Infant blood lead levels

To assess the association between prenatal/early postnatal lead exposure and development, we followed a group of urban US infants from birth to 2 years of age. Estimates of the association between lead and Bayley Mental Development Index (MDI) scores at ages 6, 12, 18, and 24 months were obtained using several regression options. In all multivariate models examined, MDI scores were associated with umbilical cord blood lead levels, but not with postnatal blood lead levels. Infants with high cord blood lead levels (10-25 jUg/dl) consistently scored 4 to 8 points lower than infants with low cord blood lead levels (< 3 jUg/dl). Infants vulnerability to lead s developmental toxicity appears to be greatest during the fetal period. 

A later analysis (Emhart et al. 1987) related PbB levels obtained at delivery (maternal and cord blood) and at 6 months, 2 years, and 3 years of age to developmental tests (MDI, PDI, Kent Infant Development Scale [KID], and Stanford-Binet IQ) administered at 6 months, 1 year, 2 years, and 3 years of age, as appropriate. After controlling for covariates and confounding risk factors, the only significant associations of blood lead with concurrent or later development were an inverse association between maternal (but not cord) blood lead and MDI, PDI, and KID at 6 months, and a positive association between 6-month PbB and 6-month KID. The investigators concluded that, taken as a whole, the results of the 21 analyses of correlation between blood lead and developmental test scores were "reasonably consistent with what might be expected on the basis of sampling variability," that any association of blood lead level with measures of development was likely to be due to the dependence of both PbB and... 

Rabinowitz MB, Leviton A, Bellinger D. 1985a. Home refinishing, lead paint and infant blood lead levels. Am J Public Health 75 403-404. 

Rabinowitz MB, Leviton A, Needleman H, et al. 1985b. Environmental correlates of infant blood lead levels in Boston. Environ Res 38 96-107. 

Tang HW, Huel G, Campagna D, et al Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero involvement of monoamine neurotransmitters. J Appl Toxicol 19 167-172, 1999 Tanis AL Lead poisoning in children including nine cases treated with edathamil cal-cium-disodium. American Journal of Diseases of Children 89 325-331, 1955 Telisman S, Prpic-Majic D, Beritic T PhB and ALAD in mentally retarded and normal children. Int Arch Occup Environ Health 52 361-369,1983 Thomson GOB, Raah GM, Hephurn WS, et al Blood-lead levels and children s behaviour—results from the Edinburgh lead study. J Child Psychol Psychiatry 30 515-528, 1989... 

Zierold, K. M. Anderson, H. (2004). Trends in blood lead levels among children enrolled in the special supplemental nutrition program for women, infants, and children from 1996 to 2000. Am. J. Public Health. 94 1513—1515. 

Studies have shown an association between umbilical blood lead concentration under 10 gg/dL and reduced head circumference (Al-Saleh et al. 2008b), effects on infant attention (Plusquellec et al. 2007), abnormal reflexes and abnormal results on neurologic soft signs scales (Emhart et al. 1986), reduced body-weight gain (Sanin et al. 2001), and decreased body-mass index (NTP 2012). Deficits in visual function in children were also seen at umbihcal blood lead levels as low as 10.5 gg/dL (Rothenberg et al. 2002). Increased maternal... 

An additional factor that may influence the effect that lead has on the brain is the age at which the child was exposed. Scientific research has shown that different parts of the brain, serving different functions, develop most rapidly at different times. Therefore, lead s interference in the development of the brain may damage different specific functions depending on when exposure occurs and which part of the brain is at a critical stage of development at the time. A 9-month-old infant who has a blood level of 30 ULg/dl for 6 months might suffer damage different from that of a 27-month-old who also has had a blood lead level of 30 p g/dl for 6 months. ... 

Blood lead measures reflect predominantly current exposure to lead. The lead level in blood is in a dynamic equilibrium, which implies that with constant exposure it is relatively stable, and this has been shown to be the case in a small group of adults (Delves et al, 1984) but that it rapidly reflects changes in exposure, and takes some time to stabilize after a change in exposure. Blood lead levels in infants are much less stable with a correlation of between 0.1 and 0.2 in three blood samples taken during the first year of life (Rabinowitz et al, 1985), probably because, for developmental and behavioural reasons, their intake is not constant. However in older children much higher correlations (r = 0.76 and 0.74) over a 3- and a 5-year gap between samples, have been achieved (Winneke et al, this volume Schroeder, this volume). 

Given these conclusions, the obvious question is, "What are the implications for the public health " First, what portion of the population is at risk Based on data from the National Center for Health Statistics (1982), approximately 3.6 million live births occurred in the United States in 1980. Data from the US National Health and Nutrition Examination Survey for about the same period (February 1979 to February 1980) indicate that about 27% of the women of child-bearing age had PbB concentrations of 10 /ig/dl or more cf. Schwartz et al, 1985). Thus, nearly 1 million infants may have been bom in the United States around 1980 to mothers with maternal PbB levels high enough to put the infants at risk for developmental impairments. Blood lead levels in the United States have probably declined somewhat since then due to reduced ambient levels (Schwartz et al, 1985), but the scope of potential concern is still significant, particularly in parts of the world where ambient levels may be greater. 

After birth the sharp distinctions among groups in terms of blood lead levels were lost. In the sample as a whole, mean postnatal blood lead level did not exceed 8 fig/dl at any age and, on most occasions, postnatal levels were not associated with infants cord blood lead classifications. In contrast to the trimodal distribution of cord blood lead levels created by our sampling strategy, the distribution of postnatal blood lead levels more closely approached normality (Rabinowitz et al, 1984). Because extreme postnatal values are much less frequent in our sample than are extreme cord blood values, we can evaluate the hypothesis of an association between infant development and prenatal lead exposure more efficiently than the hypothesis of an association between infant development and postnatal exposure. Moreover, the weak correlations between infants cord blood lead levels and their postnatal lead levels (Rabinowitz et al, 1984) mean that any cord blood lead level-outcome relationship is not likely to be confounded by infants postnatal lead exposures. 

Most of our subjects are middle to upper-middle class white infants, for whom socioeconomic status and quality of caregiving are at most only weakly associated with prenatal or postnatal blood lead levels (Bellinger et al, 1985b, 1986b). They do not display the typical association between demographic/ economic risk factors and increased lead exposure seen in most samples. As a consequence, the likelihood of observing a spurious association between elevated lead exposure and poor outcome is lower in this sample than it is in most samples recruited to study the developmental impact of lead. 

To demonstrate that infants with high cord blood lead levels are not at risk for poor development based on other aspects of their rearing context, we calculated least-squares mean MDI scores for infants in the three lead groups, using a regression equation that included the 12 a priori variables but not cord blood lead category (Figure 3). These are the scores that would be... 

The inverse association in this sample between MDI scores and umbilical cord blood lead levels in the 0 to 25 jUg/dl range appears to be robust. Estimates of its magnitude and precision are relatively independent of analytic approach. Furthermore, the association does not appear to be attributable to the inordinate influence of outliers. Most infants with high lead levels contribute to the overall poorer performance of this group relative to infants with lower levels of prenatal exposure. 

Rabinowitz, M., Leviton, A., Needleman, H., Bellinger, D. and Watemaux, C. (1985) Environmental correlates of infant blood lead levels. Env. Res., 38, 96-107 Robins, J. and Greenland, S. (1986) The role of model selection in causal inference from nonexperimental data. Am. ]. Epidemiol, 123, 392-402 SAS User s Guide (1982) (Cary, NC SAS Institute)... 

Results from several cohort studies are now available. Bellinger et al (1986) failed to find any relation, for middle-class infants, of 6-month and 12-month blood lead levels (PbB) and the Mental Development Index (MDI) of the Bayley Scales of Infant Development. Dietrich et al. (in press) reported a significant relationship of 3-month, but not 6-month, PbB with 6-month MDI... 

Wolf, A. W. Jimenez, E. Lozoff, B. Effects of iron therapy on infant blood lead levels. J. Pediatr. 2003,143,789-795. 

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