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SPECIAL ARTICLE |
a Oregon Evidence-Based Practice Center
b Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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METHODS. We searched Medline, reference lists of review articles, and tables of contents of leading pediatric journals for studies published in 1995 or later that contained new information about the prevalence, diagnosis, natural course, or treatment of elevated lead levels in asymptomatic children aged 1 to 5 years and pregnant women.
RESULTS. The prevalence of elevated blood lead levels among children and women in the United States, like that in the general population, continues to decline sharply, primarily because of marked reductions in environmental exposure, but still varies substantially among different communities and populations. Similar to the findings in 1996, our searches did not identify direct evidence from controlled studies that screening children for elevated blood lead levels results in improved health outcomes, and there was no direct evidence identified from controlled studies that screening improves pregnancy or perinatal outcomes. No new relevant information regarding the accuracy of screening for lead toxicity was identified during the update, and we did not identify evidence that demonstrates that universal screening for blood lead results in better clinical outcomes than targeted screening. Substantial new relevant information regarding the adverse effects of screening and interventions was not identified.
CONCLUSIONS. There is no persuasive evidence that screening for elevated lead levels in asymptomatic children will improve clinical outcomes. For those children who are screened and found to have elevated levels, there is conflicting evidence demonstrating the clinical effectiveness of early detection and intervention.
Key Words: lead levels • children • pregnancy • screening • intervention
Abbreviations: USPSTF—US Preventive Services Task Force • BLL—blood lead level • AHRQ—Agency for Healthcare Research and Quality • EPC—Oregon Evidence-Based Practice Center • KQ—key question • CDC—Centers for Disease Control and Prevention • CI—confidence limit • TLC—Treatment of Lead-Exposed Children • RCT—randomized, controlled trial • DMSA—meso-2,3-dimercaptosuccinic acid • SES—socioeconomic status • GM—geometric mean • FTII—Fagan Test of Infant Intelligence • RBC—red blood cell • HUD—US Department of Housing and Urban Development
In 1996, the US Preventive Services Task Force (USPSTF) recommended screening for elevated blood lead levels (BLLs) at 12 months of age in all children with identifiable risk factors and in all children living in communities in which the prevalence of elevated BLLs was high or unknown. There was insufficient evidence, however, to recommend a specific community prevalence below which targeted screening could be substituted for universal screening. The USPSTF found insufficient evidence to recommend for or against routine screening for lead exposure in asymptomatic pregnant women. The USPSTF also found insufficient evidence to recommend for or against trying to prevent lead exposure by counseling families to control lead dust by repeated household cleaning or to optimize caloric, iron, and calcium intake specifically to reduce lead absorption.1
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METHODS |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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Consistent with the scope of USPSTF recommendations, interventions needed to be relevant to primary care and feasible for delivery in primary care or by referral. Interventions were classified as pharmaceutical (chelation), environmental (residential lead paint, dust, or soil abatement), or nutritional. A primary reviewer abstracted relevant information from included studies for each of the intervention categories in KQ5.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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KQ2: Prevalence and Risk
The prevalence of elevated BLLs among children and women in the United States, like that in the general population, continues to decline sharply, primarily because of marked reductions in environmental exposure to lead (eg, gasoline, air, dietary sources, and residential paint). These reductions are largely the result of regulatory interventions at the federal, state, and local levels of government. The prevalence of elevated BLLs, however, varies substantially among different communities and populations, and children and pregnant women share many of the same risk factors for lead exposure. Correlates of higher BLLs at all ages include minority race/ethnicity, urban residence, low income, low educational attainment, older (pre-1950) housing, home renovation or remodeling, pica, use of ethnic remedies, cosmetics, lead-glazed pottery, occupational exposures, and recent immigration. Alcohol use and smoking are known risk factors among pregnant women (see Appendix 3 for a complete discussion).
Recent observational studies have demonstrated an inverse relationship between historical BLLs in children and subsequent measures of behavioral and cognitive performance at BLLs of <10 µg/dL. Observational studies of infants provide preliminary data that prenatal BLLs <10 µg/dL may be associated with neurodevelopmental delay or impairment. Study design and measurement issues, however, limit interpretation of these studies. Studies also suggest that levels of maternal exposure in this range may be associated with increased risk for spontaneous abortion, hypertension in pregnancy, and adverse effects on fetal growth2 (Appendix 3).
KQ3: Accuracy of Screening Tests
Can Screening Tests Accurately Detect Elevated BLLs?
We identified no new relevant information regarding the accuracy of screening for lead toxicity (refer to the 1996 USPSTF statement1). Blood lead testing has largely supplanted protoporphyrin levels as a screening tool because of poor performance of the latter at BLLs <25 µg/dL.3
What Is the Accuracy of Using Questionnaires (or Other Tools) for Risk-Factor Assessment at Various BLLs?
In communities where there is a low prevalence of elevated BLLs, screening will identify few cases and yield a significant proportion of false-positive test results. Older cross-sectional studies in urban and suburban populations showed that 1 or more positive responses to 5 questions (about exposures to deteriorated paint from older or renovated housing, to other lead-poisoned children, or to lead-related hobbies or industry) detected 64% to 87% of children with BLLs >10 µg/dL.1 Higher sensitivities (81%–100%) for BLLs >15 to 20 µg/dL were reported,1 but none of these studies evaluated the ability of questionnaires to detect levels >20 µg/dL, in part because so few patients had levels so high. Specificity among the studies ranged from 32% to 75%. False-negative results were predictably low (0.2%–3.5%) in low-prevalence (2%–7%) samples but increased to 19% when the population prevalence of elevated lead levels was higher (17%–28%). Questionnaires, therefore, may have greater utility in identifying children at low risk of elevated blood lead (negative predictive value) where the population prevalence is low and local risk factors are known. Negative predictive values of 96% to 100% have been reported in these settings.1,4
More recent studies of questionnaires in urban and rural settings, however, demonstrated a low prevalence of elevated BLLs and poor sensitivity and specificity.5–8 Studies of questionnaires modified for local use provide some evidence of improved clinical utility for identifying children with elevated BLLs,8–10 when compared with the panel of screening questions recommended by the Centers for Disease Control and Prevention (CDC) in 1991.11
Other studies have reported high false-positive rates for questionnaires6,8 and that resource considerations5 are important when formulating a screening program. A population-based follow-up study (n = 31904) showed that raising the action level for screening to 15 µg/dL in this sample would have eliminated the unnecessary follow-up of 5162 children, 3360 of whom were falsely identified as having elevated lead levels.12
A recent study identified housing risk factors associated with elevated BLLs (>10 µg/dL) among 481 children residing in Rochester, New York. Housing characteristics including rental status, lead-contaminated floor dust, and poor housing conditions were all associated with elevated BLLs (sensitivity: 47%–92%; specificity: 28%–76%; positive predictive value: 25%–34%; negative predictive value: 85%–93%), suggesting that housing characteristics and floor dust lead levels can be used to identify homes in which a lead hazard may exist before or during occupancy.13
Prenatal Screening With Questionnaires
A maternal survey using 4 questions recommended by the CDC was evaluated in a study of 314 new prenatal patients. The prevalence of elevated maternal lead levels (
10 µg/dL or 0.483 µmol/L) was 13%. Subjects with a positive response to at least 1 question were more likely to have elevated blood lead than those who answered negatively to all 4 questions (relative risk: 2.39; 95% confidence interval [CI]: 1.17 to 4.89; P = .01). The CDC questionnaire had a sensitivity of 75.7%. Among women who answered "no" to all 4 questions, the probability of having an elevated lead level was reduced from 13% to 6.9% (negative predictive value: 93.1%). The most predictive single item was "home built before 1960." The study also identified a high prevalence of elevated blood lead among children living with women with elevated BLLs.14
KQ5: Effectiveness of Early Detection
Detecting elevated BLLs before the development of clinical manifestations allows a clinician to recommend interventions to limit additional exposure and, when necessary, begin medical treatment with chelating agents. Early detection may also result in interventions that prevent lead exposure in other children (the child with an elevated BLL acting as a sentinel for a hazardous environment). There is relatively little convincing evidence, however, that these interventions effectively improve health outcomes. First, most available studies of asymptomatic children evaluated the effects of various interventions on BLLs rather than on clinical outcomes. Second, BLLs in childhood, after peaking at 
2 years of age, decrease without intervention,1,15 a result attributable in part to regression to the mean, random variation, laboratory error, and redistribution of lead from blood to other tissue compartments. Studies must account for these changes over time, preferably by using controls who do not receive the intervention, to adequately evaluate the interventions' effects on BLLs or health outcomes.
Effect of Screening on Clinical Outcomes
The EPC staff did not identify evidence demonstrating that universal screening for blood lead results in better clinical outcomes. The 1996 USPSTF recommendation cited several older studies that reported intensive screening programs targeting children in high-risk neighborhoods reduced case fatality rates, mortality rates, and proportions of children detected with very high BLLs or who developed symptomatic lead poisoning.1 Lacking concurrent controls, however, it was possible that the reported reductions in mortality and case fatality rates were caused by other factors such as advances in medical care rather than the effect of screening. The reduction in mean BLLs in the US population is primarily the result of diminishing exposure in the environment through regulatory interventions. The available evidence regarding the efficacy of screening programs, therefore, is weak.
Do Interventions for Elevated Lead Levels Result in Improved Health Outcomes?
Although chelating agents benefit children with symptomatic lead poisoning, no studies have demonstrated clinical benefits of chelation therapy in asymptomatic children. The Treatment of Lead-Exposed Children (TLC) trial, a large multicenter randomized, controlled trial (RCT) sponsored by the US National Institute for Environmental Health Science, enrolled children from 1994 to 1997 to assess the effect of oral chelation therapy with succimer on IQ in young children with venous BLLs of 20 to 45 µg/dL.16 Follow-up testing at 36 months demonstrated a mean IQ 1 point lower, and poorer parental ratings of behavior, among those in the succimer group compared with those in the placebo group. Although succimer-treated children did slightly better on a test of learning ability, none of the differences between groups were statistically significant.17 Reanalysis of the same data using the change in BLL as the independent variable demonstrated a 4.0-point improvement in cognitive scores for every 10 µg/dL reduction in BLL, but only in the placebo group, suggesting that factors other than declining blood lead contributed to cognitive improvement or that treatment had an adverse effect on cognitive performance.18 Assessment of neurobehavioral outcomes at 7 years of age revealed no statistically significant differences on a battery of neurobehavioral tests except that those in the succimer group had worse attention-executive function scores.19 Treatment also seemed to have an adverse effect on mean height.20 The TLC group concluded that chelation therapy was not indicated for children with BLLs <45 µg/dL.17,19
Despite evidence of efficacy in lowering blood lead on a short-term basis, there is little evidence confirming a clinical benefit from chelation therapy for children with lead levels <45 µg/dL.
We found no studies that evaluated clinical outcomes after environmental or nutritional interventions.
Effects of Chelation Therapy on BLLs
In the previously cited US National Institute for Environmental Health Science–sponsored RCT of oral chelation in young children with venous BLLs of 20 to 45 µg/dL (TLC study), which reported no effects of chelation on IQ16–19,21 (Tables 1 and 2), BLLs fell steeply in the treatment-group subjects in the first week (mean: 11 µg/dL lower) but rebounded afterward. BLLs also dropped in the placebo-group subjects but more slowly. BLLs were 77% of baseline in the succimer-treated subjects (88% of baseline among placebo) at 7 weeks after initiation of therapy. Mean BLLs among those in the treatment group were 4.5 and 2.7 µg/dL at 6 and 12 months, respectively, but the difference between those in the treatment and placebo groups at 24 months was not significant.21
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These data provide good evidence that chelating agents may result in short-term reductions in BLLs in children but suggest that these reductions may not be sustained over longer periods in the absence of repeated or continuing chelation therapy or environmental interventions. In addition, there is no evidence that these reductions result in improved neurobehavioral or health outcomes.
Effect of Residential Lead Hazard Control on BLLs
Recent studies of household dust and paint hazard control through cleaning, abatement, and education have shown mixed results. Of the 8 controlled studies published since 1995, 1 has shown a modest, but significant, decline; 5 have shown nonsignificant declines; and 2 have shown nonsignificant elevations in BLLs among children. Reduced BLLs were seen among children with higher baseline BLLs (15 or 20 µg/dL) in 2 studies (1 meta-analysis and 1 retrospective chart review with no comparison group) but not in children with lower baseline levels. Recent studies have differed from older studies in that newer paint hazard-control techniques result in lower lead-dust levels. Population venous lead levels have decreased over time, and lead-poisoned children in older studies had higher mean BLLs than those in recent studies (see Tables 3 and 4 and Appendix 4 for a detailed assessment).
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Effect of Soil Abatement on BLLs
Recent studies of soil remediation in residential areas have shown only modest or nonsignificant effects.25–27 Soil remediation in communities near lead-mining, -milling, or -smelting operations may have a beneficial effect but was not considered within the scope of review (see Appendix 6 for a detailed assessment).
Effect of Nutritional Interventions on BLLs
There is conflicting evidence whether nutritional interventions are an efficacious way to lower children's BLLs. Depending on the nutritional intervention under investigation, findings are limited, preliminary, and somewhat contradictory (Tables 5 and 6; see Appendix 7 for a detailed assessment).
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Reported adverse effects of treatment with succimer (meso-2,3-dimercaptosuccinic acid [DMSA]) include mild gastrointestinal (vomiting and diarrhea) and systemic symptoms, rashes, transient hyperphosphatasemia, neutropenia, eosinophilia, and elevations in serum transaminases. These effects occurred in up to 10% of cases.1,16–19,21
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EVIDENCE SYNTHESIS AND CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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There is no direct evidence comparing the outcomes of universal screening with the outcomes from targeted screening for elevated lead levels. Recent studies indicate that the prevalence of elevated BLLs in the United States has declined dramatically in the past 2 decades, but local prevalence is highly variable, with >10-fold differences between communities. In a community with a low prevalence of elevated BLLs, universal screening may result in disproportionate risks and costs relative to benefits. The prevalence level at which targeted screening can replace universal screening is a public health policy decision that requires consideration beyond the scientific evidence for effectiveness of early detection, such as available resources, competing public health needs, and costs and availability of alternative approaches to reducing lead exposure. Clinicians can consult their local or state health departments regarding appropriate screening policy for their populations (see Appendix 8 for recommendations from other groups).
In communities from which data suggest that universal screening is not indicated, there may be some children who are at increased risk of BLLs in the range for which individual intervention by chelation therapy or residential lead hazard control has been demonstrated to be effective. In addition to risks from housing, these children may have had exposure to other lead sources such as lead-based hobbies or industries, traditional ethnic remedies, or lead-based pottery. Selective blood lead screening of such high-risk children is appropriate even in low-prevalence communities.
Questionnaires that have been locally validated and are of known and acceptable sensitivity and specificity can assist in identifying those at high risk. In several studies, the CDC11 and similar questionnaires correctly identified 64% to 87% of urban and suburban children who had BLLs >10 µg/dL. Because of frequent false-positive results in low-prevalence communities, questionnaires may have greater utility in identifying children at low risk of elevated BLLs (negative predictive value) where the population prevalence is low and local risk factors are known. Locale-specific questionnaires that inquire about likely local sources of lead exposure may lead to improved prediction.
There are no controlled trials that have evaluated screening for elevated BLLs in pregnant women, and there are insufficient data to construct an adequate chain of evidence demonstrating benefit. The prevalence of levels >15 µg/dL seems to be quite low in pregnant women. There is some evidence that mildly elevated BLLs during pregnancy are associated with small increases in antepartum blood pressure, but there is only limited evidence that these levels have important adverse effects on reproductive outcomes. An extensive literature search failed to identify studies that have evaluated screening or intervention for lead exposure in pregnant women. There are potentially important adverse effects of chelation therapy on the fetus and of residential lead hazard control on both the pregnant woman and fetus if they are not performed according to established standards. Although removal to a lead-free environment would theoretically be effective in reducing lead exposure, it has not been specifically evaluated in pregnancy.
Community-based interventions for the primary prevention of lead exposure are likely to be more effective, and may be more cost-effective, than office-based screening, treatment, and counseling.28 Evaluating the effectiveness of community-based interventions and recommendations regarding their use are important areas of future research.
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APPENDIX 1. KQs AND CRITICAL KQs |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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KQs for children were stated as follows:
KQs for pregnant women were stated as follows:
Members of the USPSTF and AHRQ identified KQ1 and KQ5 for children and pregnant women as critical KQs. For these critical KQs, we used USPSTF methods to systematically abstract information about the design, results, and internal validity of each study and included only those studies we rated to be of fair quality or better.29 We conducted a selected review of the literature that addressed KQ2, KQ3, KQ4, and KQ6. The cost-effectiveness of screening would be examined only in the presence of adequate evidence of intervention efficacy. We did not examine KQ7 because of the lack of evidence of improved clinical outcomes for KQ5. We reviewed the populations of asymptomatic children and pregnant women separately.
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APPENDIX 2. CRITERIA FOR GRADING THE QUALITY OF INDIVIDUAL STUDIES |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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Presented below are a set of minimal criteria for each study design and a general definition of 3 categories: good, fair, and poor. These specifications are not meant to be rigid rules but, rather, are intended to be general guidelines, and individual exceptions, when explicitly explained and justified, can be made. In general, a good study is one that meets all criteria well. A fair study is one that does not meet (or it is not clear that it meets) at least 1 criterion but has no major limitations. Poor studies have at least 1 major limitation.
Systematic Reviews
Criteria include:
Definition of ratings from above-listed criteria:
Case-Control Studies
Criteria include:
Definition of ratings from above-listed criteria:
80%; diagnostic procedures and measurements accurate and applied equally to cases and controls; and appropriate attention to confounding variables.
RCTs and Cohort Studies
Criteria include:
Definition of ratings from above-listed criteria:
Diagnostic-Accuracy Studies
Criteria include:
Definition of ratings from above-listed criteria:
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APPENDIX 3. DETAIL ON PREVALENCE AND RISK |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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What Is the Prevalence of Elevated Lead in Asymptomatic Pregnant Women?
BLLs and blood umbilical cord lead levels are frequently used to assess both the mother's and fetus's level of lead exposure and risk. In 1992, 2 large surveys of low-income pregnant women found 0% and 6%1 with BLLs >15 µg/dL. A study of all women who enrolled in prenatal clinics in Mahoning County, Ohio, from 1990 to 1992 found that 13% of prenatal patients had BLLs >10 µg/dL, with 1% having BLLs >15 µg/dL.14
Population mean BLLs in women of childbearing age and pregnant women have decreased over the past 2 decades. Although it was estimated in 1990 that 4.4 million women of childbearing age, and >400000 pregnant women, had BLLs of >10 µg/dL,31 a longitudinal study of pregnant women in Boston, Massachusetts, demonstrated that umbilical cord BLLs declined 82% between 1980 and 1990.32 A recent study of 1109 infants in Quebec, Canada, found a mean cord-blood lead level of 1.5 µg/dL (0.076 µmol/L; 95% CI: 0.074 to 0.079).33 In a recent review of National Health and Nutrition Examination Survey data of 4394 women of childbearing age, the geometric mean (GM) BLL was 1.78 µg/dL.34
Are There Population-Level Risk Factors That Identify Children at Higher Risk for Elevated Lead Levels (ie, Geography, Race/Ethnicity, SES, Age)?
The highest GM BLLs in the United States occur in children aged 1 to 5 years (GM BLL: 1.9 µg/dL) and adults aged >60 years (GM BLL: 2.2 µg/dL), with the lowest levels in youth aged 6 to 19 years (GM BLL: 1.1 µg/dL).30 Children younger than 5 years are at greater risk for elevated BLLs and lead toxicity because of increased hand-to-mouth activity, increased lead absorption from the gastrointestinal tract, and the greater vulnerability of a developing central nervous system.35 GM levels are significantly higher in males than in females except among children aged 1 to 5 years.30
Correlates of higher BLLs at all ages include minority race/ethnicity, urban residence, low income, low educational attainment, older (pre-1950) housing, and recent immigration.30,36–40 These factors are associated with increased exposure to important lead sources, including dilapidated housing containing lead-based paint, lead-soldered pipes, household lead dust, and lead in dust and soil from heavy traffic and industry.1,41 There have been major reductions in the number of US homes with lead-based paint from the estimated 64 million in 1990, but 24 million housing units still contain substantial lead hazards, with 1.2 million of these units occupied by low-income families with young children.30,42
Less frequent sources of household lead exposure include contaminated clothing or materials brought home by workers in lead-using industries, lead-using home businesses or hobbies, lead-based paint and dust contamination in pre-1978 housing that is undergoing remodeling or renovation,40 dietary intake from lead-contaminated consumer products, drinking water, and lead-based pottery, and traditional ethnic remedies.3,28,30,43,44
GM BLLs among black children (2.8 µg/dL) remain significantly higher than those among Mexican American children (1.9 µg/dL) and non-Hispanic white children (1.8 µg/dL). Even among low-income families, however, GM BLLs declined significantly from 1991–1994 (3.7 µg/dL) to 1999–2002 (2.5 µg/dL).30
A woman of childbearing age with a high BLL risks transmitting lead to her unborn child.45 Ethnic background, country of origin, and immigrant status of birth mothers, pica behavior, as well as lifestyle and work patterns of pregnant women and age have shown to be associated with prenatal lead exposure in newborns. Multivariate analyses of pregnant women in Quebec revealed that both cigarette smoking (15% increase) and alcohol intake (17% increase) make significant and independent contributions to cord-blood lead concentrations.46 In a survey of 10 Quebec hospitals, umbilical cord-blood samples were obtained from 1109 newborns. Although BLLs were considered low, a statistically significant relationship was observed between maternal age and smoking during pregnancy in cord-blood lead concentrations.33
Mother/infant pairs (159) from a cohort of women receiving prenatal care in Pittsburgh, Pennsylvania, provided blood samples at delivery for lead determination. Alcohol use was associated with relatively greater cord-blood lead levels compared with maternal BLLs. No association was found with cord-blood lead level or maternal BLL with smoking, physical exertion, or calcium consumption.47
A recent study in New York City, New York, of pregnant women in their third trimester with an incident BLL of 20 µg/dL showed they had newborns with a median incident BLL of 12 µg/dL. In addition, maternal BLLs were directly associated with gestational age and pica behavior. These subjects were more than twice as likely to be foreign-born women.48
Neurotoxic Effects of Lead Exposure in Children
High levels of lead can produce serious central and peripheral neurologic complications including acute encephalopathy, which can result in coma, death, or long-term impairment.1,49,50 Prospective cohort studies across several child populations have suggested that a rise in BLL from 10 to 20 µg/dL is associated with a likely decrement of 2 to 3 points (reported range: –6 to +1) in intelligence test scores (IQ).1 The variety of test instruments that have been used, and differences in adjustment for important covariates, make direct comparison of these studies difficult, but a consistent negative effect on intellectual development has been reported.
Significant associations have been demonstrated between umbilical BLLs and neurodevelopmental testing at 2 years of age, although the association was not significant at later ages. BLLs at 2 years of age, however, were associated with neurocognitive performance at 10 years of age.35 A recent analysis of school-aged children demonstrated a stronger cross-sectional inverse association of IQ with contemporary BLLs (mean BLL: 8 µg/dL at 7 years of age) than with baseline BLLs (mean BLL: 26 µg/dL at 24 months of age), suggesting an ongoing adverse effect of lead on cognitive performance among school-aged children.51
Previous cross-sectional studies1 consistently reported small, inverse associations between blood or tooth lead level and reaction (attentional) performance, but studies that evaluated the effect of mildly elevated BLLs on other measures of neurodevelopmental function (eg, behavior, learning disorders, auditory function) produced inconclusive results. These outcomes have been evaluated less thoroughly than IQ, and more recent studies have bolstered an association between childhood lead exposure and disorders of attention and learning and of aggressive and delinquent behavior.35,49,52,53
A growing number of human epidemiology studies have reported associations between neurotoxic effects and BLLs once thought to be harmless. Several recent studies have demonstrated an inverse relationship between historical BLLs and subsequent measures of intellectual and cognitive performance at BLLs of <10 µg/dL. The shape of the dose-response curve at levels <10 µg/dL is uncertain, although data suggest that lead-associated cognitive changes may be greater with incremental changes in BLLs in this range.35,49,53–57 A recent meta-analysis of 7 prospective international cohort studies found evidence of deficits on standard IQ testing among children with maximal BLLs <7.5 µg/dL. A decline of 6.2 IQ points (95% CI: 3.8 to 8.6) was observed as BLLs increased from 1 to 10 µg/dL.58
Lead-associated effects on neurobehavioral functioning must be considered relative to other important covariates such as SES, home and parenting environment, and genetic factors.54 The contribution of childhood lead exposure to the observed variance in cognitive ability (IQ testing) is believed to be in the range of 1% to 4%, whereas social and caregiving factors may be responsible for 40%.52,54 BLLs, however, seem to be associated with a substantial proportion of the known, modifiable variance in children's cognitive ability and incur a substantial social and economic burden among those affected and on the nation.59,60
Reproductive Effects of Lead Exposure
The effects of high BLLs on reproductive outcomes have been well described.1 High paternal BLLs (>40 µg/dL or prolonged levels >25 µg/dL) are associated with impaired fertility, spontaneous abortion, and fetal growth abnormalities (preterm delivery and low birth weight). Maternal BLLs as low as 10 µg/dL have been associated with pregnancy hypertension, spontaneous abortion, and neurobehavioral effects in offspring. Studies that evaluated potential associations between parental lead exposure and congenital malformations in offspring have not demonstrated consistent patterns of defects or magnitude of risk and often lack biological indices of exposure at developmentally significant times.2
The Mexico City Prospective Lead Study examined the association of maternal prenatal BLLs during pregnancy (range: 7.5–9.0 µg/dL [0.36–0.43 µmol/L]) and child postnatal BLLs (range of median BLL from birth to 48 months: 7.0–10.0 µg/dL [0.34–0.48 µmol/L]) with head circumference in a sample of Latino immigrants living in Los Angeles, California. Multiple regression modeling showed significant negative associations (P < .05, 2-tailed) between 6-month head circumference and 36-week maternal BLL and between 36-month head circumference and 12-month BLL, but these were the only significant associations among >50 assessed in this study.61
In 272 mother/infant pairs, tibia bone lead was the only lead biomarker clearly related to birth weight (other significant birth weight predictors included maternal nutritional status, parity, education, gestational age, and smoking during pregnancy). Findings suggest that bone lead might be a better biomarker of body lead burden than BLL.62
Neurodevelopmental and Cognitive Measures and Lead Effects
Recent observational studies (prospective cohort and cross-sectional) provide limited, preliminary data that prenatal BLLs may be associated with neurodevelopmental delay or impairment. Study design and measurement issues, however, limit interpretation of these studies.
A prospective study of 103 black neonates with low-level (<5 µg/dL) parental lead exposure included a battery of 16 neonatal behavioral assessments 1 to 2 days after birth. No differences were found in 15 of the 16 domains studied, with neonates in the higher-exposure group receiving lower scores on the hand-to-mouth motor activity than did those infants in the lower-exposure group (P < .05).63 A sample of 79 black infants with low-level prenatal parental lead exposure was given the Fagan Test of Infant Intelligence (FTII) battery at 7 months of age.64 Excluding all but infants with scores in the 5th and 95th percentiles of the FTII (n = 5 in both groups) revealed that subjects rated at high risk for impairment on the FTII (lower 5th percentile) were 6 times more likely to be in the highest maternal BLL quartile (P < .004). Infants scoring in the lower 15th percentile on FTII score (n = 12) were 2 times more likely to be in the high maternal BLL quartile, although significance dropped to P < .056.64 The difference between the mean BLLs in the infants with lowest and highest FTII scores (5th and 95th percentiles) was very small, however (0.44 vs 0.94 µg/dL). Recent evidence suggests that children may demonstrate differences in evoked visual and auditory potentials associated with increased levels of prenatal lead exposure.65,66
Other Adverse Effects of Lead Exposure
Higher BLLs (>40 µg/dL) exert detrimental effects on neurologic, cardiovascular, renal, and hepatic function.1 Subclinical effects on renal function can be observed at lower levels of exposure, and children may be more vulnerable.67,68
In a cohort of women in their third trimester of pregnancy, immigrant women were more likely to have elevated BLLs and elevated blood pressure compared with nonimmigrant women. An association between elevated BLL and blood pressure was significant only in the group of immigrants.69 Past lead exposure was associated with hypertension and elevated blood pressure during pregnancy. Bone lead concentration, however, was not shown to be related to hypertension or elevated BLL in pregnancy.70
Among 110 women in their third trimester of pregnancy, those with gestational hypertension showed significantly higher BLLs than those who were normotensive, and BLL was significantly related to blood pressure even after correcting for BMI and age. The lead/ionized-calcium ratio showed a stronger association with blood pressure than with lead alone.71 A cross-sectional study of 39 pregnant women in their third trimester compared red blood cell (RBC) levels of lead and blood pressure. The study population included 20 women with normal pregnancies, 15 with mild hypertension, and 4 with severe hypertension and preeclampsia. Preeclamptic women were more likely to have an elevated RBC lead level. Rank correlation showed a significant effect of RBC lead level on blood pressure.72
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APPENDIX 4. DETAIL ON RESIDENTIAL LEAD HAZARD CONTROL ON BLLs |
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Before 1996, retrospective cohort studies, case series, and uncontrolled experiments suggested a modest decline (4–10 µg/dL) in mean BLLs in children with initial BLLs >25 µg/dL. More recent studies of newer lead-based paint hazard-control techniques that included an untreated comparison group, however, found more modest beneficial effects74,75 or no effects.76,77
A meta-analysis of 4 RCTs conducted in 1996–2000 found that interventions had no effect on mean BLLs (–0.62 µg/dL; 95% CI: –1.55 to 0.32), but there were significant reductions in the proportion of children who had BLLs >15 µg/dL (6% vs 14%; P = .008) and >20 µg/dL (2% vs 6%; P = .024) in those in the intervention group compared with controls.78
Of these 4 trials, 2 evaluated dust control and 2 evaluated providing education and equipment to families. The earlier of the 2 trials of dust control (1998) evaluated 1-time professional dust control and window-sill-paint sealing in homes of children aged 4 or younger with mean BLLs of 16.9 µg/dL.76 There were similar reductions in BLLs in the children in the intervention and control groups (–6.2 vs –5.9 µg/dL) 6 months after abatement. In the second randomized trial (1999), conducted in Jersey City, New Jersey, investigators recruited children aged 6 to 36 months who had lead paint in the home. Families (n = 113) were randomly assigned to a lead-exposure–reduction group or to an accident-prevention control group. In the lead-exposure–reduction group, staff members visited the home every 2 weeks and spent 2 hours cleaning up dust. After 1 year, there was a small but statistically significant difference in BLL change between those in the intervention and control groups, adjusted for baseline BLLs (–2.1 vs +0.1 µg/dL; P < .05).74
A follow-up study in urban children participating in the TLC trial examined the effects of a second professional lead-dust cleaning of homes 18 months after an initial cleaning and therapy commencement.79 All homes in the Philadelphia, Pennsylvania, site (n = 165) of the TLC trial were offered a second professional cleaning. Participation in the follow-up intervention was voluntary rather than randomly assigned. The mean BLL at study initiation was 26 µg/dL. The mean BLL was 15.7 µg/dL at the second cleaning visit, but 6 months later there was no difference in BLLs between children whose homes were cleaned (n = 73) and those whose homes were not cleaned (n = 86). The report did not stratify results by the original treatment assignment of the subjects (chelation versus placebo), so the effects of the combined interventions cannot be compared with those for an untreated group.
A 2003 retrospective cohort study identified children listed in the New York City child blood lead registry and compared BLLs before and 10 to 14 months after remediation with those of a control group that did not have remediation.77 Mean BLLs declined significantly from 24.3 to 12.3 µg/dL at follow-up regardless of remediation. After adjusting for confounders, the remediation effect was 11% (P = not significant). Race was identified as the only confounding factor: white and Asian children had an adjusted mean follow-up BLL 30% lower than that of black children (P < .01). The effect of remediation seemed to be stronger in younger children (10 to <36 months) than in older children (36–72 months). Another retrospective cohort study that evaluated in-home counseling, combined with professional lead-paint remediation, compared BLLs of children aged 6 months to 6 years with mean BLLs of 28.8 µg/dL with similar children who did not receive the intervention.75 Follow-up BLL was measured, on average, 69 days after abatement, 172 days after the initial sample. After adjusting for season and age of the child, the treatment-group BLL decreased 6.0 µg/dL from 28.8 to 22.8 µg/dL, and the effect of treatment was significant (P < .05). The comparison group mean BLL decreased 1.6 µg/dL from 31.1 to 29.5 µg/dL (P = not significant).
In a retrospective study that measured BLLs in children whose homes were abated from 1987 to 1990, before and after abatement policies in Massachusetts became more stringent in 1988, the mean BLL decreased from 26.0 µg/dL at baseline to 21.2 µg/dL (P < .001) measured between 2 weeks to 6 months postabatement. Reductions were only seen, however, among children whose baseline BLLs were >20 µg/dL. This study found no meaningful change in preabatement to postabatement levels by calendar year of intervention.80 The effect of different housing policies on the risk of subsequent lead exposure in homes where a child with an elevated BLL resided in the past was demonstrated in adjacent geographic regions of 2 northeastern states. Approximately 8 years later, the risk of identifying at least 1 child with an elevated BLL (>10 µg/dL) was 4 times greater in the state with less stringent housing-based lead-poisoning–prevention policies.81
A study of 1212 HUD dwellings that received interior treatment for lead hazard control in 13 states from 1994 to 1998 reported a mean 2.8 µg/dL reduction in children's (n = 240) BLLs 12 months postintervention (from a median level of 10 µg/dL at baseline).82 The effect of treatment in these studies was not compared with an untreated population. Another study of HUD dwellings in 4 Massachusetts communities found a significantly larger decline in BLLs between 1993 and 2002 among children in treated homes than among those in untreated homes, matching on preintervention BLL. Children's BLLs decreased from 7.07 and 6.62 µg/dL to 3.59 and 4.28 µg/dL in the treated and untreated homes, respectively (P = .015). The study adjusted for time and seasonality to account for the downward trend in BLLs observed among children in the general Massachusetts population, from 5.9 µg/dL in 1994 to 3.2 µg/dL in 2002.83
These trials highlight the difficulties of lead-paint hazard control as a method to reduce lead exposure. Poor, inner-city families tend to move frequently, and so treating the current residence may have limited long-term benefit to the individual child, although benefit accrues to subsequent children moving into that residence. In the Jersey City study, for example, 30% of the randomly assigned families moved during the 12-month follow-up period.74 Residential lead-paint hazard control can be costly and labor-intensive, which limits the availability of intervention, especially in poor communities.1 Recontamination by nearby lead sources, including soil lead, may occur after lead-paint hazard-control efforts in a dwelling.1,25 These limitations demonstrate the need for effective comprehensive individual interventions, as well as community-based interventions, to reduce household lead exposure. Unfortunately, available data about programs that use multiple interventions are sparse.73,84
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APPENDIX 5. DETAIL ON EFFECT OF COUNSELING AND EDUCATION INTERVENTIONS ON BLLs |
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TOPABSTRACTMETHODSRESULTSEVIDENCE SYNTHESIS AND...APPENDIX 1. KQs AND...APPENDIX 2. CRITERIA FOR...APPENDIX 3. DETAIL ON...APPENDIX 4. DETAIL ON...APPENDIX 5. DETAIL ON...APPENDIX 6. DETAIL ON...APPENDIX 7. DETAIL ON...APPENDIX 8. RECOMMENDATIONS OF...REFERENCES |
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APPENDIX 6. DETAIL ON THE EFFECT OF SOIL ABATEMENT ON BLLs |
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APPEN |
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