Correlation of maternal exposure to synthetic phenolic antioxidants with preschoolers’ physical growth partially moderated by breastfeeding: a prospective cohort study from China

Synthetic phenolic antioxidants (SPAs) are prevalent emerging environmental contaminants. This study aimed to explore the associations of maternal single and mixed SPA exposure across pregnancy with children’s physical growth trajectories from birth to 3 years of age, identify critical exposure windows, and further evaluate the potential effect modification of breastfeeding. A total of 1327 mother-child dyads were enrolled from the China National Birth Cohort (CNBC). Maternal urine samples were collected in the first, second and third trimesters, and the concentrations of nine SPAs were determined via liquid chromatography-tandem mass spectrometry. Children’s length/height and weight were measured at birth, 1.4, 6, 12 and 36 months to calculate weight-for-age Z-score (WAZ), length-for-age Z-score (LAZ) and body mass index Z-score (BMIZ). Group-based trajectory modeling (GBTM) was adopted to classify children’s physical growth trajectories. Multivariate logistic regression, Bayesian kernel machine regression (BKMR), and quantile-based g-computation (Q-gcomp) were applied to analyze the relationships between SPA exposure and growth trajectories, and restricted cubic spline (RCS) models were used to characterize the corresponding dose-response relationships. Multiple SPAs were widely detectable in maternal urine throughout gestation. After adjustment for confounding factors, first-trimester exposure to BHT-CHO correlated with elevated odds of high BMIZ growth trajectory, presenting a non-linear dose-response pattern. Third-trimester and whole-pregnancy 4-TOP exposure increased the risk of LAZ low-start with increasing trajectory. First-trimester BHA exposure reduced the likelihood of low LAZ trajectory, confirming compound-specific effects of different SPAs. Mixed exposure analyses yielded inconsistent results: BKMR revealed a positive correlation between first-trimester SPA mixture exposure and high BMIZ trajectory, whereas Q-gcomp failed to detect statistically significant overall mixture effects. Stratified analyses showed that adverse associations between BHT metabolites and abnormal weight growth trajectories were stronger in non-exclusively breastfed children. Sex-stratified results indicated that most weight-growth-related associations were more prominent in boys. This observational study showed that prenatal exposure to specific SPAs was selectively associated with adverse childhood growth trajectories, varying by SPA type and exposure window. Breastfeeding exerted only partial modifying effects and could not fully mitigate such developmental disturbances.