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Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies

BMJ 2013; 346 doi: (Published 26 March 2013) Cite this as: BMJ 2013;346:f1169
  1. Fariba Aghajafari, assistant professor of family medicine12,
  2. Tharsiya Nagulesapillai, data analyst1,
  3. Paul E Ronksley, doctoral candidate13,
  4. Suzanne C Tough, professor of paediatrics14,
  5. Maeve O’Beirne, associate professor of family medicine2,
  6. Doreen M Rabi, assistant professor of medicine135
  1. 1Department of Community Health Sciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada
  2. 2Department of Family Medicine, University of Calgary, Canada
  3. 3Calgary Institute for Population and Public Health, University of Calgary, Canada
  4. 4Department of Paediatrics, University of Calgary, Canada
  5. 5Department of Medicine, University of Calgary, Canada
  1. Correspondence to: D M Rabi Doreen.Rabi{at}
  • Accepted 5 February 2013


Objective To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables.

Design Systematic review and meta-analysis.

Data sources Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials.

Study selection Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference).

Data extraction Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality.

Results 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section.

Conclusion Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.


  • We thank Sue Ross and Rob Weaver for their comments and suggestions on an earlier version of the manuscript and Diane Lorenzetti for her guidance in formulating our literature search strategy. Preliminary results from this manuscript were presented at the Society of Obstetricians and Gynaecologists of Canada Annual Clinical Meeting on 20 June 2012 in Ottawa, Canada (abstract published in Journal of Obstetrics and Gynaecology Canada in May 2012).

  • Contributors: FA and TN contributed equally to this article and are the guarantors. They had full access to all of the data, acquired the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. FA, TN, PER, and DMR conceived and designed the study, analysed and interpreted the data, and carried out the statistical analysis. All authors drafted the manuscript. FA, TN, DMR, SCT, and MO’B critically revised the manuscript for important intellectual content. PER and DMR supervised the study.

  • Funding: FA and TN received studentship funding from the University of Calgary Institute for Public Health (Markin Fund for Health and Society); DMR is supported by an AISH (Alberta Innovate Health Solutions) population health investigator award; SCT is supported by an AISH salary support; and MO’B is supported by AISH, the Canadian Institute of Health Research, and the Canadian Foundation for Healthcare Improvement. These agencies did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; 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.

  • Ethical approval: Not required.

  • Data sharing: The statistical code and datasets are available from the corresponding author at

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