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 randomized, controlled trial in Bangladesh was led by researchers at the University of Toronto, The Hospital for Sick Children and the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), and The New England Journal of Medicine published the results today.
Vitamin D regulates bone mineral metabolism. However, 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, which is why the World Health Organization (WHO) does not recommend routine vitamin D supplementation during pregnancy. The 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 U of T, SickKids' Centre for Global Child Health and icddr,b, conducted a 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. The researchers enrolled 1,300 women in the trial, the majority of whom were vitamin D deficient at baseline, and they followed up with 1,164 infants followed up 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," says lead author Daniel Roth, an associate professor of Paediatrics and Nutritional Sciences, and a faculty member of the Joannah & Brian Lawson Centre for Child Nutrition U of T. "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," adds Roth, who is also a clinician-scientist at SickKids' Centre for Global Child Health.
The study showed that 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.