Growth and Endocrine Profiles in Large for Gestational Age Infants: Comparing Outcomes Between Diabetic and Non-Diabetic Mothers

Background: Large-for-gestational-age (LGA) infants may develop from constitutional or metabolic influences. In infants of diabetic mothers (IDMs), maternal hyperglycemia drives fetal hyperinsulinemia, excessive fat accretion, and endocrine imbalance, whereas non-diabetic LGA infants usually reflect familial growth patterns with more balanced hormonal function.

Objectives: To compare endocrine, metabolic, and growth characteristics between LGA neonates of diabetic versus non-diabetic mothers; to outline neonatal and long-term complications; and to examine mechanisms linking maternal glycemia, fetal insulin–IGF-1 axis activity, and postnatal metabolic outcomes.

Methods: A structured literature review of human studies (2000–2025) identified comparative cohorts of LGA infants born to diabetic and non-diabetic mothers. Extracted data included neonatal endocrine markers, metabolic complications, cardiac findings, and long-term growth and pubertal outcomes. Qualitative synthesis was prioritized due to heterogeneity in LGA definitions and follow-up duration.

Results: Twenty-two studies encompassing more than 12,000 LGA infants demonstrated marked endocrine divergence between groups. IDMs consistently exhibited hyperinsulinemia in 70–90%, neonatal hypoglycemia in 25–50%, and elevated IGF-1 and leptin levels at birth; corresponding abnormalities were generally below 10% in non-diabetic LGA infants. Transient hypothyroxinemia appeared in 10–15% of IDMs, while non-diabetic LGA newborns rarely showed thyroid disturbances.

Cardiac involvement was substantially higher in IDMs, with 10–25% developing hypertrophic cardiomyopathy compared to <5% in non-diabetic LGA infants. Approximately 20–30% of IDMs displayed early postnatal growth patterns characterized by GH suppression, accelerated bone age, and increased adiposity by 6–12 months.

Long-term outcomes revealed significantly heightened metabolic risk among IDMs: childhood overweight and obesity occurred in 40–55%, and insulin resistance indices were 30–50% higher than in non-diabetic LGA peers. Puberty occurred earlier by an average of 8–12 months, particularly in girls with rapid infancy weight gain. By contrast, non-diabetic LGA infants showed proportionate growth, normal IGF-1 signaling, and stable neurodevelopment, unless maternal obesity or excessive gestational weight gain was also present.

Conclusions: LGA infants of diabetic mothers show a distinct endocrine and metabolic phenotype driven by intrauterine hyperglycemia and compensatory fetal hyperinsulinemia. These infants carry substantially higher neonatal and long-term cardiometabolic risks than constitutionally large infants. Differentiating diabetic-related from constitutional LGA is critical to ensuring early endocrine evaluation, targeted monitoring, and effective preventive strategies. Optimizing maternal glycemic control remains a key modifiable factor to reduce adverse outcomes.