慢性HBV感染孕妇发生妊娠期糖尿病的危险因素及其对母婴结局的影响

李璐; 邹怀宾; 徐曼曼; 陈煜

doi:10.3969/j.issn.1001-5256.2021.10.009

慢性HBV感染孕妇发生妊娠期糖尿病的危险因素及其对母婴结局的影响

DOI: 10.3969/j.issn.1001-5256.2021.10.009

李璐^{1, 2},
邹怀宾^{1, 2},
徐曼曼^{1, 2},
陈煜^{1, 2, ,}

1.
首都医科大学附属北京佑安医院肝病中心四科，北京 100069
2.
肝衰竭与人工肝治疗研究北京市重点实验室，北京 100069

基金项目:

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10203201-005);

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10201201-001-001);

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10201201-002-002);

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10201201-002-009);

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10201201-004-002)

详细信息

通信作者:
陈煜，chybeyond1071@ccmu.edu.cn

中图分类号: R512.62
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出版历程
- 收稿日期: 2021-02-20
- 录用日期: 2021-04-09
- 出版日期: 2021-10-20

Risk factors for gestational diabetes mellitus in pregnant women with chronic HBV infection and its influence on maternal and fetal outcomes

Lu LI^{1, 2},
Huaibin ZOU^{1, 2},
Manman XU^{1, 2},
Yu CHEN^{1, 2
, ,}

1.
Fourth Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
2.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069, China

Research funding:

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10203201-005);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201-001-001);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201-002-002);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201-002-009);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201-004-002)

摘要

摘要: 目的探讨慢性HBV感染的孕妇出现妊娠期糖尿病(GDM)的相关因素、妊娠结局及其对所分娩新生儿的影响。方法回顾性纳入2017年1月—2017年12月于首都医科大学附属北京佑安医院就诊、分娩及产后随诊的317例慢性HBV感染的孕妇。根据是否合并GDM分为慢性HBV感染合并GDM组及慢性HBV感染对照组。记录入组孕妇的HBV血清学标志物、肝功能、HBV DNA定量、妊娠合并症、分娩方式及新生儿出生时情况。满足正态分布的计量资料的2组间比较采用t检验或t′检验，不满足正态分布的计量资料的2组间比较采用Mann-Whitney U检验；计数资料2组间比较采用χ²检验或Fisher精确法检验；采用二元logistic多因素回归分析慢性HBV感染的母亲出现GDM的危险因素。结果 317例母亲中慢性HBV感染合并GDM共64例，占整体人数20.19%，对照组为253例，占整体人数79.81%。慢性HBV感染合GDM组的孕妇在年龄(Z=-2.652)、基线ALT(Z=-4.393)、基线AST(Z=-2.457)及HBV DNA定量方面高于对照组(P值均＜0.05)。logistic回归分析显示，HBV DNA定量[OR(95%CI)=23.40(7.10~77.14)，P＜0.001]及高龄[OR(95%CI)=1.10(1.02~1.17)，P=0.01]是慢性HBV感染孕妇发生GDM的独立危险因素。慢性HBV感染合并GDM的孕妇在分娩时更容易出现胎膜早破(χ²=4.514，P=0.034)；所分娩的新生儿更容易出现早产(χ²=9.293，P=0.002)及胎儿宫内窘迫(P=0.018)。结论 HBV DNA定量及高龄是慢性HBV感染母亲发生GDM的危险因素。慢性HBV感染的孕妇合并GDM增加了胎膜早破、胎儿宫内窘迫及早产的发生率。
- 乙型肝炎病毒 /
- 糖尿病, 妊娠 /
- 孕妇
Abstract: Objective To investigate the factors for gestational diabetes mellitus (GDM) in pregnant women with chronic hepatitis B virus (HBV) infection, their pregnancy outcome, and related influence on neonates. Methods A retrospective analysis was performed for 317 pregnant women with chronic HBV infection who were treated, gave birth, and were followed up in Beijing YouAn Hospital, Capital Medical University, from January to December 2017, and according to the presence or absence of GDM, they were divided into chronic HBV+GDM group and chronic HBV control group. Related data were recorded, including HBV serology, liver function, HBV DNA quantification, pregnancy comorbidities, mode of delivery, and the condition of neonates at birth. The t-test or t′-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups; a binary logistic regression analysis was used to investigate the risk factors for GDM in mothers with chronic HBV infection. Results Among the 317 mothers, 64 (20.19%) had chronic HBV infection and GDM, and there were 253 mothers (79.81%) in the control group. Compared with the control group, the chronic HBV+GDM group had significantly higher age (Z=-2.652, P < 0.05), baseline alanine aminotransferase (Z=-4.393, P < 0.05), baseline aspartate aminotransferase (Z=-2.457, P < 0.05), and HBV DNA quantification (P < 0.05). The logistic regression analysis showed that HBV DNA quantification (odds ratio [OR]=23.40, 95% confidence interval [CI]: 7.10-77.14, P < 0.001) and old age (OR=10.10, 95% CI: 1.02-1.17, P=0.01) were independent risk factors for GDM in pregnant women with chronic HBV infection. The pregnant women with chronic HBV infection and GDM were more likely to experience premature rupture of membranes during delivery (χ²=4.514, P=0.034), and the neonates born to these women were more likely to experience preterm birth (χ²=9.293, P=0.002) and fetal intrauterine distress (P=0.018). Conclusion HBV DNA quantification and old age are risk factors for GDM in mothers with chronic HBV infection, and GDM in pregnant women with chronic HBV infection may increase the incidence rate of premature rupture of membranes, fetal intrauterine distress, and premature delivery.
- Hepatitis B Virus /
- Diabetes, Gestational /
- Pregnant Women

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表 1 2组患者的临床特征比较

指标	HBV感染合并GDM组 (n=64)	HBV感染对照组 (n=253)	统计值	P值
年龄(岁)	30(27~33)	28(26~31)	Z=-2.652	0.008
ALT(U/L)	18.15(14.63~31.75)	14.10(11.00~20.45)	Z=-4.393	＜0.001
AST(U/L)	21.80(17.75~33.90)	19.70(16.75~25.20)	Z=-2.457	0.014
TBil(μmol/L)	7.55(6.10~9.48)	8.20(6.55~10.70)	Z=-1.881	0.060
Alb(g/L)	36.30(34.55~37.28)	36.10(34.40~37.65)	Z=-0.013	0.990
CHO(mmol/L)	5.75(5.00~6.40)	5.90(5.10~6.70)	Z=-0.774	0.439
HBV DNA[例(%)]				＜0.001
＜2 log₁₀IU/mL	3(4.7)	131(51.8)
2~6 log₁₀IU/mL	26(40.6)	5(2.0)
＞6 log₁₀IU/mL	35(54.7)	117(46.2)
HBeAg[例(%)]			χ²=2.230	0.135
阴性	29(45.3)	141(55.7)
阳性	35(54.7)	112(44.3)
合并妊娠期高血压[例(%)]	1(1.6)	3(1.2)		0.814
合并妊娠肝内胆汁淤积症[例(%)]	3(4.7)	4(1.6)		0.169

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表 2 慢性HBV感染孕妇于分娩前出现GDM的单因素及多因素分析

参数	单因素分析结果		多因素分析结果
参数	OR(95%CI)	P值	OR(95%CI)	P值
年龄(岁)	1.08(1.01~1.15)	0.03	1.10(1.02~1.17)	0.01
ALT(U/L)	1.01(1.00~1.01)	0.05
AST(U/L)	1.01(1.00~1.02)	0.04
HBV DNA (可被检测到)	21.83(6.68~71.42)	＜0.001	23.40(7.10~77.14)	＜0.001

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表 3 慢性HBV感染母亲合并GDM对母亲分娩时的影响

母婴结局	HBV感染合并GDM组 (n=64)	HBV感染对照组 (n=253)	χ²值	P值
先兆流产[例(%)]	1(1.6)	3(1.2)		0.814
先兆早产[例(%)]	0	4(1.6)		0.178
胎膜早破[例(%)]	5(7.8)	6(2.4)	4.514	0.034
羊水浑浊[例(%)]	8(12.5)	42(16.6)	1.224	0.693
剖宫产[例(%)]	37(57.8)	112(44.3)	3.761	0.052

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表 4 慢性HBV感染母亲合并GDM对新生儿出生时的影响

新生儿结局	HBV感染合并GDM组 (n=64)	HBV感染对照组 (n=253)	χ²值	P值
性别[例(%)]			0.570	0.450
男	35(54.7)	125(49.4)
女	29(45.3)	128(50.6)
早产[例(%)]	8(12.5)	8(3.2)	9.293	0.002
胎儿窘迫[例(%)]	5(7.9)	0		0.018
新生儿窒息[例(%)]	0	3(1.2)		1.000
胎儿发育异常[例(%)]	8(12.5)	17(6.7)	3.012	0.234

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参考文献(18)

[1]	YI N, JIANG XJ, LIANG DZ, et al. Effection of hepatitis B virus infection on pregant woman with gestational diabetes mellitus and their newborn[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2015, 9(2): 93-96. DOI: 10.3877/cma.j.issn.1674-1358.2015.02.024. 伊诺, 姜秀娟, 梁东竹, 等. 乙型肝炎病毒感染对妊娠期糖尿病孕妇及新生儿的影响[J/CD]. 中华实验和临床感染病杂志(电子版), 2015, 9(2): 93-96. DOI: 10.3877/cma.j.issn.1674-1358.2015.02.024.
[2]	YI N, LIU M, LI ZH, et al. Status survey of gestational diabetes mellitus morbidity of woman with HBV infection in Beijing, 2009-2012[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2015, 9(1): 42-45. DOI: 10.3877/cma.j.issn.1674-1358.2015.01.011. 伊诺, 刘敏, 李振华, 等. 2009至2012年北京地区HBV感染妇女妊娠期糖尿病发病现状调查[J/CD]. 中华实验和临床感染病杂志(电子版), 2015, 9(1): 42-45. DOI: 10.3877/cma.j.issn.1674-1358.2015.01.011.
[3]	WANG DJ. Analysis of blood index and pregnancy outcome of pregnant women with gestational diabetes mellitus[J]. Diabetes New World, 2020, 23(15): 54-56. DOI: 10.16658/j.cnki.1672-4062.2020.15.048. 王道静. 妊娠糖尿病孕妇血液指标及妊娠结局分析[J]. 糖尿病新世界, 2020, 23(15): 54-56. DOI: 10.16658/j.cnki.1672-4062.2020.15.048.
[4]	XU CL, YING H. Influence of chronic HBV infection on maternal and neonatal outcomes of women with gestational diabetes mellitus[J]. J Clin Hepatol, 2019, 35(7): 1421-1424. DOI: 10.3969/j.issn.1001-5256.2019.07.002. 许传露, 应豪. 慢性HBV感染者妊娠期糖尿病对母婴结局的影响[J]. 临床肝胆病杂志, 2019, 35(7): 1421-1424. DOI: 10.3969/j.issn.1001-5256.2019.07.002.
[5]	NA RQMG, LI DM, MI LX, et al. Prevalence rate of gestational diabetes mellitus in China: A meta-analysis[J]. Chin J Evid-based Med, 2018, 3(18): 280-285. DOI: 10.7507/1672-2531.201710044. 娜仁其木格, 李冬梅, 米林香, 等. 中国妊娠期糖尿病患病率的Meta分析[J]. 中国循证医学杂志, 2018, 3(18): 280-285. DOI: 10.7507/1672-2531.201710044.
[6]	LING Y, WU XM, CHEN ZJ, et al. Relationship between hepatitis B virus and gestational diabetes mellitus[J]. J Hainan Med Univ, 2011, 17(8): 1099-1100. 凌奕, 吴小妹, 陈泽俊, 等. 乙型肝炎病毒携带与妊娠期糖尿病关系的研究[J]. 海南医学院学报, 2011, 17(8): 1099-1100.
[7]	LAO TT, CHAN BC, LEUNG WC, et al. Maternal hepatitis B infection and gestational diabetes mellitus[J]. J Hepatol, 2007, 47(1): 46-50. DOI: 10.1016/j.jhep.2007.02.014.
[8]	TAN J, MAO X, ZHANG G, et al. Hepatitis B surface antigen positivity during pregnancy and risk of gestational diabetes mellitus: A systematic review and meta-analysis[J]. J Viral Hepat, 2018, 25(11): 1372-1383. DOI: 10.1111/jvh.12964.
[9]	FAN XL, ZHANG WY. Hepatitis virus infection and insulin resistance[J]. World Chin J Dig, 2007, 15(19): 2077-2081. DOI: 10.3969/j.issn.1009-3079.2007.19.001. 范小玲, 张维燕. 肝炎病毒感染与胰岛素抵抗[J]. 世界华人消化杂志, 2007, 15(19): 2077-2081. DOI: 10.3969/j.issn.1009-3079.2007.19.001.
[10]	WU XM, LING Y, LI YP, et al. Effect of asymptomatic hepatovirus B carrier ongestational diabetes mellitus and outcome of pregnancy[J]. J Hainan Med Univ, 2011, 17(9): 1244-1246. DOI: 46-1049/R.20110726.1108.005. 吴小妹, 凌奕, 李跃萍, 等. 无症状乙肝病毒携带状态对妊娠期糖尿病及妊娠结局的影响[J]. 海南医学院学报, 2011, 17(9): 1244-1246. DOI: 46-1049/R.20110726.1108.005.
[11]	MAGHBOOLI Z, HOSSEIN-NEZHAD A, RAHMANI M, et al. Relationship between leptin concentration and insulin resistance[J]. Horm Metab Res, 2007, 39 (12): 903-907. DOI: 10.1055/s-2007-992812.
[12]	HOEFS JC, RENNER IG, ASKHCAVAI M, et al. Hepatitis B surface antigen in pancreatic and biliary secretions[J]. Gastroenterology, 1980, 79(2): 191-194.
[13]	WINKLER G, CSEH K, BARANYI E, et al. Tumor necrosis factor system in insulin resistance in gestational diabetes[J]. Diabetes Res Clin Pract, 2002, 56(2): 93-99. DOI: 10.1016/s0168-8227(01)00355-2.
[14]	LIU YL, KUANG JQ, LIU XZ, et al. The expression of HBcAg in HBV carrier mother's placentas and its significance[J]. Acad J Sun Yat-Sen Univ Med Sci, 2000, 21(1): 43-46. DOI: 10.3321/j.issn:1672-3554.2000.01.013. 刘颖琳, 邝健全, 刘新质, 等. HBcAg在乙型肝炎病毒携带者孕妇胎盘中的识别与意义[J]. 中山医科大学学报, 2000, 21(1): 43-46. DOI: 10.3321/j.issn:1672-3554.2000.01.013.
[15]	FENG XL, WANG HJ, LI CX. Effects of HBV infection on liver function, immune function and pregnancy outcome in pregnant women with gestational diabetes mellitus[J]. Hebei Med J, 2020, 42(11): 1712-1715. DOI: 10.3969/j.issn.1002-7386.2020.11.028. 冯晓兰, 王慧娟, 李春霞. HBV感染对妊娠期糖尿病患者肝功能, 免疫功能及妊娠结局的影响[J]. 河北医药, 2020, 42(11): 1712-1715. DOI: 10.3969/j.issn.1002-7386.2020.11.028.
[16]	QIU XT, LIU F, QIU YY, et al. Clinical analysis of pregnant women with HBV infection complicated with gestational diabetes[J]. Int J Lab Med, 2016, 37(11): 1455-1458. DOI: 10.3969/j.issn.1673-4130.2016.11.003. 邱先桃, 刘非, 丘媛媛, 等. HBV感染合并妊娠糖尿病的临床分析[J]. 国际检验医学杂志, 2016, 37(11): 1455-1458. DOI: 10.3969/j.issn.1673-4130.2016.11.003.
[17]	YANG HX. Influence of pregnancy complicated with viral hepatitis on the prognosis of pregnant women[J]. Chin J Pract Gynecol Obstetr, 2004, 20(2): 79-80. DOI: 10.3969/j.issn.1005-2216.2004.02.007. 杨慧霞. 妊娠合并病毒性肝炎对孕产妇预后的影响[J]. 中国实用妇科与产科杂志, 2004, 20(2): 79-80. DOI: 10.3969/j.issn.1005-2216.2004.02.007.
[18]	YANG H, CHEN RF, LI Z, et al. Analysis of fetal distress in pregnancy with hepatitis B virus infection[J]. Chin J Obstet Gynecol, 2002, 37(4): 211-213. DOI: 10.3760/j.issn:0529-567X.2002.04.007. 杨虹, 陈瑞芬, 李卓, 等. 妊娠合并乙型肝炎病毒感染孕妇胎儿窘迫发病原因分析[J]. 中华妇产科杂志, 2002, 37(4): 211-213. DOI: 10.3760/j.issn:0529-567X.2002.04.007.