Pregnancy Environment and Newborn Malformations
Pregnancy Environment and Newborn Malformations
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…
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.
Inclusion Criteria:

 All live births, 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)

 Non inclusion criteria :

 -  Spontaneous abortion before 22 weeks gestational age.

 -  Mother with legal protection (guardianship)

 Exclusion Criteria:

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