Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis

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); I 2 : 36%; 6 studies), ‘Any grade IVH’ (adjusted OR (CI): 2.60 (1.09 to 6.20); I 2 : 0%; 2 studies) and ‘Any stage ROP’ (adjusted OR (CI): 3.70 (1.55 to 8.84); I 2 : 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.