Trimester-specific effects of maternal exposure to organophosphate flame retardants on offspring size at birth: A prospective cohort study in China

Organophosphate flame retardants (OPFRs) are substantially applied as flame retardants and plasticizers in consumer products. Although the embryonic developmental toxicity of OPFRs has been reported, human data are limited and the critical windows of susceptibility to OPFRs exposure urgently need to be identified. Here, we investigated the trimester-specific associations between prenatal OPFR exposure and birth size for the first time. The concentrations of 15 OPFR metabolites and tris(2-chloroethyl) phosphate were repeatedly determined in urine samples of 213 pregnant women collected in the first, second, and third trimesters in Wuhan, China, and anthropometric data were retrieved from medical records. In multiple informant models, urinary concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and bis(2-butoxyethyl) phosphate (BBOEP) in the third trimester, 4-hydroxyphenyl-diphenyl phosphate (4-HO-DPHP) in the second trimester, and diphenyl phosphate (DPHP) in the first trimester were negatively associated with birth weight, among which a significant difference in exposure-effect relationships across the three trimesters was observed for BDCIPP. BBOEP concentrations in the third trimester were negatively correlated to birth length with significant varying exposure effects. Our results suggest that prenatal exposure to certain OPFRs may impair fetal growth, and the fetus is vulnerable to the developmental toxicity of BDCIPP and BBOEP in the third trimester.