An observational study in Hypospadias, sponsored by University Hospital, Montpellier. Recruiting at 1 site in France. Open to participants aged 1 Month and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-11-26.
Sponsored by University Hospital, Montpellier · Observational
This study aims to demonstrate the impact of Endocrine-Disrupting Chemicals (EDCs) on the risk of hypospadias incidence. It is a multicenter comparative case-control study, involving two groups. The first group consists of biological mothers who have given birth to children with hypospadias (Case Group), while the second group consists of biological mothers who have given birth to children without any malformations (Control Group). Through an integrative approach that combines a direct toxicological study of numerous pollutants present during pregnancy, and a comprehensive exposome assessment using validated tools, this study can significantly enhance our understanding and prevention of this malformation.
Background. Hypospadias is a birth defect of the external genital organs in boys and it ranks the second most common genital malformation in male newborns, following cryptorchidism. Its prevalence is increasing in certain global regions, with an estimated rate of 3.8 cases per 1000 male births. To date, the exact cause of hypospadias remains unknown, however genetic, hormonal, and environmental factors are likely involved. Medical and surgical treatment may be necessary. Furthermore, hypospadias is correlated with fertility issues and is also linked to testicular cancer.
Aim. After ruling out hypospadias with a genetic cause, the aim of this study is to evaluate any significant differences to environmental endocrine disrupting-chemicals (EDCs) exposure between biological mothers of children with hypospadias and those with children without malformation. It aims to demonstrate that this exposure (professional, occupational, environmental) leads to hormonal changes during the neonatal mini-puberty period.
Methods. This research will be conducted as a multicenter case-control study: mother and son with isolated anterior or middle hypospadias (Case Group) and mother and son without hypospadias (Control Group). The clinical investigator plans to enroll 200 patients.
A single visit will be performed. This consultation is part of the usual follow-up for children in the Case Group, while it is specific to the project for children in the Control Group.
During this visit, the investigator:
Case Group: Biological mother and child with hypospadias Control group: Biological mother and child without hypospadias
Non-specific Inclusion Criteria :
Specific Inclusion Criteria for Case Group:
- The child has an isolated anterior or middle hypospadias, without any other complex variations of genital development (borderline penile size, unilateral or bilateral cryptorchidism, retractile testes), without malformation syndrome and without identified genetic etiology
Specific Inclusion Criteria for Control Group:
- The child must not present any complex variations in genital development (hypospadias, borderline penis size, unilateral or bilateral cryptorchidism, retractile testes)
Exclusion Criteria:
Specific Exclusion Criteria for Case Group:
Biological mother/child pairs if a genetic variant explaining hypospadias is found during genetic analysis.
Biological mother and son with hypospadias
Other: Consultation visit (Visit 1)
Biological mother and son without hypospadias
Other: Consultation visit (Visit 1)
During visit 1, a pediatric urologist or pediatric endocrinologist will perform a clinical examination to confirm the diagnosis of hypospadias, as a part of routine care. The clinical study investigator will ask to fill out a validated European questionnaire for the exposome and use an occupation/exposure matrix to identify specific atmospheric exposure. A hair sample from the biological mother will be taken for toxicological evaluation of substances accumulated during pregnancy. From the child, a blood sample will be taken for hormonal evaluation of minipuberty and then, another sample in a 5 ml EDTA tube will be taken for DNA collection.
During visit 1, a pediatric urologist or pediatric endocrinologist will perform a clinical examination to confirm the absence of hypospadias. The clinical study investigator will ask to fill out a validated European questionnaire for the exposome and use an occupation/exposure matrix to identify specific atmospheric exposure. A hair sample from the biological mother will be taken for toxicological evaluation of substances accumulated during pregnancy. From the child, a blood sample will be taken for hormonal evaluation of minipuberty.
Evaluation of toxic exposure via hair sample analysis
An assessment of toxic substance concentrations in maternal hair will evaluate exposure to a wide range of pollutants. The collected hair samples will provide data representing the period from three months before conception to the date of study enrollment. The study will analyze 150 chemical substances and measure their concentrations to assess mothers' exposure to these pollutants during pregnancy.
Time frame: Day 1 (Visit 1)
Exposome through validated European questionnaires (QLK4-1999-01422)
Evaluation of parents' environmental exposure (exposome) will be conducted using a simplified version of a validated European questionnaire. This approach aims to elucidate potential differences in exposure between case and control groups.
Time frame: Day 1 (Visit 1)
Exposome professionnel
Assessment by the job-exposure matrix EDC (Environment disrupting chemicals)
Time frame: Day 1 (Visit 1)
Pollutant dispersion model
Examination of atmospheric pollutant concentration measurements and their potential impact on maternal exposure during gestation. This study conducts a comparative analysis between two groups: mothers of affected children (case group) and mothers of unaffected children (control group).
Time frame: Day 1 (Visit 1)
Hormonal analysis by immunoassay principle
Measurement of plasma hormone levels of mini-puberty to investigate a correlation between toxicological dosage and endocrine disruption. FSH, LH, AMH and free Testosterone will be measured by Electrochemiluminescence and Inhibin B by ELISA assay. This assessment of a mini-puberty alteration will be carried out by comparing age-based norms and the values of the control group
Time frame: Day 1 (Visit 1)
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University Hospital, Montpellier