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Maternal vitamin D supplementation during pregnancy.

ABSTRACT: Introduction:Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as asthma. Sources of data:Synthesis of systematic and narrative reviews. Areas of agreement and controversy:The findings are generally inconsistent in most areas, and, at present, there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. In most areas, the evidence tends towards maternal vitamin D being of overall benefit, but often does not reach statistical significance in meta-analyses. Growing points and areas timely for developing research:The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily. High-quality randomized placebo-controlled trials, such as the UK-based MAVIDOS trial, will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes.

SUBMITTER: Curtis EM

PROVIDER: S-EPMC6003599 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Maternal vitamin D supplementation during pregnancy.

Curtis Elizabeth M EM Moon Rebecca J RJ Harvey Nicholas C NC Cooper Cyrus C

British medical bulletin 20180601 1

<h4>Introduction</h4>Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as ast ...[more]

PMID: 29684104

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Project description:Abstract Objectives Vitamin D may have an adjunctive role in the prevention and treatment of iron deficiency (ID) through its proposed role in the regulation of erythropoiesis and circulating hepcidin concentrations. Observational studies have shown associations between low vitamin D and iron status; however, there are few data from intervention trials. In participants of the Maternal Vitamin D for Infant Growth Trial (MDIG; NCT01924013), among whom the baseline prevalence of vitamin D deficiency was 64%, we examined the effect of prenatal vitamin D supplementation on iron status during pregnancy by testing the effect of vitamin D supplementation on serum ferritin concentrations. Methods In this double-blind, dose-response, randomized trial in Dhaka, Bangladesh, women were recruited at 17–24 weeks’ gestation and randomly assigned to receive a prenatal vitamin D3 dose of 4200, 16,800, 28,000 IU/week or placebo. Serum ferritin was quantified using an electro-chemiluminescence immunoassay. Plasma C-reactive protein (CRP) was analysed by enzyme-linked immunoassay. Linear regression was used to test the hypothesized effect of vitamin D supplementation on serum ferritin (n = 1011 of 1300 enrolled). In a sensitivity analysis, we adjusted for concurrent CRP to correct for inflammation (n = 920). Regression correction was used to generate an inflammation-corrected estimate of the prevalence of ID (n = 920). Results Prevalence of ID (serum ferritin <15 µg/L) was high overall (27% corrected for inflammation; 12% uncorrected). Geometric mean (95% confidence interval) serum ferritin concentrations were lower in each of the vitamin D supplementation groups [43.1 (38.1, 48.7), 44.8 (40.4, 49.7) and 45.1 (41.5, 49.1) µg/L in the 4200, 16,800 and 28,000 IU/week groups, respectively] compared to the placebo group [50.3 µg/L (45.0, 56.2)], although none of the pairwise differences between each vitamin D group and placebo were statistically significant at the P < 0.05 threshold. Adjusting for CRP did not change the inferences. Conclusions In a population with concurrently high prevalence rates of iron and vitamin D deficiency, prenatal vitamin D supplementation did not lead to improvements in iron status by late gestation. The possibility of a negative effect of vitamin D supplementation on iron status should be further explored. Funding Sources The Bill and Melinda Gates Foundation.

Project description:BackgroundVitamin 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.ObjectivesTo 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 methodsWe 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 criteriaRandomised 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 analysisTwo 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 resultsThe 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' conclusionsVitamin 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.

Project description:Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 μg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.

Project description:OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ? 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ? 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.

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Maternal vitamin D supplementation during pregnancy.

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Maternal vitamin D supplementation during pregnancy.

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