Association of prenatal exposure to phthalates and synthetic phenols with pubertal development in three European cohorts.
Level 3 - non-randomized controlled study
Prospective cohort study
PubMed 38968838 · doi:10.1016/j.ijheh.2024.114418
What was done
This study examined associations between prenatal exposure to endocrine-disrupting chemicals and pubertal development in children from three European birth cohorts: INMA (Spain), EDEN (France), and MoBa (Norway). Concentrations of metabolites from six phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, DiNP), bisphenol A (BPA), four parabens (MePB, EtPB, PrPB, BuPB), benzophenone-3 (BP-3), and triclosan (TCS) were measured in maternal urine samples from the 1st and/or 3rd trimesters (1999–2008). Pubertal development was assessed at a single visit at ages 7–12 years in 579 girls and 644 boys using the parent-reported Pubertal Development Scale (PDS). Mixed-effect Poisson models, g-computation, and Bayesian Kernel Machine Regression (BKMR) were used to analyze individual chemical and mixture effects on overall pubertal onset, adrenarche, and gonadarche, including effect modification by child BMI.
What was found
In boys, a two-fold increase in maternal DEHP and DiNP metabolites was associated with a higher probability of pubertal onset (relative risk [RR] = 1.13, 95% CI 0.98–1.30 for DEHP; RR = 1.20, 95% CI 1.06–1.34 for DiNP), with DiNP showing a stronger association in boys with overweight or obesity. Conversely, BPA, BuPB, EtPB, and PrPB were associated with a lower probability of pubertal onset or stages in boys (e.g., BPA: RR = 0.93, 95% CI 0.85–1.01; BuPB: RR = 0.95, 95% CI 0.90–1.00 for overall puberty), with the BPA association stronger in underweight or normal-weight boys. In girls with underweight or normal weight, MEHP (RR = 0.86, 95% CI 0.77–0.95) and BPA (RR = 0.90, 95% CI 0.84–0.97) were associated with delayed gonadarche. Multipollutant mixture models identified no overall combined effect of the chemical mixtures on pubertal outcomes in boys or girls.
Why it matters
This study provides prospective multi-cohort evidence that prenatal exposures to specific plasticizers and synthetic phenols may have compound-specific, sex-dependent, and BMI-modified associations with pubertal timing in European children.
Limits
Pubertal development was evaluated cross-sectionally at a single time point using parent questionnaires rather than clinical Tanner staging by a physician. Chemical exposures were quantified from only one or two spot urine samples during pregnancy, which may not adequately reflect chronic exposure to rapidly metabolized compounds. Most individual associations were trimester-specific, and mixture models showed no aggregate effect.
Cited by
- contradicts A 2016 study found that girls with higher prenatal BPA exposure experienced earlier breast development and menarche.