Prenatal exposure to neonicotinoid insecticides, fetal endocrine hormones and birth size: Findings from SMBCS

Background: Neonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. Objectives: This study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. Methods: The study included 860 mother-child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of pNNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. Results: Higher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI ((3 = -0.15, 95 %CI: -0.26, -0.03), DIN ((3 = -0.22, 95 %CI: -0.40, -0.03), IMI ((3 = -0.20, 95 %CI: -0.35, -0.06) and NNIs ((3 = -0.23, 95 %CI: -0.42, -0.04). IMI and DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between DIN and TT3 ((3 = -0.013, 95 %CI: -0.025, -0.002), IMI and T ((3 = -0.035, 95 %CI: -0.065, -0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal DIN and IMI exposure with head circumference. Conclusions: Our findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.