Pregnancy Complications and Transgenerational Health Outcomes: Mechanistic Pathways and Future Research Horizons

Objective: Summarize evidence across six common pregnancy complications—gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), thyroid dysfunction, intrahepatic cholestasis of pregnancy (ICP), hyperemesis gravidarum (HG), and preterm birth (PTB)—and clarify short- and long-term consequences for mothers and their children. Mechanism: Adverse outcomes converge on shared pathways: abnormal placental development and perfusion, inflammatory and oxidative stress signaling, endocrine and metabolic dysregulation, and epigenetic remodeling at imprinted loci. These processes program fetal organ systems (brain, heart, lungs, kidneys) and shape lifelong disease risk. Findings in Brief: GDM increases large-for-gestational-age birth, respiratory morbidity, and later metabolic disease. HDP drive fetal growth restriction and enduring cardiovascular and neurocognitive sequelae. Thyroid dysfunction worsens obstetric outcomes and may impair offspring neurocognition. ICP raises risks of PTB and stillbirth. HG is associated with low birth weight and small for gestational age. PTB independently predicts lifelong cardio-respiratory, endocrine, and neurodevelopmental disorders. Management spans glucose control; antihypertensive therapy and magnesium sulfate; levothyroxine or antithyroid drugs; ursodeoxycholic acid; antiemetics and nutritional support; progesterone and antenatal corticosteroids. Emerging precision strategies target angiogenic balance, inflammation, and the microbiome. Conclusions: Pregnancy complications are sentinel events with intergenerational implications. Stage-appropriate screening, timely intervention, and longitudinal follow-up are essential, while multi-omics research and placental-targeted trials are needed to validate strategies that mitigate offspring risk across the life course.