Open Access

REVIEW

Research Advances on the Mechanisms and Clinical Outcomes of Hyperglycemia in Pregnancy Leading to Congenital Heart Disease in Offspring

Jiafei He^1,2, Ailixiati Alifu², Haifan Wang², Renwei Chen^1,2,*
1 School of Pediatrics, Hainan Medical University, Haikou, China
2 Hainan Women and Children’s Medical Center, Hainan Medical University, Hainan Academy of Medical, Sciences, Haikou, China
* Corresponding Author: Renwei Chen. Email:

Structural and Congenital Heart Disease https://doi.org/10.32604/schd.2026.075858

Received 10 November 2025; Accepted 06 March 2026; Published online 24 March 2026

Abstract

Hyperglycemia in pregnancy (HIP) is an important independent risk factor for congenital heart disease (CHD) in offspring. With an increasing number of women of childbearing age experiencing gestational hyperglycemia, the impact of an intrauterine hyperglycemic environment on fetal development has drawn significant attention. However, the teratogenic mechanisms underlying its effects on cardiac development remain incompletely understood. This review systematically analyzes relevant literature to summarize its underlying mechanisms and key findings: A hyperglycemic environment disrupts cardiac neural crest cell migration, differentiation, and the proliferation/apoptosis balance of cardiomyocytes by inducing oxidative stress, endoplasmic reticulum stress, and inflammatory responses during critical embryonic developmental stages (cardiac ridge and heart tube formation). The core molecular mechanisms involve abnormalities in signaling pathways such as Wnt, TGFβ, and Notch, as well as dysregulation of epigenetic controls including histone modifications and DNA methylation. Concurrently, in-depth research into the molecular mechanisms by which HIP contributes to CHD provides direction for developing early warning biomarkers (such as specific miRNAs and epigenetic markers) and potential therapeutic targets. It also offers insights into advancing intervention from pregnancy to the preconception stage and enabling proactive, lifecycle management of maternal and fetal risks through multidisciplinary collaboration.

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Keywords

Hyperglycemia in pregnancy; congenital heart disease; maternal hyperglycemia; pregestational diabetes mellitus; gestational diabetes mellitus; maternal diabetes; cardiac development; cardiovascular disease

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