Wei X, Franke N, Alsweiler JM, Brown GTL, Gamble GD, McNeill A, Rogers J, Thompson B, Turuwhenua J, Wouldes TA, Harding JE, and McKinlay CJD
Objective: To determine the relationship between transient neonatal hypoglycemia in at-risk infants and neurocognitive function at 6-7 years of corrected age., Study Design: The pre-hPOD Study involved children born with at least 1 risk factor for neonatal hypoglycemia. Hypoglycemia was defined as ≥1 consecutive blood glucose concentrations <47 mg/dl (2.6 mmol/L), severe as <36 mg/dl (2.0 mmol/L), mild as 36 to <47 mg/dL (2.0 to <2.6 mmol/L), brief as 1-2 episodes, and recurrent as ≥3 episodes. At 6-7 years children were assessed for cognitive and motor function (NIH-Toolbox), learning, visual perception and behavior. The primary outcome was neurocognitive impairment, defined as >1 SD below the normative mean in ≥1 Toolbox tests. The 8 secondary outcomes covered children's cognitive, motor, language, emotional-behavioral, and visual perceptual development. Primary and secondary outcomes were compared between children who did and did not experience neonatal hypoglycemia, adjusting for potential confounding by gestation, birthweight, sex and receipt of prophylactic dextrose gel (pre-hPOD intervention). Secondary analysis included assessment by severity and frequency of hypoglycemia., Results: Of 392 eligible children, 315 (80%) were assessed at school age (primary outcome, n = 308); 47% experienced hypoglycemia. Neurocognitive impairment was similar between exposure groups (hypoglycemia 51% vs 50% no hypoglycemia; aRD -4%, 95% CI -15%, 7%). Children with severe or recurrent hypoglycemia had worse visual motion perception and increased risk of emotional-behavioral difficulty., Conclusion: Exposure to neonatal hypoglycemia was not associated with risk of neurocognitive impairment at school-age in at-risk infants, but severe and recurrent episodes may have adverse impacts., Trial Registration: Hypoglycemia Prevention in Newborns with Oral Dextrose: the Dosage Trial (pre-hPOD Study): ACTRN12613000322730., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose. The pre-hPOD Study was funded by Lottery Health Research (241266), Cure Kids (3561), philanthropic donations to the University of Auckland Foundation (F-ILG- LRSR), Health Research Council of New Zealand (15-216), Gravida, National Centre for Growth and Development (SCH-14-14), Auckland Medical Research Foundation (1113012), A+ Trust (5696) and Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (R01HD091075). The pre-hPOD Early School-age Outcomes Study was funded by the Health Research Council of New Zealand (19/960) and the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (R01HD091075). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)