Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.

Auvergne Registry of Congenital Anomalies Department of Clinical Genetics Centre de Référence des Maladies Rares CHU Estaing Clermont Ferrand France

Brittany Registry of Congenital Anomalies CHU Rennes Univ Rennes INSERM EHESP Irset UMR_S 1085 Rennes France

Centre de Génétique Humaine Institut de Pathologie et de Génétique Charleroi Belgium

Centre of Excellence for Reproductive and Regenerative Medicine Children's Hospital Zagreb Medical School University of Zagreb Zagreb Croatia

Congenital Anomaly Register and Information Service for Wales Public Health Wales Knowledge Directorate Singleton Hospital Swansea United Kingdom

Department of Genetics Eurocat Northern Netherlands University of Groningen University Medical Center Groningen Groningen Netherlands

Department of Global Public Health and Primary Care University of Bergen Bergen Norway

Department of Medical Biology and Genetics 1st Faculty of Medicine General University Hospital Charles University Prague Czechia

Department of Medical Genetics Poznan University of Medical Sciences Poznan Poland

Department of Obstetrics and Gynaecology Medical University of Graz Graz Austria

Department of Woman Mother Child University Hospital Center Centre Hospitalier Universitaire Vaudois Lausanne Switzerland

Directorate for Health Information and Research Pietà Malta

Division of Mental and Physical Health Norwegian Institute of Public Health Bergen Norway

Epidemiology Department National Institute of Health Doutor Ricardo Jorge Lisboa Portugal

European Commission Joint Research Centre Ispra Italy

Finnish Institute for Health and Welfare Terveyden Ja Hyvinvoinnin Laitos Register of Congenital Malformations Helsinki Finland

Health Department Provincial Institute of Hygiene Antwerp Belgium

Health Intelligence R and D Health Service Executive Dublin Ireland

Health Service Executive South Department of Public Health St Finbarr's Hospital Cork Ireland

Indagine Sulle Malformazioni Congenite in Emilia Romagna Neonatal Intensive Care Unit Pediatric Section Department of Medical Sciences University of Ferrara Ferrara Italy

Institute of Clinical Physiology National Research Council Pisa Italy

Malformation Monitoring Centre Saxony Anhalt Medical Faculty Otto von Guericke University Magdeburg Germany

OMNI Net Ukraine Programs Rivne Ukraine

Paediatric Department Hospital Lillebaelt Kolding Kolding Denmark

Population Health Research Institute St George's University of London London United Kingdom

Population Health Sciences Institute Newcastle University Newcastle United Kingdom

Public Health England London United Kingdom

Rare Diseases Research Unit Foundation for the Promotion of Health and Biomedical Research in the Valencian Region Valencia Spain

Spanish Collaborative Study of Congenital Malformations Instituto de Salud Carlos 3 Madrid Spain

Université de Paris Center of Research in Epidemiology and StatisticS CRESS Obstetrical Perinatal and Pediatric Epidemiology Research Team INSERM INRA Paris France

Wessex Clinical Genetics Service Princess Anne Hospital Southampton United Kingdom

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