Active perinatal care of preterm infants in the German Neonatal Network

Humberg, Alexander; Härtel, Christoph; Rausch, Tanja K.; Stichtenoth, Guido; Jung, Philipp; Wieg, Christian; Kribs, Angela; Wense, A. von der; Weller, Ursula; Höhn, T.; Olbertz, Dirk; Felderhoff-Müser, Ursula; Rossi, Rainer; Teig, Norbert; Heitmann, Friedhelm; Schmidtke, Susanne; Bohnhorst, Bettina; Vochem, Matthias; Segerer, Hugo; Möller, Jens; Eichhorn, Joachim; Wintgens, Jürgen; Böttger, Ralf; Hubert, Mechthild; Dördelmann, Michael; Hillebrand, Georg; Roll, Claudia; Jensen, R; Zemlin, Michael; Mögel, Michael; Werner, Claudius; Schäfer, Stefan; Schaible, Thomas; Franz, Axel; Heldmann, Michael; Ehlers, Silke; Kannt, O.; Orlikowsky, Thorsten; Gerleve, Hubert; Schneider, Katja; Haase, Roland; Böckenholt, Kai; Linnemann, Knud; Herting, Egbert; Göpel, Wolfgang

doi:10.1136/archdischild-2018-316770

Cited by 35 publications

(32 citation statements)

References 16 publications

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“…The German Neonatal Network (GNN) is an ongoing multicentre population-based cohort study enrolling VLBWI with <1500 g birth weight in Germany. From 2009 until 2014, 43 tertiary German tertiary level NICUs contributed to the GNN (www.vlbw.de) 32 . Data were collected prospectively by neonatologists or trained study personal.…”

Section: Discussionmentioning

confidence: 99%

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

Humberg

Spiegler

Fortmann

et al. 2020

Sci Rep

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the German neonatal network (Gnn) † 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-lowbirthweight 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. Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are typical gastrointestinal complications in very-low-birthweight infants (VLBWI) and have a remarkable impact on mortality and long-term morbidity in this vulnerable group 1-4. In VLBWI, NEC mainly occurs during day 14-28 of life 5 and seems to have multifactorial facets including genetic predisposition, intestinal immaturity, inflammation, oxidative stress, ischemia, nutritional aspects and gut dysbiosis 2,6,7. SIP usually occurs in the first 14 days of life 8 and is mainly associated with extreme prematurity, use of non-steroidal and steroidal anti-inflammatory drugs and prolonged evacuation of meconium 9,10. Recently, we noted an increased SIP risk in infants <25 weeks of gestation who were primarily managed with less invasive respiratory care 3. Epidemiological data of infants with NEC or SIP show delayed neurodevelopment in early childhood 2,9,11 , but little is known about outcome at school age. Roze et al. found an increased rate of reduced intelligence quotient (IQ) and motor testing scores among children at school age who suffered from NEC or SIP 11 compared to controls without these complications. However, the authors did not adjust for confounding variables such as gestational age or maternal education level and did not differentiate between NEC and SIP.

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Section: Discussionmentioning

confidence: 99%

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

Humberg

Spiegler

Fortmann

et al. 2020

Sci Rep

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“…The significance of gender (including the role of sex hormones, sex chromosomes) has been well established for inflammation processes and microbiome development in animal models and observed in a variety of human studies [233]. The gender difference is particularly marked among preterm infants, where females have a distinct survival and outcome advantage at similar birth weights and gestational ages [4,234]. Female preterm infants have a decreased risk for severe courses of infectious diseases as compared with males (bacterial, viral, fungal) [234][235][236][237][238][239][240][241].…”

Section: Inflammation and Preterm Sex Differencesmentioning

confidence: 99%

“…Inflammation is particularly important for the development of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP) but also for intracerebral hemorrhage (ICH) and periventricular leukomalacia (PVL). Classical "inflammatory phenotypes" are seen in preterm infants with sepsis or NEC which are still the second most common causes of death in preterm infants after respiratory failure [4]. Acute inflammatory processes, specifically in survivors from sepsis or NEC, may not be well resolved and therefore result in SI.…”

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confidence: 99%

Preterm birth and sustained inflammation: consequences for the neonate

et al. 2020

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Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

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“…Bronchopulmonary dysplasia (BPD) is a major complication of premature birth and has been linked to chronic pulmonary inflammation leading to a high risk of mortality and long-term morbidities (1)(2)(3)(4)(5). Hence, there is an urgent need to develop early markers for the prevention of BPD.…”

Section: Introductionmentioning

confidence: 99%