Maternal pre-pregnancy overweight/obesity, in-utero exposure to toxic heavy metals, and offspring age at peak height velocity: A prospective birth cohort study

Abstract

Introduction: Research on in-utero heavy metal exposure shows inconsistent results on offspring pubertal timing. We aim to contribute to understanding the association between heavy metal exposures and age at peak height velocity (APHV), an indicator of pubertal timing, and to investigate the joint associations of heavy metal concentrations and previously known risk factors.

Methods: We included 956 mother-child dyads from the Boston Birth Cohort. Heavy metal concentrations were measured in maternal red blood cells collected 24-72 h after delivery. Offspring APHV was calculated using mixed-effects growth curve models based on repeated height measurements over time. Firstly, we investigated maternal lead, cadmium and mercury level in association with APHV using multivariate linear regression models. Secondly, we estimated the joint associations of maternal pre-pregnancy overweight/obesity (or race/ethnicity) and heavy metal concentrations with APHV, after adjusting for confounders. Thirdly, we applied a Bayesian kernel machine regression (BKMR) model to investigate the association between the heavy metal mixture and APHV.

Results: Overall, prenatal heavy metal exposure was modestly inversely (but not statistically significantly) associated with earlier offspring APHV. Both childhood and maternal pre-pregnancy overweight/obesity were associated with an earlier APHV. Non-Hispanic Black males had an earlier APHV than other race/ethnicity males. Moreover, high lead and cadmium concentrations and maternal pre-pregnancy overweight/obesity were jointly associated with APHV in males only and females only, respectively. The joint exposure of maternal pre-pregnancy overweight/obesity and high lead concentrations were associated with earlier APHV among males, and likewise maternal pre-pregnancy overweight/obesity and high cadmium concentrations with earlier APHV among females. The joint associations of non-Hispanic Black race/ethnicity and high concentrations of lead and mercury with APHV were observed in males.

Conclusions: Our findings suggest that maternal pre-pregnancy overweight/obesity prevention and environmental toxic chemicals control may help attenuate the secular trend of early puberty, particularly among non-Hispanic Black individuals.

Keywords: Metal toxicity; Overweight; Pregnancy; Prenatal exposure; Pubertal growth; Race and ethnicity.