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Meta-Analysis
. 2012 Feb 15;2(2):CD008873.
doi: 10.1002/14651858.CD008873.pub2.

Vitamin D supplementation for women during pregnancy

Luz Maria De-Regil  1 , Cristina Palacios, Ali Ansary, Regina Kulier, Juan Pablo Peña-Rosas
Affiliations
Meta-Analysis

Vitamin D supplementation for women during pregnancy

Luz Maria De-Regil et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes.

Objectives: To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011).

Selection criteria: Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy.

Data collection and analysis: Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy.

Main results: The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation.Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous. Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01).In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores.

Authors' conclusions: Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy.

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Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 3
Figure 3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
See this image and copyright information in PMC

References

References to studies

Included studies
    1. Brooke OG, Brown IRF, Bone CDM, Carter ND, Cleeve HJW, Maxwell JD, et al. Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. British Medical Journal. 1980;1:751–754. - PMC - PubMed
    1. Brooke OG, Butters F, Wood C. Intrauterine vitamin D nutrition and postnatal growth in Asian infants. British Medical Journal. 1981;283:1024. - PMC - PubMed
    1. Maxwell JD, Ang L, Brooke OG, Brown IRF. Vitamin D supplements enhance weight gain and nutritional status in pregnant Asians. British Journal of Obstetrics and Gynaecology. 1981;88:987–991. - PubMed
    1. Delvin EE, Salle BL, Glorieux FH, Adeleine P, David LS. Vitamin D supplementation during pregnancy: effect on neonatal calcium homeostasis. Journal of Pediatrics. 1986;109:328–334. - PubMed
    1. Mallet E, Gugi B, Brunelle P, Henocq A, Basuyau JP, Lemeur H. Vitamin D supplementation in pregnancy: a controlled trial of two methods. Obstetrics & Gynecology. 1986;68:300–304. - PubMed
Excluded studies
    1. Ala-Houhala M, Koskinen T, Terho A, Koivula T, Visakorpi J. Maternal compared with infant vitamin D supplementation. Archives of Disease in Childhood. 1986;61:1159–1163. - PMC - PubMed
    1. Cockburn F, Belton NR, Purvis RJ, Giles MM, Brown JK, Turner TL, et al. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. British Medical Journal. 1980;281(6232):11–14. - PMC - PubMed
    1. Bhatia V. A study of the effect of vitamin D supplementation in pregnant women, on the growth and biochemical features of the newborn baby and infant. [accessed 2010];Clinical Trials Registry - India. ( http://ctri.nic.in/Clinicaltrials/login.php)
    1. Das V, Agarwal A, Bhatia V, Pandey A, Agarwal S, Saxena P, et al. Evaluation of vitamin d status and need for supplementation in pregnant women of a rural area of North India. International Journal of Gynecology & Obstetrics. 2009;107(Suppl 2):S151.
    1. Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural north India: a pilot study. European Journal of Clinical Nutrition. 2009;63(9):1157–1159. - PubMed
Published data only (unpublished sought but not used)
    1. Appelgren KE, Nietert PJ, Hulsey TC, Hollis BW, Wagner CL. Analyzing adherence to prenatal supplement: does pill count measure up? International Journal of Endocrinology. 2010;2010:1–8. - PMC - PubMed
    1. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. Journal of Bone and Mineral Research. 2011;26(10):2341–2357. - PMC - PubMed
    1. Wagner CL, Johnson D, Hulsey TC, Ebeling M, Shary J, Smith PG, et al. Pediatric Academic Societies Annual Meeting. Canada: Vancouver; 2010. May 1–4, Vitamin D supplementation during pregnancy Part I NICHD/CTSA randomized clinical trial (RCT): safety consideration; p. 2010.
    1. Wagner CL, McNeil R, Hamilton SA, Davis DJ, Prudgen C, Winkler J, et al. Pediatric Academic Societies 2010 Annual Meeting. Canada: Vancouver; 2010. May 1–4, Vitamin D (vitD) supplementation during pregnancy: Thrasher Research Fund RCT in SC community center networks; p. 2010.
    1. Wagner CL. Evaluation of vitamin D requirements during pregnancy (ongoing trial) [accessed 21 March 2006];ClinicalTrials.gov. ( http://clinicaltrials.gov/)
Studies awaiting classification
    1. Bisgaard H. Vitamin D supplementation during pregnancy for prevention of asthma in childhood (ABCvitaminD) [accessed 31 July 2009];ClinicalTrials.gov. ( http://clinicaltrials.gov)
    1. Das V. Vitamin D and calcium nutrition in pregnancy-evaluation of optimal supplementation dose of vitamin D during antenatal period. [accessed 2010];Clinical Trials Registry - India. ( http://ctri.nic.in/Clinicaltrials/login.php)
    1. Goldring S. Effects of prenatal vitamin D supplementation on respiratory and allergic phenotypes and bone density in the first three years of life. [accessed 6 April 2011];UKCRN. ( http://public.ukcrn.org.uk)
    1. Grant C. Randomised placebo controlled study of vitamin D during pregnancy and infancy. [accessed 17 August 2010];Australian New Zealand Clinical Trials Register. ( www.anzctr.org.au)
    1. Habib MA. Evaluation of the effectiveness of vitamin D supplementation to pregnant women and their infants in Pakistan. [accessed 15 February 2011];ClinicalTrials.gov. ( http://clinicaltrials.gov/)
Other references
    1. Akcakus M, Koklu E, Budak N, Kula M, Kurtoglu S, Koklu S. The relationship between birthweight, 25-hydroxyvitamin D concentrations and bone mineral status in neonates. Annals of Tropical Paediatrics. 2006;26(4):267–275. - PubMed
    1. Alfaham M, Woodhead S, Pask G, Davies D. Vitamin D deficiency: a concern in pregnant Asian women. British Journal of Nutrition. 1995;73(6):881–887. - PubMed
    1. Ariyuki F. Growth retardation induced in rat fetuses by maternal fasting and massive doses of ergocalciferol. Journal of nutrition. 1987;117(2):342–348. - PubMed
    1. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. Journal of Clinical Endocrinology and Metabolism. 2004;89(11):5387–5391. - PubMed
    1. Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. Journal of Clinical Endocrinology and Metabolism. 2003;88(1):157–161. - PubMed
Other published versions of this review
    1. Mahomed K, Gülmezoglu AM. Vitamin D supplementation in pregnancy. Cochrane Database of Systematic Reviews. 1999;(Issue 1) Art. No.: CD000228. - PubMed

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