Person:

Thorne-Lyman, Andrew Lucian

Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen's weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence.

Background: Describing vitamin D status and its predictors in various populations is important in order to target public health measures. Objectives: To describe the status and predictors of vitamin D status in healthy Nepalese mothers and infants. Methods: 500 randomly selected Nepalese mother and infant pairs were included in a cross-sectional study. Plasma 25(OH)D concentrations were measured by LC-MS/MS and multiple linear regression analyses were used to identify predictors of vitamin D status. Results: Among the infants, the prevalence of vitamin D insufficiency (25(OH)D <50 nmol/L) and deficiency (<30 nmol/L) were 3.6% and 0.6%, respectively, in contrast to 59.8% and 14.0% among their mothers. Infant 25(OH)D concentrations were negatively associated with infant age and positively associated with maternal vitamin D status and body mass index (BMI), explaining 22% of the variability in 25(OH)D concentration. Global solar radiation, maternal age and BMI predicted maternal 25(OH)D concentration, explaining 9.7% of its variability. Conclusion: Age and maternal vitamin D status are the main predictors of vitamin D status in infants in Bhaktapur, Nepal, who have adequate vitamin D status despite poor vitamin D status in their mothers.

Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low income countries.

A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake, or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates.

We identified 5 randomized trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration, and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed effects models suggested protective effects of supplementation on low birthweight (3 trials, Risk ratio (RR)=0.40 [95% confidence interval (CI), 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (SGA) (2 trials, RR=0.67, [0.40, 1.11]. No effect on preterm delivery (<37 weeks) was evident (2 trials, RR=0.77 [0.35, 1.66]).

Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore SGA, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials should be sufficient to correct deficiency.

Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B₆, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, α-tocopherol, pyridoxal 5'-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B₆ deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (α-tocopherol <9.3 µmol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal.

Vitamin A (VA) deficiency during pregnancy is common in low income countries and a growing number of intervention trials have examined the effects of supplementation during pregnancy on maternal, perinatal, and infant health outcomes.

We systematically reviewed the literature to identify trials isolating the effects of VA or carotenoid supplementation during pregnancy on maternal, fetal, neonatal and early infant health outcomes. Meta-analysis was used to pool effect estimates for outcomes with more than one comparable study. We used GRADE criteria to assess the quality of individual studies and the level of evidence available for each outcome.

We identified 23 eligible trials of which 17 had suitable quality for inclusion in meta-analyses. VA or beta-carotene (βC) supplementation during pregnancy did not have a significant overall effect on birthweight indicators, preterm birth, stillbirth, miscarriage, or fetal loss. Among HIV-positive women, supplementation was protective against low birthweight (<2.5 kg), RR=0.79, [95% CI 0.64, 0.99], but no significant effects on preterm delivery or small-for-gestational age were observed. Pooled analysis of the results of three large randomized trials found no effects of VA supplementation on neonatal/infant mortality, or pregnancy-related maternal mortality, random effects RR=0.86, [0.60, 1.24] although high heterogeneity was observed in the maternal mortality estimate[I2=74%, p=0.02]. VA supplementation during pregnancy was found to improve hemoglobin levels and reduce anemia risk (<11.0 g/dL) during pregnancy random effects RR=0.81 [0.69, 0.94], also with high heterogeneity (I2=52%, p=0.04). We found no effect of VA/βC supplementation on mother-to-child HIV transmission in pooled analysis, although some evidence suggests that it may increase transmission.

There is little consistent evidence of benefit of maternal supplementation with VA or βC during pregnancy on maternal or infant mortality. While there may be beneficial effects for certain outcomes, there may also be potential for harm through increased HIV transmission in some populations.