Short- and Long-Term Neurodevelopmental Outcomes of Very Preterm Infants with Neonatal Sepsis: A Systematic Review and Meta-Analysis

Sepsis is commonly experienced by infants born very preterm (<32 weeks gestational age and/or <1500 g birthweight), but the long-term functional outcomes are unclear. The objective of this systematic review was to identify observational studies comparing neurodevelopmental outcomes in very preterm infants who had blood culture-proven neonatal sepsis with those without sepsis. Twenty-four studies were identified, of which 19 used prespecified definitions of neurodevelopmental impairment and five reported neurodevelopmental outcomes as continuous variables. Meta-analysis was conducted using 14 studies with defined neurodevelopmental impairment and demonstrated that very preterm infants with neonatal sepsis were at higher risk of impairments, such as cerebral palsy and neurosensory deficits, compared with infants without sepsis (OR 3.18; 95% CI 2.29–4.41). Substantial heterogeneity existed across the studies (I(2) = 83.1, 95% CI 73–89). The five studies that reported outcomes as continuous variables showed no significant difference in cognitive performance between sepsis and non-sepsis groups. Neonatal sepsis in very preterm infants is associated with increased risk of neurodevelopmental disability. Due to the paucity of longitudinal follow-up data beyond 36 months, the long-term cognitive effect of neonatal sepsis in very preterm infants could not be conclusively determined. Effects on the development of minor impairment could not be assessed, due to the small numbers of infants included in the studies.