Associations between organophosphate flame retardants and risk for nonsyndromic cleft lip and/or palate in offspring

Introduction

Nonsyndromic cleft lip and/or palate (NSCL/P) is a common congenital malformation with a complex etiology involving many environmental factors. Organophosphate flame retardants (OPFRs) are a class of emerging contaminants that are associated with adverse reproductive and developmental outcomes, but their potential role in NSCL/P risk remains unexplored.

Methods

A total of 134 NSCL/P cases and 292 controls were recruited in China between 2005 and 2021. The concentrations of six target OPFRs in placentas were quantified using gas chromatography–tandem mass spectrometry. Logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to examine the relationships between OPFR exposure and NSCL/P risk.

Results

In the logistic regression model, high TBP level was associated with an increased risk for NSCL/P, while low TCPP level was linked to elevated risk for NSCL/P. The BKMR model revealed a significant joint effect of mixed exposure to OPFRs on the increased risk for NSCL/P, with TBP associated with a significant increase in NSCL/P risk. In the WQS model, the WQS index was positively correlated with the risk for NSCL/P [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.07, 1.24], with TBP having the highest weight of 90%.

Conclusions

This study provides novel epidemiologic evidence that prenatal exposure to a mixture of OPFRs may lead to an increased risk of NSCL/P, to which TBP is a major contributor. These findings underscore the importance of reducing environmental OPFR exposures during fetal development to mitigate the burden of this common birth defect.