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.