The Effect of Vitamin D Supplementation During Pregnancy on Placental Function in Preeclampsia, Intrauterine Growth Restriction, and Preterm Birth.

Abstract

Background: The human placenta is a transitory organ playing the role of multiple organs during pregnancy. It is composed of trophoblastic cells that respond to vitamin D. Vitamin D is a secosteroid hormone that plays an important role in pregnancy. Its deficiency has been linked to multiple diseases affecting both the mother and the fetus. Objective: To highlight, through a systematic literature review, the effet of vitamin D supplementation during pregnancy on placental functions in some pregnancy-associated diseases such as preeclampsia, intrauterine growth restriction, and preterm birth. Methods: MEDLINE (Ovid), Embase, and CINAHL databases were systematically searched using “placenta” and “vitamin D” as concepts. The screening was done based on specific selection criteria. Data was abstracted and summarized in a tabular format. Results: A total of 3844 records was obtained from the 3 databases. 2456 records remained after the removal of duplicates of which 22 were used in this systematic review. These studies showed that vitamin D have been reported to affect inflammation, oxidative stress, amino acid transporters, pro-labor genes, and preeclamptic markers in case of preeclampsia, intrauterine growth restriction, and preterm birth. In fact, it decreased TNF-α, IL-10, and IL-6 wich are involved in inflammation. It increased antimicrobial peptides like HBD2, HBD3, and hCTD. Regarding oxidative stress, it decreased TXB2 production, TXB2 to 6-keto PGF1α ratio, 8-isoprostane, caspase-3 cleavage, ROCK1 activation, MP, caveolin-1, and superoxide (when induced by CoCl2), but had no effect on HO-1 and 15-F2t-isoP. Also, a negative correlation was seen between vitamin D and MDA and a positive correlation was seen between VDR and CBS. Moreover, a negative correlation was seen between vitamin D and the cell survival marker MAP1LC3B/BECN1. Different results were obtained for the association of vitamin D with VEGF, sFLT-1, PAPP-A, or PlGF which play a role in preeclampsia. However, it had no effect on MAP, UtA PI, VCAM-1, ESR1, and hCG-β. A negative correlation was seen between vitamin D and ICAM-1. Also, it increased EVT invasion, pro-MMP2, and pro-MMP9. In addition, it increased amino acid transporters SNAT2 but had no effect on SNAT4, LAT1, LAT2, 4E-BP1 Thr-37/46 and Akt Ser-473. A positive correlation was found between vitamin D and LAT3, ASCT1 or y+LAT1. Different results were obtained with SNAT1. Lastly, it decreased CRH, COX-2 which are pro-labor genes. Conclusion: Vitamin D increased some of the outcomes, decreased, or showed no effect on others. Keywords: Placenta; trophoblasts; cytotrophoblasts; vitamin D; vitamin D deficiency; calcitriol; 25(OH)D; VDR; preeclampsia; intrauterine growth restriction; preterm birth.