Assessment of Maternal Adaptive Changes in Vitamin D and Calcium Metabolism during Pregnancy through a Systematic Review and Meta-Analysis

Abstract

Background: The growing skeleton of the fetus increases the mothers need for calcium during the pregnancy. An intricate system involving vitamin D and parathyroid hormone (PTH) regulates calcium transport from mother to fetus without compromising the maternal skeleton and is accomplished by dynamic adaptive changes during pregnancy. Vitamin D binding protein (VDBP) has a critical role in the bioavailability of vitamin D. We conducted a systematic review and meta-analysis to understand the temporal adaptive changes that occur in pregnancy in the context of vitamin D and calcium metabolism. Methods: Relevant studies were retrieved from PubMed, Google Scholar, and Cochrane till October 2023 and a random-effects model was used to draw the inference. A total of twenty studies consisting of 4559 healthy pregnant women were pooled for meta-analysis. Heterogeneity, sensitivity, and publication bias were analyzed. Results: Pregnant women had higher VDBP levels than the non-pregnant controls and displayed a trimester-dependent increase that declined following parturition, and vitamin D supplementation had no effect on it. The increase in VDBP was accompanied by an increase in total vitamin D but a decrease in metabolically active free vitamin D. The biologically active vitamin D increased from the second trimester reaching twice its control levels. PTH and alkaline phosphatase (ALP) increased while zinc, an essential cofactor required for the genomic action of vitamin D receptor, declined with the progression of pregnancy. There was significant heterogeneity between the studies but no evidence of publication bias was observed. Conclusion: As pregnancy progressed, VDBP, total vitamin D, biologically active vitamin D, PTH, and ALP increased while free vitamin D and zinc levels decreased. For the regulation of calcium homeostasis and vitamin D, the biologically active form of vitamin D was above the normal range. Moreover, this meta-analysis identified several hitherto unexplained adaptive changes in vitamin D and calcium metabolism during pregnancy.