Modern understanding of the role of vitamin D in the genesis of premature birth (literature review)
DOI:
https://doi.org/10.15574/HW.2024.5(174).6672Keywords:
25(OH)D concentration, vitamin D deficiency, pregnancy, preterm birthAbstract
Preterm births remain one of the most pressing challenges in modern obstetrics, accounting for approximately 70% of perinatal mortality cases among preterm infants. Even those who survive face an increased risk of chronic lung diseases, hearing and vision impairments, and cognitive dysfunctions. The pathophysiology of preterm births is complex and remains insufficiently understood. One of the potential factors influencing preterm birth is maternal vitamin D levels during pregnancy. According to biological assumptions, adequate levels of vitamin D may reduce the risk of preterm births due to its immunomodulatory properties. However, large-scale, well-designed randomized studies are needed to confirm this and to elucidate the mechanisms of vitamin D action.
Aim - to assess the relationship between maternal vitamin D levels during pregnancy and the risk of preterm birth.
The analysis involved a search of scientific publications in databases such as "PubMed," "Google Scholar," "PMC," "Web of Science," and other reputable sources. The review included randomized controlled trials, cohort studies, case-control studies, and review articles. Key search terms included: "preterm birth," "vitamin D," "immunomodulation," and "vitamin D and immune system". Evidence suggests that vitamin D plays a role in regulating the innate and adaptive immune systems. Both "sterile" and "infectious" inflammation are triggers of preterm births, and low levels of vitamin D may exacerbate these processes. Specifically, studies have shown that higher doses of vitamin D reduce the risk of preterm births.
Conclusions. Current research highlights the role of vitamin D in regulating immune functions in reproductive tissues and its impact on pregnancy outcomes. However, the existing evidence is insufficient to determine the optimal vitamin D levels required for positive immune modulation. Additional well-designed clinical studies are needed to establish a causal relationship between vitamin D deficiency, immune system modulation, and improved reproductive outcomes through vitamin D supplementation.
The authors declare no conflict of interest.
References
Aguilar-Cordero MJ, Lasserrot-Cuadrado A, Mur-Villar N, León-Ríos XA, Rivero-Blanco T, Pérez-Castillo IM. (2020, Aug). Vitamin D, preeclampsia and prematurity: A systematic review and meta-analysis of observational and interventional studies. Midwifery. 87: 102707. https://doi.org/10.1016/j.midw.2020.102707; PMid:32438283
Alifu X, Si S, Qiu Y, Cheng H, Huang Y, Chi P et al. (2023, Aug 2). The Association of Vitamin D during Pregnancy and mRNA Expression Levels of Inflammatory Factors with Preterm Birth and Prelabor Rupture of Membranes. Nutrients. 15(15): 3423. https://doi.org/10.3390/nu15153423; PMid:37571360 PMCid:PMC10421124
AlQasrawi D, Naser E, Naser SA. (2021, May 18). Nicotine Increases Macrophage Survival through α7nAChR/NF-κB Pathway in Mycobacterium avium paratuberculosis Infection. Microorganisms. 9(5): 1086. https://doi.org/10.3390/microorganisms9051086; PMid:34070119 PMCid:PMC8158352
AlQasrawi D, Qasem A, Naser SA. (2020, Aug 13). Divergent Effect of Cigarette Smoke on Innate Immunity in Inflammatory Bowel Disease: A Nicotine-Infection Interaction. Int J Mol Sci. 21(16): 5801. https://doi.org/10.3390/ijms21165801; PMid:32823518 PMCid:PMC7461043
Antypkyn YuH, Moyseenko RA, Marushko RV, Dudyna EA, Marushko TL, Bodnaruk NN. (2022). Sytuatsyonniy analyz sostoianyia okhrani zdorovia detei v Ukrayne. Pediatrics. Eastern Europe. 10; 1: 118-135. https://doi.org/10.34883/PI.2022.10.1.017
Amegah AK. (2023, Oct 7). New estimates of preterm birth: data gaps and quality issues linger. Lancet. 402(10409): 1215-1217. https://doi.org/10.1016/S0140-6736(23)01359-4; PMid:37805200
Aparicio A, Gold DR, Weiss ST, Litonjua AA, Lee-Sarwar K, Liu YY. (2023, Apr 25). Association of vitamin D level and maternal gut microbiome during pregnancy: Findings from a randomized controlled trial of antenatal vitamin D supplementation. medRxiv. Nutrients. 15(9): 2059. https://doi.org/10.3390/nu15092059; PMid:37432235 PMCid:PMC10181263
Baczynska-Strzecha M, Kalinka J. (2016). Effect of apa1 (rs7975232), taq1 (rs731236) and bsm1 (rs154410) vitamin D receptor polymorphisms on the risk of preterm birth in a Polish population. Gynecologist gender. 87: 763-768. https://doi.org/10.5603/GP.2016.0084; PMid:27958635
Benyuk VO, Korniets NG, Oleshko VF. (2019). Premature rupture of membranes in preterm pregnancy - a modern view on etiology and pathogenesis. Health of woman. 2(138): 8-13. https://doi.org/10.15574/HW.2019.138.8
Carlberg C. (2019, Sep 13). Vitamin D Signaling in the Context of Innate Immunity: Focus on Human Monocytes. Front Immunol. 10: 2211. https://doi.org/10.3389/fimmu.2019.02211; PMid:31572402 PMCid:PMC6753645
Chan D, Bennett PR, Lee YS, Kundu S, Teoh TG, Adan M et al. (2022, Feb 21). Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response. Nat Commun. 13(1): 975. https://doi.org/10.1038/s41467-022-28620-1; PMid:35190561 PMCid:PMC8861006
Cheng H, Chi P, Zhuang Y, Alifu X, Zhou H, Qiu Y et al. (2023, Aug 16). Association of 25-Hydroxyvitamin D with Preterm Birth and Premature Rupture of Membranes: A Mendelian Randomization Study. Nutrients. 15(16): 3593. https://doi.org/10.3390/nu15163593; PMid:37630783 PMCid:PMC10459690
Cyprian F, Lefkou E, Varoudi K, Girardi G. (2019, Nov 22). Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond. Front Immunol. 10: 2739. https://doi.org/10.3389/fimmu.2019.02739; PMid:31824513 PMCid:PMC6883724
Dunlop AL, Jordan SL, Ferranti EP, Hill CC, Patel S, Hao L et al. (2019, Jan 1). Total and Free 25-Hydroxy-Vitamin D and Bacterial Vaginosis in Pregnant African American Women. Infect Dis Obstet Gynecol. 2019: 9426795. https://doi.org/10.1155/2019/9426795; PMid:30692844 PMCid:PMC6332941
Gurkan N. (2022, Aug). Vitamin D supplementation during pregnancy inhibits the activation of fetal membrane NF-κB pathway. Eur Rev Med Pharmacol Sci. 26(16): 5926-5931. doi: 10.26355/eurrev_202208_29532. Retraction in: Eur Rev Med Pharmacol Sci. 2022 Nov; 26(22): 8205. doi: 10.26355/eurrev_202211_30349.
Jefferson KK, Parikh HI, Garcia EM, Edwards DJ, Serrano MG, Hewison M et al. (2019, Jun). Relationship between vitamin D status and the vaginal microbiome during pregnancy. J Perinatol. 39(6): 824-836. https://doi.org/10.1038/s41372-019-0343-8; PMid:30858609 PMCid:PMC6535112
Kiely ME, Wagner CL, Roth DE. (2020, Jul). Vitamin D in pregnancy: Where we are and where we should go. J Steroid Biochem Mol Biol. 201: 105669. https://doi.org/10.1016/j.jsbmb.2020.105669; PMid:32302652
Knabl J, Vattai A, Ye Y, Jueckstock J, Hutter S, Kainer F et al. (2017, Nov 6). Role of Placental VDR Expression and Function in et alCommon Late Pregnancy Disorders. Int J Mol Sci. 18(11): 2340. https://doi.org/10.3390/ijms18112340; PMid:29113124 PMCid:PMC5713309
Kovacs CS, Woodland ML, Fudge NJ, Friel JK. (2005, Jul). The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab. 289(1): E133-44. https://doi.org/10.1152/ajpendo.00354.2004; PMid:15741244
Li N, Wu HM, Hang F, Zhang YS, Li MJ. (2017). Women with recurrent spontaneous abortions have decreased 25(OH) vitamin D and VDR at the fetal-maternal interface. Braz J. Med. Biol. res. 50: e6527. https://doi.org/10.1590/1414-431x20176527; PMid:28902929 PMCid:PMC5597287
Liu NQ, Kaplan AT, Lagishetty V, Ouyang YB, Ouyang Y, Simmons CF et al. (2011, May 15). Vitamin D and the regulation of placental inflammation. J Immunol. 186(10): 5968-74. https://doi.org/10.4049/jimmunol.1003332; PMid:21482732
Liu NQ, Ouyang Y, Bulut Y, Lagishetty V, Chan SY, Hollis BW et al. (2013, Jul). Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development. Endocrinology. 154(7): 2270-2280. https://doi.org/10.1210/en.2012-2270; PMid:23677931
Ma Y, Yang Y, Lv M, Zhang Y, He Q, Zhang Y et al. (2022, Dec). 1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway. Placenta. 130: 34-41. https://doi.org/10.1016/j.placenta.2022.10.012; PMid:36372042
Ma L, Zhang Z, Li L, Zhang L, Lin Z, Qin H. (2022, Nov 22). Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies. Front Nutr. 9: 1016592. https://doi.org/10.3389/fnut.2022.1016592; PMid:36483925 PMCid:PMC9722752
Mansur JL, Oliveri B, Giacoia E, Fusaro D, Costanzo PR. (2022, May 1). Vitamin D: Before, during and after Pregnancy: Effect on Neonates and Children. Nutrients. 14(9): 1900. https://doi.org/10.3390/nu14091900; PMid:35565867 PMCid:PMC9105305
Manzon L, Altarescu G, Tevet A, Schimmel MS, Elstein D et al. (2014). Vitamin D receptor polymorphism foki is associated with spontaneous idiopathic preterm birth in an Israeli population. Euro. J. Obstet. Gynecologist Reproduction Biol. 177: 84-88. https://doi.org/10.1016/j.ejogrb.2014.03.008; PMid:24702903
Matias ML, Romao-Veiga M, Ribeiro VR, Nunes PR, Gomes VJ, Devides AC et al. (2021, Apr). Progesterone and vitamin D downregulate the activation of the NLRP1/NLRP3 inflammasomes and TLR4-MyD88-NF-κB pathway in monocytes from pregnant women with preeclampsia. J Reprod Immunol. 144: 103286. https://doi.org/10.1016/j.jri.2021.103286; PMid:33578174
Menon R. (2019, Jul). Initiation of human parturition: signaling from senescent fetal tissues via extracellular vesicle mediated paracrine mechanism. Obstet Gynecol Sci. 62(4): 199-211. https://doi.org/10.5468/ogs.2019.62.4.199; PMid:31338337 PMCid:PMC6629986
Menon R, Debnath C, Lai A, Guanzon D, Bhatnagar S, Kshetrapal P et al. (2020, Apr 1). Protein Profile Changes in Circulating Placental Extracellular Vesicles in Term and Preterm Births: A Longitudinal Study. Endocrinology. 161(4): bqaa009. https://doi.org/10.1210/endocr/bqaa009; PMid:31995166 PMCid:PMC7102872
Molani-Gol R, Rafraf M. (2023, Oct 16). Maternal vitamin D in pregnancy and infant's gut microbiota: a systematic review. Front Pediatr. 11: 1248517. https://doi.org/10.3389/fped.2023.1248517; PMid:37915988 PMCid:PMC10617198
Morales-Suárez-Varela M, Uçar N, Soriano JM, Llopis-Morales A, Sanford BS, Grant WB. (2022, Oct 4). Vitamin D-Related Risk Factors for Maternal Morbidity and Mortality during Pregnancy: Systematic Review and Meta-Analysis. Nutrients. 14(19): 4124. https://doi.org/10.3390/nu14194124; PMid:36235776 PMCid:PMC9572094
Oh C, Keats EC, Bhutta ZA. (2020, Feb 14). Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Nutrients. 12(2): 491. https://doi.org/10.3390/nu12020491; PMid:32075071 PMCid:PMC7071347
Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A et al. (2023, Oct 7). National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 402(10409): 1261-1271. https://doi.org/10.1016/S0140-6736(23)00878-4; PMid:37805217
Okwaraji YB, Bradley E, Ohuma EO, Yargawa J, Suarez-Idueta L, Requejo J et al. (2024, Jun). National routine data for low birthweight and preterm births: Systematic data quality assessment for United Nations member states (2000-2020). BJOG. 131(7): 917-928. https://doi.org/10.1111/1471-0528.17699; PMid:37932234
Padhi A, Pattnaik K, Biswas M, Jagadeb M, Behera A, Sonawane A. (2019, Nov 15). Mycobacterium tuberculosis LprE Suppresses TLR2-Dependent Cathelicidin and Autophagy Expression to Enhance Bacterial Survival in Macrophages. J Immunol. 203(10): 2665-2678. https://doi.org/10.4049/jimmunol.1801301; PMid:31619537
Poladich IV, Kostenko OYu. (2023). Role of vitamin D in the genesis of recurrent reproductive loss. Ukrainian Journal Health of Woman. 5(168): 34-41. https://doi.org/10.15574/HW.2023.168.34
Polettini J, Richardson LS, Menon R. (2018, Mar). Oxidative stress induces senescence and sterile inflammation in murine amniotic cavity. Placenta. 63: 26-31. https://doi.org/10.1016/j.placenta.2018.01.009; PMid:29486853 PMCid:PMC5833301
Rathnaiah G, Zinniel DK, Bannantine JP, Stabel JR, Gröhn YT et al. (2017, Nov 6). Pathogenesis, Molecular Genetics, and Genomics of Mycobacterium avium subsp. paratuberculosis, the Etiologic Agent of Johne's Disease. Front Vet Sci. 4: 187. https://doi.org/10.3389/fvets.2017.00187; PMid:29164142 PMCid:PMC5681481
Ronzoni S, Boucoiran I, Yudin MH, Coolen J, Pylypjuk C, Melamed N et al. (2022, Nov). Guideline No. 430: Diagnosis and management of preterm prelabour rupture of membranes. J Obstet Gynaecol Can. 44(11): 1193-1208.e1. https://doi.org/10.1016/j.jogc.2022.08.014; PMid:36410937
Rosenfeld T, Salem H, Altarescu G, Grisaru-Granovskyi S, Tevet A, Birk R. (2017). Maternal and fetal vitamin D receptor polymorphisms are significantly associated with preterm birth. Ark. Gynecologist Obstet. 296: 215-222. https://doi.org/10.1007/s00404-017-4412-y; PMid:28612095
Schröder-Heurich B, Springer CJP, von Versen-Höynck F. (2020, May 15). Vitamin D Effects on the Immune System from Periconception through Pregnancy. Nutrients. 12(5): 1432. https://doi.org/10.3390/nu12051432; PMid:32429162 PMCid:PMC7284509
Song Q, Li Y, Zhou T, Xiao M, Xiao B, Wang M, Zhu Y. (2024, Jul 29). Maternal vitamin D status during pregnancy and infant's gut microbiota: a prospective cohort study. Front Nutr. 11: 1428356. https://doi.org/10.3389/fnut.2024.1428356; PMid:39135559 PMCid:PMC11317374
Sussan TE, Sudini K, Talbot CC Jr, Wang X, Wills-Karp M et al. (2017, Jan 10). Nrf2 regulates gene-environment interactions in an animal model of intrauterine inflammation: Implications for preterm birth and prematurity. Sci Rep. 7: 40194. https://doi.org/10.1038/srep40194; PMid:28071748 PMCid:PMC5223218
Tabatabaeizadeh SA, Tafazoli N, Ferns GA, Avan A, Ghayour-Mobarhan M. (2018, Aug 23). Vitamin D, the gut microbiome and inflammatory bowel disease. J Res Med Sci. 23: 75. https://doi.org/10.4103/jrms.JRMS_606_17; PMid:30181757 PMCid:PMC6116667
Tahsin T, Khanam R, Chowdhury NH, Hasan ASMT, Hosen MB, Rahman S et al. (2023, May 6). Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study. BMC Pregnancy Childbirth. 23(1): 322. https://doi.org/10.1186/s12884-023-05636-z; PMid:37149566 PMCid:PMC10163702
Talafha MM, Qasem A, Naser SA. (2024, Apr 30). Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis. Nutrients. 16(9): 1358. https://doi.org/10.3390/nu16091358; PMid:38732603 PMCid:PMC11085596
Turner DJ, Saveliev A, Salerno F, Matheson LS, Screen M, Lawson H et al. (2022, Apr 22). A functional screen of RNA binding proteins identifies genes that promote or limit the accumulation of CD138+ plasma cells. Elife. 11: e72313. https://doi.org/10.7554/eLife.72313; PMid:35451955 PMCid:PMC9106329
Vaccaro JA, Qasem A, Naser SA. (2022, Apr 4). Cathelicidin Mediates an Anti-Inflammatory Role of Active Vitamin D (Calcitriol) During M. paratuberculosis Infection. Front Cell Infect Microbiol. 12: 875772. https://doi.org/10.3389/fcimb.2022.875772; PMid:35444957 PMCid:PMC9014016
Wang LQ, Yan XT, Yan CF, Zhang XW, Hui LY, Xue M, Yu XW. (2016). Women with recurrent miscarriage have reduced expression of 25-hydroxyvitamin D3-1alpha-hydroxylase due to fetal-maternal interactions. PLoS ONE. 11: e0165589. https://doi.org/10.1371/journal.pone.0165589; PMid:28033387 PMCid:PMC5199009
Wang S, Xin X, Luo W et al. (2021). Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth. Nutrition. 89: 111349. https://doi.org/10.1016/j.nut.2021.111349; PMid:34217944
Wilson RL, Buckberry S, Spronk F, Laurence JA, Leemaqz S, O'Leary S et al. (2015, Jun 29). Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome. PLoS One. 10(6): e0131287. https://doi.org/10.1371/journal.pone.0131287; PMid:26121239 PMCid:PMC4488298
Wilson RL, Phillips JA, Bianco-Miotto T, McAninch D, Goh Z et al. (2020, Jun). Reduced Dietary Calcium and Vitamin D Results in Preterm Birth and Altered Placental Morphogenesis in Mice During Pregnancy. Reprod Sci. 27(6): 1330-1339. https://doi.org/10.1007/s43032-019-00116-2; PMid:32046423
Woo J, Guffey T, Dailey R, Misra D, Giurgescu C. (2023, Nov 1). Vitamin D Status as an Important Predictor of Preterm Birth in a Cohort of Black Women. Nutrients. 15(21): 4637. https://doi.org/10.3390/nu15214637; PMid:37960290 PMCid:PMC10649077
Xu L, Yang T, Wen M, Wen D, Jin C, An M et al. (2024, Apr). Frontiers in the Etiology and Treatment of Preterm Premature Rupture of Membrane: From Molecular Mechanisms to Innovative Therapeutic Strategies. Reprod Sci. 31(4): 917-931. https://doi.org/10.1007/s43032-023-01411-9; PMid:37989803
Yan X, Wang L, Yan C, Zhang X, Hui L, Sheng Q et al. (2016). Decreased expression of vitamin D receptor in women with recurrent pregnancy loss. Ark. biochem. 606: 128-133. https://doi.org/10.1016/j.abb.2016.07.021; PMid:27477959
Yellon SM. (2017, Jan 1). Contributions to the dynamics of cervix remodeling prior to term and preterm birth. Biol Reprod. 96(1): 13-23. https://doi.org/10.1095/biolreprod.116.142844; PMid:28395330 PMCid:PMC5803764
Zhang B, Xiao W, Qin G, Chen Z, Qiu L, Wang X, Lin Q. (2023, Jul 31). Gene loss and co-option of toll-like receptors facilitate paternal immunological adaptation in the brood pouch of pregnant male seahorses. Front Immunol. 14: 1224698. https://doi.org/10.3389/fimmu.2023.1224698; PMid:37588592 PMCid:PMC10426278
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Ukrainian Journal Health of Woman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
