Nabelvenenkatheter- und periphere zentrale katheterassoziierte Komplikationen bei Frühgeborenen mit einem Geburtsgewicht < 1250 g : Ergebnisse einer Umfrage in Österreich und Deutschland

Background and objective Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight < 1250 g and associated rates of catheter-related adverse events. Methods Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). Results In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1–10 days were bacterial infection: 4.2 ± 3.4% (range 0–10%); thrombosis: 7.3 ± 7.1% (0–20%); emboli: 0.9 ± 2.0% (0–5%); organ injury: 1.1 ± 1.9% (0–5%); cardiac arrhythmia: 2.2 ± 2.5% (0–5%); and dislocation: 5.4 ± 8.7% (0–30%); and for PICCs with a dwell time of 1–14 days bacterial infection: 15.0 ± 3.4% (range 2.5–30%); thrombosis; 4.3 ± 3.5% (0–10%); emboli: 0.8 ± 1.6% (0–5%); organ injury: 1.5 ± 2.3% (0–5%); cardiac arrhythmia: 1.5 ± 2.3% (0–5%), and dislocation: 8.5 ± 4.6% (0–30%). Conclusion The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.Hintergrund und Ziel Nabelvenenkatheter („umbilical venous catheters“ [UVC]) und periphere zentrale Venenkatheter (PICC) werden häufig bei Frühgeborenen eingesetzt, sind jedoch mit einer Reihe von schwerwiegenden Komplikationen verbunden. In Österreich und Deutschland wurde eine Umfrage durchgeführt, um die Verwendung von UVC und PICC bei Frühgeborenen mit einem Geburtsgewicht < 1250 g und die damit verbundenen Raten von katheterbedingten unerwünschten Ereignissen zu bewerten. Methoden Elektronische Befragung der teilnehmenden Zentren der NeoVitaA-Studie. Hauptergebnisparameter waren die gemeldeten Raten von UVC- und PICC-assoziierten Komplikationen (Infektion, Thrombose, Embolie, Organverletzung, Arrhythmie, Dislokation, Sonstiges). Ergebnisse Insgesamt wurden 20 neonatale Intensivstationen (NICU) mit maximaler Intensivpflege in Österreich und Deutschland (Level I) kontaktiert, wobei 12/20 (60 %) von leitenden Neonatologen beantwortet wurden. Die gemeldeten Raten für UVC mit einer Verweildauer von 1 bis 10 Tagen waren bakterielle Infektionen: 4,2 ± 3,4 % (Bereich: 0–10 %); Thrombose: 7,3 ± 7,1 % (0–20 %); Embolie: 0,9 ± 2,0 % (0–5 %); Organverletzung: 1,1 ± 1,9 % (0–5 %); Herzrhythmusstörungen: 2,2 ± 2,5 % (0–5 %); und Dislokation: 5,4 ± 8,7% (0–30 %); und bei PICC mit einer Verweildauer von 1 bis 14 Tagen bakterielle Infektionen: 15,0 ± 3,4 % (Bereich: 2,5–30 %); Thrombose: 4,3 ± 3,5 % (0–10 %); Embolie: 0,8 ± 1,6 % (0–5 %); Organverletzung: 1,5 ± 2,3 % (0–5 %); Herzrhythmusstörungen: 1,5 ± 2,3 % (0–5 %) und Verrenkungen: 8,5 ± 4,6 % (0–30 %). Schlussfolgerung Die in dieser Umfrage berichteten katheterbedingten Komplikationsraten unterschieden sich zwischen UVC und PICC und waren höher als die in der Literatur berichteten. Um zuverlässigere Daten zu diesem klinisch wichtigen Thema zu erhalten, ist eine große prospektive, multizentrische, randomisierte, kontrollierte Studie geplant, in der die Nichtunterlegenheit einer verlängerten UVC-Verweildauer (bis zu 10 Tage) gegenüber dem frühen Wechsel (bis zu 5 Tage) zu einem PICC untersucht werden soll

Epidermal growth factor-mediated activation of the MAP kinase cascade results in altered expression and function of ABCG2 (BCRP)

Epidermal growth factor (EGF) is a multifunctional growth factor known to play a major role in proliferation and differentiation processes. EGF-induced differentiation is a prerequisite for function of various cell types, among them cytotrophoblasts, a functionally important cellular fraction in human placenta. Stimulation of cytotrophoblasts with EGF results in formation of a multinuclear syncytium representing the feto-maternal interface, which protects the fetus against exogenous substances. It is well established that part of this protection system is based on ATP-binding cassette (ABC) transporters such as ABCG2 (breast cancer resistance protein, BCRP). However, little is known about regulation of transport proteins in the framework of EGF-mediated cellular differentiation. In the present work we show a significant increase of ABCG2 expression by EGF in cytotrophoblasts, BeWo, and MCF-7 cells on both mRNA and protein levels. This increase resulted in decreased sensitivity to the ABCG2 substrates mitoxantrone and topotecan. In each cell type, EGF increases expression of ABCG2 by activation of mitogen-activated protein kinase cascade via phosphorylation of extracellular regulated kinase (ERK)1/2 and c-jun NH-terminal kinase/stress-activated protein kinase (JNK/SAPK). Consequently, the increase of ABCG2 by EGF was abolished by pretreatment of cells with the tyrosine kinase inhibitor 4-(3-chloroanillino)-6,7-dimethoxyquinazoline (AG1478) or the mitogen-activated protein kinase kinase inhibitor 2′-amino- 3′methoxyflavone (PD 98059), thereby reestablishing sensitivity toward mitoxantrone. Moreover, analysis of ABCG2 expression during placental development revealed a significant increase in preterm versus term placenta. Taken together, our data show regulation of ABCG2 expression by EGF. In view of EGF signal transduction as a target for drugs (e.g., gefitinib), which are in turn substrates and/or inhibitors of ABCG2, this regulation has therapeutic consequences

Active perinatal care of preterm infants in the German Neonatal Network

Objective To determine if survival rates of preterm infants receiving active perinatal care improve over time. Design The German Neonatal Network is a cohort study of preterm infants with birth weight P75), intermediate (P25-P75) and low (<P25) survival. We compared these survival rates with data in 2014-2016. Main outcome measures Death by any cause before discharge. Results Total survival increased from 85.8% in 2011-2013 to 87.4% in 2014-2016. This increase was due to reduced mortality of NICUs with low survival rates in 2011-2013. Survival increased in these centres from 53% to 64% in the 22-24 weeks strata and from 73% to 84% in the 25-26 weeks strata. Conclusions Our data support previous reports that active perinatal care of very immature infants improves outcomes at the border of viability and survival rates at higher gestational ages. The high total number of surviving infants below 24 weeks of gestation challenges national recommendations exclusively referring to gestational age as the single criterion for providing active care. However, more data are needed before recommendations for parental counselling should be reconsidered