Prenatal Phthalate Exposures and Body Mass Index Among 4- to 7-Year-old Children: A Pooled Analysis

Abstract

Background: Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI).

Methods: We included 707 children from three prospective cohort studies enrolled in the US between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1 standard deviation increase in natural log phthalate metabolite concentrations and BMI z scores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort.

Results: Mono-3-carboxypropyl phthalate concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z scores (β = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z scores among girls (monoethyl phthalate beta = -0.14 [-0.28, 0.00]; ∑DEHP beta = -0.12 [-0.27, 0.02]).

Conclusions: Maternal urinary mono-3-carboxypropyl phthalate, a nonspecific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not in boys, suggesting that prenatal exposures may have sexually dimorphic effects on physical development.

Figure 1

Posterior mean of odds ratios and 95% credible intervals for the association of a one standard deviation increase in natural log urinary MCPP concentrations with overweight/obese status among children aged 4 to 7 years (N=707; 1,416 follow-up visits), overall and by child’s sex and race/ethnicity. Associations estimated in multiple metabolite logistic mixed effects regression models adjusted for cohort, maternal race/ethnicity, maternal age at delivery, maternal education, maternal work status during pregnancy, maternal pre-pregnancy BMI, maternal height, gestational weight gain, maternal smoking during pregnancy, natural log creatinine, calendar date of urine collection, parity, child’s sex, breastfeeding, and months of age at follow-up.

Figure 2

Posterior mean of beta coefficients and 95% credible intervals for the association of a one standard deviation increase in natural log urinary MEP concentrations with BMI z-scores among children aged 4 to 7 years (N=707; 1,416 follow-up visits), overall and by child’s sex and race/ethnicity. Associations estimated in multiple metabolite linear mixed effects regression models adjusted for cohort, maternal race/ethnicity, maternal age at delivery, maternal education, maternal work status during pregnancy, maternal pre-pregnancy BMI, maternal height, gestational weight gain, maternal smoking during pregnancy, natural log creatinine, calendar date of urine collection, parity, child’s sex, breastfeeding, and months of age at follow-up.