The Maternal Vitamin D for Infant Growth (MDIG) trial in Bangladesh shows that maternal vitamin D supplementation does not improve fetal or infant growth

TORONTO – Vitamin D supplementation in pregnancy and lactation does not affect fetal or infant growth up to one year of age, according to the results of The Maternal Vitamin D for Infant Growth (MDIG) Trial. This large randomized, controlled trial in Bangladesh was led by researchers at The Hospital for Sick Children (SickKids) and International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). The results are published in the New England Journal of Medicine.

Vitamin D regulates bone mineral metabolism. However, until now, it has been unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth, particularly in regions of the world where vitamin D deficiency is common. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes, including low newborn weight. However, evidence of health benefits from randomized controlled trials of vitamin D supplementation has been inconsistent. Due to inadequate evidence, the World Health Organization (WHO) does not recommend routine vitamin D supplementation during pregnancy. The present findings from the MDIG Trial support this position, even in populations where vitamin D deficiency and fetal–infant growth restriction are widespread.

The team from the Centre for Global Child Health, SickKids and icddr,b, conducted a randomized, double-blind, placebo-controlled trial in Bangladesh of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation up to 26 weeks after delivery). One group received only placebo in the prenatal and postpartum period. Three groups received prenatal supplementation in doses of 4200 IU/week, 16,800 IU/week, or 28,000 IU/week, and then placebo in the postpartum period. The fifth group received vitamin D supplementation at a dose of 28,000 IU/week in the prenatal period and up to 26 weeks postpartum. The primary aim of the study was to examine the effects of the vitamin D intervention on infant length at one year of age. There were 1,300 women enrolled into the trial, the majority of whom were vitamin D deficient at baseline. There were 1,164 infants followed up successfully at one year of age.

“The trial showed that vitamin D supplementation given to women during the latter half of pregnancy and in the postpartum period, even at higher than conventional doses, did not affect either fetal or infant growth up to one year of age. Vitamin D supplementation improved vitamin D status and reduced the risk of vitamin D deficiency, as expected, but nonetheless did not have effects on infant growth. Also, we did not find any clear evidence of benefits of vitamin D for other pregnancy or birth outcomes,” says Dr. Daniel Roth, a clinician-scientist in the Department of Paediatrics and the Centre for Global Child Health at SickKids and lead author of the study.

Vitamin D supplementation significantly increased maternal and infant serum 25-hydroxyvitamin D, maternal and infant calcium concentrations, and maternal urinary calcium excretion, and suppressed maternal parathyroid hormone concentrations. Women receiving the highest dose had an increased frequency of episodes of elevated urinary calcium excretion. There were no significant differences in the frequencies of clinical adverse events across groups. However, the authors acknowledged that the “trial was not powered to detect differences in infrequent maternal and infant adverse outcomes” and that “the initiation of vitamin D supplementation in mid-pregnancy did not address the question of whether earlier supplementation might have had beneficial effects.”

The results of the MDIG trial contribute important new evidence to guide recommendations about vitamin D supplementation in pregnant and lactating women, particularly in vitamin D-deficient populations where child growth faltering and adverse pregnancy outcomes remain significant public health burdens.

This work was supported by the Bill and Melinda Gates Foundation.