Associations between prenatal phthalate exposure and newborn telomere length: Effect modification by infant sex

Phthalates are endocrine-disrupting chemicals (EDCs) ubiquitously present in the environment. There are limited studies on the impact of phthalate exposure during the gestational period on neonatal telomere length.

The aim of this study is to investigate the correlation between maternal serum phthalate concentrations in early pregnancy and neonatal telomere length and whether this correlation exhibits sex-specificity.

Between September 2015 and April 2018, 474 pregnant women were selected from the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum samples from early pregnancy were measured for levels of five phthalates and four phthalate metabolites. Umbilical cord blood samples were collected to measure telomere length. The correlations between prenatal phthalate exposure and infant telomere length were assessed using multiple linear regression, Bayesian kernel machine regression (BKMR), quantile g-computation (qg-comp), and restricted cubic spline (RCS) models.

Multiple linear regression analyses revealed that per 2.7-fold increase in the concentration of butyl benzyl phthalate (BBP) and mono-ethyl phthalate (MEP), neonatal telomere length decreased by 2.66 % (95 % CI: -5.20 %, -0.05 %) and 3.43 % (95 % CI: -6.46 %, -0.30 %), respectively. Conversely, per 2.7-fold increase in di-butyl phthalate (DBP) concentration corresponded to a 3.01 % (95 % CI: 0.19 %, 5.91 %) increase in neonatal telomere length. Sex-stratified analyses demonstrated that BBP (percent change: -3.60 %; 95 % CI: -6.91 %, -0.18 %); mono-butyl phthalate (MBP) (percent change: -4.13 %; 95 % CI: -7.14 %, -1.01 %) and MEP (percent change: -7.66 %, 95 % CI: -11.53 %, -3.62 %) were inversely associated with neonatal telomere length in female infants only. Neonatal sex significantly modified the association between MEP exposure and neonatal telomere length (P-value for interaction = 0.018). Phthalate mixture was inversely associated with neonatal telomere length in female infants but not in male infants in qg-comp and BKMR models.

Our study suggests that maternal exposure to phthalates is linked to shorter telomere length in neonates, especially in female infants.