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Background: Necrotising enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting extremely preterm infants. In Sweden, the incidence of NEC among extremely preterm infants increased from 6% in 2004–2007 to 10% in 2014–2016. Extremely preterm infants have an immature gastrointestinal tract and are prone to feeding intolerance (FI), including its more severe form, prolonged FI. Prolonged FI may lead to dependence on parenteral nutrition, suboptimal nutrient intake, and adverse outcomes.

Aim: This thesis aimed to validate NEC diagnosis, examine temporal trends in incidence and growth, explore the association between early enteral feeding and NEC risk, and describe the risk factors and clinical outcomes associated with prolonged FI.

Methods: Three cohorts were studied: EXPRESS (all live-born infants <27 weeks’ gestation in Sweden, 2004–2007; n=704), EXPRESS 2 (2014–2016; n=895), and the N-Forte trial of infants born <28 weeks’gestation (2019–2021; n=228). All NEC diagnoses in EXPRESS and EXPRESS 2 were validated. Nutritional practices, growth, and outcomes were assessed, and infants with prolonged FI were compared with matched controls.

Results: After validation, the NEC incidence remained higher in the later cohort (8.2% vs 3.8%, p=0.001), while the combined outcome of NEC or death decreased (27.3% vs 32.5%, p=0.022). Early NEC (≤7 days) did not differ between cohorts, whereas late NEC (>7 days) was more common in EXPRESS 2 (adjusted hazard ratio 2.7, p=0.001). In a propensity score analysis, the increase in NEC incidence was only observed in infants with the highest baseline risk. In the EXPRESS 2 cohort, enteral feeding was advanced more rapidly (10 vs 8 ml/kg/d, p<0.001) and fortification was more common started in the first two postnatal weeks (70% vs 23%, p<0.001), accompanied by improved early postnatal growth. Neither feeding advancement nor fortification was associated with an increased risk of late NEC. In the N-Forte cohort, 14% of the infants developed prolonged FI. They reached nutritional targets later but showed no differences ingrowth or major neonatal morbidities compared with the matched controls. Prolonged FI was associated with longer exposure to central venous catheters and antibiotics.

Conclusions: The increase in NEC incidence over time was restricted to late-onset NEC (>7d) and was partly attributable to improved survival among the most extremely preterm infants. Misclassification of NEC diagnoses was common. Nutritional practices improved, and more active enteral nutrition was not associated with an increased NEC risk. Lower birth weight was a risk factor for prolonged FI, which was associated with prolonged use of central venous catheters and antibiotics, but not with impaired growth or major morbidity.