Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)

Abstract

Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. Main outcome measures NEC incidence. Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.