A Multimodal Study of the Relationship Between Exposure to Endocrine Disruptors and Occurrence of Hypospadias - HYPOLLUT

Официальное название

Exposure to Endocrine Disruptors and Occurrence of Hypospadias: Toxicological, Environmental and Hormonal Imbalance Study

Обзор

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.

Подробное описание

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

Вмешательства

• Другое 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 chil
• Другое Consultation visit (Visit 1)
  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 tak

Первичные конечные точки

• Evaluation of toxic exposure via hair sample analysis [Срок оценки: Day 1 (Visit 1)]

Вторичные конечные точки (4)

• Exposome through validated European questionnaires (QLK4-1999-01422) [Срок оценки: Day 1 (Visit 1)]
• Exposome professionnel [Срок оценки: Day 1 (Visit 1)]
• Pollutant dispersion model [Срок оценки: Day 1 (Visit 1)]
• Hormonal analysis by immunoassay principle [Срок оценки: Day 1 (Visit 1)]

Критерии участия

Non-specific Inclusion Criteria :

• Parents of legal age having signed a free and informed consent for the participation of their child
• Biological mother of a boy aged between 1 and 6 months
• Biological mother with a minimum hair length of 18 cm
• Biological mother who has signed a free and informed consent for her participation
• Biological mother and child affiliated with or beneficiaries of a national health insurance plan
• Biological mother who is fluent in written and spoken French

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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Франция · 1 центр

• CRMR DEVGEN CHU Lapeyronnie — Montpellier

Публикации

• Ea V, Bergougnoux A, Philibert P, Servant-Fauconnet N, Faure A, Breaud J, Gaspari L, Sultan C, Paris F, Kalfa N. How Far Should We Explore Hypospadias? Next-generation Sequencing Applied to a Large Cohort of Hypospadiac Patients. Eur Urol. 2021 Apr;79(4):507-515. doi: 10.1016/j.eururo.2020.12.036. Epub 2021 Jan 16. PMID 33468338
• Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001 May;16(5):972-8. doi: 10.1093/humrep/16.5.972. PMID 11331648
• Skarin Nordenvall A, Chen Q, Norrby C, Lundholm C, Frisen L, Nordenstrom A, Almqvist C, Nordenskjold A. Fertility in adult men born with hypospadias: A nationwide register-based cohort study on birthrates, the use of assisted reproductive technologies and infertility. Andrology. 2020 Mar;8(2):372-380. doi: 10.1111/andr.12723. Epub 2019 Nov 20. PMID 31670475
• Springer A, van den Heijkant M, Baumann S. Worldwide prevalence of hypospadias. J Pediatr Urol. 2016 Jun;12(3):152.e1-7. doi: 10.1016/j.jpurol.2015.12.002. Epub 2015 Dec 31. PMID 26810252
• Schneuer FJ, Milne E, Jamieson SE, Pereira G, Hansen M, Barker A, Holland AJA, Bower C, Nassar N. Association between male genital anomalies and adult male reproductive disorders: a population-based data linkage study spanning more than 40 years. Lancet Child Adolesc Health. 2018 Oct;2(10):736-743. doi: 10.1016/S2352-4642(18)30254-2. Epub 2018 Aug 30. PMID 30236382
• Asklund C, Jensen TK, Main KM, Sobotka T, Skakkebaek NE, Jorgensen N. Semen quality, reproductive hormones and fertility of men operated for hypospadias. Int J Androl. 2010 Feb;33(1):80-7. doi: 10.1111/j.1365-2605.2009.00957.x. Epub 2009 Mar 5. PMID 19281491
• Kumar S, Tomar V, Yadav SS, Priyadarshi S, Vyas N, Agarwal N. Fertility Potential in Adult Hypospadias. J Clin Diagn Res. 2016 Aug;10(8):PC01-5. doi: 10.7860/JCDR/2016/21307.8276. Epub 2016 Aug 1. PMID 27656497
• Serrano T, Chevrier C, Multigner L, Cordier S, Jegou B. International geographic correlation study of the prevalence of disorders of male reproductive health. Hum Reprod. 2013 Jul;28(7):1974-86. doi: 10.1093/humrep/det111. Epub 2013 May 12. PMID 23670171

Идентификаторы

NCT: NCT06628375 · RECHMPL22_0559

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗