A case-cohort study of perinatal exposure to potential endocrine disrupters and the risk of cryptorchidism in the Norwegian HUMIS study. (December 2021)

• Record Type: Journal Article
• Authors: Desalegn, Anteneh Assefa; Iszatt, Nina; Stigum, Hein; Jensen, Tina K.; Eggesbø, Merete
• Is Part Of: Environment international. Volume 157(2021)
• Publication Date: 2021-12
• Subjects: Congenital cryptorchidism -- Recurrent cryptorchidism -- Endocrine-disrupting chemicals -- Human breast milk -- Persistent organic chemicals -- Variable selection; BDE brominated diphenyl ether -- CPP The U.S. Collaborative Perinatal Project -- DAG directed acyclic graph -- DDE dichlorodiphenyldichloroethylene -- DDT dichlorodiphenyltrichloroethane -- HCB hexachlorobenzene -- HCH hexachlorocyclohexane -- HUMIS The Norwegian Human Milk Study -- IQR interquartile range -- LOD limit of detection -- LOQ limit of quantification -- NDL (non)-dioxin-like -- P percentile -- PBDE Polybrominated Diphenyl Ether -- PCB polychlorinated biphenyl -- PFASs poly- and perfluoroalkyl substances -- PFHxS perfluorohexane sulfonate -- PFOA perfluorooctanoate -- PFOS perfluorooctane sulfonate -- β-HCH Beta-hexachlorocyclohexane; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2021.106815
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: Exposure to endocrine-disrupting chemicals may increase the risk of cryptorchidism. Breast milk levels of persistent chemicals represent prenatal & postnatal exposure. The estrogenic organochlorine pesticide β-HCH is associated with cryptorchidism. PCB-74, PCB-114, and PCB-194 may also increase the risk of cryptorchidism. Single pollutant analysis results can be confounded by highly correlated chemicals. Abstract: Background: Exposure to endocrine-disrupting chemicals (EDCs) during the critical period of testicular descent may increase the risk of cryptorchidism and male fertility. Objective: To investigate 27 potential EDCs measured in breast milk as a proxy for perinatal exposure and the risk of cryptorchidism in a prospective cohort. Method: The Norwegian Human Milk Study (2002–2009) enrolled 2606 mother-infant pairs, of which 1326 were mother-son pairs. In a case-cohort design, we studied 641 male infants who had 27 EDCs already quantified in milk samples: 5 organochlorine pesticides, 14 polychlorinated biphenyls (PCBs), 6 brominated flame retardants, and 2 poly- and perfluoroalkyl substances. We defined cases of congenital, recurrent, persistent and ever-reported cryptorchidism based on questionnaires mothers completed when children were 1, 6, 12 and 24 months old. Variable selection via elastic net logistic regression identified the best cryptorchidism predictors while multivariable logistic regression models determined their effect estimates. Results: The prevalence of reported congenital cryptorchidism was 6.1%, with half spontaneously descending within six months of birth, after which prevalence stabilized between 2.2 and 2.4%. The ever-reported prevalence of cryptorchidism at 1, 6, 12, or 24 months was 12.2%. Elastic net models identified PCB-74 (OR = 1.31, 95% CI: 1.001–1.703), PCB-114 (OR = 1.36, 95% CI: 1.05–1.77), PCB-194 (OR = 1.28, 95% CI: 1.03–1.53) and β-HCH (OR = 1.26, 95% CI: 1.03–1.53 (per interquartile range increase in concentration of EDCs) as best predictors of congenital cryptorchidism. No EDCs were selected for either recurrent or persistent cryptorchidism, and only PCB-194 was selected by elastic net for ever-reported cryptorchidism (OR = 1.23, 95% CI: 1.01–1.51), in contrast to unpenalized multivariable logistic regression, where most of the individual congeners of PCBs showed significant associations. Conclusion: In the largest multi-pollutant analysis to date considering potential confounding from co-exposure to other chemicals, perinatal exposure to PCB-74, PCB-114, PCB-194 and β-HCH were associated with increased odds of congenital cryptorchidism. Many PCBs may falsely be associated with cryptorchidism when assessed individually, due to confounding by highly correlated chemicals. Experimental studies are warranted to confirm our findings.