Postnatal lead exposure and early sensorimotor development

ENVIRONMENTAL

RESEARCH

38, 130- 136 (1985)

Postnatal Lead Exposure and Early Sensorimotor Development’ KIM N. DIETRICH, KATHLEEN M. KRAFFT,DOUGLAS T. PEARSON, ROBERT L. BORNSCHEIN,~AUL B. HAMMOND,AND~AUL A. SUCCOP Department

of

Environmental

Health, University of Cincinnati Cincinnati, Ohio 45267

College of Medicine,

Received July I I, 1984 The relationship between postnatal lead (Pb) exposure and early sensorimotor development was prospectively investigated in a group of infants born to parents residing in leadhazardous areas of Cincinnati, Ohio. Few significant relationships were found between current or cumulative infant blood Pb levels and indices of sensorimotor development during the first year of life. When important developmental covariates such as birth weight and home environment were included in the analyses, no significant relationship between Pb exposure and development remained. To date, there appears to be no evidence in these data that postnatal low-level Pb exposure increases an infant’s risk for delays in early sensorimotor development. 0 I985 Academic Press, 1~.

INTRODUCTION

In this interim investigation, we attempted to prospectively document both exposure to lead (Pb) and infant sensorimotor development from birth to the end of the first year of life. To date, there is only one published report on the effects of early Pb exposure on sensorimotor development in infancy. Needleman et al. (1983) reported that cord blood Pb levels were inversely related to the Bayley mental development index scores at 12 months. On this basis, we hypothesized that postnatal Pb exposure would be negatively correlated with standardized indices of infant sensorimotor development during the first year. We further predicted that a significant negative correlation between postnatal Pb exposure and sensorimotor development would remain after statistically controlling for the developmental effects of perinatal status variables (e.g., birth weight) and social factors (e.g., social and cognitive stimulation in the home). MATERIALS

AND METHODS

The sample consisted of predominantly black, lower socioeconomic status infants residing in Cincinnati’s inner city. Details on study sample composition can be found in Bornschein et ul. (1985). The number of infants in any analysis ranged from 67 to 136 depending on the age and certain restrictions in the analyses which are described below. The unequal sample sizes reflect the fact that these results come from an ongoing longitudinal study and not attrition or ascertainment bias. ’ This paper was presented at The Second International Cincinnati, Ohio, April 9-l 1, 1984. 130 0013-9351/85 $3.00 Copyright 0 1985 by Academic Press. Inc. Ail rights of reproduction in any form reserved.

Conference on Prospective Studies of Lead,

131

LEADANDINFANTDEVELOPMENT

The Bayley Scales of Infant Development (Bayley, 1969) were administered at 3, 6, and 12 months. All of the infant subtests were given, including the mental development scale, psychomotor development scale, and infant behavior record. Care was taken to ensure that the infant was not noticeably sick, hungry, or fatigued at the time of testing. The examiners were trained on the Bayley scales by an experienced developmental psychologist. Intertester reliability for the Bayley mental development scale was 0.96, and at least 85% agreement was maintained for each item of the Bayley infant behavior record. The Home Observation for Measurement of the Environment (HOME) (Caldwell and Bradley, 1978) was given to the infants’ families at 6 and 12 months. The HOME consists of six subscales which measure developmentally salient aspects of the child’s domestic environment. These include emotional and verbal responsivity of the mother, avoidance of restriction and punishment, organization of the physical and temporal environment, provision of appropriate play materials, maternal involvement with child, and opportunity for variety in daily stimulation. Previous research has demonstrated the predictive validity of the HOME for later child IQ. school achievement, and malnutrition (Bradley and Caldwell. 1978). Interobserver agreement on the HOME in our study was 0.96. Both psychometricians and home visitors were unaware of the blood Pb (PbB) levels of infants in the study. Blood samples were obtained at 10 days and at quarterly intervals thereafter. Blood samples were collected either by EDTA Vacutainer (76%), finger stick (7%), or heel stick (17%), depending on the physical characteristics of the infant. Samples were analyzed for Pb by anodic stripping voltammetry using a cold digestion method (Morrell and Giridhar, 1976). Blood Pb levels were corrected for hematocrit. Quality control procedures are described in Bornschein et ~1. (1985). RESULTS

Table 1 presents geometric means and standard deviations for postnatal PbB values during the first year. Geometric mean PbB values increased from 5.3 kg/ dl at 10 days to 14.2 kg/d1 at 12 months. Variability in levels of exposure was evident at all ages, and some individual values exceeded 30 pg/dl indicating the possibility of undue Pb exposure (CDC, 1978). See the Appendix for the distribution of infants with PbB above 30 kg/dl. GEOMETRIC PbB PbB PbB PbB PbB PbB

(age)

(IO days) (3 months) (6 months) (9 months) (12 months)

MEAN

PbB N I23 I21 I36 I23 I24

VALUES

TABLE I FOR SXJDY INFANTS Mean

(kg/d11 5.3 4.9 7.0 I I.0 14.2

DLIIUNG

THE FIRST YE.~K

SD

Min

Max

I.9 I.9 1.9 I.9 I.7

I I I 1 3

19 24 33 55 46

132

DIETRICH

ET

AL.

Table 2 presents means and standard deviations for the Bayley mental development index (MDI). Although some infants in the investigation scored rather poorly (e.g., >2SD below the Bayley standardized mean of IOO), the vast majority presented a normal to superior pattern of early sensorimotor development. In addition, some stability in the rate of development over time was apparent since all the test-retest correlations were statistically significant (see Fig. 1). HOME scores varied widely among study sample families, attesting to the heterogeneity of the social-developmental environments experienced by lower socioeconomic status infants. The mean total HOME score for this sample was 31.7 (SD = 4.7) and ranged from 17 to 42 (the highest and optimal HOME score possible is 45). HOME scores below 30 are considered poor based on previous research. The mean birth weight for study infants was 3141 g (SD = 438 g) and ranged from 1814 to 4394 g. Figure 1 presents synchronous and lag Pearson product-moment correlations between log transformed current PbB (CPbB) and Bayley MD1 scores at ages 3, 6, and 12 months. Only the lag correlation between CPbB at 3 months and MD1 at 6 months was significant (r = -0.21, P < .Ol). However, after adjusting for HOME scores and birth weight, the partial correlation was substantially reduced and no longer significant (Pr = - .0.02,NS). Figure 2 presents synchronous and lag Pearson product-moment correlations between cumulative PbB (CumPbB) and Bayley MD1 scores at ages 3, 6, and 12 months. CumPbB is an index of total postnatal Pb exposure history derived from a calculation of the area under the fitted curve of each child’s PbB profile (composed of age-concurrent PbB values) from 10 days to the target ages of 3, 6, or 12 months. CumPbB is highly correlated with concurrent PbB values, but is used here as an additional index of exposure since it represents an estimate of the infants’ total Pb exposure history and is less susceptible to the effects of transitory, acute increases in PbB levels at any one point in time. As with CPbB, CumPbB values were transformed to their national logarithm to produce a more normal distribution. All of the correlations between CumPbB and MD1 were small and nonsignificant. The results presented in Figs. 1 and 2 are based on all subjects in the study at the time of these analyses, regardless of their age. This means that at the time these data were analyzed, some infants at the 3- or 6-month point may not have had a 12-month developmental examination. Thus, the number of observations presented beside each age is accurate for the synchronous correlations only. This “unrestricted” inclusion of all Bayley and PbB data for the lirst year was done TABLE MEAN

BAYLEY

INDEX

2

SCORES AT 3, 6, AND

Test (age in months)

N

Mean

SD

MD1 MD1 MD1

121 136 124

99.8 107.4 108.2

10.4 18.4 17.3

(3) (6) (12)

12 MONTHS

Min

Max

60 61 50

125 150 134

LEAD

AND

INFANT

133

DEVELOPMENT

4After correction fcf birthwfght and total HOME score, Pr= -.02, N.S. 410 day FM.

FIG. 1. Synchronous at 3, 6, and 12 months.

and lag correlations

between

current

blood

lead (CPbB)

and Bayley

MD1

scores

to increase the power of the statistical tests. Even so, little or no evidence was found for a Pb effect on early sensorimotor development. In a reanalysis of the psychometric data, we took a more prudent approach whereby only subjects with complete PbB and Bayley data for the first year were included. This restriction reduced the total number of subjects available for analysis to 67. Figure 3 presents synchronous and lag Pearson product-moment correlations between CPbB and Bayley MD1 for the restricted analysis. The results were nearly identical to the previous unrestricted analysis, with the exception of the somewhat paradoxical positive correlation between CPbB at 12 months and the 12-month Bayley MD1 (r = 0.28, P < 0.05). A positive correlation between the 12-month MD1 and CPbB at 12 months may indicate that developmentally precocious infants are more actively exploring their home environment and expanding their access to sources of Pb in dust, soils, or paint. At this point, however, the relationship is probably better explained as having occurred by chance alone. Figure 4 presents synchronous and lag Pearson product-moment correlations between CumPbB and Bayley MD1 for the restricted analysis. Again, the results were nearly identical to those reported for the unrestricted analysis of CumPbB +hmPbEO&.est

MDl(3)

-.~a+

---+CumPbN6)-.w+

-tvlDl@)

FIG. 2. Synchronous and lag correlations MD1 scores at 3. 6, and 12 months,

-CumPbB(l2)

-.a+

between

cumulative

-MDltl2)

blood

lead (C’umPbB)

and Bayley

134

DIETRICH

FCPbB(3)

cPbB(l~)-.se+ \

I\ -.,e

.04

ET AL.

.zw -

-.&?I,

11

-

MDl(3)-.sa+

CPt8(6)

-.ao*

-

I\ , .oe

&,

MDl(6) -

.u+

” =e,

CPbB(12) I .y*

-

I j

MDl(l2

*P < .os +n < .o,

$10 day PbB.

FIG. 3. Synchronous and lag correlations between current blood lead (CPbB) and Bayley MD1 scores at 3, 6, and 12 months for the restricted analysis.

and MDI. All of the synchronous and lag correlations between CumPbB and MD1 were small and nonsignificant. While the Bayley MD1 provides an overall measure of the infant’s sensorimotor status, it fails to index qualitative features of the infant’s performance which may be significant for present and future mental development. Such data are available on the Bayley infant behavior record (IBR). The IBR consists of 30 items which rate the infant’s social and objective orientations toward his environment as expressed in attitudes, interests, emotions, energy level, activity, and approach-withdrawal tendencies under stimulation. A principal axis factor analysis (Ray, 1982) of the Bayley IBR data set at 3, 6, and 12 months was executed to reduce the large number of variables to a few meaningful behavioral factors. In general, similar factors emerged at each age, although their order and loadings varied. These were Attention, Sensory Interest, Positive Mood, Activity, and Motor Maturity. Table 3 presents correlations between 12-month Bayley IBR factor scores and history of Pb exposure (CumPbB) at 6 and 12 months. Postnatal Pb exposure was only related to a single IBR factor, and only for the 12-month data set. Only the correlation between Sensory Interest at 12 months and the 12-month CumPbB was significant at the 0.05 level. The Sensory Interest factor provides an index r

CumPbB(3+

.w+ -CumPbB(6L

I\ -.04 -.cl* 1

MDl(3)

-

I\ MD1 (6) -

.88+ -

CumPbB(l2)

.02 L

I .I0 i

A.%$,-

FIG. 4. Synchronous and lag correlations between cumulative MD1 scores at 3, 6, and 12 months for the restricted analysis.

MDl( 12)

blood lead (CumPbB) and Bayley

LEAD

AND INFANT TABLE

CORRELATIONS

BETWEEN

12-MONTH

135

DEVELOPMENT 3

BAYLEY IBR FACTOR SCORES AND HISTORY or 6 AND 12 MONTHS

OF

CumPbB (6 months)

Activity Positive mood Sensory interest<’ Attention Motor maturity and absence of mouthing behavior

0.06 -0.05 -0.17* -0.11

0.01 -0.01 -0,25** -0.07

0.04

0.05

for birth weight and total HOME

scores,

EXPOSURE

CumPbB (12 months)

Factors

u After correction respectively. * P 5 0.10. ** P s 0.01.

Pb

Pr

= -0.06,

NS. and -0.12.

NS.

of the infant’s interest in visual, auditory, tactile, and social stimuli, as well as his endurance, energy level, and reactivity. Infants who score poorly on these IBR variables are likely to be lethargic and/or irritable. We regard the negative correlation between 12-month CumPbB and Sensory Interest as intriguing since in the literature on the behavioral sequelae of iron deficiency in infants, similar qualitative aspects of test behavior have been noted (/V&&ion Reviews, 1983). However, as with the MD1 results, after correction for birth weight and HOME scores, the partial correlation between Sensory Interest and CumPbB at 12 months was substantially reduced and no longer significant (J’r = -0.12, NS). DISCUSSION

Our hypothesis that postnatal Pb exposure would be related to infant sensorimotor development was not confirmed. The modest, but statistically significant lag correlation between CPbB at 3 months and the 6-month MD1 was greatly reduced and no longer significant when adjusted for birth weight and home environment. The same was true for the single significant correlation between the IBR factor of Sensory Interest and CumPbB at 12 months. At this point in our analyses, there appears to be no evidence that postnatal low-level Pb exposure increases an infant’s risk for delays in early sensorimotor development. Nevertheless, we are planning other analyses appropriate to the kinds of developmental models we have previously proposed for research in child behavioral toxicology (Dietrich and Pearson, 1983; Pearson and Dietrich, in press). For example, we intend to examine the dose-response relationship between Pb exposure and sensorimotor development under different levels of social-environmental and perinatal status variables. Infants at initially higher risk for developmental morbidity, and/or those raised in environments which provide a low level of social and intellectual stimulation may be less buffered from the putative neurotoxic effects of low-level Pb exposure. If Pb exposure affects sensorimotor development during the tirst year, a family of dose-response curves based on the infant’s social and biological protile may result. The testing of these more complex hypotheses awaits a larger database.

136

DIETRICH

ET AL.

APPENDIX Number

of Subjects

PbB (t.&dl) 2 30 =c 40 2 40 < 50 2 50 -c 60

with Indication 6 Months

of Undue Exposure 9 Months

2 -

3 1 1

by Age 12 Months 6 3 -

ACKNOWLEDGMENTS This research was supported by Program Project Grant #ESOl566-04 from the National Institute of Environmental Health Sciences. The investigators gratefully acknowledge the aid of Leslie Harris, Tari Gratton, Carol Stewart, and Susan MacDonald in the collection of psychometric, home, and biomedical data; Sandy Roda and her assistant, Jennifer Miller, for the analysis of blood samples; and Joanne Grote and Terry Mitchell for subject recruitment and follow-up. The authors also thank Nancy Knapp for typing the manuscript. REFERENCES Bayley, N. (1969). “The Bayley Scales of Infant Development.” Psychological Corp., New York. Bomschein, R. L., Hammond, I? B., Dietrich, K. N., Succop, P. A., Krafft, K. M., Clark, S., Berger, O., Pearson, D. T., and Que Hee, S. (1985). The Cincinnati prospective study of low level lead exposure and its effects on child development: Protocol and status report. Emiron. Res. 38, 4 18. Bradley, R. H., and Caldwell, B. M. (1978). Screening the environment. Amer. J. Orfhopsychia?ry 48, 114- 130. Caldwell, B. M., and Bradley, R, H. (1978). “Administration Manual: Home Observation for Measurement of the Environment.” University of Arkansas, Little Rock. Available from authors. Center for Disease Control (1978). Preventing lead poisoning in young children. J. Pe&fr. 93, 709-720. Dietrich, K. N., and Pearson, D. T. (1983). Research models in developmental behavioral toxicology. Paper presented at the biennial meeting of the Society for Research in Child Development, Detroit, Michigan, April 21-24. Morrell, G., and Giridhar, G, (1976). Rapid micromethod for blood lead analysis by anoid stripping voltammetry. Ch Chem. 22, 221-223. Needleman, H. L., Bellinger, D., Leviton, A., Rabinowitz, M., and Nichols, M. (1983). Umbilical cord blood lead levels and neuropsychological performance at 12 months. Pediutr. Res. 17, 556, abstract 3OOA. Nutr. Rev. (1983). Iron deficiency and mental development. 41, 235-237. Pearson, D. T., and Dietrich, K. N. The behavioral toxicology and teratology of childhood: Models, methods, and implications for intervention. Neuroroxicology, in press. Ray, A. A. (Ed.) (1982). “Statistical Analysis System User’s Guide: Statistics.” SAS Institute Inc., Raleigh, N.C.