A Multimodal Study of the Relationship Between Exposure to Endocrine Disruptors and Occurrence of Hypospadias - HYPOLLUT
- Conditions
- Hypospadias
- Interventions
- Other: Consultation visit (Visit 1)
- Registration Number
- NCT06628375
- Lead Sponsor
- University Hospital, Montpellier
- Brief Summary
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.
- Detailed Description
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:
* will establish the diagnosis of hypospadias (for cases) or absence of genital anomaly (for controls)
* will lead an interview using a questionnaire and a job-exposure matrix to assess EDCs during pregnancy
* will take a hair sample from the mother to measure the substances accumulated during pregnancy
* and finally, will take a blood sample from the child for hormonal evaluation of mini-puberty, and another blood sample from child in the Case Group for analysis and the participation in a DNA collection
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
- Child with another congenital anomaly or malformative syndrome
- Child with an endocrine pathology
- Biological mother or child under legal protection, guardianship, or curatorship
- Biological mother or child in the exclusion period of a previous study
- Biological mother or child included in another clinical study involving a drug
Specific Exclusion Criteria for Case Group:
Biological mother/child pairs if a genetic variant explaining hypospadias is found during genetic analysis.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Case Group Consultation visit (Visit 1) Biological mother and son with hypospadias Control Group Consultation visit (Visit 1) Biological mother and son without hypospadias
- Primary Outcome Measures
Name Time Method Evaluation of toxic exposure via hair sample analysis Day 1 (Visit 1) 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.
- Secondary Outcome Measures
Name Time Method Exposome through validated European questionnaires (QLK4-1999-01422) Day 1 (Visit 1) 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.
Exposome professionnel Day 1 (Visit 1) Assessment by the job-exposure matrix EDC (Environment disrupting chemicals)
Pollutant dispersion model Day 1 (Visit 1) 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).
Hormonal analysis by immunoassay principle Day 1 (Visit 1) 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