Association of In Utero Exposure to Polybrominated Diphenyl Ethers With the Risk of Hypospadias

Abstract

IMPORTANCE Polybrominated diphenyl ethers (PBDEs) are added to many consumer products as flame retardants, and their endocrine-disrupting properties are a growing health concern in pregnancy.OBJECTIVE To investigate whether in utero PBDE exposure as measured in maternal hair is associated with increased risk for hypospadias. DESIGN, SETTING, AND PARTICIPANTSIn this case-control study, the setting was the urology clinic of a tertiary pediatric hospital between January 3, 2011, and April 1, 2013. Participants were children diagnosed as having hypospadias and their mothers and a control group of children without hypospadias and their mothers. Dates of data analysis were September 3, 2017, to December 28, 2017.EXPOSURES Gestational exposure to 8 PBDEs as measured in the 3-cm segment closest to the skull of maternal hair by gas chromatography-mass spectroscopy as a proxy for in utero exposure. The mothers resided in the same household for the duration of their pregnancy.MAIN OUTCOMES AND MEASURES Difference in total maternal hair PBDE levels between the hypospadias and control groups.RESULTS Total PBDE levels were significantly higher among mothers of infants with hypospadias (n = 152) (total PBDE level, 51.4 pg/mg; interquartile range, 35.8-78.5 pg/mg) than among controls (n = 64) (total PBDE level, 35.8 pg/mg; interquartile range, 18.1-69.9 pg/mg) (P = .02). Of the 152 women with sufficient hair samples for analysis in the case group, 89 completed a questionnaire and were included in a multivariable analysis, and of the 64 women with sufficient hair samples for analysis in the control group, 54 completed a questionnaire and were included in a multivariable analysis. Adjusting for potential confounders, hypospadias was associated with a relative 48.2% (95% CI, 23.2%-65.4%) higher maternal level of total PBDE levels in the multivariable analysis. CONCLUSIONS AND RELEVANCEIn this analysis, mothers of children with hypospadias were exposed during pregnancy to significantly higher levels of PBDEs. The results of this study suggest that level of exposure to PBDEs during gestation may have a role in the etiology of hypospadias.

Effects of Polybrominated Diphenyl Ethers on Hormonal and Reproductive Health in E-Waste-Exposed Population: A Systematic Review

“…An increase in gestational age was supported by Chen et al [98], but Eick et al [94] and Jin et al [91] observed a negative association with PBDE exposure. Additionally, there were other studies that did not find statistically significant associations between neonatal health indices and PBDE exposure levels [109,110] or found associations that were incomparable to the results from our selection of studies, such as associations with hypospadias in neonates [111,112]. The conflicting results could have been due to the differences in confounder adjustments, the statistical analyses used, multiple chemical exposures, congener profiles, and the study design.…”

Endocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives

“…Gestational exposure to eight PBDEs was measured in mothers of boys diagnosed with hypospadias. Total PBDE levels were significantly higher (up to 48%) among mothers of infants with hypospadias than among controls ( Koren et al, 2019 , Poon et al, 2018 ). A similar study found that maternal PBDE levels were not significantly different between women with infants with hypospadias and women with unaffected infants, however only 20 hypospadias infants were included in this study ( Carmichael et al, 2010 ).…”

Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

“…Twice more risk of infants developing cryptorchidism was observed with every ten times increase in the concentration of BDE-99, BDE-100 or BDE-154 in the maternal hair [29]. Similarly, higher levels of total PBDE and five individual congeners 47,99,153,and 154) were found in the hair of mothers whose infants had hypospadias (n = 152) than among controls (n = 64) in Toronto [30,31]. In multivariable model, hypospadias was associated with a relative 48.2% (95% CI, 23.3%-65.4%) higher maternal hair level of total PBDE including 8 congeners (Poon et al, 2018).…”