妊娠晚期血清维生素D及血管内皮生长因子与子痫前期及胎儿生长受限的相关性分析

钟双飞; 沈娜; 黄满仙

doi:10.16766/j.cnki.issn.1674-4152.003336

妊娠晚期血清维生素D及血管内皮生长因子与子痫前期及胎儿生长受限的相关性分析

doi: 10.16766/j.cnki.issn.1674-4152.003336

1.
舟山市妇幼保健院妇女保健科，浙江舟山 316000
2.
舟山市妇幼保健院妇产科

基金项目:

浙江省医药卫生科技计划面上项目 2021KY383

详细信息

通讯作者:
沈娜，E-mail：lhst008@163.com

中图分类号: R714.246
计量
- 文章访问数: 197
- HTML全文浏览量: 71
- PDF下载量: 9
- 被引次数: 0
出版历程
- 收稿日期: 2023-03-30
- 网络出版日期: 2024-03-09

Correlation between serum vitamins and vascular endothelial growth factor in late pregnancy and pre-eclampsia and fetal growth restriction

1.
Department of Women's Health, Zhoushan Maternal and Child Health Hospital, Zhoushan, Zhejiang 316000, China

摘要

摘要: 目的探讨妊娠晚期血清维生素D及血管内皮生长因子(VEGF)与子痫前期及胎儿生长受限(FGR)的相关性，以期为诊治子痫前期和FGR提供依据。方法选择舟山市妇幼保健院2020年7月—2022年12月收治的妊娠晚期子痫前期孕妇124例为研究组，其中伴FGR 38例；另选择同期妊娠晚期正常孕妇54例为对照组。采用电化学免疫分析法测定2组孕妇血清25-羟维生素-D(25-OH-D)水平，酶联免疫吸附法测定血清VEGF水平。结果研究组血清25-OH-D[(73.42±6.71)nmol/L]和VEGF[(412.31±35.24)pg/mL]均低于对照组[(94.78±5.25)nmol/L、(536.21±26.23)pg/mL，P＜0.05]。FGR组血清25-OH-D[(69.20±5.96)nmol/L]和VEGF[(394.70±32.17)pg/mL]均低于无FGR组[(82.97±7.28)nmol/L、(452.17±27.49)pg/mL，P＜0.05]。25-OH-D和VEGF与子痫前期和FGR均呈负相关关系(P＜0.05)。25-OH-D预测子痫前期和FGR的灵敏度为83.30%和76.29%，特异度为77.43%和64.19%；VEGF预测子痫前期和FGR的灵敏度为80.13%和68.08%，特异度为68.92%和56.24%。25-OH-D和VEGF为子痫前期和FGR的独立影响因素。结论妊娠晚期子痫前期及FGR患者血清25-OH-D和VEGF水平下降，且与子痫前期及FGR的发生呈负相关关系。
- 妊娠晚期 /
- 子痫前期 /
- 25-羟维生素-D /
- 血管内皮生长因子 /
- 胎儿生长受限
Abstract: Objective To investigate the association between serum vitamin D and vascular endothelial growth factor (VEGF) levels in late pregnancy and pre-eclampsia and fetal growth restriction (FGR), to provide a basis for clinical diagnosis and management of pre-eclampsia and FGR. Methods The 124 patients with pre-eclampsia in the third trimester of pregnancy from July 2020 to December 2022 at Zhoushan Maternal and Child Health Hospital were selected as the study group, including 38 patients with FGR. In addition, 54 normal pregnant women in their third trimester of pregnancy from the same term as the control group. Serum 25-hydroxyvitamin D (25-OH-D) levels were measured by electrochemical immunoassay, and the serum VEGF levels were measured by enzyme-linked immunosorbent assay. Results Serum 25-OH-D [(73.42±6.71) nmol/L] and VEGF [(412.31±35.24) pg/mL] in the study group were lower than in the control group [(94.78±5.25) nmol/L, (536.21±26.23) pg/mL, P < 0.05]. Serum 25-OH-D [(69.20±5.96) nmol/L] and VEGF [(394.70±32.17) pg/mL] were lower in the FGR group than in the non-FGR group [(82.97±7.28) nmol/L, (452.17±27.49) pg/mL, P < 0.05]. Pearson analysis showed that 25-OH-D and VEGF were negatively correlated with pre-eclampsia and FGR (P < 0.05). In predicting pre-eclampsia and FGR, the sensitivity of 25-OH-D were 83.30% and 76.29%, and the specificity were 77.43% and 64.19%; VEGF had a sensitivity of 80.13% and 68.08%, and a specificity of 68.92% and 56.24%. 25-OH-D and VEGF were independent risk factors for pre-eclampsia and FGR. Conclusion The decrease in serum 25-OH-D and VEGF levels in patients with pre-eclampsia and FGR in the third trimester of pregnancy is negatively correlated with the occurrence of pre-eclampsia and FGR and is a risk factor for pre-eclampsia and FGR.
- Late pregnancy /
- Pre-eclampsia /
- 25-hydroxyvitamin D /
- Vascular endothelial growth factor /
- Fetal growth restriction

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图 1 ROC曲线分析25-OH-D和VEGF对子痫前期的预测价值

Figure 1. ROC curve analysis of the predictive value of 25-OH-D and VEGF for preeclampsia

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图 2 25-OH-D和VEGF对FGR预测价值的ROC曲线

Figure 2. ROC curve analysis of the predictive value of 25-OH-D and VEGF for FGR

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表 1 研究组与对照组孕妇血清25-OH-D和VEGF水平比较(x±s)

Table 1. Comparison of serum 25-OH-D and VEGF levels between the study group and the control group(x±s)

组别	例数	25-OH-D(nmol/L)	VEGF(pg/mL)
研究组	124	73.42±6.71	412.31±35.24
对照组	54	94.78±5.25	536.21±26.23
t值		20.775	23.177
P值		＜0.001	＜0.001

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表 2 FGR组与无FGR组子痫前期孕妇血清25-OH-D和VEGF水平比较(x±s)

Table 2. Comparison of serum 25-OH-D and VEGF levels between the pre eclampsia FGR group and the non FGR group(x±s)

组别	例数	25-OH-D(nmol/L)	VEGF(pg/mL)
FGR组	38	69.20±5.96	394.70±32.17
无FGR组	86	82.97±7.28	452.17±27.49
t值		11.236	10.177
P值		＜0.001	＜0.001

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表 3 25-OH-D和VEGF与子痫前期和FGR的相关性分析

Table 3. Correlation analysis of 25-OH-D and VEGF with preeclampsia and FGR

项目	子痫前期		FGR
项目	r值	P值	r值	P值
25-OH-D	-0.762	< 0.001	-0.624	< 0.001
VEGF	-0.698	< 0.001	-0.516	< 0.001

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表 4 25-OH-D和VEGF对子痫前期的预测价值分析

Table 4. ROC curve analysis of the predictive value of 25-OH-D and VEGF for preeclampsia

项目	AUC	95% CI	截断值	P值	灵敏度(%)	特异度(%)
25-OH-D	0.880	0.830~0.931	80.60 nmol/L	＜0.001	83.30	77.43
VEGF	0.842	0.779~0.906	475.22 pg/mL	＜0.001	80.13	68.92
25-OH-D联合VEGF	0.939	0.903~0.974		＜0.001	94.53^ab	89.91^ab
注：与25-OH-D比较，χ²值分别为3.982、4.864，^aP＜0.05；与VEGF比较，χ²值分别为4.659、7.965，^bP＜0.05。

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表 5 25-OH-D和VEGF对FGR的预测价值分析

Table 5. ROC curve analysis of the predictive value of 25-OH-D and VEGF for FGR

项目	AUC	95% CI	截断值	P值	灵敏度(%)	特异度(%)
25-OH-D	0.754	0.654~0.853	73.85 nmol/L	＜0.001	76.29	64.19
VEGF	0.665	0.562~0.768	416.50 pg/mL	0.004	68.08	56.24
25-OH-D联合VEGF	0.859	0.782~0.935		＜0.001	84.90^ab	86.80^ab
注：与25-OH-D比较，χ²值分别为4.413、7.476，^aP＜0.05；与VEGF比较，χ²值分别为5.871、9.628，^bP＜0.05。

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表 6 25-OH-D和VEGF与子痫前期关系的多因素logistic回归分析

Table 6. Multivariate logistic regression analysis of the relationship between 25-OH-D, VEGF and preeclampsia

变量	B	SE	Waldχ²	P值	OR值	95% CI
25-OH-D	1.498	0.517	8.395	0.004	4.473	1.624~12.321
VEGF	1.561	0.627	6.198	0.013	4.764	1.394~16.280

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表 7 25-OH-D和VEGF与FGR关系的多因素logistic回归分析

Table 7. Multivariate logistic regression analysis of the relationship between 25-OH-D, VEGF and FGRs

变量	B	SE	Waldχ²	P值	OR值	95% CI
25-OH-D	1.637	0.625	6.860	0.009	5.140	1.510~17.496
VEGF	1.546	0.621	6.198	0.013	4.693	1.389~15.850

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参考文献(20)

[1]	邹晓译, 杨宁, 蔡伟, 等. 妊娠前半期体重增加与妊娠期高血压疾病风险的前瞻性队列研究[J]. 中华心血管病杂志, 2022, 50(10): 987-992. doi: 10.3760/cma.j.cn112148-20220816-00632 ZOU X Y, YANG N, CAI W, et al. Association between weight gain during the first half of pregnancy and the risk of hypertension disorder of pregnancy: a prospective cohort study[J]. Chinese Journal of Cardiology, 2022, 50(10): 987-992. doi: 10.3760/cma.j.cn112148-20220816-00632
[2]	BARR L C, LIBLIK K, JOHRI A M, et al. Maternal cardiovascular function following a pregnancy complicated by preeclampsia[J]. Am J Perinatol, 2022, 39(10): 1055-1064. doi: 10.1055/s-0040-1721694
[3]	ZHOU W B, WANG H Y, YANG Y Q, et al. Trophoblast cell subtypes and dysfunction in the placenta of individuals with preeclampsia revealed by single cell RNA sequencing[J]. Mol Cells, 2022, 45(5): 317-328. doi: 10.14348/molcells.2021.0211
[4]	储华, 陆艳, 刘明松. 孕期子宫动脉超声参数动态分析与子痫前期风险的相关性研究[J]. 中华全科医学, 2022, 20(9): 1545-1547, 1582. doi: 10.16766/j.cnki.issn.1674-4152.002645 CHU H, LU Y, LIU M S. Study on the correlation between dynamic analysis of uterine artery ultrasound parameters during pregnancy and the risk of preeclampsia[J]. Chinese Journal of General Practice, 2022, 20(9): 1545-1547, 1582. doi: 10.16766/j.cnki.issn.1674-4152.002645
[5]	罗希, 赵锦秀, 田恬. 子痫前期患者血清sICAM-1、PAPP-A、VEGF表达及预测价值[J]. 中国计划生育学杂志, 2021, 29(4): 815-818. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202104045.htm LUO X, ZHAO J X, TIAN T. Expression and predictive value of serum sICAM-1, PAPP-A and VEGF levels in preeclampsia[J]. Chinese Journal of Family Planning, 2021, 29(4): 815-818. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202104045.htm
[6]	郑莉莉. 血清HMGB1、D25-(OH)-D和APN与妊娠期高血压关系[J]. 中国计划生育学杂志, 2021, 29(10): 2170-2172. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202110033.htm ZHENG L L. The relationship between serum HMGB1, D25- (OH) - D, and APN and gestational hypertension[J]. Chinese Journal of Family Planning, 2021, 29(10): 2170-2172. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202110033.htm
[7]	中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2015)[J]. 中华妇产科杂志, 2015, 50(10): 721-728. doi: 10.3760/cma.j.issn.0529-567x.2015.10.001 Gestational Hypertension Group, Obstetrics and Gynecology Branch, Chinese Medical Association. Guidelines for the Diagnosis and Treatment of Pregnancy Induced Hypertension (2015)[J]. Chinese Journal of Obstetrics and Gynecology, 2015, 50(10): 721-728. doi: 10.3760/cma.j.issn.0529-567x.2015.10.001
[8]	谢幸, 孔北华, 段涛. 妇产科学[M]. 9版. 北京: 人民卫生出版社, 2018: 135-137. XIE X, KONG B H, DUAN T. Obstetrics And Gynecology[M]. 9 edition. Beijing: People' s Health Publishing House, 2018: 135-137.
[9]	GU S Y, ZHOU C C, PEI J D, et al. Esomeprazole inhibits hypoxia/endothelial dysfunction-induced autophagy in preeclampsia[J]. Cell Tissue Res, 2022, 388(1): 181-194. doi: 10.1007/s00441-022-03587-z
[10]	UZUNOV A V, SECARA D C, MEHEDINTU C, et al. Preeclampsia and neonatal outcomes in adolescent and adult patients[J]. J Med Life, 2022, 15(12): 1488-1492. doi: 10.25122/jml-2022-0264
[11]	颜雪梅, 孔繁娟, 王爱华, 等. 2012—2019年妊娠期高血压疾病流行现状及妊娠结局分析[J]. 中国生育健康杂志, 2021, 32(3): 252-256. https://www.cnki.com.cn/Article/CJFDTOTAL-SYJK202103012.htm YAN X M, KONG F J, WANG A H, et al. Analysis of the Epidemic Status and Pregnancy Outcome of Hypertension during Pregnancy from 2012 to 2019[J]. Chinese Journal of Reproductive Health, 2021, 32(3): 252-256. https://www.cnki.com.cn/Article/CJFDTOTAL-SYJK202103012.htm
[12]	AMINI P, AMROVANI M, NASSAJ Z S, et al. Hypertension: potential player in cardiovascular disease incidence in preeclampsia[J]. Cardiovasc Toxicol, 2022, 22(5): 391-403. doi: 10.1007/s12012-022-09734-w
[13]	钱佳娇, 曹成石, 纪岩松. 超声监测胎儿脑脐血流诊断子痫前期孕妇发生胎儿生长受限价值[J]. 中国计划生育学杂志, 2022, 30(12): 2844-2847. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202212037.htm QIAN J J, CAO C S, JI Y S. Value of fetal middle cerebral artery and umbilical artery blood flow monitored by ultrasound for diagnosing the fetal growth restriction of pregnant women with preeclampsia[J]. Chinese Journal of Family Planning, 2022, 30(12): 2844-2847. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202212037.htm
[14]	黄杨, 孟琳, 吕慧, 等. 血清胎盘蛋白-13及甲胎蛋白对子痫前期发生胎儿宫内生长受限的预测价值[J]. 安徽医药, 2023, 27(2): 354-357. https://www.cnki.com.cn/Article/CJFDTOTAL-AHYY202302032.htm HUANG Y, MENG L, LYU H, et al. Predictive value of serum PP-13 and AFP for fetal intrauterine growth restriction in patients with preeclampsia[J]. Anhui Medical and Pharmaceutical Journal, 2023, 27(2): 354-357. https://www.cnki.com.cn/Article/CJFDTOTAL-AHYY202302032.htm
[15]	刘庆, 李蓓, 周雪飞. 子痫前期孕妇血清VEGF、CRP、STOX1、sFlt-1水平变化及妊娠结局分析[J]. 海南医学, 2021, 32(11): 1418-1421. doi: 10.3969/j.issn.1003-6350.2021.11.016 LIU Q, LI B, ZHOU X F. Changes of serum VEGF, CRP, STOX1, sFlt-1 levels in pregnant women with preeclampsia and analysis of pregnancy outcome[J]. Hainan Medical Journal, 2021, 32(11): 1418-1421. doi: 10.3969/j.issn.1003-6350.2021.11.016
[16]	胡凤丽. 子痫前期孕妇动脉弹性与氧化应激损伤、血管内皮功能的相关性[J]. 中国计划生育学杂志, 2021, 29(6): 1282-1285. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202106049.htm HU F L. Correlation between arterial elasticity of pregnant women with preeclampsia and their oxidative stress injury and vascular endothelial function[J]. Chinese Journal of Family Planning, 2021, 29(6): 1282-1285. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202106049.htm
[17]	李庆华, 肖凌艺, 曹庆瑛. Salusin-α、VEGF、sFlt-1水平与妊娠期高血压疾病患者围产结局相关性分析[J]. 河北医药, 2022, 44(6): 852-855. https://www.cnki.com.cn/Article/CJFDTOTAL-HBYZ202206011.htm LI Q H, XIAO L Y, CAO Q Y. Correlation analysis of salusin-α, VEGF, sFlt-1 levels and perinatal outcome of patients with hypertension in pregnancy[J]. Hebei Med J, 2022, 44(6): 852-855. https://www.cnki.com.cn/Article/CJFDTOTAL-HBYZ202206011.htm
[18]	李力, 郭祥翠, 陈贝贝, 等. VEGF与VEGFR1通路相关基因的多态性与子痫前期的相关性分析[J]. 中华医学遗传学杂志, 2022, 39(8): 893-897. LI L, GUO X C, CHEN B B, et al. Association of polymorphisms of VEGF and VEGFR1 pathways-related genes and risk of pre-eclampsia[J]. Chinese Journal of Medical Genetics, 2022, 39(8): 893-897.
[19]	聂文静, 寇应琳. 血清25-(OH)-D、D-D表达水平与妊娠期高血压疾病的相关性[J]. 医药论坛杂志, 2021, 42(4): 94-96, 100. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202104025.htm NIE W J, KOU Y L. The correlation between serum 25-(OH) -D, D-D expression levels and gestational hypertension[J]. Journal of Medical Forum, 2021, 42(4): 94-96, 100. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202104025.htm
[20]	高颖, 林胜兰. 血清钙离子、D-二聚体和25-羟基维生素D与妊娠期高血压疾病的相关性分析[J]. 中国妇幼保健, 2018, 33(3): 533-535. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB201803018.htm GAO Y, LIN S L. Correlation analysis of serum calcium ions, D-dimer, and 25-hydroxyvitamin D with gestational hypertension[J]. Chin Matern Child Health Care, 2018, 33(3): 533-535. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB201803018.htm