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Research

Long term trends in prevalence of neural tube defects in Europe: population based study

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5949 (Published 24 November 2015) Cite this as: BMJ 2015;351:h5949
  1. Babak Khoshnood, senior researcher1,
  2. Maria Loane, lecturer in public health2,
  3. Hermien de Walle, registry leader3,
  4. Larraitz Arriola, epidemiologist4,
  5. Marie-Claude Addor, medical geneticist5,
  6. Ingeborg Barisic, professor6,
  7. Judit Beres, senior researcher in genetics7,
  8. Fabrizio Bianchi, epidemiologist and registry leader8,
  9. Carlos Dias, head of the department of epidemiology9,
  10. Elizabeth Draper, professor of perinatal and paediatric epidemiology10,
  11. Ester Garne, neonatologist and registry leader11,
  12. Miriam Gatt, consultant in public health12,
  13. Martin Haeusler, professor13,
  14. Kari Klungsoyr, professor14,
  15. Anna Latos-Bielenska, professor15,
  16. Catherine Lynch, specialist in public health medicine16,
  17. Bob McDonnell, consultant in public health medicine17,
  18. Vera Nelen, director18,
  19. Amanda J Neville, registry leader19,
  20. Mary T O’Mahony, specialist in public health medicine20,
  21. Annette Queisser-Luft, senior physician21,
  22. Judith Rankin, professor22,
  23. Anke Rissmann, professor of pediatrics23,
  24. Annukka Ritvanen, registry leader and chief physician24,
  25. Catherine Rounding, acting registry leader25,
  26. Antonin Sipek, medical geneticist and neonatologist26,
  27. David Tucker, CARIS registry manager27,
  28. Christine Verellen-Dumoulin, professor28,
  29. Diana Wellesley, consultant in clinical genetics29,
  30. Helen Dolk, professor of epidemiology and health services research2
  1. 1Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Biostatistics and Epidemiology, INSERM U1153, Maternité de Port-Royal, 75014 Paris, France
  2. 2EUROCAT Central Registry, Centre for Maternal, Fetal and Infant Research, Institute of Nursing Research, University of Ulster, Newtownabbey, UK
  3. 3EUROCAT Northern Netherlands Registry, University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
  4. 4Public Health Division of Gipuzkoa, Instituto BIO-Donostia Basque Government CIBER Epidemiología y Salud Pública - CIBERESP, San Sebatian, Spain
  5. 5Service de Genetique Medicale Maternite, CHUV, Lausanne, Switzerland
  6. 6Children’s University Hospital of Zagreb, Clinical Hospital Sisters of Mercy, Zagreb, Croatia
  7. 7National Institute of Health Development, Department of Hungarian Congenital Abnormality Registry and Surveillance, Budapest, Hungary
  8. 8CNR Institute of Clinical Physiology and Tuscany Registry of Congenital Defects, “Gabrielle Monasterio” Foundation, Pisa, Italy
  9. 9Instituto Nacionale de Saude Dr. Ricardo Jorge, Lisbon, Portugal
  10. 10Department of Health Sciences, University of Leicester, Leicester, UK
  11. 11Hospital Lillebaelt, Kolding, Denmark
  12. 12Department of Health Information and Research, Guardamangia, Malta
  13. 13Medical University of Graz, Graz, Austria
  14. 14Medical Birth Registry of Norway, Norwegian Institute of Public Health and Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  15. 15Department of Medical Genetics, University of Medical Sciences, Poznan, Poland
  16. 16Public Health Department, HSE South, Lacken, Kilkenny, Ireland
  17. 17Health Service Executive, Dublin, Ireland
  18. 18Provincial Institute for Hygiene, Antwerp, Belgium
  19. 19Registro IMER - IMER Registry (Emilia Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy
  20. 20 Department of Public Health, Health Service Executive - South, Ireland
  21. 21Birth Registry Mainz Model, Childrens Hospital, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
  22. 22Institute of Health and Society, Newcastle University, Newcastle, UK
  23. 23Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University, Magdeburg, Germany
  24. 24National Institute for Health and Welfare, Helsinki, Finland
  25. 25National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK
  26. 26National Registry of Congenital Anomalies of the Czech Republic, Department of Medical Genetics, Thomayer University Hospital, Prague, Czech Republic
  27. 27Public Health Wales, Swanseaa, UK
  28. 28Center for Human Genetics, Institut de Recherche Scientifique en Pathologie et en Génétique, Charleroi, Belgium
  29. 29University Hospitals Southampton, Faculty of Medicine and Wessex Clinical Genetics Service, Southampton, UK
  1. Correspondence to: B Khoshnood babak.khoshnood{at}inserm.fr
  • Accepted 19 October 2015

Abstract

Study question 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.

Summary answer and limitations 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.

What this study adds 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.

Funding, competing interests, data sharing 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.

Footnotes

  • Contributors: BK, HdW, ML, and HD conceived the study. BK did the statistical analysis, with the assistance of ML, and wrote the first draft of the article. HD, ML, and HdW made substantial contributions to interpretation of results and revision of the manuscript. All other co-authors were registry representatives from EUROCAT participating registries. They contributed and validated their data and participated in the interpretation of results and critical revision of manuscript. BK and ML are the guarantors.

  • Funding: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013 (grant No 2010 22 04). The funding body had no role in study design, analysis, or reporting.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from corresponding author) and declare: HD and ML received support from the European Commission DG Sanco during the conduct of this study; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: No additional data available.

  • Transparency: The lead authors (the manuscript’s guarantors) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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