Serum 24,25‐dihydroxyvitamin D Is Suppressed Across Pregnancy In Adolescents with Low Vitamin D Status

Abstract

BackgroundLow maternal serum 25(OH)D has been associated with preeclampsia, low birth weight, and offspring bone health. Serum concentrations of the hormone 1,25(OH)2D (calcitriol) rise in pregnancy, yet the importance of calcitriol and parathyroid hormone (PTH) to calcium homeostasis during pregnancy is uncertain. Possible alterations in serum 24,25(OH)2D, the catabolite of 25(OH)D, remain largely unexplored across gestation, and assessment of 24,25(OH)2D could improve understanding of pregnancy adaptations in vitamin D metabolism.MethodsWe supplemented 79 pregnant adolescents at risk of vitamin D inadequacy with 2000 International Units (IU) or 200 IU of vitamin D3 daily and sought to determine how the serum 25(OH)D response related to circulating calcitriol, 24,25(OH)2D, and PTH. Serum was collected at study entry, midway through the study, and delivery. We measured serum 25(OH)D, calcitriol, and 24,25(OH)2D by LC‐MS/MS and PTH by immunoassay. We used pre‐post and longitudinal analyses to assess change in serum markers.ResultsAt study entry (18 ± 5 wk gestation, mean ± sd), serum 25(OH)D was 25 ± 9 ng/ml, and it changed 0.5 ± 10 ng/ml between entry and delivery. Calcitriol was elevated above non‐pregnant levels at entry and peaked in the 3rd trimester. Calcitriol and 25(OH)D were weakly correlated at delivery, yet baseline and change in 25(OH)D did not predict calcitriol concentrations across pregnancy. In contrast, serum 24,25(OH)2D and 25(OH)D were highly correlated throughout pregnancy (r≥0.85, p<0.001), but change in 24,25(OH)2D relative to that of 25(OH)D varied by baseline vitamin D status. When serum 25(OH)D increased any amount over pregnancy, the increase in 24,25(OH)2D was attenuated in teens with baseline 25(OH)D <20 ng/ml (n=27) vs. ≥20 ng/ml (n=52). Change in 24,25(OH)2D was related to change in serum calcium (r=0.40, p=0.001). Change in the 1,25(OH)2D/24,25(OH)2D ratio was positively related to change in serum PTH (r=0.30, p=0.02), a hormone that elevates 1,25(OH)2D and suppresses the renal 24‐hydroxylase in the non‐pregnant state. Those with baseline 25(OH)D <20 ng/ml drove this association of 1,25(OH)2D/24,25(OH)2D and PTH (p=0.01).ConclusionsOur results imply that production of 24,25(OH)2D across pregnancy is suppressed/constrained when 25(OH)D supply is limited, perhaps to preserve 25(OH)D and adequate production of calcitriol. Serum 24,25(OH)2D and vitamin D metabolite ratios may be useful indicators of vitamin D and calcium homeostasis during pregnancy.Support or Funding InformationThis research was supported by USDA grant 2011‐03424 and NIH award T32‐DK007158. Content does not represent the official views of the NIH.