Outcomes at School Age for Infants With Neonatal Hypoglycemia

Source: Wei X, Franke N, Alsweiler JM, et al. Neonatal hypoglycemia and neurocognitive function at school age: a prospective cohort study. J Pediatr. 2024;272:114119; doi: 10.1016/j.jpeds.2024.114119.Investigators from the University of Auckland, Auckland, New Zealand, conducted a cohort study to assess the association between brief transitional neonatal hypoglycemia and neurocognitive development during the early school age years. Study participants originally had been enrolled in a randomized controlled trial in which newborns at risk for hypoglycemia received multiple doses of dextrose gel or placebo. Risk factors included maternal diabetes, birth at 35–36 weeks’ gestation, birth weight <2,500 g, and small for gestational age at birth. Hypoglycemia was defined as a blood glucose <47 mg/dL, and severe hypoglycemia was defined as a glucose <36 mg/dL. Newborns with ≥3 episodes were considered to have recurrent hypoglycemia. Participants in the original trial who were enrolled in the current study were assessed for cognitive and motor development using multiple standardized instruments when they were 6–7 years old. The primary outcome was neurocognitive impairment, defined as a score that was >1 standard deviation (SD) below the mean on ≥1 of the assessments. Secondary outcomes included executive dysfunction, motor impairment, language impairment, episodic memory impairment, composite cognitive score, low numeracy, emotional/behavioral difficulty, and visual perception. These outcomes were compared using regression analyses among children who had hypoglycemia as newborns and those who didn’t, after controlling for multiple confounders. Secondary analyses were conducted to assess outcomes in children with severe or recurrent neonatal hypoglycemia.Of 392 eligible children, 315 (80%) had developmental testing at a mean age of 6.8 ±0.3 years. Among these participants, 47% had experienced neonatal hypoglycemia. Rates of neurocognitive delay were 51% and 50%, respectively, in participants with and without neonatal hypoglycemia (adjusted rate ratio, 0.94; 95% CI, 0.75, 1.17). There also were no significant differences between the 2 groups for any of the secondary outcomes. In the secondary analyses, compared to those with no neonatal hypoglycemia, visual perception was significantly worse among children who had recurrent or severe hypoglycemia. Children who had severe neonatal hypoglycemia were at higher risk for emotional/behavioral difficulty than those without hypoglycemia. There were no other statistically significant differences between those with no hypoglycemia and either recurrent or severe hypoglycemia for the other outcomes.The authors conclude that neonatal hypoglycemia was not associated with an increased risk of neurocognitive impairment when assessed in the early school-age years.Dr Beam has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Neonatal hypoglycemia continues to be the most common metabolic disturbance in the newborn.1 Several prior investigators have examined the long-term consequences of neonatal hypoglycemia at different time points in development.2 (See AAP Grand Rounds. 2022;48[1]:4.)3 The current researchers examined early school-age outcomes in at-risk infants who received varying doses of dextrose gel prophylactically versus placebo to prevent neonatal hypoglycemia. The results of the original study showed that any dose of dextrose gel given prophylactically to infants at risk for neonatal hypoglycemia helped to reduce the risk of neonatal hypoglycemia but not NICU admission.3,4There has been continued disagreement about what specific glucose level constitutes neonatal hypoglycemia.5 Most centers have screening protocols to detect asymptomatic hypoglycemia in at-risk neonates. However, the long-term effects of periods of hypoglycemia remain unclear. The current study adds to the growing evidence that, though there may be some effects on development, neonatal hypoglycemia in general does not affect overall neurodevelopmental outcomes.Research continues to emerge regarding longer-term outcomes of neonatal hypoglycemia. There do not appear to be increased adverse neurodevelopmental outcomes at school age in infants with neonatal hypoglycemia.Are any of our readers similarly disturbed by the study findings of neurocognitive delay in ~50% of the children? Will this percentage increase, decrease, or remain unchanged as the study participants age?