Improving vitamin D status in pregnant women in South Asia may reduce the risk of neonatal morbidity and mortality. To inform the design of antenatal vitamin D trials to test these hypotheses, pharmacokinetic and safety studies were conducted to characterize the effect of vitamin D3 supplementation on vitamin D status (25-hydroxyvitamin D concentration) and calcium homeostasis in 75 non-pregnant and pregnant (third-trimester) participants in Dhaka, Bangladesh. Participants were assigned to a single-dose (70,000 IU) or weekly-dose oral vitamin D3 regimen. In the weekly-dose study, pregnant women were randomized to a higher (70,000 IU, then 35,000 IU/week) or a lower dose (14,000 IU/week). All non-pregnant participants in the weekly-dose group received the higher dose for 10 weeks.

Participants' baseline vitamin D status was suboptimal and worse in the winter, when 25% of pregnant women (7/28) had vitamin D deficiency defined by [25(OH)D]<25 nmol/L. Analysis of ultraviolet B (UVB) radiation exposure by polysulphone badge dosimetry and NASA satellite data suggested that outdoor air pollutants during the winter may absorb sufficient UVB to diminish the cutaneous synthesis of vitamin D3 in this region.

In the single-dose study, the response to 70,000 IU was similar in pregnant and non-pregnant participants. In the weekly-dose studies, the higher dose induced a greater average rise in [25(OH)D] and higher final mean [25(OH)D] compared to the lower dose in pregnant women (98 nmol/L vs. 76 nmol/, P=0.04). At 10 weeks, the target [25(OH)D]>80 nmol/L was reached in 90% of higher- versus 56% of lower-dose participants. However, nearly all newborns in both groups had cord [25(OH)D]>80 nmol/L. Pregnant women had an attenuated rise in [25(OH)D] compared to non-pregnant women receiving the same higher dose, but this may have been due to physiologic plasma volume expansion. Single- and weekly-dose regimens did not cause hypercalcemia and there were no observed supplement-related clinical adverse events.

In summary, these studies established preliminary pharmacokinetic and safety data to guide vitamin D3 supplementation in the third-trimester of pregnancy. Further research is required to establish the safety of these regimens and to determine whether the observed elevations in [25(OH)D] are associated with improvements in maternal-infant health.