Predictors of neonatal hypoglycemia: a systematic review and meta analysis

Abstract

Background Neonatal hypoglycemia (NH) is a common metabolic disorder linked to significant neurological morbidity. Identifying predictors is essential for targeted screening, yet a comprehensive synthesis of their relative strengths and clinical implications is lacking. Objective To systematically identify, quantify, and synthesize the predictors of NH through a meta-analysis and propose a novel clinical framework for risk stratification. Methods We conducted a systematic review and meta-analysis of observational studies (2015–2025) from PubMed, Cochrane Library, and ScienceDirect. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. A tiered causal framework was developed to categorize predictors by clinical actionability. Results From 19 included studies, meta-analysis revealed significant predictors. Birth asphyxia (OR 4.11, 95% CI 1.35–12.49) and neonatal hypothermia (OR 4.06, 95% CI 2.30–7.18) were the strongest risks. Other key predictors included, cesarean delivery (OR 1.56, 95% CI 1.16–2.09), preterm birth (OR 2.06), small-for-gestational-age status (OR 1.99), and gestational diabetes (OR 2.00). To translate these statistical associations into clinical practice, we propose a novel tiered causal framework developed post hoc as a hypothesis-generating model to categorize predictors by clinical actionability and temporal proximity to the hypoglycemic event: Tier 1 (Acute Precipitants: asphyxia, hypothermia, sepsis) contains the highest-risk, modifiable triggers; Tier 2 (Intrinsic Infant Factors: prematurity, SGA) defines the vulnerable phenotype; Tier 3 (Maternal/Perinatal Antecedents: GDM, pre-eclampsia) serves as screening flags. Conclusion This review not only quantifies the hierarchy of NH risk but also introduces a novel tiered framework that shifts the clinical paradigm from passive screening of at-risk infants to active prevention of acute metabolic insults. Prioritizing bundled interventions against Tier 1 precipitants especially birth asphyxia and hypothermia alongside recognition of Tier 2/3 factors could fundamentally improve neonatal metabolic outcomes. Clinical trial number Not applicable.