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Observational Study
. 2015 Nov 24:351:h5949.
doi: 10.1136/bmj.h5949.

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

Babak Khoshnood  1 , Maria Loane  2 , Hermien de Walle  3 , Larraitz Arriola  4 , Marie-Claude Addor  5 , Ingeborg Barisic  6 , Judit Beres  7 , Fabrizio Bianchi  8 , Carlos Dias  9 , Elizabeth Draper  10 , Ester Garne  11 , Miriam Gatt  12 , Martin Haeusler  13 , Kari Klungsoyr  14 , Anna Latos-Bielenska  15 , Catherine Lynch  16 , Bob McDonnell  17 , Vera Nelen  18 , Amanda J Neville  19 , Mary T O'Mahony  20 , Annette Queisser-Luft  21 , Judith Rankin  22 , Anke Rissmann  23 , Annukka Ritvanen  24 , Catherine Rounding  25 , Antonin Sipek  26 , David Tucker  27 , Christine Verellen-Dumoulin  28 , Diana Wellesley  29 , Helen Dolk  2
Affiliations
Observational Study

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

Babak Khoshnood et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Trends in total prevalence of non-chromosomal neural tube defects in Europe, 1991-2011: restrictive cubic spline estimates of pooled data in EUROCAT registries
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Fig 2 Trends in live birth prevalence of non-chromosomal neural tube defects in Europe, 1991-2011: restrictive cubic spline estimates of pooled data in EUROCAT registries
See this image and copyright information in PMC

Comment in

References

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