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

The German Neonatal Network (GNN)

doi:10.1038/s41598-020-58761-6

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

The German Neonatal Network (GNN)

Department of Pediatric and Adolescent Medicine

36 Citations (Scopus)

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.

Original language	English
Article number	2373
Journal	Scientific Reports
Volume	10
Issue number	1
Pages (from-to)	2373
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-020-58761-6
Publication status	Published - 11.02.2020

Funding

ethics. Approval by the local ethic committee for research in human subjects of the University of Lübeck (file number 08–022) and by the local ethic committees of all participating centres has been given. Written informed parental consent was given for the research and publication of the results of each infant included in the study. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). The authors would like to thank all nurses, doctors and participating NICUs for their support and especially all participating infants and their parents. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). The sponsor had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 5 Gender Equality

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10.1038/s41598-020-58761-6

Cite this

@article{c9beb4cf7c3d4aa794807dc567c0a6cc,

title = "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.",

author = "\{The German Neonatal Network (GNN)\} and Alexander Humberg and Juliane Spiegler and Fortmann, \{Mats Ingmar\} and Michael Zemlin and Janina Marissen and Isabelle Swoboda and Rausch, \{Tanja K.\} and Egbert Herting and Wolfgang G{\"o}pel and Christoph H{\"a}rtel and Christian Wieg and Angela Kribs and \{von der Wense\}, Axel and Ursula Weller and Thomas H{\"o}hn and Olbertz, \{Dirk M.\} and Ursula Felderhoff-M{\"u}ser and Rainer Rossi and Norbert Teig and Friedhelm Heitmann and Susanne Schmidtke and Bettina Bohnhorst and Matthias Vochem and Holger Michel and Jens M{\"o}ller and Eichhorn, \{Joachim G.\} and J{\"u}rgen Wintgens and Ralf B{\"o}ttger and Mechthild Hubert and Michael D{\"o}rdelmann and Georg Hillebrand and Claudia Roll and Reinhard Jensen and Mario R{\"u}diger and Julia Sandk{\"o}tter and Stefan Sch{\"a}fer and Thomas Schaible and Axel Franz and Malik Aydin and Silke Ehlers and Claudius Werner and Thorsten Orlikowsky and Hubert Gerleve and Katja Schneider and Claudius Werner and Kai B{\"o}ckenholt and Knud Linnemann and Dirk M{\"u}ller and Corinna Gebauer and Florian Guthmann",

note = "Funding Information: ethics. Approval by the local ethic committee for research in human subjects of the University of L{\"u}beck (file number 08–022) and by the local ethic committees of all participating centres has been given. Written informed parental consent was given for the research and publication of the results of each infant included in the study. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). Funding Information: The authors would like to thank all nurses, doctors and participating NICUs for their support and especially all participating infants and their parents. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). The sponsor had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = feb,

day = "11",

doi = "10.1038/s41598-020-58761-6",

language = "English",

volume = "10",

pages = "2373",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Springer Science and Business Media, LLC",

number = "1",

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TY - JOUR

T1 - Surgical necrotizing enterocolitis but not spontaneous intestinal perforation is associated with adverse neurological outcome at school age

AU - The German Neonatal Network (GNN)

AU - Humberg, Alexander

AU - Spiegler, Juliane

AU - Fortmann, Mats Ingmar

AU - Zemlin, Michael

AU - Marissen, Janina

AU - Swoboda, Isabelle

AU - Rausch, Tanja K.

AU - Herting, Egbert

AU - Göpel, Wolfgang

AU - Härtel, Christoph

AU - Wieg, Christian

AU - Kribs, Angela

AU - von der Wense, Axel

AU - Weller, Ursula

AU - Höhn, Thomas

AU - Olbertz, Dirk M.

AU - Felderhoff-Müser, Ursula

AU - Rossi, Rainer

AU - Teig, Norbert

AU - Heitmann, Friedhelm

AU - Schmidtke, Susanne

AU - Bohnhorst, Bettina

AU - Vochem, Matthias

AU - Michel, Holger

AU - Möller, Jens

AU - Eichhorn, Joachim G.

AU - Wintgens, Jürgen

AU - Böttger, Ralf

AU - Hubert, Mechthild

AU - Dördelmann, Michael

AU - Hillebrand, Georg

AU - Roll, Claudia

AU - Jensen, Reinhard

AU - Rüdiger, Mario

AU - Sandkötter, Julia

AU - Schäfer, Stefan

AU - Schaible, Thomas

AU - Franz, Axel

AU - Aydin, Malik

AU - Ehlers, Silke

AU - Werner, Claudius

AU - Orlikowsky, Thorsten

AU - Gerleve, Hubert

AU - Schneider, Katja

AU - Werner, Claudius

AU - Böckenholt, Kai

AU - Linnemann, Knud

AU - Müller, Dirk

AU - Gebauer, Corinna

AU - Guthmann, Florian

N1 - Funding Information: ethics. Approval by the local ethic committee for research in human subjects of the University of Lübeck (file number 08–022) and by the local ethic committees of all participating centres has been given. Written informed parental consent was given for the research and publication of the results of each infant included in the study. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). Funding Information: The authors would like to thank all nurses, doctors and participating NICUs for their support and especially all participating infants and their parents. The German Neonatal Network is funded by the German Ministry for Education and Research (BMBF-grant-No: 01ER0805 and 01ER1501). The sponsor had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/2/11

Y1 - 2020/2/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85079334134

U2 - 10.1038/s41598-020-58761-6

DO - 10.1038/s41598-020-58761-6

M3 - Journal articles

C2 - 32047169

AN - SCOPUS:85079334134

SN - 2045-2322

VL - 10

SP - 2373

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 2373

ER -

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

Abstract

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UN SDGs

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