Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect.

Abstract

BACKGROUND:

Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions.

OBJECTIVE:

To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias.

DESIGN, SETTING, AND PARTICIPANTS:

A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed.

RESULTS:

Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, p<0.00005). Association of occupational and environmental exposures increases this risk.

CONCLUSIONS:

This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk.

PATIENT SUMMARY:

Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.

• Authors: Nicolas Kalfa, Françoise Paris, Pascal Philibert, Mattea Orsini, Sylvie Broussous, Nadège Fauconnet-Servant, Françoise Audran, Laura Gaspari, Hélène Lehors, Myriam Haddad, Jean-Michel Guys, Rachel Reynaud, Pierre Alessandrini, Thierry Merrot, Kathy Wagner, Jean-Yves Kurzenne, Florence Bastiani, Jean Bréaud, Jean-Stéphane Valla, Gérard Morisson Lacombe, Eric Dobremez, Amel Zahhaf, Jean-Pierre Daures, Charles Sultan
• Journal: European urology (Eur Urol) Vol. 68 Issue 6 Pg. 1023-30 (Dec 2015) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 26007639 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Endocrine Disruptors

Topics

• Child
• Child, Preschool
• Endocrine Disruptors (adverse effects)
• Environmental Exposure (adverse effects)
• Female
• France
• Humans
• Hypospadias (chemically induced)
• Infant
• Infant, Newborn
• Male
• Occupational Exposure (adverse effects)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Prospective Studies