International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?

doi:10.1136/bmj.38336.664352.82

BMJ, doi: 10.1136/bmj.38336.664352.82, (Published 18 February 2005)

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International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?

Lorenzo D Botto ¹, Alessandra Lisi ², Elisabeth Robert-Gnansia ³, J David Erickson ¹, Stein Emil Vollset ⁴, Pierpaolo Mastroiacovo ², Beverley Botting ⁵, Guido Cocchi ⁶, Catherine de Vigan ⁷, Hermien de Walle ⁸, Maria Feijoo ⁹, Lorentz M Irgens ¹⁰, Bob McDonnell ¹¹, Paul Merlob ¹², Annukka Ritvanen ¹³, Gioacchino Scarano ¹⁴, Csaba Siffel ¹⁵, Julia Metneki ¹⁵, Claude Stoll ¹⁶, Richard Smithells ¹⁷, Janine Goujard ⁷

¹ National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
² International Centre on Birth Defects, Rome 00195, Italy
³ Institut Européen des Génomutations, 69005 Lyon, France
⁴ Section for Epidemiology and Medical Statistics, University of Bergen, NO-5018 Bergen, Norway
⁵ Office for National Statistics, London SW1V 2QQ
⁶ Department of Neonatalogy and Preventive Paediatrics, University of Bologna, 40138 Bologna, Italy
⁷ Paris Birth Defects Registry, INSERM U149, 94807 Villejuif Cedex, France
⁸ Northern Netherlands Registry of Birth Defects, Department of Medical Genetics, University of Groningen, 9713 AW Groningen, Netherlands
⁹ Portuguese Birth Defects Registry (CERAC), National Institute of Health, 1649-016 Lisbon, Portugal
¹⁰ Medical Birth Registry, Norwegian Institute of Public Health, NO-5018 Bergen
¹¹ Dublin EUROCAT Registry of Congenital Anomalies, Department of Public Health, Eastern Regional Health Authority, Dublin 8, Republic of Ireland
¹² Department of Neonatology, Rabin Medical Center, Petah Tikva 49100, Israel
¹³ Finnish Register of Congenital Malformations, National Research and Development Centre for Welfare and Health (STAKES), FIN-00531 Helsinki, Finland
¹⁴ Department of Genetics, AO "G Rummo," Benevento, Italy
¹⁵ Hungarian Congenital Abnormality Registry, Department of Human Genetics and Teratology, National Center for Epidemiology, H-1966 Budapest, Hungary
¹⁶ Strasbourg Birth Defects Registry, Faculty of Medicine, University of Strasbourg, 67085 Strasbourg Cedex, France
¹⁷ University of Leeds, Leeds

Objectives To evaluate the effectiveness of policies and recommendationson folic acid aimed at reducing the occurrence of neural tubedefects.

Design Retrospective cohort study of births monitoredby birth defect registries.

Setting 13 birth defects registriesmonitoring rates of neural tube defects from 1988 to 1998 inNorway, Finland, Northern Netherlands, England and Wales, Ireland,France (Paris, Strasbourg, and Central East), Hungary, Italy(Emilia Romagna and Campania), Portugal, and Israel. Cases ofneural tube defects were ascertained among liveborn infants,stillbirths, and pregnancy terminations (where legal). Policiesand recommendations were ascertained by interview and literaturereview.

Main outcome measures Incidences and trends in ratesof neural tube defects before and after 1992 (the year of thefirst recommendations) and before and after the year of localrecommendations (when applicable).

Results The issuing of recommendationson folic acid was followed by no detectable improvement in thetrends of incidence of neural tube defects.

Conclusions Recommendationsalone did not seem to influence trends in neural tube defectsup to six years after the confirmation of the effectivenessof folic acid in clinical trials. New cases of neural tube defectspreventable by folic acid continue to accumulate. A reasonablestrategy would be to quickly integrate food fortification withfuller implementation of recommendations on supplements.

(Accepted 9 December 2004)

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