Pregnancy Environment and Newborn Malformations

NCT ID: NCT01613638

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1657 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-05
• Study Completion Date: 2020-12-31

Brief Summary

Congenital malformations rate is about 3% in France. There are already 5 registries in France, covering about 16% of French births: Paris Registry, (about 38 000 births /year), Alsace Registry, (about 23 000 births/year), Rhône-Alpes Registry, (about 56 000 births/year), Auvergne Registry, (about 14 000 births/year), and la Réunion Registry. The aim of malformation registries is to carry out epidemiologic surveillance of congenital anomalies. The objectives are mainly to provide essential epidemiologic information on congenital anomalies, to facilitate the early warning of teratogenic exposures, to act as an information and resource centre regarding clusters, to provide data for research related to the causes and prevention of congenital anomalies.

A previous study was carried out in Brittany in 2008-2009, by the perinatal network of Ille et Vilaine, in collaboration with two research teams (Inserm U1085 and Inserm U 936), to record all cases of 4 types of congenital anomalies: congenital heart disease, spina bifida, diaphragmatic hernia and hypospadia. The results showed prevalence rates similar to those observed by Eurocat for spina bifida and diaphragmatic hernia, but a higher prevalence regarding congenital heart diseases and hypospadia. In this study the investigators could not determine whether this was due to a real higher frequency or to a particular exhaustiveness in the recording methodology.

There are hypothesis about the role of intrauterine exposure to pesticides, known as endocrine disruptors, and the risk of congenital genital anomalies. Brittany is an intensive agricultural area, and it is thus worth studying the impact of pesticides exposure on congenital anomalies.

There are also hypothesis on the impact of occupational exposure to solvents on congenital anomalies (Garlantezec 2009), and on the role of alcohol exposure (which concerns about 8% pregnant women in France) on oro-facial clefts and congenital heart diseases.

The Registry of congenital anomalies in Brittany was set up in 2010. The main aim is to study the impact of intra-uterine exposure to solvents, pesticides and alcohol on the risk of congenital malformations diagnosed at births, by measuring the exposure both directly in meconium, and indirectly by questionnaires.

Secondary objectives are to study other risk factors such as medicine intake, pregnancy illness…

Detailed Description

Population based case-control study:

2 controls per case will be included, corresponding to the first 2 births without congenital anomalies, with same sex and same birth place, following the case.

INVESTIGATION METHODOLOGY :

All maternity in Brittany were proposed to participate. In each maternity, the referent practitioner informs the parents and includes the cases.

For each case and control, meconium samples and a mother's lock are collected by nurses or midwives, medical data are collected from medical reports by the registry investigator, and a self-questionnaire is filled by the mother.

Meconium samples are immediately stored in a freezer (-20°C), secondarily transported to a biological storage centre at the university hospital and then dispatched to specialised laboratories for toxicological analyses: INERIS (for solvents and pesticides) and Toxicology Unit, University hospital Rennes (for Alcohol).

For dead fetuses (stillbirths or termination of pregnancy), meconium will be collected by the pathologist in charge of the autopsy, after parents' consent.

Evaluation of exposure:

• direct evaluation: by toxicological analyses in meconium samples: Alcohol, Solvents and pesticides
• indirect evaluation: by maternal self-questionnaire including data on occupational and domestic exposures, hobbies, life habits…, precise address (for spatial location)

Particular cases: mild congenital heart defects, genital anomalies and hip dislocation diagnosed later after birth (after the period oh meconium and before the age of one): these cases will be spotted through the Registry, there won't be any biological sample for them, but mothers will be contacted by main investigator and medical data and mother questionnaires will be collected. There won't be any control included for those cases included after birth.

Associations between exposure risk factors (alcohol, solvents and pesticides) and the risk of congenital malformations will be estimated by a multivariate analysis.

• Exposure to solvents will be estimated by assay in meconium and by occupational questionnaire
• Exposure to alcohol will be estimated by assay of Ethylglucuronide et de Ethylsulfate in meconium.
• Exposure to pesticides will be estimated by assay in meconium, by questionnaire and by spatial location.

Conditions

Congenital Malformation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Congenital malformations

All livebirths, fetal deaths with gestational age (GA) ≥22 weeks and terminations of pregnancy (at any gestational age) after prenatal diagnosis of malformation.

• born from mothers living in Brittany at delivery
• with a congenital anomaly according to Eurocat criteria, diagnosed or suspected (and then confirmed) at birth
• or with mild congenital heart defects, genital anomalies or hip dislocation diagnosed after birth (and before the age of one)

Group Type: OTHER

meconium samples + maternal self-questionnaire

Intervention Type: OTHER

meconium samples + maternal self-questionnaire

control

2 controls per case will be included, corresponding to the first 2 births without congenital anomalies, with same sex and same birth place, following the case.

Group Type: OTHER

meconium samples + maternal self-questionnaire

Intervention Type: OTHER

meconium samples + maternal self-questionnaire

Interventions

meconium samples + maternal self-questionnaire

meconium samples + maternal self-questionnaire

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

All live births, fetal deaths with gestational age (GA) ≥22 weeks and terminations of pregnancy for medical reasons (IMG) from 20 weeks of amenorrhea (SA) included.

• born from mothers living in Brittany at delivery
• with a congenital anomaly according to Eurocat criteria, diagnosed or suspected (and then confirmed) at birth
• or with mild congenital heart defects, genital anomalies or hip dislocation diagnosed after birth (and before the age of one) Suspicion of chromosomal abnormality or genetic syndrome on purely clinical criteria but not yet authenticated by genetic analyzes. If the chromosomal or genetic abnormalities are secondarily authenticated, these cases will be excluded a posteriori.

• Spontaneous abortion before 22 weeks gestational age.
• IMG before the 20 week term amenorrhea
• Chromosomal abnormalities or syndromes genetic authenticated by karyotype or analysis in molecular biology, in antenatal
• Mother with legal protection (guardianship)

Exclusion Criteria

• Prenatally suspected malformations, which are not confirmed by postnatal screening or clinical evolution

• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florence Rouget, MD

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Philippe Lefevre, MD

Role: PRINCIPAL_INVESTIGATOR

Fougères Hospital

Joëlle Gueguen, MD

Role: PRINCIPAL_INVESTIGATOR

Saint-Grégoire Hospital

Isabelle Blanchot, MD

Role: PRINCIPAL_INVESTIGATOR

Clinique La Sagesse - Rennes

Maria Vernis, MD

Role: PRINCIPAL_INVESTIGATOR

Saint Malo hospital

Dominique Chaumet, MD

Role: PRINCIPAL_INVESTIGATOR

Vitré Hospital

Joseph Abi-Fadel, MD

Role: PRINCIPAL_INVESTIGATOR

Redon Hospital

Philippe Rebour, MD

Role: PRINCIPAL_INVESTIGATOR

Lannion Hospital

Michel Turban, MD

Role: PRINCIPAL_INVESTIGATOR

Dinan Hospital

Claire Combescure, MD

Role: PRINCIPAL_INVESTIGATOR

Saint-Brieuc Hospital

Joseph Magagi, MD

Role: PRINCIPAL_INVESTIGATOR

Polyclinique du Littoral - Saint-Brieuc

Michel Collet, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Brest

David Somerville, MD

Role: PRINCIPAL_INVESTIGATOR

Polyclinique de Keraudren - Brest

Alain Hassoun, MD

Role: PRINCIPAL_INVESTIGATOR

Clinique Pasteur - Brest

Charles Bellot, MD

Role: PRINCIPAL_INVESTIGATOR

Quimper Hospital

Philippe Tillaut, MD

Role: PRINCIPAL_INVESTIGATOR

Lorient Hospital

Hubert Journel, MD

Role: PRINCIPAL_INVESTIGATOR

Vannes Hospital

Claire Duhaut, MD

Role: PRINCIPAL_INVESTIGATOR

Clinique Océane - Vannes

Patrick Vallée, MD

Role: PRINCIPAL_INVESTIGATOR

Pontivy Hospital

Marie-Agnès Guillou, MD

Role: PRINCIPAL_INVESTIGATOR

Ploermël Hospital

Locations

Polyclinique de Keraudren

Brest, Brittany Region, France

Brest University Hospital

Brest, Brittany Region, France

Lannion Hospital

Lannion, Brittany Region, France

Lorient Hospital

Lorient, Brittany Region, France

Ploermel Hospital

Ploërmel, Brittany Region, France

Quimper Hospital

Quimper, Brittany Region, France

Rennes University Hospital

Rennes, Brittany Region, France

Saint-Brieuc Hospital

Saint-Brieuc, Brittany Region, France

Saint-Grégoire Hospital

Saint-Grégoire, Brittany Region, France

Clinique Océane

Vannes, Brittany Region, France

Vannes Hospital

Vannes, Brittany Region, France

Countries

France

References

Meyer-Monath M, Beaumont J, Morel I, Rouget F, Tack K, Lestremau F. Analysis of BTEX and chlorinated solvents in meconium by headspace-solid-phase microextraction gas chromatography coupled with mass spectrometry. Anal Bioanal Chem. 2014 Jul;406(18):4481-90. doi: 10.1007/s00216-014-7836-2. Epub 2014 May 18.

Reference Type: BACKGROUND

PMID: 24838489 (View on PubMed)

Meyer-Monath M, Chatellier C, Cabooter D, Rouget F, Morel I, Lestremau F. Development of liquid chromatography methods coupled to mass spectrometry for the analysis of substances with a wide variety of polarity in meconium. Talanta. 2015 Jun 1;138:231-239. doi: 10.1016/j.talanta.2015.02.058. Epub 2015 Mar 19.

Reference Type: BACKGROUND

PMID: 25863396 (View on PubMed)

Meyer-Monath M, Chatellier C, Rouget F, Morel I, Lestremau F. Development of a multi-residue method in a fetal matrix: analysis of meconium. Anal Bioanal Chem. 2014 Dec;406(30):7785-97. doi: 10.1007/s00216-014-8243-4. Epub 2014 Nov 9.

Reference Type: BACKGROUND

PMID: 25381610 (View on PubMed)

Rouget F, Bihannic A, Cordier S, Multigner L, Meyer-Monath M, Mercier F, Pladys P, Garlantezec R. Petroleum and Chlorinated Solvents in Meconium and the Risk of Hypospadias: A Pilot Study. Front Pediatr. 2021 Jun 2;9:640064. doi: 10.3389/fped.2021.640064. eCollection 2021.

Reference Type: RESULT

PMID: 34150682 (View on PubMed)

Other Identifiers

B110827-40

Identifier Type: OTHER

Identifier Source: secondary_id

11/22-811

Identifier Type: OTHER

Identifier Source: secondary_id

2010-A01445-34

Identifier Type: OTHER

Identifier Source: secondary_id

PHRC/10-02 - PENEW

Identifier Type: -

Identifier Source: org_study_id