In utero exposure to perfluoroalkyl substances and early childhood BMI trajectories: A mediation analysis with neonatal metabolic profiles

By Xiaojing Zeng, Ting Chen, Yidan Cui, Jian Zhao, Qian Chen, Zhangsheng Yu, Yongjun Zhang, Lianshu Han, Yan Chen, and Jun Zhang
Sci Total Environ
January 9, 2023
DOI: 10.1016/j.scitotenv.2023.161504


In utero perfluoroalkyl substances (PFAS) exposure has been associated with childhood adiposity, but the mechanisms are poorly known.


To investigate the potential mediating role of neonatal metabolites in the relationship between prenatal PFAS exposure and childhood adiposity trajectories in the first four years of life.


We analyzed the data for 1671 mother-child pairs from the Shanghai Birth Cohort study. We included those with PFAS exposure information in early pregnancy, neonatal metabolites data and at least three child anthropometric measurements at 6, 12, 24 and/or 48 months. Body mass index (BMI) z-score trajectories were identified using latent class growth mixture modeling. The associations between PFAS concentrations and trajectory classes were assessed using multinomial logistic regression. Screening and penalization-based selection was used to identify neonatal amino acids and acylcarnitines with significant mediation effects.


Three BMI z-score trajectories in early childhood were identified: a persistent increase trajectory (Class 1, 2.2 %), a stable trajectory (Class 2, 66 %), and a transient increase trajectory (Class 3, 32 %). Increased odds of being in Class 1 were observed in association with one log-unit increase in concentrations of perfluorooctane sulfonate (odds ratio [OR], 1.76 [95 % CI, 0.96-3.23], Class 2 as reference; OR, 2.36 [95 % CI, 1.27-4.40], Class 3 as reference), perfluorononanoic acid (OR, 1.90 [95 % CI, 0.97-3.72], Class 2 as reference; OR, 2.23 [95 % CI, 1.12-4.42], Class 3 as reference) and perfluorodecanoic acid (OR, 1.95 [95 % CI, 1.12-3.38], Class 2 as reference; OR, 2.14 [95 % CI, 1.22-3.76], Class 3 as reference). The effect of prenatal PFAS exposure on being in Class 1 was significantly but partly mediated by octanoylcarnitine (2.64 % for perfluorononanoic acid and 3.70 % for sum of 10 PFAS).


In utero PFAS exposure is a risk factor for persistent growth in BMI z-score in early childhood. The alteration of neonatal acylcarnitines suggests a potential molecular pathway.

View on PubMed