Vitamin D supplementation in pregnancy: a systematic review

Abstract

1. ABSTRACT Background It is unclear whether the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25(OH)-vitamin D during pregnancy, and how this might best be achieved. CRD42011001426. Aim/ Research Questions What are the clinical criteria for vitamin D deficiency in pregnant women?What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)-vitamin D?Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)?What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy?Is supplementation with vitamin D in pregnancy likely to be cost-effective? Methods We performed systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases were searched 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 Relevant authors were contacted for any unpublished findings and additional data if necessary. 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)-vitamin D concentration) or supplementation of participants with vitamin D or vitamin D containing food e.g. oily fish. Outcomes Offspring: Birth weight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes, low birth weight, serum calcium concentration, blood pressure and rickets. Mother: Preeclampsia, gestational diabetes, risk of caesarean section and bacterial vaginosis. Results 76 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)-vitamin D and 1) offspring birth weight in meta-analysis of 3 observational studies using log-transformed 25(OH)-vitamin D concentrations after adjustment for potential confounding factors (pooled regression coefficient 5.63g/10% change maternal 25(OH)D, 95% CI 1.11,10.16), but not in those 4 studies using natural units, or across intervention studies; 2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of 6 intervention studies (all found to be at high risk of bias; mean difference 0.05mmol/l, 95% CI 0.02, 0.05); 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. Limitations Study methodology varied widely in ...

Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials

“…Thorne-Lyman and Fawzi (7) evaluated observational studies and RCTs and found an association of vitamin D supplementation and diet, with a lower incidence of low birth weight; other outcomes were not significantly affected by the interventions. Finally, Harvey et al (10) assessed observational studies and RCTs for the effect of serum vitamin D levels, or supplementation of women with vitamin D or food containing vitamin D on maternal and neonatal outcomes. In comparison with these 3 earlier systematic reviews (Supplemental Table 2, available online), the current metaanalysis predefined several other relevant maternal and neonatal outcomes, excluded observational studies that were prone to several biases, and included a larger number of RCTs and time spans ranging to as recently as 2014.…”

“…The effects of vitamin D supplementation on maternal and neonatal outcomes in randomized controlled trials (RCTs) have been previously examined in 3 systematic reviews and/or meta-analyses (7,9,10). These studies had several limitations, including deficiencies in study design (inclusion of quasi-randomized trials and observational studies), and are restricted by the outcomes evaluated.…”

Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: The Generation R Study

“…There is also a body of research linking suboptimal vitamin D during pregnancy with increased risk of pregnancy related disorders such as gestational diabetes, pre-eclampsia and offspring being small for gestational age (Aghajafari et al, 2013, Wei et al, 2013, Harvey et al, 2014 and other research linking suboptimal vitamin D levels early in life with adverse health outcomes later in life (Boucher, 1998, McGrath, 2001, Brannon and Picciano, 2011, Christesen et al, 2012, Thorne-Lyman and Fawzi, 2012, Zipitis and Akobeng, 2008, Ponsonby et al, 2010.…”

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…Larger-scale clinical trials of vitamin D supplementation during pregnancy that systematically measure skeletal mineral content and morphology in newborns, and larger and carefully executed associational studies, are needed to be certain whether vitamin D deficiency in utero has any effects on skeletal mineralization at term or later in childhood. Several systematic reviews agree with the conclusion that current data are insufficient to know if vitamin D supplementation during pregnancy confers any skeletal or nonskeletal benefits on fetuses (244,560,561).…”