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Hypoglycaemia and hyperglycaemia in neonatal encephalopathy: a systematic review and meta-analysis
  1. Simona Puzone1,
  2. Mario Diplomatico2,
  3. Elisabetta Caredda1,
  4. Anna Maietta1,
  5. Emanuele Miraglia Del Giudice1,
  6. Paolo Montaldo3
  1. 1 Department of Neonatal Intensive Care, University of Campania Luigi Vanvitelli, Naples, Italy
  2. 2 Department of Neonatal Intensive Care, AORN San Giuseppe Moscati, Avellino, Italy
  3. 3 Imperial Neonatal Service, Centre for Perinatal Neuroscience, Department of Paediatrics, Imperial College London, London, UK
  1. Correspondence to Dr Paolo Montaldo, Imperial Neonatal Service, Centre for Perinatal Neuroscience, Department of Paediatrics, Imperial College London, London, W12 0HS, UK; p.montaldo{at}imperial.ac.uk

Abstract

Importance Although hypoglycaemia and hyperglycaemia represent the most common metabolic problem in neonates, there is still uncertainty regarding the effects of glucose homoeostasis on the neurological outcomes of infants with neonatal encephalopathy (NE).

Objective To systematically investigate the association between neonatal hypoglycaemia 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 (Grading of Recommendations, Assessment, Development and Evaluation (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 82 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 to 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 to 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 high-risk infants.

PROSPERO registration number CRD42022368870.

  • Neonatology
  • Intensive Care Units, Neonatal
  • Neurology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Contributors SP and MD searched the literature, extracted the data, and drafted the manuscript. EC provided consensus on the extracted data and assisted with developing the manuscript. AM and EMDG assisted with the revision of the manuscript. PM conceived the idea, assisted with developing the manuscript and supervised the entire work. PM is responsible for the overall content as the guarantor. All authors critically revised the intellectual content of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.