In an article entitled, “Maternal Vitamin D Supplementation and Infantile Rickets: Secondary Analysis of a Randomized Trial,” being early released this week in Pediatrics, Dr. Maria-Elena Lautatzis from Health Sciences Centre Winnipeg and colleagues from the Hospital for Sick Children, the International Centre for Diarrhoeal Disease Research, Bangladesh and the University of Adelaide present a secondary analysis of a randomized placebo-controlled trial conducted in Bangladesh that examined the effect of 5 different prenatal and postnatal maternal vitamin D supplementation dosing regimens on infant biochemical rickets at ages 6–12 months (10.1542/peds.2023-063263).
Women and children in low- and middle-income countries (LMICs), including Bangladesh, carry a high burden of vitamin D deficiency, making the study uniquely relevant and the results highly generalizable for maternal child health in LMICs. And unlike in the US (AAP Policy), breastfeeding infants in Bangladesh do not routinely receive vitamin D supplementation, and this facilitated a more direct assessment of the effect of maternal vitamin D supplementation on infant risk for rickets.
The Maternal Vitamin D for Infant Growth (MDIG) study enrolled 1300 healthy expectant women (weeks 17–24 of pregnancy) in Dhaka, Bangladesh, and randomized them to 1 of 5 groups:
- placebo in prenatal and postpartum periods
- prenatal vitamin D3 (4200 IU/week) and placebo postpartum
- prenatal vitamin D3 (16800 IU/week) and placebo postpartum
- prenatal vitamin D3 (28000 IU/week) and placebo postpartum or
- vitamin D3 (28000 IU/ week) prenatal and to 6-months postpartum.
(Note that these are weekly and not daily doses, with the highest maternal dose corresponding to 4000 IU/day, which is the tolerable upper intake level for women, including those who are expectant and lactating.) All mothers also received 500 mg of calcium and an iron-folic acid supplement daily.
The main original study outcome was infant growth, and no differences were found between groups.
In this secondary analysis, biochemical rickets screening with serum alkaline phosphatase (ALP), calcium and phosphorus was conducted in infants at 6–12 months. Any infant with abnormal levels was referred to a physician who obtained an x-ray and additional blood work, including a vitamin D level.
By consensus, the authors defined “biochemical rickets” as
- ALP of >450U/L OR
- ALP >350 U/L plus one or more of the following: calcium <2.2 mmol/L (8.8 mg/dL), phosphate <1.6 mmol/L (4.96 mg/dL) or elevated parathyroid hormone level (the last not available in real time).
Overall, 790 infants were screened, and 39 (4.9%) had biochemical rickets. The prevalence was highest (7.9%, 13 infants) in group #1 (prenatal and postnatal placebo) and lowest (1.3%, 2 infants) in group #5 (28000 IU of vitamin D prenatally and to 6 months postpartum). Among infants of mothers who received any dose of vitamin D prenatally and placebo postnatally, risk for rickets was the same as for those whose mothers received placebo prenatally and postnatally.
In this study, 99% of infants were exclusively or partially breastfed; infants receiving correctly mixed formula are at very low risk for vitamin D deficiency or rickets due to formula supplementation. Rates of exclusive breastfeeding through 5 months are 65% in Bangladesh, which is high by comparison to other LMICs, and hence these study results are highly applicable regionally.
Although there were study limitations (incomplete x-ray information, for example), this result strongly suggests that high-dose postnatal maternal vitamin D supplementation will be a reasonable public health strategy for rickets prevention in tandem with breastfeeding promotion. Future research on optimal maternal vitamin D dose and duration for clinical rickets prevention is needed to guide health policy, but this study takes a giant leap toward improving maternal child health in LMICs.
