BackgroundAlthough urinary concentrations of phthalate metabolites are frequently used as biomarkers in epidemiologic studies, variability during pregnancy has not been characterized.MethodsWe measured phthalate metabolite concentrations in spot urine samples collected from 246 pregnant Dominican and African-American women. Twenty-eight women had repeat urine samples collected over a 6-week period. We also analyzed 48-hr personal air samples (n = 96 women) and repeated indoor air samples (n = 32 homes) for five phthalate diesters. Mixed-effects models were fit to evaluate reproducibility via intraclass correlation coefficients (ICC). We evaluated the sensitivity and specificity of using a single specimen versus repeat samples to classify a woman’s exposure in the low or high category.ResultsPhthalates were detected in 85–100% of air and urine samples. ICCs for the unadjusted urinary metabolite concentrations ranged from 0.30 for mono-ethyl phthalate to 0.66 for monobenzyl phthalate. For indoor air, ICCs ranged from 0.48 [di-2-ethylhexyl phthalate (DEHP)] to 0.83 [butylbenzyl phthalate (BBzP)]. Air levels of phthalate diesters correlated with their respective urinary metabolite concentrations for BBzP (r = 0.71), di-isobutyl phthalate (r = 0.44), and diethyl phthalate (DEP; r = 0.39). In women sampled late in pregnancy, specific gravity appeared to be more effective than creatinine in adjusting for urine dilution.ConclusionsUrinary concentrations of DEP and DEHP metabolites in pregnant women showed lower reproducibility than metabolites for di-n-butyl phthalate and BBzP. A single indoor air sample may be sufficient to characterize phthalate exposure in the home, whereas urinary phthalate biomarkers should be sampled longitudinally during pregnancy to minimize exposure misclassification.

Background: Research suggests that prenatal phthalate exposures affect child executive function and behavior.Objective: We evaluated associations between phthalate metabolite concentrations in maternal prenatal urine and mental, motor, and behavioral development in children at 3 years of age.Methods: Mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), and four di-2-ethylhexyl phthalate metabolites were measured in a spot urine sample collected from 319 women during the third trimester. When children were 3 years of age, the Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using the Bayley Scales of Infant Development II, and behavior problems were assessed by maternal report on the Child Behavior Checklist.Results: Child PDI scores decreased with increasing loge MnBP [estimated adjusted β-coefficient = –2.81; 95% confidence interval (CI): –4.63, –1.0] and loge MiBP (β = –2.28; 95% CI: –3.90, –0.67); odds of motor delay increased significantly [per loge MnBP: estimated adjusted odds ratio (OR) = 1.64; 95% CI: 1.10, 2.44; per loge MiBP: adjusted OR =1.82; 95% CI: 1.24, 2.66]. In girls, MDI scores decreased with increasing loge MnBP (β = –2.67; 95% CI: –4.70, –0.65); the child sex difference in odds of mental delay was significant (p = 0.037). The ORs for clinically withdrawn behavior were 2.23 (95% CI: 1.27, 3.92) and 1.57 (95% CI: 1.07, 2.31) per loge unit increase in MnBP and MBzP, respectively; for clinically internalizing behaviors, the OR was 1.43 (95% CI: 1.01, 1.90) per loge unit increase in MBzP. Significant child sex differences were seen in associations between MnBP and MBzP and behaviors in internalizing domains (p < 0.05).Conclusion: Certain prenatal phthalate exposures may decrease child mental and motor development and increase internalizing behaviors.

Experimental evidence has shown that certain phthalates can disrupt endocrine function and induce reproductive and developmental toxicity. However, few data are available on the extent of human exposure to phthalates during pregnancy. As part of the research being conducted by the Columbia Center for Children's Environmental Health, we have measured levels of phthalates in 48-hr personal air samples collected from parallel cohorts of pregnant women in New York, New York, (n = 30) and in Krakow, Poland (n = 30). Spot urine samples were collected during the same 48-hr period from the New York women (n = 25). The following four phthalates or their metabolites were measured in both personal air and urine: diethyl phthalate (DEP), dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP), and butyl benzyl phthalate (BBzP). All were present in 100% of the air and urine samples. Ranges in personal air samples were as follows: DEP (0.26-7.12 microg/m3), DBP (0.11-14.76 microg/m3), DEHP (0.05-1.08 microg/m3), and BBzP (0.00-0.63 microg/m3). The mean personal air concentrations of DBP, di-isobutyl phthalate, and DEHP are higher in Krakow, whereas the mean personal air concentration of DEP is higher in New York. Statistically significant correlations between personal air and urinary levels were found for DEP and monoethyl phthalate (r = 0.42, p < 0.05), DBP and monobutyl phthalate (r = 0.58, p < 0.01), and BBzP and monobenzyl phthalate (r = 0.65, p < 0.01). These results demonstrate considerable phthalate exposures during pregnancy among women in these two cohorts and indicate that inhalation is an important route of exposure.

The mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis.