Shirley Poon1,2, Gideon Koren3,4, Amanda Carnevale1,2, Katarina Aleksa1,5,6, Juejing Ling2, Jak Ozsarfati1, Bhushan M Kapur1,2,7,8, Darius Bagli9. 1. Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. 3. Western University, London, Ontario, Canada. 4. currently with the Division of Clinical Pharmacology, Maccabi Research Institute Tel Aviv, Tel Aviv, Israel. 5. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. 6. School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada. 7. Department of Clinical Pathology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada. 8. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 9. Department of Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
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 Participants: In 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 Relevance: In 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.
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 Participants: In 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 Relevance: In 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.
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