Phthalates, a class of chemicals found widely in consumer products including plastic toys, food contaminants and food packaging, personal care products, cosmetics, air fresheners, and some medications, have been shown to be anti-androgenic in numerous laboratory and epidemiological studies. In a prior cohort enrolled in 2000–2002, we observed associations between prenatal urinary concentrations of di-ethyl hexyl phthalate (DEHP) and dibutyl phthalate (DBP) metabolites and less male-typed play behavior in preschool age boys. The aim of this study was to examine phthalate exposure in pregnancy in relation to play behavior at age 4 years in a larger cohort of pregnant women enrolled in The Infant Development and the Environment Study (TIDES) between 2010 and 2012 at four study sites (Minneapolis, MN; Rochester, NY; San Francisco, CA; Seattle, WA). Maternal urinary metabolites of DEHP, DiBP, DnBP, BBzP, and DEP were measured during the first (n=498) and third trimester (n=468) and mothers completed the Preschool Activities Inventory (PSAI), a validated maternal questionnaire designed to assess child toy preference and sex-typed play behavior when children were 4–5 years of age. After adjusting for child age, maternal education, race, urine dilution, parental attitudes about opposite sex-typed play behavior, and presence of a same sex older sibling, we observed associations between first trimester (mean 10.7±2.1 weeks gestation) (log10) SpG-adjusted MnBP, MiBP, and MBzP and lower masculine scores in boys (β-coefficient [95% confidence intervals]: MnBP −2.18, [-4.16, −0.20]), MiBP −2.1[-4.3,0.1], and MBzP -2.42 [-4.12, −0.71]). In girls, first trimester maternal urinary MBzP was associated with lower masculine scores (-2.12 [-3.98,-0.25]), while third trimester (mean 32.8±3.0 weeks gestation) maternal urinary MiBP was associated with higher masculine scores (2.69 [0.68,4.70]). Third trimester maternal urinary phthalate levels were not associated with play behavior in boys. These findings in boys are largely consistent with previous studies that report that prenatal phthalate exposure is associated with less masculine play behavior. No associations in girls have been previously reported.
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We observed associations between MiBP, MnBP, and MBzP, and masculine play in boys. As shown previously, these metabolites were highly significantly correlated in our population (r=0.63 for MnBP and MiBP; r= 0.56 for MBzP and MnBP; r=0.44, MBzP and MiNP), suggesting possible co-exposure through common sources (Frederiksen et al., 2010). Because MBzP and MnBP are correlated and may share the parent phthalate BBzP, we conducted analyses jointly adjusting for MBzP and MnBP. We found no appreciable difference in phthalate associations with masculine score in boys or girls, suggesting that both MBzP and MnBP are independently associated with play behavior (Supplemental Table 19). In contrast to our earlier study (Swan et al., 2010), we did not observe a significant association between prenatal maternal DEHP metabolites and masculine play in boys. DEHP exposure has decreased in the general population over time (CDC, 2019), raising the possibility that lower DEHP exposure in the TIDES cohort accounts for the lack of association. A comparison of urinary phthalate metabolite concentrations in the TIDES cohort with those in our Study for Future Families (SFF) cohort (recruited ten years earlier) show a greater than 50% reduction in all metabolites with the exception of the DBP metabolite MiBP, which increased by 48% (Swan et al., 2015). These observations reflect exposure trends in the US population over the same time period (CDC, 2019), likely due to changes in product formulation resulting from consumer pressure and the restriction of phthalates in some children's items implemented by the 2008 Consumer Product Safety Information Act (U.S. Consumer Product Safety Commission, 2017), supporting the efficacy of such measures at reducing harmful exposures and protecting public health.This work was supported by the National Institutes of Health (Grant numbers R01ES016863?04, R01ES025169-05, P30ES023515, P30ES005022).
This work was supported by the National Institutes of Health (Grant numbers R01ES016863–04 , R01ES025169-05 , P30ES023515 , P30ES005022 ).
- Endocrine disruption
- Play behavior
- Prenatal exposure