title: Pharmacokinetics of high-dose weekly oral vitamin D3 supplementation during the third trimester of pregnancy in Dhaka, Bangladesh.
abstract: A pharmacokinetic study was conducted to assess the biochemical dose-response and tolerability of high-dose prenatal vitamin D3 supplementation in Dhaka, Bangladesh (23°N). Pregnant women at 27-30 weeks gestation (n = 28) were randomized to 70,000 IU once + 35,000 IU/week vitamin D3 (group PH: pregnant, higher dose) or 14,000 IU/week vitamin D3 (PL: pregnant, lower dose) until delivery. A group of non-pregnant women (n = 16) was similarly administered 70,000 IU once + 35,000 IU/week for 10 weeks (NH: non-pregnant, higher-dose). Rise (∆) in serum 25-hydroxyvitamin D concentration ([25(OH)D]) above baseline was the primary pharmacokinetic outcome. Baseline mean [25(OH)D] were similar in PH and PL (35 nmol/L vs. 31 nmol/L, p = 0.34). A dose-response effect was observed: ∆[25(OH)D] at modeled steady-state was 19 nmol/L (95% CI, 1 to 37) higher in PH vs. PL (p = 0.044). ∆[25(OH)D] at modeled steady-state was lower in PH versus NH but the difference was not significant (-15 nmol/L, 95% CI -34 to 5; p = 0.13). In PH, 100% attained [25(OH)D] ≥ 50 nmol/L and 90% attained [25(OH)D] ≥ 80 nmol/L; in PL, 89% attained [25(OH)D] ≥ 50 nmol/L but 56% attained [25(OH)D] ≥ 80 nmol/L. Cord [25(OH)D] (n = 23) was slightly higher in PH versus PL (117 nmol/L vs. 98 nmol/L; p = 0.07). Vitamin D3 was well tolerated; there were no supplement-related serious adverse clinical events or hypercalcemia. In summary, a regimen of an initial dose of 70,000 IU and 35,000 IU/week vitamin D3 in the third trimester of pregnancy was non-hypercalcemic and attained [25(OH)D] ≥ 80 nmol/L in virtually all mothers and newborns. Further research is required to establish the safety of high-dose vitamin D3 in pregnancy and to determine if supplement-induced [25(OH)D] elevations lead to maternal-infant health benefits.
authors.affiliation: Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. daniel.roth@sickkids.ca
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Roth
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mahmud
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.forename: Evana
authors.initials: E
authors.lastname: Akhtar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Black
authors.forename: Abdullah H
authors.initials: AH
authors.lastname: Baqui
mesh_terms: D000293:Adolescent; D000328:Adult; D001459:Bangladesh; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D055815:Young Adult
chemical_list: D002762:Cholecalciferol