Early Feeding for the Prevention of Neonatal Hypoglycaemia: A Systematic Review and Meta-Analysis

Abstract

<b><i>Background:</i></b> Poor feeding, among other factors, predisposes neonates to hypoglycaemia. Early feeding is widely recommended to prevent hypoglycaemia in those at risk, but the effectiveness of this is uncertain. This review aimed to summarise and analyse the evidence on the effectiveness of early feeding for prevention of neonatal hypoglycaemia. <b><i>Methods:</i></b> Four databases and three clinical trial registries were searched from inception to May 24, 2023. Published and unpublished randomised controlled trials (RCTs), quasi-RCTs, cluster randomised trials, non-randomised studies of interventions, and observational studies with comparison groups were considered for inclusion with no language or publication date restrictions. We included studies of neonates who were fed early (within 60 min of birth or study defined) versus delayed. Study quality was assessed using the Cochrane Risk of Bias 1 tool or Effective Public Health Practice Project Quality Assessment tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RevMan 5.4.1 or R was used to synthesise results in random-effects meta-analyses. This review was registered prospectively with PROSPERO (CRD42022378904). <b><i>Results:</i></b> A total of 175,392 participants were included across 19 studies, of which two were RCTs, 14 cohort studies, two cross-sectional studies, and one a case-control study. Most studies (13/19) were conducted in low- or lower-middle-income countries. Early feeding may be associated with reduced neonatal hypoglycaemia (four cohort studies, 744 infants, odds ratio [OR] 0.19 (95% CI: 0.10–0.35), <i>p</i> &lt; 0.00001, <i>I</i>² = 44%) and slightly reduced duration of initial hospital stay (one cohort study, 1,673 infants, mean difference: –0.20 days [95% CI: −0.31 to −0.09], <i>p</i> = 0.0003), but the evidence is very uncertain. One RCT found early feeding had little or no effect on the risk of neonatal mortality, but three cohort studies found early feeding may be associated with reduced risk (136,468 infants, OR 0.51 [95% CI: 0.37–0.72]; low certainty evidence; <i>p</i> &lt;0.0001; <i>I</i>² = 54%). <b><i>Conclusion:</i></b> We found that early feeding may reduce the incidence of neonatal hypoglycaemia, but the evidence is very uncertain. Given its many other benefits, early feeding should continue to be recommended. This review was primarily funded by the Aotearoa Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health.