Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ

Abstract

Background: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. Objective: We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. Method: The study sample consisted of 1,282 mother–child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002–2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at , 18–25, and of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test–Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy. Results: Higher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular (95% CI: , )]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di- n -octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex. Conclusions: We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047

Prenatal Exposure to Nonpersistent Chemical Mixtures and Offspring IQ and Emotional and Behavioral Problems

“…The strongest contributors to the overall negative mixture association on nonverbal IQ were MECPP, MCPP, monoisobutyl phthalate (MiBP), and dimethylthiophosphate (DMTP). In a previous work where we used the same population to investigate phthalate metabolites exposure in association with nonverbal IQ using separate regression analyses, we showed that the averaged concentrations of MCPP and PA across pregnancy had the largest association with nonverbal IQ with larger effect estimates as compared to the estimates observed in this study . These different findings indicate that by modeling co-occurring chemical exposures, exposure biomarkers combinations playing a substantial role in the association with a certain outcome might be identified, that are missed in single regression models that do not adjust for or take into account coexposure effects.…”

“…In real world situations, fetal exposure to these nonpersistent chemicals co-occurs in exposure combinations. Except for a small number of studies, − the majority of studies investigating the association between prenatal exposure to these chemicals and neurodevelopment in children, including our previous work, − have applied single exposure models, which have important limitations . For example, co-occurring chemical exposures may join additively to produce larger effects which cannot be investigated. − Further, single exposure analyses may be biased if potential cochemical confounding exists.…”

Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

“…We selected the LOD cut-off of 20% because with this cut-off we were able to include the maximum number of participants in the analyses with adequate variability in the bisphenol data to detect associations. This approach is in line with previous studies in the field (Philips et al, 2018 ; Sol et al, 2020 ; van den Dries et al, 2020 ). Bisphenols A, S and F met those inclusion criteria (Supplementary Table S1).…”

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort

“…Interestingly, the inverse associations between blood exposure biomarkers and the AC z-score were stronger for first-trimester blood THM concentrations, suggesting that early pregnancy may be a potentially vulnerable window. This is biologically plausible given that early pregnancy is crucial for the development of the placenta and fetal organs, , which is sensitive to environmental toxicants. − Numerous epidemiological studies have found that exposure to certain environmental pollutants during the first trimester was associated with reduced fetal growth parameters. − Our results also showed that THM exposures can impair fetal growth in the second trimester, possibly via altering hormone regulation, disrupting placental growth and/or triggering the oxidative stress response. , Early-onset growth retardation is a significant concern given its association with various adverse health outcomes in children and adults. , However, more mechanistic studies are needed to clarify our observed trimester-specific associations.…”