Can first trimester vitamin D levels predict adverse maternal outcomes in patients who do not take vitamin D supplements?

Year 2024, Volume: 10 Issue: 5, 474 - 481, 04.09.2024

Burcu Dinçgez , Gülten Özgen , Levent Özgen

https://doi.org/10.18621/eurj.1509016

Abstract

Objectives: Vitamin D deficiency is claimed to be associated with adverse perinatal outcomes. Here, we aimed to compare adverse maternal outcomes according to vitamin D levels and determine the predictive role of first-trimester vitamin D for adverse maternal outcomes in patients not receiving vitamin D supplementation.

Methods: This study was designed as a retrospective study. A total of 232 patients were divided into three groups: vitamin D deficient (n=127), vitamin D insufficient (n=57), and vitamin D sufficient group (n=48). Then, the vitamin D deficiency group was divided into severe (n=72) and mild (n=55) vitamin D deficiency. Sociodemographic characteristics, first-trimester vitamin D levels, and adverse maternal outcomes such as gestational diabetes mellitus, preeclampsia, preterm birth, and intrauterine growth restriction were compared between the groups. The predictive role of first-trimester vitamin D levels for adverse maternal outcomes was evaluated by ROC analysis.

Results: Gestational diabetes was more common in the vitamin D deficient group than in the vitamin D insufficient group (P=0.024). However, preeclampsia, preterm delivery, and composite adverse outcomes were more common in the vitamin D deficient group than in the vitamin D sufficient group (P=0.044, P=0.008, and P=0.023, respectively). There was no difference in maternal outcomes between the mild and severe vitamin D deficiency groups. First-trimester vitamin D levels ≤19 ng/mL predicted adverse outcomes with 73.2% sensitivity and 49.2% specificity (AUC=0.630, P=0.006).

Conclusions: We recommend screening vitamin D levels in the first trimester, especially in high-risk groups, due to the increased incidence of adverse outcomes. We believe that more research is needed to clarify the relationship between vitamin D and adverse outcomes and the effect of supplementation on these outcomes.

Keywords

First trimester, maternal outcomes, supplementary nutrients, vitamin D

Ethical Statement

University of Health Sciences, Bursa Yuksek Ihtisas Training and Research Hospital, local ethics committee (2024-TBEK 2024/06-10).

References

• 1. Tahsin T, Khanam R, Chowdhury NH, et al. Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study. BMC Pregnancy Childbirth. 2023;23(1):322. doi: 10.1186/s12884-023-05636-z.
• 2. Lee SB, Jung SH, Lee H, et al. Maternal vitamin D deficiency in early pregnancy and perinatal and long-term outcomes. Heliyon. 2023;22;9(9):e19367. doi: 10.1016/j.heliyon.2023.e19367.
• 3. Díaz L, Noyola-Martínez N, Barrera D, et al. Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts. J Reprod Immunol. 2009;81(1):17-24. doi: 10.1016/j.jri.2009.02.005.
• 4. Grundmann M, von Versen-Höynck F. Vitamin D - roles in women's reproductive health? Reprod Biol Endocrinol. 2011;2(9):146. doi: 10.1186/1477-7827-9-146.
• 5. Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on pregnancy and the placenta. Placenta. 2010;31(12):1027-1034. doi: 10.1016/j.placenta.2010.08.015.
• 6. Wei SQ, Qi HP, Luo ZC, Fraser WD. Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2013;26(9):889-99. doi: 10.3109/14767058.2013.765849.
• 7. Shand AW, Nassar N, Von Dadelszen P, Innis SM, Green TJ. Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for pre-eclampsia. BJOG. 2010;117(13):1593-1598. doi: 10.1111/j.1471-0528.2010.02742.x.
• 8. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500-1503. doi: 10.1016/S0140-6736(01)06580-1.
• 9. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007;85(3):788-795. doi: 10.1093/ajcn/85.3.788.
• 10. Zhang H, Wang S, Tuo L, et al. Relationship between Maternal Vitamin D Levels and Adverse Outcomes. Nutrients. 2022;14(20):4230. doi: 10.3390/nu14204230.
• 11. Saraf R, Morton SM, Camargo CA Jr, Grant CC. Global summary of maternal and newborn vitamin D status - a systematic review. Matern Child Nutr. 2016;12(4):647-668. doi: 10.1111/mcn.12210.
• 12. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 30. Clinical management guidelines for obstetrician-gynecologists. Gestational Diabetes. Washington DC: ACOG; 2001.
• 13. Ni M, Zhang Q, Zhao J, et al. Relationship between maternal vitamin D status in the first trimester of pregnancy and maternal and neonatal outcomes: a retrospective single center study. BMC Pediatr. 2021;21(1):330. doi: 10.1186/s12887-021-02730-z.
• 14. Kingdom J, Ashwal E, Lausman A, et al. Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies. J ObstetGynaecol Can. 2023;45(10):102154. doi: 10.1016/j.jogc.2023.05.022.
• 15. Abd Aziz NH, Yazid NA, Abd Rahman R, et al. Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women. Int J Environ Res Public Health. 2020;8:17(9):3291. doi: 10.3390/ijerph17093291.
• 16. Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR. 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension. 2011;57(1):63-69. doi: 10.1161/HYPERTENSIONAHA.110.160929.
• 17. Tarcin O, Yavuz DG, OzbenB, et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab. 2009;94(10):4023-4030. doi: 10.1210/jc.2008-1212.
• 18. Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and placental-decidual function. J Soc GynecolInvestig. 2004;11(5):263-271. doi: 10.1016/j.jsgi.2004.02.002.
• 19. Magnus P, Eskild A. Seasonal variation in the occurrence of pre-eclampsia. BJOG. 2001;108(11):1116-1119. doi: 10.1111/j.1471-0528.2003.00273.x.
• 20. Bodnar LM, Catov JM, Roberts JM. Racial/ethnic differences in the monthly variation of preeclampsia incidence. Am J Obstet Gynecol. 2007;196(4):324.e1-5. doi: 10.1016/j.ajog.2006.11.028.
• 21. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007;92(9):3517-3522. doi: 10.1210/jc.2007-0718.
• 22. Haugen M, Brantsaeter AL, Trogstad L, et al.Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009;20(5):720-726. doi: 10.1097/EDE.0b013e3181a70f08.
• 23. Al-Shaikh GK, Ibrahim GH, Fayed AA, Al-Mandeel H. Impact of vitamin D deficiency on maternal and birth outcomes in the Saudi population: a cross-sectional study. BMC Pregnancy Childbirth. 2016;16:119. doi: 10.1186/s12884-016-0901-4.
• 24. Vaidya A, Williams JS. Vitamin D and insulin sensitivity: can gene association and pharmacogenetic studies of the vitamin D receptor provide clarity? Metabolism. 2012;61(6):759-761. doi: 10.1016/j.metabol.2011.12.009.
• 25. Eggemoen ÅR, Waage CW, Sletner L, Gulseth HL, Birkeland KI, Jenum AK. Vitamin D, Gestational Diabetes, and Measures of Glucose Metabolism in a Population-Based Multiethnic Cohort. J Diabetes Res. 2018;2018:8939235. doi: 10.1155/2018/8939235.
• 26. Lu M, Xu Y, Lv L, Zhang M. Association between vitamin D status and the risk of gestational diabetes mellitus: a meta-analysis. Arch Gynecol Obstet. 2016;293(5):959-966. doi: 10.1007/s00404-016-4010-4.
• 27. Wu C, Song Y, Wang X. Vitamin D Supplementation for the Outcomes of Patients with Gestational Diabetes Mellitus and Neonates: A Meta-Analysis and Systematic Review. Int J Clin Pract. 2023;2023:1907222. doi: 10.1155/2023/1907222.
• 28. Wang M, Chen Z, Hu Y, et al. The effects of vitamin D supplementation on glycemic control and maternal-neonatal outcomes in women with established gestational diabetes mellitus: A systematic review and meta-analysis. Clin Nutr. 2021;40(5):3148-3157. doi: 10.1016/j.clnu.2020.12.016.
• 29. Liu N, Kaplan AT, Low J, et al. Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway. Biol Reprod. 2009;80(3):398-406. doi: 10.1095/biolreprod.108.073577.
• 30. De-Regil LM, Palacios C, Lombardo LK, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2016;(1):CD008873. doi: 10.1002/14651858.CD008873.pub3.
• 31. Bodnar LM, Platt RW, Simhan HN. Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes. Obstet Gynecol. 2015;125(2):439-447. doi: 10.1097/AOG.0000000000000621.
• 32. Perez-Ferre N, Torrejon MJ, Fuentes M, et al. Association of low serum 25-hydroxyvitamin D levels in pregnancy with glucose homeostasis and obstetric and newborn outcomes. Endocr Pract. 2012;18(5):676-684. doi: 10.4158/EP12025.OR.
• 33. Chien MC, Huang CY, Wang JH, Shih CL, Wu P. Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses. Nutr Diabetes. 2024;14(1):35. doi: 10.1038/s41387-024-00296-0.
• 34. Monier I, Baptiste A, Tsatsaris V, et al. First Trimester Maternal Vitamin D Status and Risks of Preterm Birth and Small-For-Gestational Age. Nutrients. 2019;11(12):3042. doi: 10.3390/nu11123042.
• 35. Flood-Nichols SK, Tinnemore D, Huang RR, Napolitano PG, Ippolito DL. Vitamin D deficiency in early pregnancy. PLoS One. 2015;10(4):e0123763. doi:10.1371/journal.pone.0123763.
• 36. Baker AM, Haeri S, Camargo CA Jr, Stuebe AM, Boggess KA. A nested case-control study of first-trimester maternal vitamin D status and risk for spontaneous preterm birth. Am J Perinatol. 2011;28(9):667-672. doi: 10.1055/s-0031-1276731.
• 37. Fernández-Alonso AM, Dionis-Sánchez EC, Chedraui P, González-Salmerón MD, Pérez-López FR. Spanish Vitamin D and Women's Health Research Group. First-trimester maternal serum 25-hydroxyvitamin D₃ status and pregnancy outcome. Int J Gynaecol Obstet. 2012;116(1):6-9. doi: 10.1016/j.ijgo.2011.07.029.
• 38. Rodriguez A, García-Esteban R, Basterretxea M, et al. Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes. BJOG. 2015;122(12):1695-1704. doi: 10.1111/1471-0528.13074.
• 39. Wang S, Xin X, Luo W, et al. Association of vitamin D and gene variants in the vitamin D metabolic pathway with preterm birth. Nutrition. 2021;89:111349. doi: 10.1016/j.nut.2021.111349.