Vitamin D deficiency and its association with fetal growth restriction in pregnant women
DOI:
https://doi.org/10.15574/PP.2025.1(101).4551Keywords:
25(OH)D concentration, vitamin D deficiency, pregnancy, fetal growth restriction, placental dysfunctionAbstract
Vitamin D deficiency is common among pregnant women and is associated with an increased risk of obstetric complications, particularly fetal growth restriction (FGR). The main pathogenetic mechanism of FGR is impaired transplacental nutrient transport due to vascular dysfunction and decreased expression of vitamin D receptors (VDR).
Aim - to determine serum vitamin D levels in pregnant women and evaluate its role in the development of FGR.
Materials and methods. A total of 140 pregnant women were examined: 90 with vitamin D deficiency and FGR (main group), and 50 with optimal 25(OH)D levels and a physiological course of pregnancy (control group). Serum levels of 25(OH)D, parathyroid hormone (PTH), calcium, and phosphorus were assessed. VDR expression in the placenta was evaluated by immunohistochemistry. Placental blood flow was assessed using Doppler ultrasonography, and fetal status was evaluated by ultrasound. Statistical analysis was performed using MedStat v.5.2 and EZR v.3.4.1, with a significance level of p<0.05.
Results. The mean serum 25(OH)D level in the main group was 15.2±5.1 ng/mL, compared to 30.5±7.4 ng/mL in the control group. Elevated PTH levels (62.3±9.5 pg/mL), decreased calcium and phosphorus concentrations, and reduced placental VDR expression were observed in the main group. These changes were associated with impaired placental blood flow (increased pulsatility and resistance indices in the umbilical artery) and the development of FGR.
Conclusions. Vitamin D deficiency contributes to the development of FGR through disruption of calcium-phosphorus metabolism, downregulation of VDR expression, and placental vascular dysfunction. Timely assessment and correction of vitamin D levels in pregnancy are essential for the prevention of adverse perinatal outcomes.
The study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the local ethics committee of the participating institution. Informed consent was obtained from all participants.
The author declares no conflict of interest.
References
Abbasalizadeh S, Abam F, Mirghafourvand M, Abbasalizadeh F, Taghavi S, Hajizadeh K. (2020, Nov). Comparing levels of vitamin D, calcium and phosphorus in normotensive pregnant women and pregnant women with preeclampsia. J Obstet Gynaecol. 40(8): 1069-1073. https://doi.org/10.1080/01443615.2019.1678575; PMid:31814492
Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, Marazita ML, Simhan HN. (2010, May). Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr. 140(5):999-1006. Epub 2010 Mar 3. https://doi.org/10.3945/jn.109.119636; PMid:20200114 PMCid:PMC2855265
Chen YH, Liu ZB, Ma L, Zhang ZC, Fu L, Yu Z et al. (2020, Oct). Gestational vitamin D deficiency causes placental insufficiency and fetal intrauterine growth restriction partially through inducing placental inflammation. J Steroid Biochem Mol Biol. 203: 105733. Epub 2020 Aug 9. https://doi.org/10.1016/j.jsbmb.2020.105733; PMid:32784046
Dahma G, Neamtu R, Nitu R, Gluhovschi A, Bratosin F, Grigoras ML et al. (2022, Jul 22). The Influence of Maternal Vitamin D Supplementation in Pregnancies Associated with Preeclampsia: A Case-Control Study. Nutrients. 14(15): 3008. https://doi.org/10.3390/nu14153008; PMid:35893862 PMCid:PMC9330723
Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M et al. (2024, Jun 3). Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 109(8): 1907-1947. https://doi.org/10.1210/clinem/dgae290; PMid:38828931
Hu KL, Zhang CX, Chen P, Zhang D, Hunt S. (2022, Feb 27). Vitamin D Levels in Early and Middle Pregnancy and Preeclampsia, a Systematic Review and Meta-Analysis. Nutrients. 14(5): 999. https://doi.org/10.3390/nu14050999; PMid:35267975 PMCid:PMC8912474
Lorenzon F, Gregorio T, Niebisch F, Stolte RCK, Dos Santos GJ et al. (2021, Sep). Maternal vitamin D administration attenuates metabolic disturbances induced by prenatal exposure to dexamethasone in a sex-dependent manner. J Steroid Biochem Mol Biol. 212: 105941. Epub 2021 Jun 18. https://doi.org/10.1016/j.jsbmb.2021.105941; PMid:34147644
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
Mao D, Yuen LY, Ho CS, Wang CC, Tam CH, Chan MH et al. (2021). Maternal and Neonatal 3-epi-25-hydroxyvitamin D Concentration and Factors Influencing Their Concentrations. J Endocr Soc. 6(1): bvab170. https://doi.org/10.1210/jendso/bvab170; PMid:34909515 PMCid:PMC8664761
Mao D, Yuen LY, Ho CS, Wang CC, Tam CH, Chan MH et al. (2023). The Association of Prenatal Vitamin D Status With Pregnancy and Neonatal Outcomes. J Endocr Soc. 8(1): bvad142. https://doi.org/10.1210/jendso/bvad142; PMid:38075561 PMCid:PMC10701472
Nguyen TP, Yong HE, Chollangi T, Borg AJ, Brennecke SP, Murthi P. (2015, Jul). Placental vitamin D receptor expression is decreased in human idiopathic fetal growth restriction. J Mol Med (Berl).;93(7):795-805. Epub 2015 Feb 27. https://doi.org/10.1007/s00109-015-1267-1; PMid:25716068
Poladich IV, Govsieiev DO. (2024). Peculiarity of vitamin D status in pregnant women. Ukrainian Journal Health of Woman. 4(173): 46-51. https://doi.org/10.15574/HW.2024.4(173).4651
Raia-Barjat T, Sarkis C, Rancon F, Thibaudin L, Gris JC et al. (2021, Oct 20). Vitamin D deficiency during late pregnancy mediates placenta-associated complications. Sci Rep. 11(1): 20708. https://doi.org/10.1038/s41598-021-00250-5; PMid:34671075 PMCid:PMC8528848
Rouached M, El Kadiri Boutchich S, Al Rifai AM, Garabédian M, Fournier A. (2008, Aug). Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 74(3):389-90. https://doi.org/10.1038/ki.2008.169; PMid:18626497
Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW. (2021, Jul 2). Novel mineral regulatory pathways in ovine pregnancy: II. Calcium-binding proteins, calcium transporters, and vitamin D signaling. Biol Reprod. 105(1): 232-243. https://doi.org/10.1093/biolre/ioab063; PMid:33822885
Stenhouse C, Suva LJ, Gaddy D, Wu G, Bazer FW. (2022). Phosphate, Calcium, and Vitamin D: Key Regulators of Fetal and Placental Development in Mammals. Adv Exp Med Biol. 1354: 77-107. https://doi.org/10.1007/978-3-030-85686-1_5; PMid:34807438
Vivanti AJ, Monier I, Salakos E, Elie C, Tsatsaris V, Senat MV et al. (2020). Vitamin D and pregnancy outcomes: Overall results of the FEPED study. J Gynecol Obstet Hum Reprod. 49(8): 101883. https://doi.org/10.1016/j.jogoh.2020.101883; PMid:32730862
Wang J, Qiu F, Zhao Y, Gu S, Wang J, Zhang H. (2022, Oct). Exploration of fetal growth restriction induced by vitamin D deficiency in rats via Hippo-YAP signaling pathway. Placenta. 128: 91-99. Epub 2022 Sep 9. https://doi.org/10.1016/j.placenta.2022.08.062; PMid:36103800
Wei SQ, Qi HP, Luo ZC, Fraser WD. (2013, Jun). Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 26(9): 889-899. Epub 2013 Feb 11. https://doi.org/10.3109/14767058.2013.765849; PMid:23311886
Yang L, Ma J, Zhang X, Fan Y, Wang L. (2012, Oct). Protective role of the vitamin D receptor. Cell Immunol.;279(2):160-6. Epub 2012 Oct 29. https://doi.org/10.1016/j.cellimm.2012.10.002; PMid:23246677
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Ukrainian Journal of Perinatology and Pediatrics
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “Ukrainian Journal of Perinatology and Pediatrics” 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 “MODERN PEDIATRICS. UKRAINE” 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.
