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

Babak Khoshnood, Maria Loane, Hermien de Walle, Larraitz Arriola, Marie-Claude Addor, Ingeborg Barisic, Judit Beres, Fabrizio Bianchi, Carlos Dias, Elizabeth Draper, Ester Garne, Miriam Gatt, Martin Haeusler, Kari Klungsoyr, Anna Latos-Bielenska, Catherine Lunch, Bob McDonnell, Vera Nelen, Amanda Neville, Mary O'Mahony & 10 others Annette Queisser-Luft, Judith Rankin, Anke Rissmann, Annukka Ritvanen, Catherine Rounding, Antonin Sipek, David Tucker, Christine Verellun-Dumoulin, Diana Wellesley, Helen Dolk

Research output: Contribution to journalArticle

86 Citations (Scopus)

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 11353 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 10000 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.
LanguageEnglish
Pages1-6
Number of pages6
JournalBMJ Open
Volume351
Early online date24 Nov 2015
DOIs
Publication statusE-pub ahead of print - 24 Nov 2015

Fingerprint

Neural Tube Defects
Live Birth
Population
Folic Acid
Anencephaly
Registries
Parturition
Spinal Dysraphism
Nonlinear Dynamics
Fetal Death
Artifacts
Observational Studies
Public Health
Outcome Assessment (Health Care)
Confidence Intervals
Food
Pregnancy

Keywords

  • EUROCAT
  • Neural Tube Defects

Cite this

Khoshnood, Babak ; Loane, Maria ; de Walle, Hermien ; Arriola, Larraitz ; Addor, Marie-Claude ; Barisic, Ingeborg ; Beres, Judit ; Bianchi, Fabrizio ; Dias, Carlos ; Draper, Elizabeth ; Garne, Ester ; Gatt, Miriam ; Haeusler, Martin ; Klungsoyr, Kari ; Latos-Bielenska, Anna ; Lunch, Catherine ; McDonnell, Bob ; Nelen, Vera ; Neville, Amanda ; O'Mahony, Mary ; Queisser-Luft, Annette ; Rankin, Judith ; Rissmann, Anke ; Ritvanen, Annukka ; Rounding, Catherine ; Sipek, Antonin ; Tucker, David ; Verellun-Dumoulin, Christine ; Wellesley, Diana ; Dolk, Helen. / Long term trends in prevalence of neural tube defects in Europe: population based study. In: BMJ Open. 2015 ; Vol. 351. pp. 1-6.
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abstract = "Study questionWhat 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?MethodsThis was a population based, observational study using data on 11353 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 limitationsOverall, the pooled total prevalence of NTD during the study period was 9.1 per 10000 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 addsIn 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 sharingThe 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.",
keywords = "EUROCAT, Neural Tube Defects",
author = "Babak Khoshnood and Maria Loane and {de Walle}, Hermien and Larraitz Arriola and Marie-Claude Addor and Ingeborg Barisic and Judit Beres and Fabrizio Bianchi and Carlos Dias and Elizabeth Draper and Ester Garne and Miriam Gatt and Martin Haeusler and Kari Klungsoyr and Anna Latos-Bielenska and Catherine Lunch and Bob McDonnell and Vera Nelen and Amanda Neville and Mary O'Mahony and Annette Queisser-Luft and Judith Rankin and Anke Rissmann and Annukka Ritvanen and Catherine Rounding and Antonin Sipek and David Tucker and Christine Verellun-Dumoulin and Diana Wellesley and Helen Dolk",
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Khoshnood, B, Loane, M, de Walle, H, Arriola, L, Addor, M-C, Barisic, I, Beres, J, Bianchi, F, Dias, C, Draper, E, Garne, E, Gatt, M, Haeusler, M, Klungsoyr, K, Latos-Bielenska, A, Lunch, C, McDonnell, B, Nelen, V, Neville, A, O'Mahony, M, Queisser-Luft, A, Rankin, J, Rissmann, A, Ritvanen, A, Rounding, C, Sipek, A, Tucker, D, Verellun-Dumoulin, C, Wellesley, D & Dolk, H 2015, 'Long term trends in prevalence of neural tube defects in Europe: population based study', BMJ Open, vol. 351, pp. 1-6. https://doi.org/10.1136/bmj.h5949

Long term trends in prevalence of neural tube defects in Europe: population based study. / Khoshnood, Babak; Loane, Maria; de Walle, Hermien; Arriola, Larraitz; Addor, Marie-Claude; Barisic, Ingeborg; Beres, Judit; Bianchi, Fabrizio; Dias, Carlos; Draper, Elizabeth; Garne, Ester; Gatt, Miriam; Haeusler, Martin; Klungsoyr, Kari; Latos-Bielenska, Anna; Lunch, Catherine; McDonnell, Bob; Nelen, Vera; Neville, Amanda; O'Mahony, Mary; Queisser-Luft, Annette; Rankin, Judith; Rissmann, Anke; Ritvanen, Annukka; Rounding, Catherine; Sipek, Antonin; Tucker, David; Verellun-Dumoulin, Christine; Wellesley, Diana; Dolk, Helen.

In: BMJ Open, Vol. 351, 24.11.2015, p. 1-6.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long term trends in prevalence of neural tube defects in Europe: population based study

AU - Khoshnood, Babak

AU - Loane, Maria

AU - de Walle, Hermien

AU - Arriola, Larraitz

AU - Addor, Marie-Claude

AU - Barisic, Ingeborg

AU - Beres, Judit

AU - Bianchi, Fabrizio

AU - Dias, Carlos

AU - Draper, Elizabeth

AU - Garne, Ester

AU - Gatt, Miriam

AU - Haeusler, Martin

AU - Klungsoyr, Kari

AU - Latos-Bielenska, Anna

AU - Lunch, Catherine

AU - McDonnell, Bob

AU - Nelen, Vera

AU - Neville, Amanda

AU - O'Mahony, Mary

AU - Queisser-Luft, Annette

AU - Rankin, Judith

AU - Rissmann, Anke

AU - Ritvanen, Annukka

AU - Rounding, Catherine

AU - Sipek, Antonin

AU - Tucker, David

AU - Verellun-Dumoulin, Christine

AU - Wellesley, Diana

AU - Dolk, Helen

PY - 2015/11/24

Y1 - 2015/11/24

N2 - Study questionWhat 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?MethodsThis was a population based, observational study using data on 11353 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 limitationsOverall, the pooled total prevalence of NTD during the study period was 9.1 per 10000 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 addsIn 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 sharingThe 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.

AB - Study questionWhat 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?MethodsThis was a population based, observational study using data on 11353 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 limitationsOverall, the pooled total prevalence of NTD during the study period was 9.1 per 10000 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 addsIn 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 sharingThe 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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KW - Neural Tube Defects

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DO - 10.1136/bmj.h5949

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EP - 6

JO - BMJ Open

T2 - BMJ Open

JF - BMJ Open

SN - 2044-6055

ER -