common construction, painting, and 17

maintenance history. Afte r property management provides this information, the other 18

occupants, can take steps to protect their children from lead poisoning and have their children 19

screened for lead. 20

4. Visual inspection and clearance dust testing after RRP jobs to ensure no lead dust hazards 21

remain. 22

E. Provide Loans, Grants, and Other Financial Incentives for Hazard Remediation 2338

Jurisdictions and financial institutions should assist property owners in obtaining financial 1

assistance to remediate lead hazards. HUD’s Lead Hazard Control Pro gram Grants assist 300 2

homes in 30-50 communities each year. Jurisdictions that receive a formula allocation of 3

Community Development Block Grant (CDBG) and HOME funds have broad discretion in using 4

these block grants for a wide range of purposes, including housing rehabilitation and lead 5

hazard control, according to their Consolidated Plan, and should ensure that available data on 6

lead poisoning is taken into account in setting priorities. Private lenders offer loans on their 7

own initiative, as well as un der federal programs like FHA’s 203(k) buy

- rehab program, HUD’s 8

Title 1 program, and USDA’s Rural Housing Administration programs , and in response to 9

requirements under the Community Reinvestment Act. To advance the availability of financial 10

assistance, jurisdictions should seek prioritization of lead remediation through set-asides and 11

favorable financing terms, encourage financial institutions to make strategic investments in 12

lead remediation, and promote the adoption of tax credits for this purpose

. Because 13

intervention investments will have more durable results if they improve each unit across the 14

spectrum of environmental health and energy-efficiency, multi-purpose funding is needed to 15

leverage categorical programs, and public officials should require effective inter-agency 16

coordination to optimize repairs in the same home by various funding streams

. 17

F. Assist Families in Taking Self-Protective Actions 18

Parents and caregivers in all families who live in pre-1978 buildings, and especially families 19

living in high risk housing need effective direction and supportive services to protect their children. 20

Implementation of primary prevention requires that all families know how to protect their 21

own children from lead exposure in their own homes. Every effort should be made to train and 22

educate families in basic tactics in maintenance, and in communications with landlords, contractors, 2339

and others who can influence the presence of lead hazards in their homes. Service providers who are 1

in the home or otherwise in communication with high-risk families can help through observation, 2

education, advocacy and referrals. 3

4



### V. Environmental Interventions 5 6 KEY POINTS/RECOMMENDATIONS 7 **CDC should emphasize the importance of environmental assessments to identify and mitigate lead** 8 **ha zards before children demonstrate BLLs above the reference value. Prevention strategies must**  9 **be adopted to reduce environmental exposures from lead in soil, dust, paint and water before** 10 **children are exposed.** 11 12 **If lead hazards trigger a response in any unit in a multi-family housing complex, the same response** 13 **action should be applied to all similar untested units in the housing complex ,**  **unless a risk** 14 **assessment demonstrates that no**  **lead hazards are present in the other units.** 15 16

17 The goal of primary prevention is that all homes will become lead-safe and not contribute to 18

childhood lead exposure. Given the involuntary nature of lead exposures associated with housing and 19

other sources, and the risks associated with lead exposure, all exposures should be kept as low as 20

possible. Controlling potential lead exposures in a child’s environment before they cause damage will 21

be the only way to prevent childhood lead poisoning. Special vigilance is also needed around 22

renovation and remodeling activities in older homes, when lead dust levels are known to spike. 23

Lead-contaminated dust, soil, paint, and water are all associated with blood lead levels above 24

the reference value in children, as are other risk factors, such as parent’s occupation, age of housing, 25

poverty and ethnicity. Although most published research associating environmental lead exposures 26

and BLLs for children was done with children who had significantly higher levels than is common 27

today, there are notable exceptions, such as the recent NHANES analyses of dus t and children’s BLLs 28

[ 75 , 76 ]

. 2940

Multiple risk factors/ exposures contribute to BLLs less than 10 μg/dL. In fact investigations 1

conducted in response to a child with a BLL greater than 15 μg/dL often fail to identify a single source 2

or risk factor and the challenge is even greater for lower level exposures. The inability to identify a 3

single source of exposure in these cases underlines the fact that lead remains a multi-media pollutant 4

requiring integrated exposure assessment and reduction. However in the U.S., lead-based paint 5

hazards, including deteriorated paint, and lead-contaminated dust and soil still remain by far the 6

largest contributors to childhood lead exposure on a population basis [ 56 ]. 7

Although the U.S. Environmental Protection Agency has established recommended lead 8

exposure limits for dust, soil, and water in homes, these levels are not health based and were not 9

selected to be protective of exposures below 10 μg/dL. For example, the current hazard standard for 10

dust lead levels for floors of 40 μg/ft 2 is associated with potential exposures among children above 11

the reference value. Recent analysis of NHANES blood and dust lead data, for example, indicates that 12

when floor dust lead is less than 12 μg/ft 2 , the geometric mean BLL is 3.9 μg/dL [ 75 , 76 ]

. Water and 13

dust lead levels are currently under review by EPA. (See 14

http://yosemite.epa.gov/sab/sabproduct.nsf/RSSRecentHappeningsBOARD/9c733206a5d642578525 15

7695004f0cb1!OpenDocument&TableRow=2.2 and 16

http://water.epa.gov/lawsregs/rulesregs/sdwa/lcr/index.cfm#LongTermRevisions 17

A successful primary prevention strategy must start with an environmental assessment in 18

order to set priorities and inform the selection of appropriate response actions. Environmental 19

inspections and testing are also necessary responses to cases where a child has already been exposed 20

(See Table 2). 21

Significant research on children with BLLs greater than 25 μg/dL has focused on the efficacy of 22

a range of lead hazard controls and abatement of lead hazards (including dust, soil, and paint) and in 2341

uncontrolled trials has shown statistically significant declines in BLLs in the range of 20-30 percent at 1

follow up (reference [ 70 ] p. 95). Only very limited research has examined the efficacy of lead 2

abatement techniques and interim controls for children with BLLs as low as 5-9 μg/dL [ 77 ]. Evaluation 3

of the decline in BLLs following environmental interventions is problematic because bone lead stores 4

may remain a significant contributor to BLLs for many years following removal from further exposure 5

and/or chelation. 6

As we pursue and prioritize a primary prevention model, we move beyond the goal of 7

interventions just aimed at loweri ng a child’s BLL . The new emphasis must be on efforts that are 8

successful at reducing exposures to known sources. Prevention requires that we reduce 9

environmental exposures from soil, dust, paint and water before it contributes to a child’s 10

exposure. Beca use blood lead integrates all sources of exposure including lead released from bone 11

stores, it should not be used as a sole measure to determine whether or not a specific environmental 12

exposure has been successfully addressed. Instead, environmental measurements, e.g., soil, or dust 13

testing, are a more direct and preferred means of assessing whether an intervention has succeeded. 14

Environmental testing is a useful means to focus limited hazard control resources. 15

Environmental testing protocols have now been standardized and trained professionals who are 16

either certified or licensed are available to carry them out ([ 78 ] ; 17

<http://portal.hud.gov/hudportal/HUD?src=/program_offices/healthy_homes/lbp/hudguidelines ) 18

([ 79 ] ; <http://portal.hud.gov/hudportal/documents/huddoc?id=DOC_19537.pdf> ). 19

Observations by health departments and peer-reviewed studies have indicated that specific 20

addresses are often linked to repeated cases of elevated BLLs in children. For example, in Jefferson 21

County, Kentucky, 79 homes housed 35% of the 524 cases identified in one five-year period [ 80 ]. 22

Another study showed that neighborhoods based on census tracts predict rates of elevated BLL s 2342

amo ng children [ 81 ]

. In one study, lead hazard controls employed in select units significantly reduced 1

the likelihood of another child being lead poisoned compared to units where hazards were not 2

reduced[ 44 ]. Rental status, along with other housing characteristics, is also a predictor of BLLs greater 3

than 10 μg/dL [ 9 ]. Such information can be used to focus resources for environmental testing and 4

evaluation on homes where lead hazards are more likely to be found. 5

Environmental investigations in housing built before 1978 should include: 6

- History of child’s exposure and questionnaire on potential sources of exposure; 7

- Visual inspection of the home or facility where the child spends considerable time to identify 8

peeling paint, moisture damage, and other relevant housing conditions; 9

- Measurements of lead levels in dust (with single surfaces wipe samples), soil, water, and paint 10

that is not intact or otherwise separating from the substrate should be conducted. 11

Environmental assessments in response to children with elevated BLLs are also appropriate in 12

homes built after 1978 when the use of lead paint was restricted. In one large national survey three 13

percent of homes built from 1978-1998 had lead-based paint hazards [ 82 ]. However, the focus of 14

these assessments will vary based on individual circumstances and exposure sources other than lead 15

paint hazards should be considered before conducting environmental testing. 16

En vironmental assessments in housing built in 1978 or after should include: 17

- History of child’s exposure and questionnaire on potential sources of exposure; 18

- Visual inspection of the home and any other facility where the child spends considerable time 19

to identify potential exposure sources and other relevant conditions; 20

- Environmental sampling if conditions suggest that potential lead sources are present (e.g. 21

water, soil, dust). 2243

In addition, environmental assessments may include investigation of potential exposures from 1

other sources including, but not limited to, toys and other products, pottery cosmetics, folk remedies, 2

food and candy with significant lead content. The potential for take home exposures must also be 3

evaluated based on the parent’s occupation and hobbies. In some subpopulations such as 4

immigrants, imported products, foods, and folk remedies may be more commonly found and 5

therefore a more substantial contributor to lead exposures among children than in other 6

communities. 7

8

Recommendations 9

Although the long-term goal is to eliminate lead hazards in housing and child occupied 10

environments, it is clear that this aspiration cannot be achieved overnight. Many environmental 11

assessments in housing are still going to be triggered by the presence of a child with a BLL that 12

exceeds a defined threshold. Any venous BLL that is above the reference value for children should 13

trigger an environmental investigation to evaluate potential sources of exposure. 14

Any individual exposure that is significantly above the reference value suggests that one or 15

more source or pathway of exposure exists in the child’s environment that requires exposure 16

reduction. Exposures to lead hazards in homes or other child occupied facilities significantly 17

contribute to children’s BLLs ab ove the reference value. These hazards include lead levels above EPA 18

guidelines and/or regulations covering dust, soil, drinking water, and the presence of deteriorated 19

paint above specified quantities. 20

In situations where any lead hazards are present, the results of the environmental 21

investigation should be used to prioritize and plan hazard controls to reduce exposures. Hazard 22

control options should be developed by licensed or certified lead-based paint risk assessors and 2344

should be performed based on documented guidance and regulations ([ 78 ] ; 1

<http://portal.hud.gov/hudportal/HUD?src=/program_offices/healthy_homes/lbp/hudguidelines). If 2

environmental investigations uncover lead hazards triggering a response in a single unit in multi3

family housing, the response action should be applied to all similar untested units within the housing 4

development, unless a risk assessment shows that the other units are free of lead hazards. 5



### VI. Research Needs 6

KEY POINTS/RECOMMENDATIONS 7 **CDC should encourage additional research directed towards developing interventions capable of** 8 **maintaining children’s BLLs below the reference value.** 9 10 **Additional research priorities should include efforts to improve the use of data from screening** 11 **programs, develop next generation point- of**  **-care lead analyzers, and improve the understanding of** 12 **epigenetic mechanisms of lead action.** 13 14

15 Evaluation of interventions to reduce exposure 16

It is axiomatic that reduction of exposure to lead will prevent the consequences of exposure. 17

In many cases, interventions to reduce exposure will require little or no evaluation, and can be 18

implemented with the full expectation that they will work. Preventing the importation of le ad

19

painted toys and children’s jewelry, for example, should reduce or prevent exposure from that 20

source. Less clear, however, is the efficacy of specific interventions to keep blood lead 21

concentrations below the reference value in children living in pre-1978 housing. Funding agencies 22

should seek out and support work to develop and evaluate effective, broadly useful interventions 23

that work in the complex exposure situations that are commonly encountered. In addition, when 24

primary prevention programs are implemented, program officials should establish ways of measuring 25

their effectiveness. 26

27

Secondary Prevention 2845

Evidence that nutritional interventions affect BLLs is limited. However, higher dietary calcium, 1

iron, vitamin C, and zinc have been associated with lower blood lead concentrations at least in 2

infancy [ 83 ][ 84 ]. Calcium, zinc, and vitamin C are thus worth further investigation. Iron deficiency and 3

higher BLLs can occur in the same children and may have similar consequences [ 23 ]; children exposed 4

to lead should be evaluated for anemia and iron deficiency according to current AAP guidelines [ 57 ], 5

and any deficiency corrected. AAP does state that, although correction of iron deficiency may also 6

reduce the absorption of lead, that “iron supplement ation in a child with iron deficiency anemia who 7

also has lead poisoning without chelation therapy seems to increase blood lead concentrations and 8

decrease basal lead excretion.” This situation is rare, and the effect was seen in only one study [ 85 ] in 9

children with BLLs >25 μg/dL. The ACCLPP recommends that research to clarify this specific situation 10

be supported, but that lead-exposed children with BLLs <25 μg/dL be treated the same as any other 11

children as far as iron is concerned. 12

Children with cognitive or behavioral problems associated with lead exposure would benefit 13

from interventions that improve academic performance in children such as those participating i n 14

Head Start. The ACCLPP has charged another Work Group to recommend strategies on the 15

educational needs of children with elevated BLLs. Because lead exerts long-lasting effects and the 16

effect of lead on a child may not be demonstrable until the child is well into the elementary school 17

years, this report appropriately focuses recommendations for educational needs across the age span 18

of infancy through 21 years. The document will include a consideration of research needs specific to 19

this area. 20

21

Sources and routes of exposure in older children 2246

Blood lead concentrations are lower in older children, but most studies find a stronger 1

association between blood lead and IQ for the concurrent blood lead measurements, than for a 2

child’s peak blood lead at age 2 yea rs. Although much is known about behavior and exposure in 3

toddlers, older children have not been extensively studied and how they are exposed is less well 4

understood. Older children are more mobile, the scale of their environment is larger, and the source s 5

and routes of exposure likely differ from those for younger children. A systematic analysis of what is 6

already known for older children could provide a sound rationale for the design of additional research 7

on exposure pathways in these children. Research into the various lead suspension, transport, and 8

redeposition mechanisms at the neighborhood level, and how these impact lead exposures is needed. 9

Also additional research into urban lead remediation done throughout a neighborhood, rather than 10

on an individual property basis, could add to our understanding of exposure reduction among 11

children with relatively low level exposures. 12

13

Research on other uses of the results from screening programs 14

Although NHANES is a large, ongoing U.S. survey that currently inc ludes children’s BLL s, it 15

does not provide prevalence estimates for elevated BLLs for any segment smaller than a multi-state 16

region. Individual states and cities often have screening data, but it is not population-based. The 17

relationship between distribution of BLLs in the population and in a screened sample can vary, and 18

findings from NHANES and state lead programs should be viewed as complementary. Population19

based estimates of BLLs ≥10μg/dL in high risk neighborhoods in Chicago were similar to those 20

calculated using surveillance data collected by the health department [ 86 ]. 21

As the number of children tested and reported to CDC increases, the NHANES and national 22

surveillance estimates become closer . The percent of children with BLLs ≥ 10 μg/ dL reported to CDC 2347

decreased from 7.6% in 1997 to 3.1% in 2001, close to the NHANES estimate of 2.2% for 1999-2000 1

[ 87 ] . In 2008, among the children tested for lead and reported to CDC, 0.83% were ≥ 10 μg/ dL . The 2

2007

- 2008 NHANES estimate for BLLs ≥ 10 μg/dl was 1.22%, although this estimate is statistically 3

unstable. (CDC, unpublished data) These instances raise the possibility that a predictable relation 4

exists between the two methods. Since population-based surveys are difficult to conduct, it would be 5

helpful to have additional comparisons between surveillance programs (screening) and population6

based survey data to see if there are reliable associations between them. If there are, this would be 7

helpful both for prioritizing prevention activities and assessing progress at the state and local level. 8

9

Better point- of

-care lead analyzers 10

Given the present focus on lower BLLs, development of new point- of

- care (POC) lead 11

analyzers with better sensitivity, as well as increased accuracy and precision (e.g. +/- 1 μg/dL) at BLLs 12

<5 μg/dL would be desirable. Current POC lead analyzers appear to provide their optimal 13

performance at around the 10 μg/dL. It is at higher BLLs where POC lead analyzers performance is 14

relatively poorer. Beyond that, developing new analytical approaches based on improved 15

electrochemistry, use of novel plasma on a chip technology, non-destructive techniques based on 16

MμXRF, or other portable multi-elemental analyzers that would include other hazardous elements 17

might meet the needs of both the clinical and the research communities. 18

19

Epigenetic mechanism of lead action 20

A promising new area of research suggests that epigenetic mechanisms may play a role in how 21

early life exposure to lead influences development of the brain and other organ systems. These 22

alterations involve chemical modifications to the DNA, or regions surrounding the DNA, but do not 2348

involve mutations to the DNA sequence itself. Such alterations can influence patterns of gene 1

expression, and can persist even in the absence of continued exposure to lead. Epigenetic changes, 2

in the appropriate context, also have the potential for transgenerational inheritance [ 88

- 91 ]. Such 3

changes have been linked to elevated BLLs in human cohorts [ 92 ]. It will be critical to understand how 4

lead modifies epigenetic profiles, particularly since some of these alterations appear to be labile and 5

thus could be mitigated through subsequent behavioral experiences or other interventions. Studies 6

examining such relationships would further our understanding of how behavioral, academic, or other 7

interventions could be used to attenuate lead-related adverse health effects. 8

9 10

1149 

### VII. References 1 2 1. Centers for Disease Control and Prevention/National Center for Environmental Health. 3 Publications List . November 25, 2011]; Available from: 4 http://www.cdc.gov/nceh/lead/publications/. 5

2. Centers for Disease Control and Prevention. Preventing Lead Poisoning in Young Children . CDC, 6 Atlanta: 2005. 7

3. Centers for Disease Control and Prevention. Guidelines for the Identification and Management of 8 Lead Exposure in Pregnant and Lactating Women . CDC, Atlanta: 2010. 9

4. Healey, N., H. Jones‐Otazo, M. Walker & A. Knafla. 2010. Toxicological Review and Recommended 10 Toxicological Reference Values for Environmental Lead Exposure in Canada . FINAL REPORT. 11 Prepared under contract to Health Canada. Prepared for the Contaminated Sites Division, Safe 12 Environments Directorate, Healthy Environment and Consumer Safety Branch, Health Canada, 13 Ottawa. 14

5. Carlisle JC, Dowling KC, Siegel DM, and Alexeeff GV, A blood lead benchmark for assessing risks 15 from childhood lead exposure. J Environ Sci Health A Tox Hazard Subst Environ Eng, 2009. 16 44 :1200- 8. 17

6. Wilhelm M, Heinzow B, Angerer J, and Schulz C, Reassessment of critical lead effects by the 18 German Human Biomonitoring Commission results in suspension of the human biomonitoring 19 values (HBM I and HBM II) for lead in blood of children and adults. Int J Hyg Environ Health, 2010. 20 213 :265- 9. 21

7. Canfield RL et al., Intellectual impairment in children with blood lead concentrations below 10 22 microg per deciliter. N Engl J Med, 2003. 348 :1517- 26. 23

8. Bellinger DC and Needleman HL, Intellectual impairment and blood lead levels. The New England 24 journal of medicine, 2003. 349 :500-2; author reply 00- 2. 25

9. Lanphear BP et al., Low-level environmental lead exposure and children's intellectual function: an 26 international pooled analysis. Environ Health Perspect, 2005. 113 :894- 9. 27

10. Chandramouli K, Steer CD, Ellis M, and Emond AM, Effects of early childhood lead exposure on 28 academic performance and behaviour of school age children. Archives of Disease in Childhood, 29 2009. 94 :844- 8. 30

11. Nigg JT, Nikolas M, Mark Knottnerus G, Cavanagh K, and Friderici K, Confirmation and extension 31 of association of blood lead with attention-deficit/hyperactivity disorder (ADHD) and ADHD 32 symptom domains at population-typical exposure levels. Journal of Child Psychology and 33 Psychiatry and Allied Disciplines, 2010. 51 :58- 65. 34

12. Fewtrell LJ, Pruss-Ustun A, Landrigan P, and Ayuso-Mateos JL, Estimating the global burden of 35 disease of mild mental retardation and cardiovascular diseases from environmental lead 36 exposure. Environmental Research, 2004. 94 :120- 33. 37

13. Bellinger DC, Stiles KM, and Needleman HL, Low-level lead exposure, intelligence and academic 38 achievement: A long-term follow-up study. Pediatrics, 1992. 90 :855- 61. 3950

14 . Needleman HL, Schell A, Bellinger D, Leviton A, and Allred B, The long-term effects of exposure to 1 low doses of lead in childhood: An 11-year follow-up report. New England Journal of Medicine, 2 1990. 322 :83- 88. 3

15. Dietrich KN, A higher level of analysis: Bellinger's, interpreting the literature on lead and child 4 development. Neurotoxicology and Teratology, 1995. 17 :223-5; discussion 49- 51. 5

16. Pocock SJ, Smith M, and Baghurst P, Environmental lead and children's intelligence: a systematic 6 review of the epidemiological evidence. BMJ, 1994. 309 :1189- 97. 7

17. Chen A, Dietrich KN, Ware JH, Radcliffe J, and Rogan WJ, IQ and blood lead from 2 to 7 years of 8 age: are the effects in older children the residual of high blood lead concentrations in 2-year-olds? 9 Environmental Health Perspectives, 2005. 113 :597-601. 10

18. Gollenberg AL, Hediger ML, Lee PA, Himes JH, and Louis GM, Association between lead and 11 cadmium and reproductive hormones in peripubertal U.S. girls. Environmental Health 12 Perspectives, 2010. 118 :1782- 7. 13

1 9. Gump BB et al., Low-level prenatal and postnatal blood lead exposure and adrenocortical 14 responses to acute stress in children. Environ Health Perspect, 2008. 116 :249-55. 15

20. Gump BB et al., Blood lead (Pb) levels: further evidence for an environmental mechanism 16 explaining the association between socioeconomic status and psychophysiological dysregulation 17 in children. Health Psychol, 2009. 28 :614- 20. 18

21. Karmaus W et al., Immune function biomarkers in children exposed to lead and organochlorine 19 compounds: a cross-sectional study. Environ Health, 2005. 4 :5. 20

22. Selevan SG et al., Blood lead concentration and delayed puberty in girls. New England Journal of 21 Medicine, 2003. 348 :1527- 36. 22

23. Wasserman GA et al., Lead exposure and intelligence in 7-year-old children: the Yugoslavia 23 Prospective Study. Environmental Health Perspectives, 1997. 105 :956- 62. 24

24. Flynn JR, Massive IQ gains in 14 nations: What IQ tests really measure. Psychological Bulletin, 25 1987. 101 :171-91. 26

25. Flynn JR, What is Intelligence? Beyond the Flynn Effect 2009, Cambridge UK: Cambridge University 27 Press. 28

26. Ohmann S et al., Cognitive functions and glycemic control in children and adolescents with type 1 29 diabetes. Psychological Medicine, 2010. 40 :95-103. 30

27. Li Y, Dai Q, Jackson JC, and Zhang J, Overweight is associated with decreased cognitive functioning 31 among school-age children and adolescents. Obesity, 2008. 16 :1809- 15. 32

28. Centers for Disease Control and Prevention. Building Blocks for Primary Prevention: Protecting 33 Children from Lead-Based Paint Hazards . CDC, Atlanta: 2005. 34

29. Dietrich KN et al., Effect of chelation therapy on the neuropsychological and behavioral 35 development of lead-exposed children after school entry. Pediatrics, 2004. 114 :19-26. 36

30. Bellinger DC, Leviton A, and Sloman J, Antecedents and correlates of improved cognitive 37 performance in children exposed in utero to low levels of lead. Environmental Health 38 Perspectives, 1990. 89 :5

- 11. 3951

31. Bellinger DC, Lead neurotoxicity and socioeconomic status: conceptual and analytical issues. 1 Neurotoxicology, 2008. 29 :828- 32. 2

32. Guilarte TR, Toscano CD, McGlothan JL, and Weaver SA, Environmental enrichment reverses 3 cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol, 2003. 4 53 :50- 6. 5

33. Schneider JS, Lee MH, Anderson DW, Zuck L, and Lidsky TI, Enriched environment during 6 development is protective against lead-induced neurotoxicity. Brain Res, 2001. 896 :48- 55. 7

34. Brockel BJ and Cory-Slechta DA, Lead, attention, and impulsive behavior: Changes in a fixed-rati o 8 waiting-for-reward paradigm. Pharmacology Biochemistry and Behavior, 1998. 60 :545- 52. 9

35. Leasure JL et al., Low-level human equivalent gestational lead exposure produces sex-specific 10 motor and coordination abnormalities and late-onset obesity in year- ol d mice. Environ Health 11 Perspect, 2008. 116 :355- 61. 12

36. Rossi-George A, Virgolini MB, Weston D, and Cory-Slechta DA, Alterations in glucocorticoid 13 negative feedback following maternal Pb, prenatal stress and the combination: a potential 14 biological unifying mechanism for their corresponding disease profiles. Toxicol Appl Pharmacol, 15 2009. 234 :117-27. 16

37. Davis JM and Svendsgaard DJ, U-shaped dose-response curve-shaped dose-response curves: Their 17 occurrence and implications for risk assessment. Journal of Toxicology and Environmental Health, 18 1990. 30 :71- 83. 19

38. Kern M and Audesirk G, Stimulatory and inhibitory effects of inorganic lead on calcineurin. 20 Toxicology, 2000. 150 :171- 8. 21

39. Kern M, Wisniewski M, Cabell L, and Audesirk G, Inorganic lead and calcium interact positively in 22 activation of calmodulin. Neurotoxicology, 2000. 21 :353-63. 23

40. Binns HJ, Campbell C, and Brown MJ, Interpreting and managing blood lead levels of less than 10 24 microg/dL in children and reducing childhood exposure to lead: recommendations of the Centers 25 for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention. 26 Pediatrics, 2007. 120 :e1285- 98. 27

41. Jones RL et al., Trends in blood lead levels and blood lead testing among US children aged 1 to 5 28 years, 1988-2004. Pediatrics, 2009. 123 :e376- 85. 29

42. Yeoh B, Woolfenden S, Wheeler D, Alperstein G, and Lanphear B, Household interventions for 30 prevention of domestic lead exposure in children. Cochrane database of systematic reviews, 31 2008:CD006047. 32

43. Gould E, Chil dhood lead poisoning: conservative estimates of the social and economic benefits of 33 lead hazard control. Environmental Health Perspectives, 2009. 117 :1162- 7. 34

44. Brown MJ, Costs and benefits of enforcing housing policies to prevent childhood lead poisoning. 35 Medical decision making : an international journal of the Society for Medical Decision Making, 36 2002. 22 :482- 92. 37

45. Levin R, U.S. Environmental Protection Agency. Reducing lead in drinking water , 1986. 38

46. Schwartz J, Societal benefits of reducing lead exposure. Environmental Research, 1994. 66 :105- 39 24. 4052

47. Chisolm JJ, Jr., Lead poisoning in children and its prevention , in U.S. Senate Committee on Labor 1 and Public Welfare, Subcommittee on Health, 91st Congress, 2nd Session. 1970: Washington, DC. 2 p. 206-15. 3

48. Centers for Disease Control and Prevention. Preventing Lead Poisoning in Young Children . CDC, 4 Atlanta: 1991. 5

49. Centers for Disease Control and Prevention. Preventing Lead Exposure in Young Children: A 6 Housing-Based Approach to Primary Prevention of Lead Poisoning . CDC, Atlanta: 2004. 7

50. Binns HJ, LeBailly SA, Poncher J, Kinsella TR, and Saunders SE, Is there lead in the suburbs? Risk 8 assessment in Chicago suburban pediatric practices. Pediatric Practice Research Group. 9 Pediatrics, 1994. 93 :164- 71. 10

51 . Binns HJ, LeBailly SA, Fingar AR, and Saunders S, Evaluation of risk assessment questions used to 11 target blood lead screening in Illinois. Pediatrics, 1999. 103 :100- 6. 12

52. France EK, Gitterman BA, Melinkovich P, and Wright RA, The accuracy of a lead questionnaire in 13 predicting elevated pediatric blood lead levels. Archives of Pediatrics and Adolescent Medicine, 14 1996. 150 :958-63. 15

53. Tejeda DM, Wyatt DD, Rostek BR, and Solomon WB, Do questions about lead exposure predict 16 elevated lead levels? Pediatrics, 1994. 93 :192- 4. 17

54. Casey R, Wiley C, Rutstein R, and Pinto-Martin J, Prevalence of lead poisoning in an urban cohort 18 of infants with high socioeconomic status. Clinical Pediatrics, 1994. 33 :480- 4. 19

55. Dalton MA, Sargent JD, and Stukel TA, Utility of a risk assessment questionnaire in identifying 20 children with lead exposure. Archives of Pediatrics and Adolescent Medicine, 1996. 150 :197-202. 21

56. Levin R et al., Lead exposures in U.S. Children, 2008: implications for prevention. Environmental 22 Health Perspectives, 2008. 116 :1285- 93. 23

57. Baker RD and Greer FR, Diagnosis and prevention of iron deficiency and iron-deficiency anemia in 24 infants and young children (0-3 years of age). Pediatrics, 2010. 126 :1040- 50. 25

58. Six KM and Goyer RA, The influence of iron deficiency on tissue content and toxicity of ingested 26 lead in the rat. The Journal of laboratory and clinical medicine, 1972. 79 :128-36. 27

59. Barton JC, Conrad ME, Nuby S, and Harrison L, Effects of iron on the absorption and retention of 28 lead. The Journal of laboratory and clinical medicine, 1978. 92 :536- 47. 29

60. Centers for Disease Control and Prevention. Screening Young Children for Lead Poisoning: 30 Guidance for State and Local Public Health Officials . CDC, Atlanta: 1997. 31

61. American Academy of Pediatrics Policy Statement: Lead Exposure in Children: Prevention, 32 Detection and Management. Pediatrics, 2005. 116 :1036-46. 33

62. Centers for Disease Control and Prevention. Notes From the Field: Outbreak of Acute Lead 34 Poisoning Among Children Aged < 5 Years

--- Zamfara, Nigeria, 2010. Morbidity Mortality Weekly 35 Report, 2010. 59 :846. 36

63. Geltman PL, Brown MJ, and Cochran J, Lead Poisoning among refugee children resettled in 37 Massachusetts, 1995 to 1999. 2001. 108 :158. 3853

64. Falk H, International Environmental Health for the Pediatrician: Case Study of Lead Poisoning. 1 Pediatrics, 2003. 112 :259- 64. 2

65. Centers for Disease Control and Prevention. Evaluation and Recommendations for Preventing 3 Lead Poisoning among the Internally Displaced Roma Population in Kosovo from the Centers for 4 Disease Control and Prevention . CDC, 2011. 5

66. Centers for Disease Control and Prevention. Elevated blood lead levels among internationally 6 adopted children

-- United States, 1998. Morbidity Mortality Weekly Report, 2000. 49 :97-100. 7

67. Centers for Disease Control and Prevention. Lead Poisoning Words to Know from A to Z . CDC, 8 Atlanta: 2011. 9

68. Clinical Laboratory Improvement Amendments of 1988 . Pub. L. No. 100-578, 102 Stat. 2903, 42 10 U.S.C. § 263a: 1988. 11

69. Centers for Disease Control and Prevention. Interpreting and Managing Blood Lead Levels <10 12 μg/dL in Children and Reducing Childhood Exposures to Lead. Recommendations of CDC's 13 Advisory Committee on Childhood Lead Poisoning Prevention. Morbidity Mortality Weekly Report, 14 2007. 56

. 15

70. Centers for Disease Control and Prevention. Managing Elevated Blood Lead Levels Among Young 16 Children. Recommendations from the Advisory Committee on Childhood Lead Poisoning 17 Prevention. CDC, Atlanta: 2002. 18

71. American Academy of Pediatrics Committee on Drugs. Treatment guidelines for lead exposure in 19 children. Pediatrics, 1995. 96 :155- 60. 20

72. US Department of Housing and Urban Development. American healthy homes survey: lead and 21 arsenic . US Department of Housing and Urban Development. American healthy homes survey: 22 lead and arsenic, 2011. 23

73. Franko EM, Palome JM, M.J. B, Moore CM, and Kennedy LV, Centers for Disease Control and 24 Prevention. Children with Elevated Blood Lead Levels Related to Home Renovation, Repair, and 25 Painting Activities - New York State, 2006-2007. Morbidity Mortality Weekly Report, 2009. 58 :55- 26 58. 27

74. Alliance for Healthy Homes. Lead Safe Housing Policy Guidance . Alliance for Healthy Homes. Lead 28 Safe Housing Policy Guidance, 29

75. Dixon SL et al., Exposure of U.S. children to residential dust lead, 1999-2004: II. The contribution 30 of lead-contaminated dust to children's blood lead levels. Environmental Health Perspectives, 31 2009. 117 :468-74. 32

76. Gaitens JM et al., Exposure of U.S. children to residential dust lead, 1999-2004: I. Housing and 33 demographic factors. Environmental Health Perspectives, 2009. 117 :461- 7. 34

77. Clark S et al., Effects of HUD-supported lead hazard control interventions in housing on children's 35 blood lead. Environmental Research, 2011. 111 :301-11. 36

78. Department of Housing and Urban Development. Guidelines for the Evaluation and Control of 37 Lead-Based Paint Hazards in Housing. 1995. 38

79. U.S. Environmental Protection Agency. Lead Requirements for Lead-Based Paint Activitites in 39 Target Housig and Child-Occupied Facilites . U.S. Environmental Protection Agency. Lead 4054

Requirements for Lead-Based Paint Activitites in Target Housig and Child-Occupied Facilites, 1 Federal Register: 1996. 2

80. Reissman DB, Staley F, Curtis GB, and Kaufmann RB, Use of geographic information system 3 technology to aid Health Department decision making about childhood lead poisoning prevention 4 activities. Environmental Health Perspectives, 2001. 109 :89-94. 5

81. Kaplowitz SA, Perlstadt H, and Post LA, Comparing lead poisoning risk assessment methods: 6 census block group characteristics vs. zip codes as predictors. Public Health Rep, 2010. 125 :234- 7 45. 8

82. Jacobs DE et al., The prevalence of lead-based paint hazards in U.S. housing. Environ Health 9 Perspect, 2002. 110 :A599-606. 10

83. Schell LM et al., Relationship between blood lead concentration and dietary intakes of infants 11 from 3 to 12 months of age. Environmental Research, 2004. 96 :264- 73. 12

84. Houston DK and Johnson MA, Does vitamin C intake protect against lead toxicity? Nutrition 13 Reviews, 2000. 58 :73- 5. 14

85. Ruff HA, Markowitz ME, Bijur PE, and Rosen JF, Relationships among blood lead levels, iron 15 deficiency, and cognitive development in two-year-old children. Environmental Health 16 Perspectives, 1996. 104 :180- 5. 17

86. Dignam TA et al., High-intensity targeted screening for elevated blood lead levels among children 18 in 2 inner-city Chicago communities. American Journal of Public Health, 2004. 94 :1945-51. 19

87. Meyer PA et al., Surveillance for elevated blood lead levels among children - United States, 1997- 20 2001. Morbidity Mortality Weekly Report, 2003. 52 (SS10) :1

- 21. 21

88. Rothenberg SJ et al., Increased ERG a- and b-wave amplitudes in 7- to 10-year-old children 22 resulting from prenatal lead exposure. Invest Ophthalmol Vis Sci, 2002. 43 :2036-44. 23

89. Fox DA et al., Gestational lead exposure selectively decreases retinal dopamine amacrine cells and 24 dopamine content in adult mice. Toxicol Appl Pharmacol, 2011. 256 :258-67. 25

90. Dolinoy DC, Das R, Weidman JR, and Jirtle RL, Metastable epialleles, imprinting, and the fetal 26 origins of adult diseases. Pediatric Research, 2007. 61 :30R-37R. 27

91. Jirtle RL and Skinner MK, Environmental epigenomics and disease susceptibility. Nat Rev Genet, 28 2007. 8 :253- 62. 29

92. Giddabasappa A et al., Low-level gestational lead exposure increases retinal progenitor cell 30 proliferation and rod photoreceptor and bipolar cell neurogenesis in mice. Environ Health 31 Perspect, 2011. 119 :71- 7. 32

33 34