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 2005;330:571 (12 March), doi:10.1136/bmj.38336.664352.82 (published 18 February 2005)

Paper

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

Lorenzo D Botto, senior fellow¹, Alessandra Lisi, epidemiologist², Elisabeth Robert-Gnansia, programme director³, J David Erickson, epidemiology team leader¹, Stein Emil Vollset, professor⁴, Pierpaolo Mastroiacovo, director², Beverley Botting, programme director⁶, Guido Cocchi, professor⁷, Catherine de Vigan, programme director¹⁷, Hermien de Walle, programme director⁸, Maria Feijoo, programme director⁹, Lorentz M Irgens, programme director⁵, Bob McDonnell, programme director¹⁰, Paul Merlob, professor¹¹, Annukka Ritvanen, programme director¹², Gioacchino Scarano, director¹³, Csaba Siffel, programme director¹⁴, Julia Metneki, head of department¹⁴, Claude Stoll, programme director¹⁵, Richard Smithells, emeritus professor (deceased)¹⁶, Janine Goujard, director¹⁷

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 Medical Birth Registry, Norwegian Institute of Public Health, NO-5018 Bergen, ⁶ Office for National Statistics, London SW1V 2QQ, ⁷ Department of Neonatalogy and Preventive Paediatrics, University of Bologna, 40138 Bologna, Italy, 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 Dublin EUROCAT Registry of Congenital Anomalies, Department of Public Health, Eastern Regional Health Authority, Dublin 8, Republic of Ireland, ¹¹ Department of Neonatology, Rabin Medical Center, Petah Tikva 49100, Israel, ¹² Finnish Register of Congenital Malformations, National Research and Development Centre for Welfare and Health (STAKES), FIN-00531 Helsinki, Finland, ¹³ Department of Genetics, AO "G Rummo," Benevento, Italy, ¹⁴ Hungarian Congenital Abnormality Registry, Department of Human Genetics and Teratology, National Center for Epidemiology, H-1966 Budapest, Hungary, ¹⁵ Strasbourg Birth Defects Registry, Faculty of Medicine, University of Strasbourg, 67085 Strasbourg Cedex, France, ¹⁶ University of Leeds, Leeds, ¹⁷ Paris Birth Defects Registry, INSERM U149, 94807 Villejuif Cedex, France

Correspondence to: L D Botto icbd{at}icbd.org

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 monitored by birthdefect registries.

Setting 13 birth defects registries monitoring rates of neuraltube defects from 1988 to 1998 in Norway, Finland, NorthernNetherlands, England and Wales, Ireland, France (Paris, Strasbourg,and Central East), Hungary, Italy (Emilia Romagna and Campania),Portugal, and Israel. Cases of neural tube defects were ascertainedamong liveborn infants, stillbirths, and pregnancy terminations(where legal). Policies and recommendations were ascertainedby interview and literature review.

Main outcome measures Incidences and trends in rates of neuraltube defects before and after 1992 (the year of the first recommendations)and before and after the year of local recommendations (whenapplicable).

Results The issuing of recommendations on folic acid was followedby no detectable improvement in the trends of incidence of neuraltube defects.

Conclusions Recommendations alone did not seem to influencetrends in neural tube defects up to six years after the confirmationof the effectiveness of folic acid in clinical trials. New casesof neural tube defects preventable by folic acid continue toaccumulate. A reasonable strategy would be to quickly integratefood fortification with fuller implementation of recommendationson supplements.

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