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Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis
  1. Chandra Prakash Rath1,2,
  2. Madhusudhan Shivamallappa1,2,
  3. Saravanan Muthusamy1,2,
  4. Shripada C Rao1,2,3,
  5. Sanjay Patole1,3
  1. 1 Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia
  2. 2 Neonatology, Perth Children's Hospital, Nedlands, Western Australia, Australia
  3. 3 School of Medicine, University of Western Australia, Crawley, Western Australia
  1. Correspondence to Dr Shripada C Rao, Perth Children's Hospital, Nedlands, Australia; shripada.rao{at}


Objective To explore the association between hyperglycaemia and adverse outcomes in very preterm infants.

Design Systematic review and meta-analysis. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. Subgroup analysis was conducted based on study design (cohort and case control).

Main outcome measures Association between hyperglycaemia in preterm neonates (<32 weeks or <1500 g) and mortality and morbidities.

Findings Forty-six studies (30 cohort and 16 case control) with data from 34 527 infants were included. Meta-analysis of unadjusted ORs from cohort studies found hyperglycaemia to be significantly associated with mortality, any-grade intraventricular haemorrhage (IVH), severe IVH, any-stage retinopathy of prematurity (ROP), severe ROP, sepsis, chronic lung disease and disability. However, pooling of adjusted ORs found significant associations only for mortality (adjusted OR (CI): 2.37 (1.40 to 4.01); I2: 36%; 6 studies), ‘Any grade IVH’ (adjusted OR (CI): 2.60 (1.09 to 6.20); I2: 0%; 2 studies) and ‘Any stage ROP’ (adjusted OR (CI): 3.70 (1.55 to 8.84); I2: 0%; 2 studies). Meta-regression analysis found glucose levels >10 mmol/L to be associated with increased odds of mortality compared with <10 mmol/L. Pooled analysis from case–control studies were similar to cohort studies for most outcomes but limited by small sample size. Longer duration of hyperglycaemia was associated with adverse outcomes. GRADE of evidence was ‘Low’ or ‘Very low’.

Conclusion Hyperglycaemia in very preterm infants is associated with higher odds of mortality, any-grade IVH and any-stage ROP. A limitation was lack of availability of adjusted ORs from many of the included studies.

PROSPERO registration number CRD42020193016.

  • neonatology
  • endocrinology
  • mortality

Data availability statement

Data are available on reasonable request. Data are available from the corresponding author and would be provided on reasonable request.

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Data availability statement

Data are available on reasonable request. Data are available from the corresponding author and would be provided on reasonable request.

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  • Contributors CPR and SCR conceptualised and designed the study, data collection instruments, drafted the initial manuscript, carried out the initial analyses, and reviewed and revised the manuscript. MS, SM and CPR collected data, reviewed and revised the manuscript. SP coordinated and supervised data collection, and critically reviewed 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.