Objective  This study aims to evaluate the effect of vitamin D supplementation in the earliest stages of pregnancy (12-16 weeks) on the development of preeclampsia (PE) in primiparous women.

Methods  Primiparous women who visited Maternal and Child Care Center of Qinhuangdao from January 1, 2019 to January 31, 2022 were recruited as study subjects. According to the random number table method, primiparous women were randomly divided into the control group (calcium carbonate D3 tablets) and the experimental group (calcium carbonate D3 tablets+vitamin D). The main observed outcome of the study was the incidence of preeclampsia. Preterm birth, neonatal birth weight, neonatal height at birth, mode of delivery, and neonatal Apgar scores were the secondary observed outcomes. A Logistic regression was used to explore the relationship between vitamin D supplementation and study outcomes. In addition, serum 25 hydroxyvitamin D was measured by ELISA before and after the intervention.

Results  A total of 586 primiparas were recruited, 70 were lost, and 516 were included (264 in the control group and 252 in the experimental group). The incidences of PE, preterm birth, cesarean birth, and birth weight in the experimental group were significantly lower than those of the control group (P<0.05). After the end of the intervention, the serum level of 25 hydroxyvitamin D had increased significantly in both groups (P<0.05), while there was no significant change in calcium ions (P>0.05). Furthermore, serum 25 hydroxyvitamin D levels were significantly higher in the experimental group than in the control group (P<0.05). In addition, the birth length, 1-minute Apgar, 5-minute Apgar and 10-minute Apgar scores of the experimental group were all higher than the control group (P<0.05). Multivariate Logistic analysis showed that vitamin D supplementation was the independent protective factor for PE [OR=0.336, 95%CI (0.120, 0.939), P=0.037], cesarean section[OR=0.539, 95%CI (0.364, 0.798), P=0.002], misoprostol-induced delivery[OR=0.066, 95%CI (0.009, 0.504), P=0.009], preterm birth [OR=0.487, 95%CI (0.238, 0.995), P=0.048] and low birth weight [OR=0.391, 95%CI (0.189, 0.806, P=0.011].

Conclusion  Vitamin D supplementation reduces the incidence of PE and reduces the incidence of adverse pregnancy and fetal outcomes.

1.Abalos E, Cuesta C, Grosso AL, et al. Global and regional estimates of preeclampsia and eclampsia: a systematic review[J]. Eur J Obstet Gynecol Reprod Biol, 2013, 170(1): 1-7. DOI: 10.1016/j. ejogrb.2013.05.005.

2.李可, 朱大伟, 陈建昆, 等. 子痫前期发病机制与临床治疗研究进展[J]. 解放军医学杂志, 2019, 44(5): 423-429. [Li K, Zhu DW, Chen JK, et al. Progress in the pathogenesis and clinical treatment of pre-eclampsia[J]. Journal of PLA Medical Science, 2019, 44(5): 423-429.]DOI: 10.11855/j.issn.0577-7402.2019.05.11.

3.许燕滨. miR-17-5p调控MCL-1与子痫前期的相关性研究[D]. 广州: 南方医科大学, 2018.

4.姚玲飞, 盛晶莹, 廖瑜. 拉贝洛尔对妊娠期重度高血压疾病患者心肾功能及血清炎症细胞因子水平的影响[J]. 中国妇幼保健, 2023, 38(21): 4119-4122. [Yao LF, Sheng JY, Liao Y. The effect of labetalol on cardiac and renal function and serum inflammatory cytokine levels in patients with severe hypertensive disorder complicating pregnancy[J]. Chinese Journal of Maternal and Child Health Care, 2023, 38(21): 4119-4122.] DOI: 10.19829/j. zgfybj. issn.1001-4411.2023.21.013.

5.Duley L. Pre-eclampsia and the hypertensive disorders of pregnancy[J]. Br Med Bull, 2003, 67(1): 161-176. DOI: 10.1093/bmb/ldg005.

6.O'Callaghan KM, Kiely M. Systematic review of vitamin D and hyperten-sive disorders of pregnancy[J]. Nutrients, 2018, 10(3): 294. DOI: 10.3390/nu10030294.

7.Vata PK, Chauhan NM, Nallathambi A, et al. Assessment of prevalence of preeclampsia from Dilla region of Ethiopia[J]. BMC Res Notes, 2015, 8: 816. DOI: 10.1186/s13104-015-1821-5.

8.高宇蝶, 李瑞满. 子痫前期预防与治疗的研究进展[J]. 中国计划生育学杂志, 2023, 31(10): 2515-2520. [Gao YD, Li RM. Progress in prevention and treatment of pre-eclampsia[J]. Chinese Journal of Family Planning, 2023, 31(10): 2515-2520.] DOI: 10.3969/j.issn.1004-8189. 2023.10.053.

9.宁蓓蓓, 邓丽君, 马惠静, 等. 二甲双胍防治子痫前期的研究进展[J]. 现代药物与临床, 2022, 37(12): 2902-2905. [Ning BB, Deng LJ, Ma HJ, et al. Progress in metformin in the prevention and treatment of pre-eclampsia[J]. Modern Drugs and Clinics, 2022, 37(12): 2902-2905.] DOI: 10.7501/j.issn.1674-5515.2022.12.042.

10.Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin[J]. Am J Obstet Gynecol, 2022, 226(2S): S1108-S1119. DOI: 10.1016/j.ajog.2020.08.045.

11.Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units[J]. N Engl J Med, 1993, 329(17): 1213-1218. DOI: 10.1056/NEJM199310213291701.

12.Duley L, Meher S, Hunter KE, et al. Antiplatelet agents for preventing pre-eclampsia and its complications[J]. Cochrane Database Syst Rev, 2019, 2019(10): CD004659. DOI: 10.1002/14651858.CD004659.

13.Hastie R, Tong S, Wikström AK, et al. Aspirin use during pregnancy and the risk of bleeding complications: a Swedish population-based cohort study[J]. Am J Obstet Gynecol, 2021, 224(1): 95, e1-95, e12. DOI: 10.1016/j.ajog.2020.07.023.

14.刘晓兰, 张玉霞, 丁桂凤. 子痫前期孕妇维生素D及血脂等实验室指标水平与妊娠结局分析[J]. 重庆医学, 2024, 53(4): 493-497.[Liu XL, Zhang YX, Ding GF. Analysis of the laboratory indicators of vitamin D and blood lipids in pregnant women with pre-eclampsia and their pregnancy outcomes[J]. Chongqing Medical Journal, 2024, 53(4): 493-497.] DOI: 10.3969/j.issn.1671-8348. 2024.04.003.

15.刘然, 翟燕红. 维生素D缺乏与不良妊娠结局的相关性研究[J]. 标记免疫分析与临床, 2022, 29(9): 1603-1606. [Liu R, Zhai YH. Research on the correlation between vitamin D deficiency and adverse pregnancy outcomes[J]. Marker Immunoassay and Clinical, 2022, 29(9): 1603-1606.] DOI: 10.11748/bjmy.issn.1006-1703.2022.09.036.

16.Haugen M, Brantsæter AL, Trogstad L, et al. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women[J]. Epidemiology, 2009, 20(5): 720-726. DOI: 10.1097/EDE.0b013e3181a70f08.

17.Kabuyanga RK, Tugirimana PL, Sifa B, et al. Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women: a randomised clinical trial in Eastern Democratic Republic of the Congo[J]. BMC Pregnancy Childbirth, 2024, 24(1): 107. DOI: 10.1186/s12884-024-06277-6.

18.Hollis BW, Johnson D, Hulsey TC, et al. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and efectiveness[J]. J Bone Miner Res, 2011, 26(10): 2341-2357. DOI: 10.1002/jbmr.463.

19.谢幸, 孔北华, 段涛, 主编. 妇产科学. 第9版[M]. 北京: 人民卫生出版社, 2018: 83.

20.Sasan SB, Zandvakili F, Soufizadeh N, et al. The effects of vitamin D supplement on prevention of recurrence of preeclampsia in pregnant women with a history of preeclampsia[J]. Obstet Gynecol Int, 2017, 2017: 8249264. DOI: 10.1155/2017/8249264.

21.Fogacci S, Fogacci F, Banach M, et al. Vitamin D supplementation and incident preeclampsia: a systematic review and meta-analysis of randomized clinical trials[J].Clin Nutr, 2020, 39(6): 1742-1752. DOI: 10.1016/j.clnu.2019.08.015.

22.Naghshineh E, Sheikhaliyan S. Effect of vitamin D supplementation in the reduce risk of preeclampsia in nulliparous women[J]. Adv Biomed Res, 2016, 5: 7. DOI: 10.4103/2277-9175.175239.

23.Nausheen S, Habib A, Bhura M, et al. Impact evaluation of the efficacy of different doses of vitamin D supplementation during pregnancy on pregnancy and birth outcomes: a randomised, controlled, dose comparison trial in Pakistan[J]. BMJ Nutr Prev Health, 2021, 4(2): 425-434. DOI: 10.1136/bmjnph-2021-000304.

24.Sablok A, Batra A, Thariani K, et al. Supplementation of vitamin D in pregnancy and its correlation with feto-maternal outcome[J]. Clin Endocrinol (Oxf), 2015, 83(4): 536-541. DOI: 10.1111/cen.12751.

25.Uwitonze AM, Uwambaye P, Isyagi M, et al. Periodontal diseases and adverse pregnancy outcomes: is there a role for vitamin D?[J]. J Steroid Biochem Mol Biol, 2018, 180: 65-72. DOI: 10.1016/j.jsbmb.2018.01.010.

26.Karamali M, Beihaghi E, Mohammadi A, et al. Effects of high-dose vitamin d supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia[J]. Horm Metab Res, 2015, 47(12): 867-872. DOI: 10.1055/s-0035-1548835.