糖尿病母亲婴儿先天性心脏病发病机制研究进展

沿 李(济宁医学院，中国;)
培正 杜(济宁医学院，中国;)
陆宇 任(济宁医学院，中国;)
雪云 任(济宁医学院附属医院，中国;)

摘要

母体糖尿病是子代先天性心脏病（congenital heart disease, CHD）的明确高危因素，糖尿病母亲婴儿（infants of diabetic mothers, IDMs）患CHD的风险显著高于普通新生儿，已成为围产期新生儿健康的重要威胁。本文系统梳理IDMs并发CHD的流行病学特点与常见心脏畸形类型，深入探讨其多维度发病机制，包括母体高血糖的直接毒性效应、胎儿高胰岛素血症的介导作用、氧化应激与内质网应激的损伤机制、表观遗传学调控紊乱及核心发育信号通路异常，分析基因易感性与不良宫内代谢环境的交互作用，为IDMs-CHD的早期筛查、临床预防及精准干预提供理论支撑，契合中华新生儿科杂志临床导向与学术要求。

关键词

糖尿病母亲婴儿；先天性心脏病；发病机制；高血糖；高胰岛素血症；表观遗传学；信号通路

参考

齐宇洁.糖尿病母亲的婴儿临床心脏病变情况[J].中华实用儿科临床杂志,2014,29(13):1014.

CODAZZI A C,IPPOLITO R,NOVARA C,et al.Hypertrophic cardiomyopathy in infant newborns of diabetic mother[J].Italian Journal of Pediatrics,2021,47(1):197.

LEMAITRE M,BOURDON G,BRUANDET A,et al.Pre-gestational diabetes and the risk of congenital heart defects in the offspring[J].Diabetes & Metabolism,2023,49(4):101446.

HUANG P C,HUYBRECHTS K F,STRAUB L,et al.Maternal Diabetes Types and the Risk of Pregnancy Loss and Specific Malformations in the Infant[J].Birth Defects Research,2025,117(12):e70009.

LUO Liu.母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究[J].中国当代儿科杂志,2020,22(10):1092.

MALAZA N,MASETE M,ADAM S,et al.A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes[J].International Journal of Environmental Research and Public Health,2022,19(17):10846.

ANDRADE C.Exposure of Pregnancy to Pregestational Diabetes,Gestational Diabetes,and Antidiabetic Medications[J].The Journal of Clinical Psychiatry,2024,85(1):24f15318.

马芬芳.糖尿病母亲新生儿先天性心脏病筛查及危险因素分析[J].中国卫生标准管理,2023,14(14):16.

梁进涛.糖尿病合并妊娠与先天性心脏病研究进展[J].国际儿科学杂志,2010,37(05):484.

刘英战,张聪.早产儿先天性心脏病与产妇孕早期患病的关系探讨[J].医药前沿,2020,10(30):112-113.

石婉明,何怡华,商建峰,等.先天性心脏病胎儿胎盘病理特征分析[J].中华医学超声杂志(电子版),2016,13(8):582-586.

徐友宁.糖尿病母亲妊娠期血糖控制情况与新生儿早期并发症的关系[J].首都医药,2010,17(12):38.

MADURO C,CASTRO L F de,MOLEIRO M L,et al.Pregestational Diabetes and Congenital Heart Defects[J].Revista Brasileira De Ginecologia E Obstetricia,2022,44(10):953-961.

PAPAZOGLOU A S,MOYSIDIS D V,PANAGOPOULOS P,et al.Maternal diabetes mellitus and its impact on the risk of delivering a child with congenital heart disease[J].The Journal of Maternal-Fetal & Neonatal Medicine,2022,35(25):7685-7694.

LIU Y,YUE L,CHANG L.Maternal Gestational Diabetes Mellitus and Congenital Heart Disease in Offspring:A Meta-Analysis[J].Hormone and Metabolic Research,2024,56(8):574-584.

WANG M,ZHANG T H,LI Y,et al.Atractylenolide-I Alleviates Hyperglycemia-Induced Heart Developmental Malformations[J].Phytomedicine,2024,129:155698.

HE L,WANG X,JIN Y,et al.Identification and validation of the miRNA-mRNA regulatory network in fetoplacental arterial endothelial cells of gestational diabetes mellitus[J].Bioengineered,2021,12(1):3503-3515.

DESSÌ A,BOSCO A,CESARE MARINCOLA F,et al.Sardinian Infants of Diabetic Mothers:A Metabolomics Observational Study[J].International Journal of Molecular Sciences,2023,24(18):13724.

AL-BILTAGI M,EL RAZAKY O,EL AMROUSY D.Cardiac changes in infants of diabetic mothers[J].World Journal of Diabetes,2021,12(8):1233-1247.

AJAZ S,KAKROO S A,AMIN H,et al.Fetal Echocardiography in Gestational Diabetes Mellitus[J].Cureus,2025,17(7):e89050.

KRAUSE A,SCHWAB K O,TROST J,et al.Gestational diabetes mellitus:the role of IGF-1 and leptin in cord blood[J].Journal of Perinatal Medicine,2025,53(7):937-944.

CHENG X M,HU Y Y,YANG T,et al.Reactive Oxygen Species and Oxidative Stress in Vascular-Related Diseases[J].Oxidative Medicine and Cellular Longevity,2022,2022:7906091.

JAKUBCZYK K,DEC K,KAŁDUŃSKA J,et al.Reactive oxygen species-sources,functions,oxidative damage[J].Polski Merkuriusz Lekarski,2020,48(284):124-127.

CHEN T,CHEN H,WANG A,et al.Methyl Parathion Exposure Induces Development Toxicity and Cardiotoxicity in Zebrafish Embryos[J].Toxics,2023,11(1):84.

CLARE K,DILLON J F,BRENNAN P N.Reactive Oxygen Species and Oxidative Stress in the Pathogenesis of MAFLD[J].Journal of Clinical and Translational Hepatology,2022,10(5):939-946.

WANG G,SHEN W B,CHEN A W,et al.Diabetes and Early Development:Epigenetics,Biological Stress,and Aging[J].American Journal of Perinatology,2025,42(8):977-987.

盛伟.先天性心脏病圆锥动脉干畸形NKX2-5基因CpG岛甲基化状态分析[J].中国产前诊断杂志（电子版）,2010,02(03):12.

夏慧苏,余细勇,朱杰宁.97例先天性心脏病儿童DNMT表达情况分析[J].医学理论与实践,2017,30(4):471-473.

ROTEM R S,WEISSKOPF M G,BATEMAN B,et al.Maternal periconception hyperglycemia,preconception diabetes,and risk of major congenital malformations in offspring[J].Human Reproduction,2024,39(12):2816-2829.

WANG G,LU W,SHEN W B,et al.Small Molecule Activators of Mitochondrial Fusion Prevent Congenital Heart Defects Induced by Maternal Diabetes[J].JACC.Basic to translational science,2024,9(3):303-318.

YE F,LU X,VAN NECK R,et al.Novel circRNA-miRNA-mRNA networks regulated by maternal exercise in fetal hearts of pregestational diabetes[J].Life Sciences,2023,314:121308.

CHOUDHURY T Z,GARG V.Molecular genetic mechanisms of congenital heart disease[J].Current Opinion in Genetics & Development,2022,75:101949.

LI Y,YANG P,WANG X,et al.Uric Acid Disrupts Heart Development in Zebrafish by Inhibiting the Wnt Signaling Pathway[J].Cardiovascular Toxicology,2025,25(11):1689-1705.

WANG G,WANG B,YANG P.Epigenetics in Congenital Heart Disease[J].Journal of the American Heart Association,2022,11(7):e025163.

ALOQAB F W,ALMAJED M R,BINSANAD N A,et al.Maternal diabetes as a teratogenic factor for congenital heart defects in infants of diabetic mothers[J].Birth Defects Research,2023,115(7):764-769.

MORTON S U,QUIAT D,SEIDMAN J G,et al.Genomic frontiers in congenital heart disease[J].Nature Reviews.Cardiology,2022,19(1):26-42.

ASHIQ S,SABAR M F.Association of maternal hypertension and diabetes with variants of the NKX2-5,LEFTY1 and LEFTY2 genes[J].Molecular Biology Reports,2023,50(6):5013-5020.

SARIĆ N,ISHIBASHI N.The role of primary cilia in congenital heart defect-associated neurological impairments[J].Frontiers in Genetics,2024,15:1460228.

李依寰,黄鹏,王婷婷,等.母亲MTR基因多态性与先天性心脏病易感性关联[J].中国公共卫生,2022,38(2):161-166.

KHATAMI M,GHORBANI S,ADRIANI M R,et al.Novel Point Mutations in 3’-Untranslated Region of GATA4 Gene[J].Current Medical Science,2022,42(1):129-143.

ASHIQ S,HYDER S N,ASHIQ K,et al.Role of Vascular Endothelial Growth Factor as a Potential Biomarker in Congenital Heart Defects[J].The Journal of Tehran Heart Center,2023,18(4):237-243.

ASHIQ S,SABAR M F,HYDER S N.Genetic Risk Score Constructed from Polymorphisms in the VEGFA,TBX5,and SMAD7 Genes[J].The American Journal of Cardiology,2023,203:368-375.

ZHANG S,WANG J,SUN L,et al.Investigation of the genetic and clinical features of laterality disorders in prenatal diagnosis[J].Archives of Gynecology and Obstetrics,2024,310(2):695-704.

DOI: http://dx.doi.org/10.12345/yzlcyxzz.v9i5.39859