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

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.

• Authors: Anteneh Assefa Desalegn, Nina Iszatt, Hein Stigum, Tina K Jensen, Merete Eggesbø
• Journal: Environment international (Environ Int) Vol. 157 Pg. 106815 (12 2021) ISSN: 1873-6750 [Electronic] Netherlands
• PMID: 34388676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Environmental Pollutants
• Hydrocarbons, Chlorinated
• Polychlorinated Biphenyls

Topics

• Child
• Child, Preschool
• Cohort Studies
• Cryptorchidism (chemically induced, epidemiology)
• Environmental Pollutants (analysis, toxicity)
• Female
• Humans
• Hydrocarbons, Chlorinated (analysis)
• Infant
• Male
• Milk, Human (chemistry)
• Polychlorinated Biphenyls (analysis, toxicity)
• Pregnancy
• Prospective Studies