Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort

Abstract

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p<0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B=-0.37, p=0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B=-0.48, p<0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

Figures

Figure 1

Prenatal High (A) and Low Molecular Weight (B) Phthalate Metabolite Concentrations (in μM) in maternal urine and Performance on the Orientation Domain of the Brazelton Neonatal Assessment Scale Legend: Median molar phthalate metabolite concentration within quartiles is plotted against the adjusted mean orientation score for each quartile. Models are adjusted as in Table 3, and include a sex and sex-phthalate interaction term. There was an inverse, linear association between high molecular weight phthalates and mean score on the orientation BNBAS domain among girls. Boys and girls had similar trends for high molecular weight phthalates below 1µM. Although boys and girls showed opposite patterns of effect for low molecular weight phthalates, there were no significant associations, either overall or sex-stratified.

Figure 2

Relationship between Prenatal Low (A) and High (B) Molecular Weight Phthalate Metabolite Concentrations in Maternal Urine and Performance on the Motor Domain of the Brazelton Neonatal Assessment Scale Figure 2 Legend: Median molar phthalate metabolite concentration within quartiles is plotted against the adjusted mean motor score for each quartile. Models are adjusted as in Table 3, and include a sex and sex-phthalate interaction term. Among boys, there appeared to be a slight positive association between increasing LMWP phthalate concentrations and improved motor performance (Figure 2A) (B = 0.09, p = 0.01) although it was non-linear at the second quartile. Overall, neither boys nor girls demonstrated monotonic relationships.

Figure 3

Prenatal High Molecular Weight Phthalates Metabolite Concentrations in Maternal Urine and Examiner Assessment of the Quality of Alertness Supplementary Item on the Brazelton Neonatal Behavioral Assessment Scale Figure 3 Legend: Median molar phthalate metabolite concentration within quartiles is plotted against the adjusted mean orientation score for each quartile. Models are adjusted for examiner and maternal race. The relationship between high molecular weight phthalate metabolite concentrations and Quality of Alertness appeared to be limited to girls. Among girls, there was an adjusted mean 0.48 point decline (95% CI -0.83, -0.12) per log unit increase in the sum of high molecular weight metabolites.