Surgical necrotizing enterocolitis but not spontaneous intestinal perforation is associated with adverse neurological outcome at school age

Abstract

Gastrointestinal complications during the neonatal period, i.e. necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP), are associated with adverse short-term outcome in very-low-birthweight infants (VLBWI, <1500 g birth weight). However, little is known about the neurological outcome of survivors at school age. We analysed data of 2241 infants followed-up at the age of 6 years. To determine the effect of NEC and SIP on cognitive outcome in consideration of other important confounding factors, we used multivariable logistic regression models. In addition, infants with surgical diagnosis of NEC (n = 43) or SIP (n = 41) were compared to NEC (n = 43) or SIP (n = 41) negative controls using Mahalanobis distance matching. Infants with a history for NEC had a three times increased risk (RR 3.0 [1.8-4.2], p < 0.001) to develop IQ scores <85 while history of surgical SIP did not increase the relative risk for lower IQs at school age (RR 1.0 [0.4-2.1], p = 1.000). In a matched-cohort analysis, we confirmed that infants with surgical NEC had lower mean IQ results than unaffected controls (±SD) (85±17 vs. 94±14, p = 0.023) while no differences were found for history of SIP. Our results reflect that the different aetiology and inflammatory extent of NEC and SIP may lead to disparate neurodevelopment trajectories. Hence, our data suggest a potential role of early gut-brain axis distortion in infants with NEC which needs to be further explored.

Figure 1

Enrollment, in- and exclusion for analysis of neurologic and motor development at the age of 6 years. In- and exclusion for motor function and intelligence testing in 6 year old children born as VLBWI; *Reasons for not participating the follow-up assessment despite selection were: no current contact data available n = 1349, parents declined invitation for follow-up n = 519, parents were interested to participate but were not available at suggested follow-up dates n = 131, no-show despite arranged follow-up assessment n = 65; **Reasons for no WPPSI assessment included: WPPSI or other cognitive test within 12 months n = 161, language problems n = 24, child not motivated n = 39, serious disorder not related to prematurity (e.g. trisomy 21) n = 7, other reasons n = 10.

Figure 2

(a) Total, verbal and performance intelligence quotient scores in infants with and without NEC. Boxplot of IQ scores (total, verbal, performance) for matched infants with history of NEC and without a history of NEC. p-values are derived from T-Test. (b) Total, verbal and performance intelligence quotient scores in infants with and without SIP. Boxplot of IQ scores (total, verbal, performance) for matched infants with history of SIP and without a history of SIP. p-values are derived from T-Test.