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105)11-1-110 

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EPA AIR DOCKET 

tunning Head: Lead Exposure and Infant Development 

LEAD EXPOSURE AND NEUROBEHAVIORAL DEVELOPMENT IN LATER INFANCY 

Kim N. Dietrich, Ph.D.* 

Paul A. Succop, Ph.D.* 

Robert L. Bornschein, Ph.D.* 

Kathleen M. Krafft, Ph.D.*** 

Omer Berger, M.D.** 

Paul B. Hammond, D.V.M., Ph.D.* 

C. Ralph Buncher, Sc.D.* 

*From the University of Cincinnati College of Medicine, Department of 

Environmental Health, Cincinnati, OH 45267-0056 

**From the University of Cincinnati College of Medicine, Department of 

Pediatrics, Cincinnati, OH 45267-0056. 

***From E.I. Du Pont de Nemours Inc., Specialty Services, Wilmington, DE 

19885-0800. 

Presented at Advances in Lead Research: Implications for Health, National 

Institute of Environmental Health Sciences, Research Triangle Park, NC, January 

9, 1989. 

Corresponding Author: Kim N. Dietrich, Ph.D. 

University of Cincinnati College of Medicine 

Department of Environmental Health 

Cincinnati, OH 45267-0056 1 

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TITLE: LIAD EXPOSURE AND NEUROBEHAVIORAL DEVELOPMENT IN UTER INFANCY 

AUTHORS: Kim N. Dietrich, Ph.-D. 

Paul A. Succop, Ph.D. 

Robert L. Bornschein, Ph.D. 

Kathleen M. Krafft, Ph.D. 

Omer Berger, M.D. 

Paul B. Hammond, D.V.M., Ph.D. 

C. Ralph Buncher, Sc.D. 

KEY WDTODS: Lead, Fetus, Infant, Development, Growth, Prospective-Studies 
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ABSTRACT 

A prospective methodology was used to assess the neurobehavioral effects of 

fetal and postnatal lead exposure during the first two years of life. Lead was 

measured in whole blood prenatally in mothers and at quarterly intervals in the 

infant. Prenatal blood lead levels were low (M - 8.0 jig/dl). However, 

approximately 25 percent of the study infants had at least one serial blood lead 

level of 25 M9/dl or higher during the second year of life. Multiple regression 

and structural equation analyses revealed statistically significant 

relationships between prenatal and neonatal blood lead level and 3 and 6 month 

Bayley Mental and/or Psychomotor Development Index. However, by 2 years of age 

no statistically significant effects of prenatal or postnatal lead exposure on 

neurobehavioral development could be detected. Data consistent with the 

hypothesis that a postnatal neurobehavioral growth catch-up occurred in infants 

exposed fetally to higher levels of lead are presented. 
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INTRODUCTION 

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For most U.S. children, there has been a substantial reduction in lead 

exposure as a direct result ©f regulatory policies governing acceptable levels 

of the metal in atmosphere aind diet (1). However, the level of lead exposure at 

which adverse effects to heailth are believed to occur has been correspondingly 

reduced. Much of these new data on the health effects of low level lead 

exposure have come from prospective studies initiated at the beginning of this 

decade. Since most of these studies recruited pregnant women, the first 

available reports dealt with the effects of fetal lead exposure on perinatal 

outcomes and early postnatal development. 

Lower level fetal lead exposure has been associated with poorer neonatal 

physical status in several prospective studies. Decreased gestational age 

and/or delayed fetal maturatiion (2,3,4), lower birth weight (5,6), and an 

increased risk for minor physical anomalies (7) have been associated with fetal 

lead exposure as assessed by prenatal, umbilical cord, or neonatal blood lead 

levels in the range common arftOTig women and neonates in developed countries. 

Lead-related deficits in early postnatal neurobehavioral status have been 

reported by several prospective studies. Ernhart and her colleagues have 

reported a significant covartate-adjusted relationship between maternal blood 

lead level at delivery and thie Abnormal Reflexes cluster on the Brazelton 

Neonatal Behavioral Assessment Scale, and the Soft Signs and Muscle Tonus score 

on the Graham/Rosenblith Behavioral Examination of the Neonate (8). These same 

investigators found a significant covariate-adjusted negative relationship 

between maternal blood lead level at delivery and 6 month scores on the mental 
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and psychomotor indexes of the Bayley Scales of Infant Development (9). 

However, there appeared to be no significant covariate-adjusted relationships 

between indices of fetal or early postnatal lead exposure and Bayley scores at 1 

or 2 years. 

A somewhat different pattern of results were reported by Bellinger and his 

coworkers in Boston. As in the Cleveland study, a significant covariateadjusted negative relationship between fetal lead exposure (in this case, cord 

blood lead level) and 6 month Bayley mental index was found (10). However, 

these investigators later reported a continuous inverse relationship between 

cord blood lead level and Bayley mental index through 2 years of age (11,12). 

In our own study, we have reported an inverse relationship between maternal 

prenatal blood lead level and covariate-adjusted Bayley mental index scores at 3 

and 6 months. These effects appeared to be strongest in male infants and 

infants from the poorest families. In addition, deficits or delays in early 

mental development appeared to be partly mediated by lead-related lower birth 

weight, and decreased gestational maturity (2). 

The prospective studies substantially differ from one another in terms of 

postnatal lead exposure during infancy. At the low end of the exposure spectrum 

is the Boston study where the mean blood lead level was less than 8 Mg/dl at all 

ages sampled (12). This was a middle-class sample at relatively low risk for 

undue pediatric lead intoxication. The Cleveland study and our own are somewhat 

intermediate in terms of postnatal blood lead level. In Cleveland, a mean 2 

year blood lead level of 16.74 Mg/dl was reported (9), while 2 year olds in the 

Cincinnati cohort had an average blood lead of 17.45 /ig/dl (this report). 
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Among the published prospective studies, the highest postnatal lead 

exposures are found in a longitudinal investigation of children residing near a 

primary lead smelter in Port Pirie, Australia. In this cohort of over 600 

children, a geometric mean 2 year blood lead level of 21.2 Mg/dl was reported 

(13). Further, these investigators reported a statistically significant inverse 

relationship between prenatal, 6 month, and integrated postnatal blood lead 

level and 2 year Bayley mental index scores after controlling for 14 covariates, 

including maternal intelligence. However, in regression analyses controlling 

for both maternal intelligence and a standard measure of caretaking quality, 

only 6 month blood lead level continued to be inversely associated with Bayley 

scores at borderline significance (14). 

There appears to be general agreement among the prospective studies that low 

level prenatal lead exposure may have some small effect on early neurobehavioral 

development (2,8,9,10,11,12,14). However, as others have noted (11), the 

implications of these adverse low-level lead effects for regulatory policy 

depend on the magnitude of the inverse relationships and their stability over 

time. Therefore, one of the substantive issues for lead studies is whether such 

early deficits persist into later life. To address this important question, the 

Cincinnati Lead Program Project continues to follow study subjects into their 

early school years with a variety of regular biomedical and neurobehavioral 

assessments. 

The primary purpose of this paper is to report on the relationship between 

prenatal/postnatal lead exposure and the developmental status of 2 year old 

infants in the Cincinnati cohort. It was hypothesized that low to moderate 

prenatal and postnatal lead exposure would be inversely associated with indices 
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of 2 year neurobehavioral development after adjustment for relevant covariates 

and/or confounders. 

METHODS 

The cohort at 2 years of age consisted of 297 infants for whom developmental 

data from the Bayley Scales of Infant Development were available. This sample 

included 3 sets of twins. Mothers of these infants were recruited prenatally 

between 1979 and 1984. Study families resided in predesignated lead-hazardous 

areas of Cincinnati, Ohio. This geographical area has a long history of cases 

of pediatric lead poisoning. Results of environmental studies with this cohort 

have shown conclusively that lead from paint, dust and soil associated with poor 

housing stock is the major contributor to body burden (15,16). Informed consent 

for participation in the study was obtained at prenatal recruitment and again at 

delivery to obtain permission for infant follow-up. Women known to be drug 

addicted, alcoholic, diabetic or those with a known neurological or 

psychological disorder were excluded from prenatal recruitment. Infants were 

excluded if they were less than 35 weeks gestation and/or 1,500 grams birth 

weight. Further, eligible infants must have had an Apgar score of 6 or greater 

at 5 minutes and have no serious medical condition or congenital anomaly. 

Descriptive statistics on mothers and infants excluded from the study and those 

families who refused to participate have been published elsewhere (2). 

Table 1 presents perinatal statistics on infants for whom 2 year 

developmental data were available. In general, study infants were healthy at 

birth with a mean birth weight of 3147.97 grams and gestational age (17) of 39.7 

weeks. The sample was predominantly black (86.2%) with a nearly even percentage 
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of male and female births. Table 2 presents descriptive statistics on study 

mothers and their families. Mothers were predominantly from the lower social 

classes (23), unmarried, and on some form of public assistance. 

Blood was collected for liead analyses prenatally from the mother, and at 

quarterly intervals from the infant beginning at 10 gestationally-corrected 

days. Lead was measured in whiole blood using anodic stripping voltammetry. The 

microanalytical laboratory at the University of Cincinnati Department of 

Environmental Health participjates in several quality control programs. The 

performance of this laboratory has been uniformly excellent throughout the 

course of the current study. Detailed descriptions of our collection methods, 

analytic methodology, and precision have been published elsewhere (2,18). Most 

blood samples were collected by venipuncture, although finger stick and heel 

stick methods were used when the physical or behavioral characteristics of the 

infant demanded it. Collection methods other than venipuncture were used most 

often with neonates and youngpr infants. For example, at 10 days only 26.2% of 

the samples were collected by venipuncture while at 2 years 90.9% of the samples 

were collected by this methods Environmental contamination of samples collected 

by methods other than venipuncture has not been a problem in this study due to 

the controlled clinical conditions under which phlebotomy takes place (2). 

Table 3 presents descriptive statistics on blood lead variables for subjects 

in the 2 year follow-up sample. Prenatal and neonatal blood lead levels were 

low, with only a handful reaching or exceeding 25 -ig/dl. Most subjects reached 

their highest blood lead leve'l diuring the second year. Approximately 25% of 

study subjects had at least orae serial blood lead determination of 25 M9/dl or 

greater during the second year. 
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Infants were given developmental assessments at 3, 6, 12, and 24 months of 

age. Our primary measure of infant neurobehavioral development was the Bayley 

Scales of Infant Development (19) which provides a three part assessment: A 

Mental Development Index (MDI) which assesses sensorimotor coordinations, 

perceptual acuities, objective and visual-spatial relations, imitation, 

prelinguistic and linguistic behaviors, and memory, a Psychomotor Development 

Index (PDI) designed to provide a measure of the coordination of the large body 

muscles and finer manipulatory skills of the hands and fingers, and an Infant 

Behavior Record (IBR) which is a 30 item rating scale completed by the 

psychologist after the MDI and PDI examinations. The IBR assesses the infant's 

social, objective, affective, and motivational behaviors. All biomedical and 

neurobehavioral evaluations took place at a prenatal and children's welfare 

clinic located in the heart of the study recruitment area. .Behavioral 

evaluations always occurred before the medical examination and phlebotomy, and 

care was taken to insure that the infant was healthy, fed, and unmedicated when 

tested. The Bayley scales were administered by the first author (KND) or a 

trained assistant with whom adequate intertester reliability had been previously 

established. All examinations were conducted without knowledge of the infant's 

prenatal or postnatal blood lead level. 

Table 4 presents descriptive statistics on the performance of study infants 

on the Bayley MDI at each age. The rather dramatic drop in MDI at 2 years is 

not unusual for lower socioeconomic status infants, and probably reflects the 

relatively greater number of items at this age which require a verbal or 

nonverbal response to representational stimuli, rather than some type of 

sensorimotor manipulation. 
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To reduce the Bayley IBR to a few meaningful psychologic factors, we factor 

analyzed the 30 rating variables and calculated factor scores for each subject 

using the factor scoring coefficients. For example, Table 5 presents results of 

a factor analysis of the Bayley IBR at 24 months. The factor structure found at 

2 years revealed 4 interpretable behavioral dimensions: Mood (Factor 1), 

Activity Level (Factor 2), Attention Span (Factor 3), and Reactivity (Factor 4). 

Undue lead exposure is known to covary with a number of social and biologic 

risks which may mimic, obscure, or otherwise interact with the effects of 

toxicant exposure on child development (20,21). Consequently, a substantial 

amount of social and medical background data were collected on all subjects and 

tested as potential confounders of the blood lead-behavioral development 

relationship. Perinatal variables included birth weight, length, head 

circumference, ponderal index, gestational age (17), Obstetrical and Postnatal 

Complications Scales (22), 1 and 5 minute Apgar scores, maternal age, parity, 

gravidity, number of cigarettes smoked per day during pregnancy, composite index 

of tobacco and alcohol consumption (a dichotomous variable indicating use or 

non-use of tobacco and/or alcohol during pregnancy), maternal total iron binding 

capacity during pregnancy, child sex (0=male, l=female) and child race (0=white, 

l=black). Child health variables included current illness, and iron status as 

assessed by hemoglobin, hematocrit, and total iron binding capacity. 

Sociohereditary variables included socioeconomic status (23), developmental 

stimulation in the home (24), maternal intelligence (25), and number of children 

in the home. Any covariable bivariately associated with Bayley outcomes at a 

liberal p. value of 0.10 or less was classified as a potential covariate. 

Further any covariable associated with both prenatal and/or postnatal lead 

exposure and Bayley outcomes at p_=0.10 or less was classified as a potential 

confounder. 

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DATA ANALYSES 

The data analytic procedures used in this series involved multiple 

regression analyses with both backward elimination of nonsignificant covariates 

and confounders (reduced model) and multiple regression analyses retaining all 

potential covariates and confounders regardless of their statistical 

significance in multivariable models. The latter strategy was employed to 

determine the statistical robustness of any blood lead-behavior relationship, 

and if any positive findings were model-specific (26). Data analyses were 

conducted for singleton births as well as for the full cohort which included 3 

sets of twins. Results of both analyses were compared. Parameter estimates for 

independent variables in either reduced or original regression models did not 

differ as a function of whether twins were present or excluded from the sample. 

RESULTS 

Earlier Findings 

Our earliest series of studies dealt with the relationship between prenatal 

exposure to lead and fetal growth, maturation, and early postnatal 

neurobehavioral development (2,5). We have reported a statistically significant 

covariate-adjusted relationship between fetal lead exposure variables and Bayley 

MDI scores at 3 and 6 months (2). These reported effects appeared to be 

strongest among male infants and infants from the poorest families. For 

example, Table 6 presents results of multiple regression analyses examining the 

relationship between prenatal (maternal) and neonatal (10 day) blood lead level 

and performance on the Bayley MDI at 6 months. In this reanalysis, all 

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covariates and confounders were retained in the final model regardless of their 

individual statistical significance. Lead variables were analyzed both in 

micrograms per decilitre and transformed to their natural logarithm. Prenatal 

blood lead was significantly related to 6 month MDI after statistical adjustment 

for all 10 potential covariates and confounders in untrimmed regression models. 

However, this relationship was only negative for male infants who exhibited a 

covariate-adjusted reduction of 0.867 MDI points for each Mg/dl of prenatal 

blood lead (fi = 0.0105). The parameter estimate for female infants was positive 

and statistically insignificant. Neonatal blood lead level was also inversely 

related to 6 month Bayley MDI after adjustment for all potential covariates and 

confounders. In this instance, the effect was most evident among those infants 

from the poorest families. For example, for those infants with Hollingshead 

socioeconomic status (S.E.S.) scores at or below the sample.median of 17, there 

was a covariate adjusted reduction of 0.757 MDI points for each M9/dl of 

neonatal blood lead (fi = 0.0316). The parameter estimate for infants above the 

sample median was negative as well, but statistically insignificant. 

In a structural equation analysis, we also found an indirect effect of 

prenatal blood lead on both 3 and 6 month MDI and PDI through lead-related lower 

birth weight and decreased gestational maturity (2). For example, in a 

structural analysis of relationships among prenatal blood lead, covariates, and 

6 month Bayley variables, each log increment in prenatal blood lead was 

associated with a reduction of 157 grams birth weight, and about 1/2 week 

gestation. In turn, birth weight and gestation were positively related to both 

Bayley MDI and PDI. Another structural analysis was conducted in an interim 

analysis of 12 month Bayley data with similar results (28). 

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These results have been previously published or presented at scientific 

meetings. They are reviewed here in order to put our new findings into their 

appropriate context. The primary focus of this paper is on the relationship 

between fetal and postnatal lead exposure and the developmental status of 

infants in the Cincinnati cohort at 2 years of age. The substantive issue at 

hand is whether the lead related reductions in earlier indices of 

neurobehavioral status persist in evaluations of the older infant. 

Two-Year Follow-Up 

Table 7 presents results of multiple regression analyses examining the 

relationship between prenatal and postnatal blood lead level and performance on 

the Bayley MDI at 24 months. No statistically significant relationships between 

prenatal or postnatal blood lead variables and Bayley MDI were found. Indeed, 

in many cases the parameter estimates were positive rather than negative. For 

prenatal (maternal) blood lead expressed in Mg/dl this positive relationship was 

actually statistically significant (fi = 0.0217). 

Although not presented in Table 7, we also examined the potential 

interactions among prenatal and postnatal exposure variables. These analyses 

tested the hypothesis that those infants with both higher prenatal and higher 

postnatal blood lead levels may exhibit a deficit in 2 year MDI when compared to 

their less exposed peers. The results forthcoming from these statistical 

analyses were similarly insignificant. 

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Analyses of the relationship between prenatal and postnatal blood lead level 

and Bayley IBR factor scores also yielded statistically insignificant results. 

Unfortunately, we could not adequately examine the relationship between lead 

exposure variables and 2 yeair Bayley PDI, since only 170 of these examinations 

could be completed. The rather lengthy and demanding nature of the MDI protocol 

conducted first in the assessment series prevented many 2 year olds from 

completing the PDI. Structural equation analyses were also conducted to 

determine if there was a continued adverse impact of prenatal lead exposure on 

Bayley MDI through fetal growth and maturational variables. The results of 

these analyses were consisterntly negative. 

The only significant independent predictors of 2 year Bayley MDI were child 

sex (Beta = 5.184, t = 3.25, fi = 0.0013) with females outperforming males; birth 

length (Beta = 1.0694, t = 3.28, fi = 0.0012); and maternal intelligence (Beta = 

0.1860, t = 2.20, fi = 0.0288|. Other covariables which were bivariately 

associated with 2 year Bayley MDI but eliminated from the trimmed regression 

models were birth weight, head circumference, gestational age, Postnatal 

Complication Scale score, and HOME score. 

The lack of inverse relationships between measures of fetal lead exposure 

and 2 year MDI and IBR factors suggests that those infants of mothers with 

higher prenatal blood lead levels may have recovered from their very early 

developmental deficits. The phenomenon of catch-up in physical growth has been 

well documented by auxologists who have studied infants compromised by 

intrauterine or early extrauterine influences (29). Further, studies of the 

neurobehavioral development of infant twins have shown corresponding catch-up 

growth in neurobehavioral development (30). 

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We examined the possibility of lead-related catch-up neurobehavioral growth 

in an exploratory analysis. Bayley MDI raw scores were used as a measure of 

behavioral "growth". Bayley MDI raw scores represent the number of items passed 

at the age of testing and thus provide a rough gauge of the accrual of 

sensorimotor and cognitive skills over the first 2 years of life. A ratio was 

calculated to express the relative change or increase in MDI raw score between 3 

and 24 months (i.e., 100*[MDIRAW 24 - MDIRAW 3]/[MDIRAW3]). The mean percent 

increase in MDI raw score in the study sample was 275.43%+72.5. The relative 

increase in MDIRAW between 3 and 24 months ranged from a low of 144.68% to a 

high of 892.31%. 

Our primary interest was in the relationship among these change scores and 

fetal lead exposure, and fetal growth and maturational variables such as birth 

weight and gestational age. We were particularly interested in these fetal 

developmental factors because the effects of prenatal lead exposure on early 

neurobehavioral development were shown to be partly mediated through them (2). 

The results of these analyses are presented in Figure 1. For this analysis, 

the variables of prenatal blood lead, birth weight, gestation, and head 

circumference were grouped by quartiles. The means and standard deviations for 

groups 1 through 4 are given in the figure legend. Analysis of variance 

revealed that all 4 perinatal variables were significantly associated with the 

percent increase in MDI raw score at fi < 0.05. Those infants with the highest 

prenatal lead exposure or those having the lowest birth weight, shortest 

gestational age, or smallest head circumference evidenced the greatest degree of 

postnatal neurobehavioral growth catch-up. 

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It is interesting to compare the prenatal blood lead and birth weight 

variables in this figure. Their relationships to the neurobehavioral growth 

index appear to mirror each other. This is as one might expect given that 

prenatal blood lead and birth weight were related to early neurobehavioral 

status at 3 and 6 months and the influence of prenatal blood lead on early 

developmental indices appeared to be mediated through birth weight (2). These 

findings are consistent with a hypothesis of neurobehavioral catch-up growth for 

infants whose central nervous system growth and development may have been 

compromised by lead exposure or other factors which influenced prenatal growth 

and maturation. 

DISCUSSION 

We failed to find a persistent effect of fetal lead exposure on infant 

neurobehavioral development over the first two years of life. These results are 

in accord with one previous study (9), but not with studies conducted by 

Bellinger and his associates who have reported a continuous inverse relationship 

between cord blood lead level and Bayley MDI between 6 months and two years 

(10,11,12). Our results also do not confirm those reported by Port Pirie, 

Australia investigators who found a significant inverse relationship between 

early postantal blood lead level and 2 year Bayley MDI. However, this 

relationship was no longer statistically significant after the HOME variable was 

entered. 

We also failed to find a statistically significant relationship between 

indices of postnatal lead exposure and Bayley MDI or IBR factors. These 

findings are in agreement with those reported by the Cleveland and Boston 

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P. 18 

71 

studies (9,10,11,12), but are somewhat discordant with findings from the Port 

Pirie, Australia study (14). These investigators reported a statistically 

significant inverse relationship between integrated postnatal blood lead level 

and 2 year Bayley MDI after adjustment for 14 covariates, including maternal 

intelligence. However, after inclusion of the HOME variable this relationship 

was no longer statistically significant. The more positive nature of the Port 

Pirie findings may suggest a threshold for an effect on 2 year Bayley MDI since 

mean postnatal blood lead levels in this sample were somewhat higher than those 

reported in the Cleveland study and our own. Nevertheless, we were somewhat 

surprised by the absence of an association between postnatal lead exposure and 

Bayley variables, especially given the fact that a substantial number of 

subjects in the Cincinnati cohort had at least one serial blood lead level which 

equalled or exceeded the current level of concern as established by the Centers 

for Disease Control (31). 

Although we did not find any significant relationships between lead exposure 

indices and the neurobehavioral status of older infants, two caveats are 

probably in order. First, the Bayley scales may be somewhat limited in their 

ability to measure more complex perceptual-performance, information processing, 

and linguistic skills which may indeed be compromised by early exposure to lead. 

Fetal and postnatal lead exposure at low to moderate levels may produce adverse 

neurobehavioral sequelae which may only be measureable in the older child. The 

evaluation of such effects must await maturation of the Cincinnati cohort. 

Second, at least two major longitudinal studies have reported a significant 

relationship between early lower level lead exposure and the neurobehavioral 

status of infants at 2 years (12,14). Public health officials, governmental 

17 
P.19 

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agencies, and industry must make policy decisions based upon all of the 

available scientific data, not any single study. Our negative findings at 2 

years do not imply that lower level pediatric lead exposure is without any 

continuing harmful effects. 

18 
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REFERENCES 

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P.21 

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20 
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P.22 

12.) Bellinger, D., Leviton, A., Waternaux, C , Needleman, H., and Rabinowitz, 

M. Longitudinal analyses of prenatal and postnatal lead exposure and 

early cognitive development. N. Engl. J. Med. 375:1037-1043 (1987). 

13.) McMichael, A.J., Baghurst, P.A., Robertson, E.F., Vimpani, G.V., and Wigg, 

N.R. The Port Pirie Cohort Study: Blood lead concentrations in early 

childhood. Med. J. Aust. J43:499-503 (1985). 

14.) Wigg, N.R., Vimpani, G.V., McMichael, A.J., Baghurst, P.A., Robertson, 

E.F., and Roberts, R.J. Port Pirie Cohort Study: Childhood blood lead 

and neuropsychological development at age two years. J. Epid. Comm. 

Health 42:213-219 (1988). 

15.) Clark, C.S., Bornschein, R.L., Succop, P., Que Hee, S.S., Hammond, P.B., 

and Peace, B. Condition and type of housing as an indicator of potential 

environmental lead exposure and pediatric blood lead levels. Environ. 

Res. 38:46-53 (1985). 

16.) Bornschein, R.L., Succop, P., Dietrich, K.N., Clark, CS. , Que Hee, S., 

and Hammond, P.B. The influence of social and environmental factors on 

dust lead, hand lead, and blood lead levels in young children. Environ. 

Res. 38:108-118 (1985). 

17.) Ballard, J.L., Novak, K.K., and Driver, M.A. Simplified score for 

assessment of fetal maturation in newly born infants. J. Pediatr. 

95:769-774 (1979). 

21 
P.23 

-•rir.j-i !-».i->.t-T._- •'. - ^.-! -. t v - s nv-VkV.".".- - .•.»*-._jj^_«_ ••*>. ..,.-.v . v.* :»:o"jLi.iVvv/.v.,.viv.''.'T'..V--'/..v»v«N't««v.«•»'»''.''•"».•.• »>**>-»•«-,',•.- -

18.) Roda, S.M., Greenland, R.D., Bornschein, R.L., and Hammond, P.B. Anodic 

stripping voltammetry procedure modified for improved accuracy of blood 

lead analysis. Clin. Chem. 34:563-567 (1988). 

19.) Bayley, N. The Bayley Scales of Infant Development. Psychological 

Corporation, New York (1969). 

20.) Pearson, D.T., and Dietrich, K.N. The behavioral toxicology and 

teratology of childhood: Models, methods, and implications for 

intervention. Neurotoxicology 6:165-182 (1985). 

21.) Dietrich, K.N., Krafft, K.M., Pearson, D.T., Harris, L.C, Bornschein, 

R.L., Hammond, P.B., and Succop, P.A. Contribution of social and 

developmental factors to lead exposure during the first year of life. 

Pediatrics 75:1114-1118 (1985). 

22.) Littman, B., and Parmelee, A.H. Medical correlates of infant development. 

Pediatrics 57:470-474 (1978). 

23.) Hollingshead, A.B. Four factor index of social status, working paper. 

New Haven, CT, Yale University (1975). 

24.) Caldwell, B.M., and Bradley, R.H. Home Observation for Measurement of the 

Environment (H.O.M.E.) Manual. Little Rock, AK, University of Arkansas at 

Little Rock (1979). 

22 
P.24 

25.) Silverstein, -A.B. Two and four-subtest short forms of the Wechsler Adult 

Intelligence Scale-Revised. J. Consulting Clin. Psychol. 50:415-418 

(1982). 

26.) SAS User's Guide: Statistics. SAS Institute Inc., Cary, NC (1985). 

27.) Joreskog, K.G., and Sorbom, D. LISREL IV: Analysis of Linear Structural 

Relationships by the Method of Maximum Likelihood, User's Guide. 

International Educational Services, Chicago, IL (1985). 

28.) Dietrich, K.N., Krafft, K.M., Bier, M., Berger, 0., Succop, P.A., and 

Bornschein, R.L. Neurobehavioral effects of fetal lead exposure: The 

first year of life. Paper presented at the EPA/EEC workshop Lead Exposure 

and Neurobehavioral Effects in Children, Edinburgh, Scotland, September 

(1986). 

29.) Tanner, J.M., Catch-up growth in man. British Med. Bull. 37:233-238 

(1981). 

30.) Wilson, R.S. Growth and development of human twins. Human Growth Vol. 3 

(J.M. Tanner, and F. Falkner, Eds.), Plenum, New York (1986), pp. 197-211. 

31.) Preventing lead poisoning in young children: A statement by the Centers 

for Disease Control. U.S. Department of Health and Human Services 

publication No. 99-2230. Atlanta, Centers for Disease Control (1985). 

23 
P.25 

ACKNOWLEDGEMENTS 

This research was supported by a Program Project Grant from the National 

Institute of Environmental Health Sciences (#P01-ES-01566-09), Dr. Paul B. 

Hammond, Principal Investigator. The authors gratefully acknowledge the 

indispensable assistance of Mariana Bier, Leslie Harris, Susan Naraine, Holly 

Jason, Suzanne Leibee, and Jill Edwards for the collection of behavioral and 

sociodemographic data, Sandy Roda and Robert Greenland for blood lead analyses, 

Terri Mitchell for phlebotomy and the collection of biomedical data, and JoAnn 

Grote for subject recruitment and patient scheduling. The authors also 

acknowledge the assistance of the Babies Milk Fund Association and Findlay 

Street Clinic staff. This paper is dedicated to the memory of Tassie Lee Vaison 

Walker, long-time caretaker at Findlay Clinic and good friend of the Cincinnati 

Lead Study. 

24 
I I I J !.l-L.b-,l ; l.1JTIA,4UUX X •^I"-^-""^* ' .-»..•_ J-.'-U-,-'LM. .«-J.-l. -4,Wr^,^W„, 

FIGURE LEGEND 

Figure 1. Percent increase in MDI raw score by fetal biological risk 

groups. Percent change in MDI raw score between 3 and 24 months was calculated 

as (100*[MDIRAW24-MDIRAW3]/MDIRAW3). Prenatal blood lead is measured in 

micrograms per decilitre, birth weight in grams, gestational age in weeks, and 

head circumference in centimeters. Group means: Prenatal blood lead, Group 1, 

M = 4.25± 1.16, Group 2, M = 6.61± 0.61, Group 3, M - 8.53± 0.63, Group 4, M = 

13.00±3.28; Birth weight, Group 1, M - 2553.58±235.32, Group 2, M. -

2977.43175.29, Group 3, M = 3303.24 ±107.05, Group 4, M **• 3757.35±228.26; 

Gestational age, Group 1, M = 37.03±0.94, Group 2, M = 39.26+0.44, Group 3, M = 

41.00±0, Group 4, M = 42.3610.50; Head circumference, Group 1, M = 31.8910.53, 

Group 2, M = 33.2910.29, Group 3, M = 34.1710.23, Group 4, M = 35.5010.83. 

25 
PERCENT INCREASE IN MDI RAW SCORE 

BY FETAL BIOLOGICAL RISK GROUPS 

I 

• 

• 

• 

X 

: 

I 

\ 

l

\ 

* \ 

'£ 

s 

j 

i 

> 

t 

•v 

• m 

c o 

i: 3-2

4 K Raw Scon 

X Increas

e i

n MDI 

330 

320 

310 

300 

290 

280 

270 

260 

250 

240 

( 

^•o** X 

• 

i 

Jroup | 

X. ^^^^^ ^, —_^^L ___>r 

• f 

Group 2 Group 3 

Groups 

__.__. .L. 

al Prenatal Blood Lead 

- # - Birth Height 

A Geetatlonal Age 

Hesd Circumference 

Broup 4 
""""""" "" T *'^n" -

 l""iP('"^T*''*r'~'*fn*l'*T" -••"•«-:-.--

TABLE 1 

Perinatal Statistics on Infants in Study Sample 

1 

- •.****» «--. > v «-V.*» v ' f

Study Variable 

Birth Weight 

Gestational Age(a) 

Birth Length (cms) 

Birth Head 

Circumference (cms) 

Obstetrical 

Complications 

Scale(b) 

Postnatal 

Complications 

Scale(b) 

APGAR Score at 

Five Minutes 

Percent Female 

Percent Black 

Mean 

3147.97 

39.57 

49.25 

33.78 

82.65 

94.44 

8.85 

52 

86 

6% 

2% 

Standard Deviation 

472.95 

1.69 

2.47 

1.37 

5.73 

9.47 

0.40 

Lowest 

1814 

35 

42 

30 

68 

30 

6 

Highest 

4400 

43 

56 

39 

95 

100 

9 

(a)As assessed by standardized physical examination of the neonate (12). 

(b)As assessed by Littman-Parmelee Obstetrical and Postnatal Complications 

Scales (22). 

27 
."» ^a. a'.i.J^JT_". 

-—r . 1 1 »T ; »[•» • g « I 

• ,'Cl' . i aaa iJO.> > .' ." ^ !. . . . Y*. 'a -i.. . .T T->.'FT . •* • r» . .-SV--•-.:*-•' 

P.29 

' " . '.. ' '.".-.-. - ^. ' -.*.'. • •. • 

TABLE 2 

Descriptive Statistics on Families in Study Sample 

Study Variable 

Maternal Age at 

Birth of Child 

Maternal I.Q.(a) 

Socioeconomic 

Status(b) 

Number of Children 

in the Home 

Total H.O.M.E. 

Score(c) 

Percentage 

Unmarried 

Mean 

22.55 

75 

17.42 

2.57 

32.71 

83 

Standard Deviation 

4.40 

9.48 

5.69 

1.38 

5.27 

3% 

Lowest 

15 

55 

8 

1 

14 

Highest 

37 

110 

53 

9 

43 

(a)Wechsler Adult Intelligence Scale-Revised (Short Form) (25) 

(b)Hollingshead Four Factor Index of Socioeconomic Status (23) 

(c)Home Observation for Measurement of the Environment (HOME) (24) 

28 
*. i. ' 1. KX'I 

P.30 

^'.,-:-l 

TABLE 3 

Descriptive Statistics on Blood Lead Variables^) 

Blood Lead Variable 

Prenatal (Maternal) 

Blood Lead 

Neonatal (10 Day) 

Blood Lead 

Neonatal (3 Month) 

Blood Lead 

Maximum First Year 

Blood Lead 

Maximum Second Year 

Blood Lead 

24 Month (Concurrent) 

Blood Lead 

N 

261 

297 

297 

297 

297 

297 

Mean 

8.09 

4.76 

6.18 

15.85 

21.11 

17.45 

Standard Deviation 

3.64 

3.15 

3.75 

8.17 

11.38 

9.16 

Low 

1 

1 

1 

5 

6 

4 

High 

27 

26 

26 

56 

85 

70 

(

a)ln micrograms per decilitre, whole blood. All values have been normal 

ized to a standard hematocrit of 35 percent packed cell volume. 

29 
P.31 

•". .\V.V"*V.. ,',V/ .'ANV.V .ViV/VA'.' 

TABLE 4 

Descriptive Statistics on Bayley Mental Development Index 

at 3, 6, 12, and 24 Months*8) 

Bavlev Variable 

3 Month MDI 

6 Month MDI 

12 Month MDI 

24 Month MDI 

N 

273 

288 

296 

284 

Mean 

100.38 

107.69 

111.89 

88.08 

Standard Devi 

9.91 

16.28 

14.46 

13.77 

ation Low 

60 

61 

50 

50 

High 

125 

150 

137 

132 

(

a)The Bayley Scales of Infant Development have a standardized 

population mean and standard deviation of 100 1 16. 

30 
r "1 

TABLE 5 

Factor Analysis of the Bayley Infant Behavior Record 

at Twenty-Four Months (a) 

* Bayley Variable 

Emotional Tone 

Endurance 

Social Orientation 

To Examiner 

Cooperativeness 

Fearfulness 

Manipulation of 

Objects 

Goal Directedness 

Imaginative Use 

of Toys 

Vocalizations 

Activity Level 

Body Motion 

Energy 

Banging Toys 

Fine Motor 

Coordination 

Social Orientation 

To Persons 

Attention Span 

Social Orientation 

To Mother 

Interest In Sounds 

Object Orientation 

Reactivity 

Tension 

Factor 1 

0.79 

0.75 

0.72 

0.68 

-0.62 

0.34 

0.33 

0.32 

0.31 

Factor 2 

0.31 

-0.44 

0.48 

0.87 

0.87 

0.80 

0.46 

Factor 3 

0.35 

0.51 

0.31 

0.33 

-0.41 

0.59 

0.55 

0.51 

0.49 

0.41 

0.36 

Factor 4 

0.35 

. 

0.34 

0.48 

0.57 

0.54 

(

a)lnfant Behavior Record variables with factor loadings of 0.30 

or greater are shown. 

31 
P.33 

. * . .**- _ .'a . ** . .-&FW-' l

.\TT' f ;T~~I. -.•»'*-"> ..^-.,V..A- >» 

TABLE 6 

Results of Multiple Regression Analyses Examining the 

Relationship Between Prenatal and Neonatal Blood Pb (PbB) Level 

and Performance on the Bayley Mental Index at 6 Months of Age(a) 

Blood Pb Variable 

Log Prenatal PbB 

Log Prenatal PbB 

by Child Sex 

Prenatal PbB (Mg/dl) 

Prenatal PbB (/xg/dl) 

by Child Sex 

Log Neonatal PbB 

Log Neonatal PbB 

by S.E.S. 

Neonatal PbB (/ig/dl) 

Neonatal PbB (/xg/dl) 

by S.E.S. 

N 

249 

283 

Beta 

-5.9103 

11.2481 

-0.8859 

1.5335 

-11.9301 

0.5836 

-3.1544 

0.1626 

Standard Error 

2.6758 

4.0686 

0.3400 

0.5146 

5.0188 

0.2820 

1.2999 

0.0762 

t 

-2.21 

2.76 

-2.60 

2.98 

-2.38 

2.07 

-2.43 

2.13 

P 

0.0281 

0.0061 

0.0099 

0.0032 

0.0181 

0.0395 

0.0159 

0.0338 

(

a)Covariates and confounders in regression models included birth weight, 

gestational age, Obstetrical Complications Scale, Postnatal Complications 

Scale, child sex, child race, Composite Index of Tobacco and Alcohol 

Consumption, maternal age, socioeconomic status, and parity. 

32 
..v • n-ii. ».>-,•»' N-, . if .Z^rffaJrilr . .-.^Vvv'^;

!"^"?!5"*G1.-lrtV/3vi'i'^.-.%v^^i'v^KiiX^Ss'i"'«'.-.•vVw%•/•'.• -,TT:v'"---7*T.'-**.'*rr«^^.Vs.'_TT:

5S 

*'"'."• ' ^ 

TABLE 7 

Results of Multiple Regression Analyses Examining the Relationship 

Between Prenatal and Postnatal Blood Pb (PbB) Level and Performance 

on the Bayley Mental Index at 24 Months of AgeUJ 

Blood Pb Variable 

Log Prenatal PbB 

Prenatal PbB (Mg/dl) 

Log Neonatal 

10 Day PbB 

Neonatal 10 Day 

PbB (^g/dl) 

Log Neonatal 

3 Month PbB 

Neonatal 3 Month 

PbB (Mg/dl) 

Log Maximum PbB 

1st Year 

Maximum PbB 

1st Year (Mg/dl) 

Log Maximum PbB 

2nd Year 

Maximum PbB 

2nd Year (Mg/dl) 

Log PbB 24 Months 

PbB 24 Months (Mg/dl) 

N 

237 

270 

270 

270 

270 

270 

Beta 

3.2956 

0.5058 

0.2434 

-0.0162 

1.3452 

0.2351 

2.2155 

0.1338 

2.3227 

0.0961 

3.1969 

0.1270 

Standard Error 

1.7123 

0.2188 

1.2049 

% 

0.2483 

1.3306 

0.2090 

1.6277 

0.0962 

1.6498 

0.0692 

1.6971 

0.0877 

t 

1.92 

2.31 

0.20 

-0.07 

1.01 

1.12 

1.36 

1.39 

1.41 

1.39 

1.88 

1.45 

P 

0.0555 

0.0217 

0.8400 

0.9480 

0.3129 

0.2618 

0.1747 

0.1655 

0.1603 

0.1663 

0.0607 

0.1490 

(

a)other significant covariates and confounders in reduced regression 

models included child sex, maternal intelligence (I.Q.), and birth 

length. 

33