Vitamin D supplementation in pregnancy and lactation to promote infant growth

The New England Journal of Medicine

Aug 2018

DOI: 10.1056/NEJMoa1800927

Citations:112

Influential Citations:6

Interventional (Human) Studies

Enhanced Details

Methods

Randomized, double-blind, placebo-controlled, dose-ranging trial in Dhaka, Bangladesh; generally healthy pregnant women enrolled at 17–24 weeks gestation; 1300 pregnancies randomized into five groups (placebo; prenatal vitamin D at three dose levels; prenatal vitamin D with postpartum vitamin D); primary outcome: length-for-age z score at 1 year; follow-up through 12 months; co-supplementation with calcium, iron, and folic acid provided.

Intervention

Weekly oral vitamin D3 tablets with prenatal doses of 4200 IU/week, 16,800 IU/week, or 28,000 IU/week; one group also received 28,000 IU/week postpartum for 26 weeks; prenatal supplementation started 17–24 weeks of gestation and continued until birth; postpartum supplementation for 26 weeks in the prenatal+postpartum 28,000 group. Calcium 500 mg/day, iron 66 mg/day, and folic acid 350 μg/day were provided to all participants throughout. Tablets were identical in appearance; dosing mostly observed by staff with up to four doses possibly unobserved; missed doses allowed up to 7 days after schedule.

Results

Primary outcome (infant length-for-age z score at 1 year) did not differ across groups (mean roughly −0.93 to −1.11; P = 0.25). No significant differences in other infant growth measures, birth outcomes, or morbidity. Vitamin D supplementation produced dose-dependent increases in maternal, cord, and infant 25-hydroxyvitamin D and lowered maternal iPTH at delivery; the highest prenatal dose with postpartum supplementation maintained infant 25-hydroxyvitamin D ≥30 nmol/L up to 6 months and increased maternal calcium and urinary calcium excretion, with rare hypercalcemia/hypercalciuria and no increase in adverse events. Conclusion: In a population with widespread prenatal vitamin D deficiency and fetal/infant growth restriction, maternal vitamin D supplementation from midpregnancy to birth or to 6 months postpartum did not improve fetal or infant growth, and does not support routine vitamin D supplementation for growth benefits (aligned with WHO guidance).

Limitations

Not powered to detect differences in infrequent maternal and infant adverse outcomes; midpregnancy initiation (17–24 weeks) may limit benefits from earlier supplementation; potential attenuation of effects due to cosupplementation with calcium; participants had relatively good baseline health and high facility-delivery rates, limiting generalizability to poorer settings; few cases of radiologic rickets (n=4), limiting assessment of preventive effect; findings may not generalize to populations with different vitamin D deficiency prevalence or growth-restriction risk; no assessment beyond 1 year."

Abstract

Background It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. Methods We conducted a randomized, double‐blind, placebo‐controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length‐for‐age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). Results Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length‐for‐age z scores. Scores were as follows: placebo, ‐0.93±1.05; prenatal 4200, ‐1.11±1.12; prenatal 16,800, ‐0.97±0.97; prenatal 28,000, ‐1.06±1.07; and prenatal and postpartum 28,000, ‐0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25‐hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. Conclusions In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013.) show less