Importance Although hypoglycaemia and hyperglycaemia represent the most common
metabolic problem in neonates, there is still uncertainty regarding the effects of glucose
homeostasis on the neurological outcomes of infants with neonatal encephalopathy (NE).
Objective To systematically investigate the association between neonatal hypo and
hyperglycaemia with adverse outcome in children who suffered from NE.
Study selection We searched Pubmed, Embase, and Web of Science databases to identify
studies which reported prespecified outcomes and compared infants with NE who had been
exposed to neonatal hypoglycaemia or hyperglycaemia with infants not exposed.
Data analysis We assessed the risk of bias (ROBINS-I), quality of evidence (GRADE) for
each of the studies. REVMAN was used for meta-analysis (inverse variance, fixed effects).
Main outcome Death or neurodevelopmental outcomes at 18 months of age or later.
Results Eighty-two studies were screened, 28 reviewed in full, and 12 included. Children
who were exposed to neonatal hypoglycaemia had higher odds of neurodevelopmental
impairment or death (6 studies, 685 infants; 40.6 vs. 25.4%; OR= 2.17, 95%CI=1.46– 3.25;
p=0.0001). Neonatal exposure to hyperglycaemia was associated with death or neurodisability at 18 months or later (7 studies, 807 infants; 46.1 vs. 28.0%; OR=3.07,
95%CI=2.17– 4.35; p<0.00001). These findings were confirmed in the subgroup analysis,
which included only the infants who underwent therapeutic hypothermia.
Conclusions These data suggest that neonatal hypoglycaemia and hyperglycaemia may be
associated with the neurodevelopmental outcome later on in infants with NE. Further studies
with long-term follow-up are needed to optimise the metabolic management of these highrisk infants.