Prenatal exposure to multiple organochlorine compounds and childhood body mass index

Abstract

Background: Prenatal exposure to organochlorine compounds (OCs) has been associated with increased childhood body mass index (BMI); however, only a few studies have focused on longitudinal BMI trajectories, and none of them used multiple exposure mixture approaches.

Aim: To determine the association between in-utero exposure to eight OCs and childhood BMI measures (BMI and BMI z-score) at 4 years and their yearly change across 4-12 years of age in 279 Rhea child-mother dyads.

Methods: We applied three approaches: (1) linear mixed-effect regressions (LMR) to associate individual compounds with BMI measures; (2) Bayesian weighted quantile sum regressions (BWQSR) to provide an overall OC mixture association with BMI measures; and (3)Bayesian varying coefficient kernel machine regressions (BVCKMR) to model nonlinear and nonadditive associations.

Results: In the LMR, yearly change of BMI measures was consistently associated with a quartile increase in hexachlorobenzene (HCB) (estimate [95% Confidence or Credible interval] BMI: 0.10 [0.06, 0.14]; BMI z-score: 0.02 [0.01, 0.04]). BWQSR results showed that a quartile increase in mixture concentrations was associated with yearly increase of BMI measures (BMI: 0.10 [0.01, 0.18]; BMI z-score: 0.03 [0.003, 0.06]). In the BVCKMR, a quartile increase in dichlorodiphenyldichloroethylene concentrations was associated with higher BMI measures at 4 years (BMI: 0.33 [0.24, 0.43]; BMI z-score: 0.19 [0.15, 0.24]); whereas a quartile increase in HCB and polychlorinated biphenyls (PCB)-118 levels was positively associated with BMI measures yearly change (BMI: HCB:0.10 [0.07, 0.13], PCB-118:0.08 [0.04, 012]; BMI z-score: HCB:0.03 [0.02, 0.05], PCB-118:0.02 [0.002,04]). BVCKMR suggested that PCBs had nonlinear relationships with BMI measures, and HCB interacted with other compounds.

Conclusions: All analyses consistently demonstrated detrimental associations between prenatal OC exposures and childhood BMI measures.

Keywords: Bayesian varying coefficient kernel machine regressions; Bayesian weighted quantile sum regressions; Body mass index; Chemical mixture; Organochlorine compounds; Outcome trajectories.

Figure 1.

Overview of exclusion criteria in the Rhea study.

Figure 2.

Results of the linear mixed-effect regression^a in n = 279 mother-child pairs from the Rhea study. Coefficient estimates and 95% confidence intervals (CI) for the relationship^a between a one-quartile increase in the individual exposure to organochlorine compounds (OC) and childhood body mass index (BMI) at 4 years (A), yearly change in BMI from 4 to 12 years of age (B), BMI z-score (z-BMI) at 4 years (C) and yearly change in BMI z-score from 4 to 12 years of age (D). DDE indicates dichlorodiphenyldichloroethylene; HCB, hexachlorobenzene; PCB, polychlorinated biphenyl congeners (118, 153, 138, 156, 170, and 180). ^aAdjusted for maternal age at birth (years), maternal education at recruitment (≤6 years, >6–≤12 years, or >12 years), parity (nulliparous or multiparous), and maternal BMI before pregnancy (kg/m²), child sex (M/F), and child age at clinical follow-up visit (years). *Statistically significant after correcting for multiple testing (Table S1).

Figure 3.

Results of the Bayesian weighted quantile sum regression* in n = 279 mother-child pairs from the Rhea study. Coefficient estimates and 95% credible intervals (CrI) for the relationship* between a one-quartile increase in the overall mixture exposure to organochlorine compounds and both childhood body mass index (BMI) at 4 years (A), yearly change in BMI from 4 to 12 years of age (B), BMI z-score (z-BMI) at 4 years (C) and yearly change in BMI z-score from 4 to 12 years of age (D). The weights and 95% CrI identifying the individual contribution of each OC to the mixture are shown in gray. DDE indicates dichlorodiphenyldichloroethylene; HCB, hexachlorobenzene; PCB, polychlorinated biphenyl congeners (118, 153, 138, 156, 170, and 180).DDE indicates dichlorodiphenyldichloroethylene; HCB, hexachlorobenzene; PCB, polychlorinated biphenyl congeners (118, 153, 138, 156, 170, and 180)*Adjusted for maternal age at birth (years), maternal education at recruitment (≤6 years, >6–≤12 years, or >12 years), parity (nulliparous or multiparous) and maternal BMI before pregnancy (kg/m²), child sex (M/F), and child age at clinical follow-up visit (years).

Figure 4.

Results of the Bayesian varying coefficient kernel machine regression* in n = 279 mother-child pairs from the Rhea study. Coefficient estimates and 95% credible intervals (CrI) for the relationship* between a one-quartile increase (from 50th percentile to 75th percentile) in the exposure to a single organochlorine compound and childhood body mass index (BMI) at 4 years (A) and yearly change in BMI from 4 to 12 years of age (B) BMI z-score (z-BMI) at 4 years (C) and yearly change in BMI z-score from 4 to 12 years of age (D). DDE indicates dichlorodiphenyldichloroethylene; HCB, hexachlorobenzene; PCB, polychlorinated biphenyl congeners (118, 153, 138, 156, 170, and 180)*Adjusted for maternal age at birth (years), maternal education at recruitment (≤6 years, >6–≤12 years, or >12 years), parity (nulliparous or multiparous) and maternal BMI before pregnancy (kg/m²), child sex (M/F), and child age at clinical follow-up visit (years)