Health Technol Assess. 2014 Jul;18(45):1-190.
Harvey NC1, Holroyd C1, Ntani G1, Javaid K2, Cooper P1, Moon R1, Cole Z1, Tinati T1, Godfrey K1, Dennison E1, Bishop NJ3, Baird J1, Cooper C1.
1Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
2National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
3Academic Unit of Child Health, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved.
To answer the following questions:
- (1) What are the clinical criteria for vitamin D deficiency in pregnant women?
- (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D?
- (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)?
- (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy?
- (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective?
We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers.
INCLUSION AND EXCLUSION CRITERIA:
Subjects: pregnant women or pregnant women and their offspring. Exposure: either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). Outcomes: offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis.
Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5.
Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition.
The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required.
This study is registered as PROSPERO CRD42011001426.
The National Institute for Health Research Health Technology Assessment programme.
Download the PDF from VitaminDWiki.
- Pregnancy category listing with many associated searches
- Variety of pregnancy problems with low vitamin D – systematic review Sept 2012
- Prenatal Vitamin D (35,000 weekly, 3rd trimester) resulted in 1 cm taller infants at age 1 year – RCT Aug 2013
Meta-analysis of Pregnancy and Vitamin D
- Gestational diabetes risk reduced 1.5X by Vitamin D – meta-analysis March 2021
- Gestational Diabetes – increased risk if poor Vitamin D Receptor – Meta-Analysis Jan 2021
- Small vitamin D doses given during pregnancy do not reduce childhood asthma – meta-analysis Dec 2020
- Multiple Sclerosis 40 percent more likely if mother had low vitamin D – meta-analysis Jan 2020
- Pregnancies helped by Vitamin D (insulin and birth weight in this case) – 28th meta-analysis Oct 2019
- Preeclampsia 2.7 X less likely if 50,000 IU of Vitamin D every 2 weeks – meta-analysis Sept 2019
- Autism risk increased 30 percent by Cesareans (both low vitamin D) – meta-analysis Sept 2019
- Vitamin D treats Gestational Diabetes, decreases hospitalization and newborn complications – meta-analysis March 2019
- Birth size and weight increased by Vitamin D – meta-analysis Feb 2019
- Pregnancies helped by Vitamin D in many ways – 27th meta-analysis Jan 2019
- Vitamin D supplementation reduced SGA, fetal mortality, infant mortality – JAMA Meta – May 2018
- Gestational Diabetes 39 percent more likely if insufficient Vitamin D – Meta-analysis March 2018
- Preeclampsia reduced 2X by Vitamin D, by 5X if also add Calcium – meta-analysis Oct 2017
- Preeclampsia risk reduced 60 percent if supplement with Vitamin D (they ignored dose size) – meta-analysis Sept 2017
- Small for gestational age is 1.6 X more likely if mother was vitamin D deficient – meta-analysis Aug 2017
- Miscarriage 2 times more likely if low vitamin D – meta-analysis May 2017
- Fewer than half of pregnancies will get even 20 ng of vitamin D with 800 IU daily dose – meta-analysis May 2017
- Low Vitamin D results in adverse pregnancy and birth outcomes – Wagner meta-analysis March 2017
- Bacterial vaginosis in pregnancy increased prematurity risk by 60 percent - meta-analysis 1999
- Preterm birth rate reduced by 43 percent with adequate Vitamin D supplementation – meta-analysis Feb 2017
- Vitamin D during pregnancy reduces risk of childhood asthma by 13 percent – meta-analysis Dec 2016
- Vitamin D helps during pregnancy – meta-analysis Feb 2016
- Preterm birth 30 percent more likely if low vitamin D – meta-analysis May 2016
- Preterm birth extended by 2 weeks with Omega-3 – Meta-analysis Nov 2015
- Gestational Diabetes Mellitus 1.5X more likely if low vitamin D – meta-analysis Oct 2015
- Infant wheezing 40 percent less likely if mother supplemented with vitamin D, vitamin E, or Zinc – meta-analysis Aug 2015
- Birth weight and length increased with high levels of vitamin D – meta-analysis March 2015
- Pregnancy and Vitamin D – meta-analysis April 2015
- More vitamin D needed during pregnancy – meta-analysis Oct 2014
- Preeclampsia rate cut in half by high level of vitamin D – meta-analysis March 2014
- Preeclampsia 2.7X more frequent if low vitamin D – meta-analysis Sept 2013
- 2X more preeclampsia when vitamin D less than 30 ng, etc. - meta-analysis March 2013
- 2X more likely to have preeclampsia if less than 20 ng of vitamin D – Meta-analysis Jan 2013
- Multiple Sclerosis 23 percent more likely if born in April vs. Oct – meta-analysis Nov 2012
- Pregnancy and vitamin D meta-analysis – July 2012
- Low vitamin D increased probability of low birth weight by 60 percent – meta-analysis June 2012
- Gestational diabetes 60 percent more likely below 20 ng of vitamin D – meta-analysis Feb 2012
- Premature or low birth weight resulted in children 3X more likely to be anxious – meta-analysis May 2011
- Overview Pregnancy and vitamin D has the following summary
|IU||Cumulative Benefit||Blood level||Cofactors||Calcium||$*/month|
|200|| Better bones for mom|
with 600 mg of Calcium
|6 ng/ml increase||Not needed||No effect||$0.10|
|400|| Less Rickets (but not zero with 400 IU)|
3X less adolescent Schizophrenia
Fewer child seizures
|20-30 ng/ml||Not needed||No effect||$0.20|
|2000|| 2X More likely to get pregnant naturally/IVF |
2X Fewer dental problems with pregnancy
8X less diabetes
4X fewer C-sections (>37 ng)
4X less preeclampsia (40 ng vs 10 ng)
5X less child asthma
2X fewer language problems age 5
|42 ng/ml||Desirable||< 750 mg||$1|
|4000|| 2X fewer pregnancy complications |
2X fewer pre-term births
|49 ng/ml|| Should have |
|< 750 mg||$3|
|6000||Probable: larger benefits for above items|
Just enough D for breastfed infant
More maternal and infant weight
|< 750 mg||$4|