Transient neonatal hypoglycemia and the developing brain: Associations, mechanisms, and clinical implications

BackgroundTransient neonatal hypoglycemia (TNH) has long been viewed as a benign, self-limited phenomenon. For this review, TNH refers mainly to hypoglycemia in late preterm and term infants during the first 48-72 h of life, usually at glucose levels below 47 mg/dL (2.6 mmol/L). Emerging data suggest that specific patterns of early low glucose (especially when recurrent, severe, or occurring in high-risk) infants may be linked to later neurodevelopmental difficulties.ObjectiveTo synthesize contemporary clinical, epidemiological, and mechanistic evidence on the impact of TNH on long-term brain development, with emphasis on domain-specific outcomes.MethodsWe conducted a structured narrative review of human studies on TNH, continuous glucose monitoring, and neurodevelopmental outcomes, integrating population-based cohorts, clinical studies, and systematic reviews with key mechanistic data.ResultsAcross heterogeneous cohorts, TNH is associated with an increased risk of selective neurodevelopmental differences (particularly in executive function, visuomotor integration, fine motor skills, and early literacy) while global cognitive scores are often preserved. Prospective cohorts and registry studies indicate that recurrent or prolonged episodes, especially in infants who are small for gestational age or born to mothers with diabetes, more often precede later difficulties, although many exposed infants develop typically. Population-based analyses also report associations between neonatal hypoglycemia and later learning, attention, or autism spectrum diagnoses, but these findings remain confounded and non-causal.ConclusionsTNH appears to be a marker of increased neurodevelopmental vulnerability in specific subgroups rather than uniformly benign or inevitably harmful. Careful identification and physiologically informed treatment of at-risk neonates, together with structured long-term follow-up, are warranted.