537 - Impact of Dysglycemia on Neurodevelopment in Therapeutic Hypothermia–Treated Neonates With Hypoxic–Ischemic Encephalopathy: A Systematic Review and Meta-analysis

Publication Number: 1516.537

Jiaqi Li, Children's Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic); Xiaoshan Ji, Children's Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic); Ting Peng, Children' Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic); mengmeng Ge, Children's Hospital, Shanghai, Shanghai, China (People's Republic); Guoqiang Cheng, Children's Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic); Wenhao Zhou, Guangzhou medical university, Guangzhou, Guangdong, China (People's Republic); Siyuan Jiang, Children's Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic)

Background: Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neonatal death and long-term neurodisability. Dysglycemia is frequent in HIE, yet effect sizes and the implicated dimensions are inconsistent across studies, particularly in the therapeutic hypothermia (TH) era.

Objective: To quantify associations between early neonatal dysglycemia and adverse outcomes in term infants with HIE treated with TH, and to identify which glycemic metrics are most prognostic.

Design/Methods: Following PRISMA 2020 (PROSPERO CRD420251059899), we searched the Cochrane Library, PubMed, and Web of Science from inception to March 2025. Eligible studies enrolled TH-treated HIE neonates, compared hypoglycemia, hyperglycemia, or glycemic variability with appropriate comparators, and reported calculable odds ratios (ORs) for MRI-defined brain injury or neurodevelopment. Primary outcomes were long-term adverse outcomes (severe neurodevelopmental impairment or death at ≥ 18 months) and short-term adverse outcomes (MRI-detected brain injury). Analyses were conducted in Stata 18.0.

Results: For long-term outcomes, hypoglycemia (after exclusion of two influential outliers) was associated with adverse outcome (OR = 2.03, 95% CI 1.37-3.02); hyperglycemia remained positively associated (OR = 2.55, 95% CI 1.58-4.10), with residual heterogeneity (Fig. 3b); and variability showed a strong association (OR = 5.21, 95% CI 3.22-8.44). Event-based subgroups indicated that burden/duration metrics were most informative: hypoglycemia by duration (OR = 5.97, 95% CI 2.02-17.68) and by area-under-the-curve (AUC; OR = 2.84, 95% CI 1.71-4.72) and hyperglycemia by AUC (OR = 6.27, 95% CI 3.27-12.04) were significant, whereas isolated lowest/highest glucose values were not (Fig. 3a-b). For short-term outcomes, hypoglycemia was associated with MRI-defined injury (OR = 2.47, 95% CI 1.24-4.93). Hyperglycemia showed no consistent association with short-term MRI injury (Fig. 2e). Limited data suggested an association between variability and short-term unfavorable outcomes (OR = 2.28, 95% CI 1.09-4.77). Hypoglycemia defined by duration was associated with short-term adverse outcomes (OR = 3.41, 95% CI 1.27-9.81).

Conclusion(s): In TH-treated HIE, sustained glycemic exposure and variability carry the greatest prognostic value. These findings support standardized definitions and monitoring, with management strategies aimed at minimizing time in hypoglycemia, limiting hyperglycemic burden, and reducing glycemic variability.

flowchart


Association of glycemia with primary and secondary adverse outcomes


Subgroup analysis by event for primary and secondary adverse outcomes