Congenital anomalies: risk factors, management, and outcome


Babak Khoshnood


Congenital Anomalies (CA) constitute one of the principal causes of infant mortality, morbidity, and disability in industrialized countries. Their etiology remains for the most part unknown, which constitutes an important barrier for their prevention. Nevertheless, periconceptional supplementation with folic acid represents an important possibility for primary prevention of neutral tube defects. In addition, primary prevention of CA can be achieved with: i) the elimination or avoidance of known teratogenic substances, ii) optimal management of certain chronic or pregnancy-associated diseases (notably, diabetes).

Important progress has taken place in prenatal screening for CA, in particular for chromosomal anomalies including Down syndrome, as well as, structural birth defects such as gastrointestinal and congenital heart defects. There have also been notable improvements in the postnatal clinical management and thus the outcomes of certain CA, especially congenital heart defects. Optimal management of many anomalies requires their prenatal detection, which can guide postnatal management, including a transfer in-utero or the newborn’s rapid transfer to a specialized clinical service.


The objectives are to study, using population-based data:

  1. the associations between different categories of CA and their potential risk factors (in particular, assisted reproduction technologies and, in the context of long-standing European collaborations, certain groups of medications)
  2. practice patterns and performance of prenatal screening and postnatal management of children with CA
  3. the outcomes, particularly long-term outcomes of children with CA, and iv) evaluation of the effectiveness of policies for prevention of CA.

Principal themes

Given the great heterogeneities that exist in the domain of CA, we have chosen to study three distinct anomalies:

  1. Congenital heart defects, which are the principal focus of our current and future projects. They comprise a large and very heterogeneous group of anomalies, many of which are curable but only if optima medical and/or surgical treatment begins soon after birth; prenatal screening for congenital heart defects is recommended and increasingly often performed to enable optimal postnatal medical management.
  2. Down syndrome, an anomaly for which several prenatal screening techniques are available, including the recently introduced non-invasive prenatal testing (NIPT) based on analysis of fetal DNA.
  3. Neural tube defects, which represent the most important and clearest example of the possibility of primary prevention for a group of CA.

Main data sources:

  • REMAPAR : Paris Registry of Congenital Malformations (established in 1981)
  • EPICARD (EPIdémiologie des enfants ou fœtus porteurs de CARDiopathies congénitales), Population-based, prospective cohort study of newborns with congenital heart defects with a follow-up of 8 years.

Selected Publications (2012-2017):

Team members for the theme of congenital anomalies

Babak Khoshnood (Epidémiologiste, Inserm), François Goffinet (Obstétricien-Epidémiologiste Université Paris Descartes), Nathalie Lelong (Statisticienne, responsable d’étude, Inserm), Nathalie Bertille (Statisticienne), Alexandra Lecourbe (Coordinatrice d’étude), Cécile Leclerc (Coordinatrice d’étude).

Principal collaborations

National collaborations

  • Establishment of a Federation of French Registries of congenital malformations (Registre des Antilles dirigé par Bruno Schaub, registre CEMC-Auvergne dirigé par Isabelle Perthus, registre de Bretagne dirigé par Florence Rouget, registre de la Réunion dirigé par Hanitra Randrianaivo, registre REMERA-Rhône Alpes dirigé par Emmanuelle Amar) in relation with the Public Health France (Anne Gallay, Nolwenn Regnault, Eugénia Gomes) and Inserm Charles Persoz, Corinne Alberti)
  • Damien Bonnet (Hôpital Necker Enfants Malades, AP-HP, Centre de référence M3C, Université Paris Descartes, Paris)
  • Christophe Delacourt (Hôpital Necker Enfants Malades, AP-HP, Service de pneumologie pédiatrique, Université Paris Descartes, Paris)
  • Lucile Houyel (Hôpital Marie Lannelongue, Service de chirurgie des cardiopathies congénitales, Le Plessis-Robinson)
  • Jean-Marie Jouannic (Hôpital Trousseau, AP-HP, Centre pluridisciplinaire de diagnostic prénatal, UPMC, Paris)

International collaborations

  • European surveillance of congenital anomalies (JRC-EUROCAT)
  • Safety of medication use in pregnancy (Euromedicat)
  • Establishing a linked European Cohort of Chilldren with Congenital Anomalies (Eurolinkcat)
  • International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR)
  • Johanna Calderon, neuropsychologist, research associate, Harvard University, Boston
  • Babak Choodari-Oskooei, biostatistician, MRC unit, University College, London
  • Mithat Gönen, senior statistician, Sloan Cancer Center, New York