Background There is limited information about the mortality and neurodevelopmental outcomes of very preterm infants (<32 weeks) with spontaneous intestinal perforation (SIP).

Objective To explore the association between SIP and neurodevelopmental outcomes and mortality in very preterm infants.

Data sources Medline, EMBASE, Cochrane Library, EMCARE and MedNar.

Study selection Databases were searched until September 2021. Studies comparing outcomes of ‘SIP’ versus ‘no SIP or necrotising enterocolitis (NEC)’ were included.

Data extraction Neurodevelopmental outcomes at ≥1 year corrected age were extracted as the main outcome measure. Data were pooled separately for adjusted and unadjusted ORs using the random-effects model. The evidence level was assessed using the GRADE (Grading of Recommendations, Assessments, Development and Evaluations) framework.

Results Eighteen cohort studies (13 606 infants) were included. Meta-analysis of unadjusted ORs showed that SIP was significantly associated with increased odds of mortality, cerebral palsy, composite outcome of death or disability, visual impairment and hearing impairment. However, pooling of adjusted ORs (aOR) found significant associations only for mortality (aOR (95% CI) 2.27 (2.07 to 2.49); I²: 0%; four studies (n=10 695)), severe disability (aOR (95% CI) 2.06 (1.38 to 3.08); I²: 0%; two studies (n=321)) and composite outcome of ‘death or disability’ (aOR (95% CI) 2.18 (1.55 to 3.06); I²: 0%; two studies (n=321)). The level of evidence was ‘low’ or ‘very low’.

Limitations Lack of information on aORs from many studies.

Conclusions SIP in very preterm infants is associated with higher odds of mortality, severe disability, and death or disability.