Association of Prenatal Phthalate Exposure with Pubertal Development in Spanish Boys and Girls

Abstract

Background: Phthalates are widespread, anti-androgenic chemicals known to alter early development, with possible impact on puberty timing.Aim: To investigate the association of prenatal phthalate exposure with pubertal development in boys and girls.Methods: Urinary metabolites of six different phthalate diesters (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and non-phthalate plasticizer DINCH® were quantified in two urine samples collected during pregnancy from mothers participating in the INMA Spanish cohort study. Pubertal assessment of their children at age 8-10 years (409 boys, 379 girls) was conducted using the Pubertal Development Scale reported by parents. Logistic and Weighted Quantile Sum (WQS) regression was employed to examine associations between prenatal phthalates and odds of puberty onset (stage 2+), adrenarche, and gonadarche. Effect modification by child weight status was explored by stratified analysis.Results: Prenatal exposure to DEHP was associated with higher odds (OR=1.52, 95%CI=1.07-2.15) of puberty onset in boys and higher odds (OR=1.43, 95%CI=1.01-2.03) of adrenarche in girls. In boys, prenatal exposure to DEP, DnBP, and DEHP was also associated with higher odds (ORs=1.67-2.26 per log-unit increase in concentrations) of adrenarche or gonadarche in those who were normal weight, and BBzP exposure with lower odds (OR=0.37, 95%CI=0.16-0.86) of adrenarche in those who were overweight/obese. In girls, DnBP was associated with higher odds (OR=1.53, 95%CI=1.01-2.32) of gonadarche only in those who were overweight/obese. In the WQS model, the phthalate mixture was not associated with puberty development in boys or girls.Conclusion: Prenatal exposure to certain phthalates was associated with puberty development, especially higher odds of puberty in normal-weight boys. However, there was no evidence of effect of the phthalate mixture on advancing or delaying puberty in boys or girls.

Keywords: phthalates, plasticizers, pregnancy, puberty, Pubertal Development Scale