Early Neonatal Hyperglycemia and Neurodevelopmental Outcomes in Preterm Infants: A Retrospective Cohort Study

Abstract

Introduction: Hyperglycemia is prevalent in preterm infants and associated with adverse neurodevelopmental outcomes. However, hyperglycemia is defined inconsistently across studies. We aimed to investigate the link between early neonatal hyperglycemia and early childhood neurodevelopment, and whether this relationship is causal. Methods: We conducted a retrospective study of 220 preterm infants with gestational age ≤28 weeks. Blood glucose measurements from the first 7 days of life were used to assess hyperglycemia. We calculated: average glucose, number of hyperglycemic days, and binary indicators based on thresholds of > 8.3 mmol/L (hyperglycemia) and > 10.0 mmol/L (severe hyperglycemia). Neurodevelopmental outcomes at 18–24 months corrected were language and gross motor delay. Associations were evaluated using univariate and multivariate logistic regression models adjusted for sex, gestational age, small-for-gestational-age status, and maternal education. Causal inference was performed using a probabilistic computation tree logic-based approach for observational data. Results: In univariate analyses, higher 3-day average glucose was associated with increased odds of gross motor delay (OR 1.16, 95% CI 1.00–1.35, p=.048). After adjustment, hyperglycemia measures were not associated with neurodevelopmental outcomes. Lower gestational age was consistently associated with higher odds of language delay (OR 0.73, 95% CI 0.58–0.92, p=.007). We identified a causal relationship between extreme prematurity (gestational age ≤25 weeks) and language delay (p=.03) but found no causal effect of hyperglycemia on neurodevelopmental outcomes. Conclusion: Early neonatal hyperglycemia was not independently associated with neurodevelopmental outcomes after adjustment.