Maternal Growth Hormone/Insulin-like Growth Factor Axis and Placental Growth Hormone in Pregnancies Complicated by Diabetes and Thyroid Disease: A Systematic Review Integrating Mechanistic Evidence

Background: Pregnancies complicated by diabetes or thyroid dysfunction carry heightened risks for abnormal foetal growth and adverse perinatal outcomes. The hormonal pathways linking these conditions to placental function and maternal metabolic adaptation remain incompletely understood. Placental growth hormone (PGH), the insulin-like growth factor (IGF) axis and maternal thyroid hormones interact to regulate insulin sensitivity, nutrient transfer and foetal development. Aim: This study aims to synthesise mechanistic and clinical evidence describing how the maternal growth hormone (GH)/IGF axis and PGH behave in pregnancies affected by diabetes or thyroid disease and to clarify their combined influence on placental physiology and foetal growth. Methodology: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines, a systematic search of PubMed, Embase, Scopus, Web of Science and the Cochrane Library was performed from database inception to October 2025. Experimental, observational and mechanistic studies examining PGH, IGFs or maternal thyroid hormones in diabetic or thyroid-affected pregnancies were eligible. Study selection, data extraction and quality appraisal were conducted independently by multiple reviewers. Results: Thirty-three studies met the inclusion criteria. PGH consistently increased from mid-pregnancy and was linked to reduced maternal insulin sensitivity, particularly through phosphatidylinositol 3-kinase/p85-mediated signalling in diabetic pregnancies. Higher maternal or foetal IGF concentrations were associated with large-for-gestational-age outcomes, whereas reduced IGF-binding proteins were related to foetal growth restriction. Low maternal thyroid hormone levels and altered thyroid function correlated with increased risk of gestational diabetes, impaired placental haemodynamics and neurodevelopmental variation in offspring. Mechanistic studies demonstrated direct hormonal cross-talk among thyroid hormones, GH-receptor activity and IGF expression in placental tissue. Conclusion: Disruption of the PGH–IGF–thyroid hormonal network contributes to maternal metabolic imbalance and abnormal foetal growth. Integrating these endocrine pathways may support the development of predictive biomarkers and targeted interventions for high-risk pregnancies.