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Background: Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO 2 ) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk-benefit ratios of different SpO 2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany., Methods: In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO 2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO 2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO 2 ranges was calculated using chi-squared and Mann Whitney U tests., Results: Nine of the ten participating NICUs met their SpO 2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p  = 0.02; and 26.6% vs. 17.7%, p  < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found., Conclusion: In our patient population, a lower SpO 2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Willgerodt, Bührer, Rossi, Kühn, Rüdiger, Avenarius, Böttger, Olbertz, Proquitte, Bittrich, Haase, Fröhlich, Höhne and Thome.)

Background and Objective: Intrauterine growth restriction (IUGR) poses additional challenges in extremely low gestational age newborns (ELGANs). We assessed disturbed hematopoiesis and morbidities associated with this disorder. Methods: This single-center retrospective case-control study compared perinatal hematological profiles, major morbidities, and mortality of 49 infants (gestational age <28 weeks, birth weight ≤ 3rd percentile, and compromised placental function) and 98 infants (birth weight >10th percentile) matched for gestational age, year, and sex. Results: IUGR-ELGANs had significantly elevated nucleated red blood cells and lower neutrophil and platelet counts at birth and on the third day of life. During the first week of life, IUGR-ELGANs received more red blood cell, platelet, and plasma transfusions and were more intensively treated with antibiotics. Rates of infections acquired during the first week (59.2 vs. 17.3%, p < 0.001), severe bronchopulmonary dysplasia or death (42.9 vs. 17.3%, p < 0.01), and mortality (36.7 vs. 7.1%, p < 0.001) were markedly elevated in IUGR-ELGANs, but not of hemorrhages or other morbidities. Conclusions: IUGR-ELGANs have high rates of acquired infections during the first week of life and display severe pulmonary morbidity leading to bronchopulmonary dysplasia or death. The high rate of transfusions observed in these infants warrants further scrutiny., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Reibel, Dame, Bührer and Muehlbacher.)

Objective: To investigate and compare nurses' perceived care-related distress and experiences in end-of-life situations in neonatal and pediatric intensive care units. Study design: Single-center, cross-sectional survey. Administration of an anonymous self-report questionnaire survey to nurses of two tertiary neonatal intensive care units (NICUs), and two tertiary pediatric intensive care units (PICUs) in Berlin, Germany. Results: Seventy-three (73/227, response rate 32.2%) nurses completed surveys. Both, NICU (32/49; 65.3%) and PICU (24/24; 100.0%) nurses, reported "staffing shortages" to be the most frequent source of distress in end-of-life situations. However, when asked for the most distressing factor, the most common response by NICU nurses (17/49) was "lack of clearly defined and agreed upon therapeutic goals", while for PICU nurses (12/24) it was "insufficient time and staffing". No significant differences were found in reported distress-related symptoms in NICU and PICU nurses. The interventions rated by NICU nurses as most helpful for coping were: "discussion time before the patient's death" (89.6%), "team support" (87.5%), and "discussion time after the patient's death" (87.5%). PICU nurses identified "compassion" (98.8%), "team support", "personal/private life (family, friends, hobbies)", and "discussion time after the patient's death" (all 87.5%) as most helpful. Conclusions: Distress-related symptoms as a result of end-of-life care were commonly reported by NICU and PICU nurses. The most frequent and distressing factors in end-of-life situations might be reduced by improving institutional/organizational factors. Addressing the consequences of redirection of care , however, seems to be a more relevant issue for the relief of distress associated with end-of-life situations in NICU, as compared to PICU nurses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garten, Danke, Reindl, Prass and Bührer.)

Objective: Immature platelet counts (IPC) may prove useful in guiding platelet transfusion management in preterm neonates. However, the relationship between IPCs and thrombopoietin (Tpo) concentrations has not been evaluated in preterm neonates. Methods: Prospective cohort study in thrombocytopenic ( n = 31) and non-thrombocytopenic very low birth weight (VLBW) infants ( n = 38), and healthy term neonates (controls; n = 41). Absolute platelet counts (APCs), IPCs, and Tpo concentrations were assessed by a fully-automated hematological analyzer (IPC, APC) and by ELISA (Tpo concentrations) in parallel on day 1 of life (d1), d3, and d7. Results: In healthy term neonates, APCs remained stable between d1 and d3. In non-thrombocytopenic VLBW infants, APCs increased from d1 to d7, while in the thrombocytopenia group, APCs declined from d1 to d3, before they slightly increased again by d7. Median IPCs were similar in healthy term vs. non-thrombocytopenic VLBW infants and remained stable between d1 and d3 ( p > 0.05). Notably, IPCs significantly increased between d3 and d7 in both non-thrombocytopenic and thrombocytopenic VLBW infants. However, in thrombocytopenic VLBW infants, IPC values were significantly lower at each time point as compared to non-thrombocytopenic VLBWs ( p < 0.001). In each subgroup, Tpo concentrations increased from d1 to d3. The median Tpo concentrations were significantly higher in thrombocytopenic as compared to non-thrombocytopenic VLBW infants at d3 ( p = 0.01) and d7 ( p = 0.002). Discussion: Term infants, thrombocytopenic, and non-thrombocytopenic preterm infants display similar developmental changes in indices of megakaryopoietic activity. In thrombocytopenic preterm infants, however, the responsive increases in Tpo and immature platelets appear to be developmentally limited., Competing Interests: MC served on the advisory board of SYSMEX Deutschland GmbH (Hamburg, Germany). AW is employed by the company Labor Berlin – Charité Vivantes GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sallmon, Weimann, Bührer, Metze, Dame and Cremer.)

A meta-analysis update of randomized controlled trials investigating recombinant human erythropoietin suggests improved neurodevelopmental outcome in preterm infants. There was substantial heterogeneity, which could be ascribed to a single trial. Exclusion of this trial featuring a high risk of bias abolished heterogeneity and any effects of recombinant human erythropoietin treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fischer, Reibel, Bührer and Dame.)

Objective: To investigate the prevalence and characteristics of neonates with life-limiting or life-threatening conditions who receive care focused exclusively on comfort. Methods: Retrospective chart review of all newborn infants admitted to a level III perinatal center within a 5 year period. Results: 1,777 of 9,878 infants (18.0%) had life-limiting or life-threatening conditions. 149 (1.5% of all neonates) were categorized as comfort care patients with death being anticipated within hours to weeks. 34.2% of comfort care patients suffered from conditions specific to the neonatal period, 28.9% were preterm infants at the limit of viability, and 22.8% were patients with congenital complex chronic conditions. In 80.5% of all comfort care patients treatment goals were re-directed toward a comfort-care-only regimen only once that life-prolonging therapies were demonstrated to be unhelpful. 136/149 comfort care patients (91.3%) died in hospital, while 13 (8.7%) were discharged home or into a hospice. Median age at death for comfort care patients was 3 days after birth (interquartile range 1-15.5 days), and delivery room death immediately after birth occurred in 37 patients (27.2%). Conclusions: The vast majority of neonatal comfort care patients died in the hospital during the first week of life. However, almost one in 10 comfort care patients were discharged to home or hospice, suggesting that planning transition out of the NICU should be routinely discussed for all infants receiving comfort care.

Background: The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear., Methods: In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated., Results: Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure ( p  < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure., Conclusion: We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

Background: Expectant parents of very preterm infants, physicians, and policy makers require estimates for chances of survival and survival without morbidity. Such estimates should derive from a large, reliable, and contemporary data base of easily available items known at birth., Objective: To determine short-term outcome and risk factors in very-low-birth-weight preterm infants based on administrative data., Methods: Anonymized routine data sets transmitted from hospital administrations to statutory health insurance companies were used to assess survival and survival free of major morbidities in a large cohort of preterm infants in Germany., Results: After exclusion of infants with lethal malformations, there were 13,147 infants with a birth weight below 1,500 g admitted to neonatal care 2008-2012, of whom 1,432 infants (10.9%) died within 180 days. Estimated 180 days survival probabilities were 0.632 (95% confidence interval 0.583-0.677) for infants with 250-499 g birth weight, 0.817 (0.799-0.834) for 500-749 g, 0.931 (0.920-0.940) for 750-999 g, 0.973 (0.967-0.979) for 1,000-1,249 g, and 0.985 (0.981-0.988) for 1,250-1,499 g. Estimated probabilities for survival without major morbidity (surgically treated intraventricular hemorrhage, necrotizing enterocolitis, intestinal perforation, or retinopathy) were 0.433 (0.384-0.481) for 250-499 g, 0.622 (0.600-0.643) for 500-749 g, 0.836 (0.821-0.849) for 750-999 g, 0.938 (0.928-0.946) for 1,000-1,249 g, and 0.969 (0.964-0.974) for 1,250-1,499 g, respectively. Prediction of survival and survival without major morbidities was moderately improved by adding sex, small for gestational age, and severe or moderate congenital malformation, increasing receiver operating characteristic areas under the curve from 0.839 (0.827-0.850) to 0.862 (0.852-0.874) (survival) and from 0.827 (0.822-0.842) to 0.852 (0.846-0.863) (survival without major morbidities), respectively., Conclusion: The present analysis encourages attempts to use administrative data to investigate the association between risk factors and outcome in preterm infants.

White matter disease in preterm infants comes along with focal destructions or with diffuse myelination disturbance. Recent experimental work with transgenic mice paves the way for a unifying molecular model for both types of brain injury, placing oxygen sensing by oligodendrocyte precursor cells (OPCs) at the center stage. Mice genetically altered to mimic high local oxygen tension in oligodendroglia lineage cells (via deletion of hypoxia-inducible factor, HIF) develop white matter disease resembling cystic periventricular leukomalacia within the first 7 days of life. Mice in which local hypoxia is mimicked in oligodendroglial cells (via genetic inhibition of HIF decay) display arrested OPC maturation and subsequent hypomyelination, reminiscent of the diffuse white matter disease observed in preterm infants and infants with congenital heart disease. These recent experimental findings on oxygen sensing and myelination are awaiting integration into a clinical framework. Gene regulation in response to hyperoxia or hypoxia, rather than oxidative stress, may be an important mechanism underlying neonatal white matter disease.