Higher Maternal Serum Alkyl-substituted Organophosphate Ester Concentrations at 9 to 13+6 Gestational Weeks Are Associated with Increased Birth Weight and Large-for-Gestational-Age Risk: A Prospective Cohort Study.

BACKGROUND: Evidence linking maternal organophosphate ester (OPE) exposure during early gestational weeks with infant birth weight outcomes remains limited. OBJECTIVE: This prospective cohort study examined associations of maternal serum OPE concentrations at 9 to 13+6 gestational weeks with infant birth weight, large for gestational age (LGA), and small for gestational age (SGA). METHODS: Among 1, 039 pregnant females in a Qingdao birth cohort, 16 serum OPEs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Individual OPEs were evaluated per interquartile-range increase in ln-transformed concentration using multivariable linear regression and modified Poisson regression. Quantile g-computation (Qgcomp), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) assessed OPE mixtures. RESULTS: Tris(isobutyl) phosphate (TIBP) and tris(2-ethylhexyl) phosphate (TEHP) were associated with higher birth weight [TIBP: β = 77 g, 95% confidence interval (CI): (37, 117); TEHP: β = 40 g, 95% CI: (18, 63)]. TEHP was associated with higher LGA risk [adjusted risk ratio (aRR) = 1.27, 95% CI: (1.09, 1.48)] and lower SGA risk [aRR = 0.71, 95% CI: (0.57, 0.90)]; p-cresyl diphenyl phosphate (pCDP) was also associated with lower SGA risk [aRR = 0.69, 95% CI: (0.53, 0.91)]. In Qgcomp models, total OPE mixture exposure was associated with higher LGA risk [aRR = 1.41, 95% CI: (1.10, 1.80)]. Alkyl-substituted OPE mixture was associated with higher LGA risk in Qgcomp and higher birth weight in WQS; halogenated OPE mixture showed no significant associations. CONCLUSIONS: Maternal serum concentrations of selected OPEs at 9 to 13+6 gestational weeks, particularly alkyl-substituted OPEs, were associated with higher birth weight and LGA risk. These findings warrant confirmation in studies with repeated exposure assessment and additional longitudinal fetal growth indicators.