title: Long term trends in prevalence of neural tube defects in Europe: population based study.
abstract: OBJECTIVE
  What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?
  
  
  METHODS
  This was a population based, observational study using data on 11,353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends.
  
  
  CONCLUSIONS
  Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10,000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD.
  
  
  CONCLUSIONS
  In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification.
  
  
  BACKGROUND
  The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.
authors.affiliation: Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Biostatistics and Epidemiology, INSERM U1153, Maternité de Port-Royal, 75014 Paris, France babak.khoshnood@inserm.fr.
authors.forename: Babak
authors.initials: B
authors.lastname: Khoshnood
authors.affiliation: EUROCAT Central Registry, Centre for Maternal, Fetal and Infant Research, Institute of Nursing Research, University of Ulster, Newtownabbey, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Loane
authors.affiliation: EUROCAT Northern Netherlands Registry, University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
authors.forename: Hermien
authors.initials: H
authors.lastname: de Walle
authors.affiliation: Public Health Division of Gipuzkoa, Instituto BIO-Donostia Basque Government CIBER Epidemiología y Salud Pública - CIBERESP, San Sebatian, Spain.
authors.forename: Larraitz
authors.initials: L
authors.lastname: Arriola
authors.affiliation: Service de Genetique Medicale Maternite, CHUV, Lausanne, Switzerland.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Children's University Hospital of Zagreb, Clinical Hospital Sisters of Mercy, Zagreb, Croatia.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Barisic
authors.affiliation: National Institute of Health Development, Department of Hungarian Congenital Abnormality Registry and Surveillance, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Beres
authors.affiliation: CNR Institute of Clinical Physiology and Tuscany Registry of Congenital Defects, "Gabrielle Monasterio" Foundation, Pisa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: Instituto Nacionale de Saude Dr. Ricardo Jorge, Lisbon, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Dias
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Draper
authors.affiliation: Hospital Lillebaelt, Kolding, Denmark.
authors.forename: Ester
authors.initials: E
authors.lastname: Garne
authors.affiliation: Department of Health Information and Research, Guardamangia, Malta.
authors.forename: Miriam
authors.initials: M
authors.lastname: Gatt
authors.affiliation: Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Haeusler
authors.affiliation: Medical Birth Registry of Norway, Norwegian Institute of Public Health and Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Klungsoyr
authors.affiliation: Department of Medical Genetics, University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Latos-Bielenska
authors.affiliation: Public Health Department, HSE South, Lacken, Kilkenny, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lynch
authors.affiliation: Health Service Executive, Dublin, Ireland.
authors.forename: Bob
authors.initials: B
authors.lastname: McDonnell
authors.affiliation: Provincial Institute for Hygiene, Antwerp, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Nelen
authors.affiliation: Registro IMER - IMER Registry (Emilia Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Neville
authors.affiliation: Department of Public Health, Health Service Executive - South, Ireland.
authors.forename: Mary T
authors.initials: MT
authors.lastname: O'Mahony
authors.affiliation: Birth Registry Mainz Model, Childrens Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Queisser-Luft
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Rankin
authors.affiliation: Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Rissmann
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Annukka
authors.initials: A
authors.lastname: Ritvanen
authors.affiliation: National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rounding
authors.affiliation: National Registry of Congenital Anomalies of the Czech Republic, Department of Medical Genetics, Thomayer University Hospital, Prague, Czech Republic.
authors.forename: Antonin
authors.initials: A
authors.lastname: Sipek
authors.affiliation: Public Health Wales, Swanseaa, UK.
authors.forename: David
authors.initials: D
authors.lastname: Tucker
authors.affiliation: Center for Human Genetics, Institut de Recherche Scientifique en Pathologie et en Génétique, Charleroi, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen-Dumoulin
authors.affiliation: University Hospitals Southampton, Faculty of Medicine and Wessex Clinical Genetics Service, Southampton, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Wellesley
authors.affiliation: EUROCAT Central Registry, Centre for Maternal, Fetal and Infant Research, Institute of Nursing Research, University of Ulster, Newtownabbey, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Dolk
mesh_terms: D000025:Abortion, Eugenic / Q000706:statistics & numerical data; D019587:Dietary Supplements / Q000706:statistics & numerical data*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005313:Fetal Death; D005492:Folic Acid / Q000627:therapeutic use*; D063105:Food Assistance; D006801:Humans; D050498:Live Birth / Q000453:epidemiology; D020380:Needs Assessment; D009436:Neural Tube Defects / Q000453:epidemiology / Q000517:prevention & control; D011050:Policy Making; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011256:Pregnancy Outcome / Q000453:epidemiology; D015995:Prevalence; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid