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Purpose: Postnatal closure of a myelomeningocele (MMC) is a complex procedure with frequent complications following surgery. Bacterial colonization of the placode may cause infection and subsequent complications. The objectives of this study were to determine the preoperative bacterial colonization rates, to assess the antibiotic regimen, and to evaluate the overall postoperative infection rate., Methods: All consecutive patients undergoing MMC closure in our hospital from January 2010 to January 2020 were evaluated. Epidemiological data, surgical data, complication characteristics, and microbiological results were documented., Results: A total of 45 patients were evaluated; in 41 patients, a wound swab of the placode was performed directly before MMC closure (91%). All patients received a prophylactic antibiotic treatment for a mean of 5.6 ± 2.7 days around the performed MMC closure. In three patients with a wound swab (7.3%), a bacterial colonization could be detected-none of the patients developed a subsequent infection. Overall, 7 other patients developed an infection (15.6%), three local surgical site infections, and four shunt-related infections. After applying a standardized perioperative prophylactic antibiotic treatment with ampicillin and gentamicin, the infection rate was observed to be lower compared with that of a non-standardized treatment (6% vs. 45%; p = 0.019)., Conclusions: In neonates who undergo MMC closure in the first 48 h after birth, the colonization rate of the placode was lower than previously reported. While the data presented cannot proof the benefit of a perioperative antibiotic prophylaxis, as compared with no prophylaxis, infection rates are low with a standardized antibiotic regime comprising ampicillin and gentamicin.

Lung ultrasound is a well-studied diagnostic procedure in emergency medicine. Over the last several years, international research groups have investigated the role of lung ultrasound to evaluate neonatal respiratory diseases. Specific diagnostic algorithms and key features of a neonatal pneumothorax have been released. Compared to X-ray examination, lung ultrasound has many advantages, such as faster diagnostic time, lack of exposure to ionizing radiation, and excellent sensitivity and specificity. Thus, lung ultrasound contributes to the improvement of medical healthcare in the neonatal intensive care unit. We consider the use of lung ultrasound as a new standard procedure to diagnose a pneumothorax in neonatology., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0-102 ml) and contained a median of 0.77 × 10 8 TNC (range: 0.01-13.0 × 10 8 ). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.

Objectives: Neonates with dextro-transposition of the great arteries (d-TGA) may experience rapid haemodynamic deterioration and profound hypoxaemia after birth. We report on d-TGA patients with severe acidosis, encephalopathy and their treatment with systemic hypothermia., Methods: This study is a single-centre retrospective cohort analysis of newborns with d-TGA., Results: Ninety-five patients (gestational age ≥35 weeks) with d-TGA and intended arterial switch operation were included. Ten infants (10.5%) with umbilical arterial blood pH > 7.10 experienced profound acidosis (pH < 7.00) within the first 2 h of life. Six of these patients displayed signs of encephalopathy and received therapeutic hypothermia. Apgar scores at 5 min independently predicted the development of neonatal encephalopathy during postnatal transition (unit Odds Ratio 0.17, 95% confidence interval 0.06-0.49, P = 0.001). Infants treated with hypothermia had a more severe preoperative course and required more often mechanical ventilation (100% vs 35%, P = 0.003), treatment with inhaled nitric oxide (50% vs 2.4%, P = 0.002) and inotropic support (67% vs 3.5%, P < 0.001), as compared to non-acidotic controls. The median age at cardiac surgery was 12 (range 6-14) days in cooled infants and 8 (4-59) days in controls (P = 0.088). Postoperative morbidity and total duration of hospitalization were not increased in infants receiving preoperative hypothermia. Mortality in newborns with severe preoperative acidosis was zero., Conclusions: Newborn infants with d-TGA have a substantial risk for profound acidosis during the first hours of life. Systemic hypothermia for encephalopathic patients may delay corrective surgery without compromising perioperative outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: In very low birth weight (<1,500 g, VLBW) infants, morbidity and mortality have decreased substantially during the past decades, and both are known to be lower in girls than in boys. In this study, we assessed sex-specific changes over time in length of hospital stay (LOHS) and postmenstrual age at discharge (PAD), in addition to survival in VLBW infants., Methods: This is a single-center retrospective cohort analysis based on quality assurance data of VLBW infants born from 1978 to 2018. Estimation of sex-specific LOHS over time was based on infants discharged home from neonatal care or deceased. Estimation of sex-specific PAD over time was based on infants discharged home exclusively. Analysis of in-hospital survival was performed for all VLBW infants., Results: In 4,336 of 4,499 VLBW infants admitted from 1978 to 2018 with complete data (96.4%), survival rates improved between 1978-1982 and 1993-1997 (70.8 vs. 88.3%; hazard ratio (HR) 0.20, 95% confidence interval 0.14, 0.30) and remained stable thereafter. Boys had consistently higher mortality rates than girls (15 vs. 12%, HR 1.23 [1.05, 1.45]). Nonsurviving boys died later compared to nonsurviving girls (adjusted mean survival time 23.0 [18.0, 27.9] vs. 20.7 [15.0, 26.3] days). LOHS and PAD assessed in 3,166 survivors displayed a continuous decrease over time (1978-1982 vs. 2013-2018: LOHS days 82.9 [79.3, 86.5] vs. 60.3 [58.4, 62.1] days); PAD 40.4 (39.9, 40.9) vs. 37.4 [37.1, 37.6] weeks). Girls had shorter LOHS than boys (69.4 [68.0, 70.8] vs. 73.0 [71.6, 74.4] days) and were discharged with lower PAD (38.6 [38.4, 38.8] vs. 39.2 [39.0, 39.4] weeks)., Discussion/conclusions: LOHS and PAD decreased over the last 40 years, while survival rates improved. Male sex was associated with longer LOHS, higher PAD, and higher mortality rates., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Use of real-time continuous glucose monitoring (rtCGM) systems has been shown to be a low-pain, safe, and effective method of preventing hypoglycemia and hyperglycemia in people with diabetes of various age groups. Evidence on rtCGM use in infants and in patients with conditions other than diabetes remains limited., Objective: This case study describes the off-label use of rtCGM and the use of an open-source app for glucose monitoring in a newborn with prolonged hypoglycemia secondary to transient congenital hyperinsulinism during the perinatal period., Methods: The Dexcom G6 rtCGM system (Dexcom, Inc) was introduced at 39 hours of age. Capillary blood glucose checks were performed regularly. In order to benefit from customizable alert settings and detect hypoglycemic episodes, the open-source rtCGM app xDrip+ was introduced at 9 days of age., Results: Time in range (45-180 mg/dL) for interstitial glucose remained consistently above 90%, whereas time in hypoglycemia (<45 mg/dL) decreased. Mean glucose was maintained above 70 mg/dL at 72 hours of life and thereafter. Daily sensor glucose profiles showed cyclic fluctuations that were less pronounced over time., Conclusions: While off-label use of medication is both common practice and a necessity in newborn infants, there are few examples of off-label uses of medical devices, rtCGM being a notable exception. Real-time information allowed us to better understand glycemic patterns and to improve the quality of glycemic control accordingly. Severe hypoglycemia was prevented, and measurement of serum levels of insulin and further lab diagnostics were performed much faster, while the patient's individual burden caused by invasive procedures was reduced. Greater customizability of threshold and alert settings would be beneficial for user groups with glycemic instability other than people with diabetes, and for hospitalized newborn infants in particular. Further research in the field of personal and off-label rtCGM use, efficacy studies evaluating the accuracy of low glucose readings, and studies on the differences between algorithms in translating raw sensor data, as well as customization of commercially available rtCGM systems, is needed., (©Katarina Braune, Mandy Wäldchen, Klemens Raile, Sigrid Hahn, Tebbe Ubben, Susanne Römer, Daniela Hoeber, Nora Johanna Reibel, Michael Launspach, Oliver Blankenstein, Christoph Bührer. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.12.2020.)

Aim: Hypocarbia induced by mechanical ventilation has been considered a main cause of cystic periventricular leukomalacia (cPVL). However, hypocarbia may occur spontaneously in response to intracellular metabolic acidosis. We aimed to assess whether hypocarbia is more common during mechanical respiratory support than during spontaneous ventilation in infants with cPVL., Method: In this single-centre, retrospective chart analysis, we compared partial pressure of carbon dioxide (pCO 2 ) during the first 96 hours of life in infants with cPVL during endotracheal mechanical ventilation, non-invasive respiratory support, or without respiratory support., Results: Cystic periventricular leukomalacia was diagnosed in 23 infants born between 2006 and 2017. Gestational age was 24 weeks in two infants and ranged between 28 and 32 weeks in 21 infants. In these 21 infants, pCO 2 less than 35 mm Hg during the first 96 ours of life accounted for 9/60 (15%) measurements during endotracheal mechanical ventilation, 16/116 (14%) during non-invasive respiratory support and 14/42 (33%) in infants without respiratory support (P = .014)., Conclusion: In our series of infants with cPVL, hypocarbia was more common without respiratory support than during endotracheal mechanical ventilation and non-invasive respiratory support. This would suggest that hypocarbia is a symptom rather than a cause of cPVL in these infants., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objectives: To compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth., Methods: A retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children's examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years., Results: Overall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%., Conclusions: ANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease., Synopsis: First-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk., (© 2020 Thorsten Braun et al., published by De Gruyter, Berlin/Boston.)

Background: There are growing concerns about the increasing rate of caesarean section (CS) worldwide. Various strategies have been implemented to reduce the proportion of CS to a reasonable level. Most research on medical indications for CS focuses on nationwide evaluations. Comparative research between different countries is sparse. The aim of this study was to evaluate differences in the rate and indications for CS between Japan and Germany in 2012 and 2013., Methods: Comparison of the overall rate and medical indications for CS in two cohort studies from Germany and Japan. We used data from the German Perinatal Survey and the Japan Environment and Children's Study (JECS)., Results: We analyzed data of 1 335 150 participants from the German perinatal survey and of 62 533 participants from JECS and found significant differences between the two countries in CS rate (30.6% vs 20.6%) and main medical indications: cephalopelvic disproportion (3.2% vs 1.3%; OR: 2.4 [95% CI: 2.2-2.6]), fetal distress (7.3% vs 2.3%; OR: 3.4 [95%-CI: 3.2-3.6]), and past uterine surgery/repeat CS (8.4% vs 8.8%; OR: 0.9 [95%-CI: 0.9-1])., Conclusion: There are differences in the rate and medical indications for CS between Germany and Japan at the population level. Fetal distress was identified as a medical indication for CS more often Germany than in Japan. Considering the substantial diagnostic uncertainty of electronic fetal monitoring (EFM) as the major indicator for fetal distress, it would seem to be reasonable to rethink CS decision algorithms., (© 2020 The Authors. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Importance: Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds., Objective: To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability., Design, Setting, and Participants: Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018., Interventions: Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state., Main Outcome and Measures: The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth., Results: Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups., Conclusions and Relevance: Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age., Trial Registration: ClinicalTrials.gov Identifier: NCT01393496.

Objective: A standardized guideline for treatment of posthemorrhagic hydrocephalus in premature infants is still missing. Because an early ventriculoperitoneal shunt surgery is avoided due to low body weight and fragility of the patients, the neurosurgical treatment focuses on temporary solutions for CSF diversion as a minimally invasive approach. Neuroendoscopic lavage (NEL) was additionally introduced for early elimination of intraventricular blood components to reduce possible subsequent complications such as shunt dependency, infection, and multiloculated hydrocephalus. The authors report their first experience regarding neurodevelopmental outcome after NEL in this patient cohort., Methods: In a single-center retrospective cohort study with 45 patients undergoing NEL, the authors measured neurocognitive development at 2 years with the Bayley Scales of Infant Development, 2nd Edition, Mental Developmental Index (BSID II MDI) and graded the ability to walk with the Gross Motor Function Classification System (GMFCS). They further recorded medication with antiepileptic drugs (AEDs) and quantified ventricular and brain volumes by using 3D MRI data sets., Results: Forty-four patients were alive at 2 years of age. Eight of 27 patients (30%) assessed revealed a fairly normal neurocognitive development (BSID II MDI ≥ 70), 28 of 36 patients (78%) were able to walk independently or with minimal aid (GMFCS 0-2), and 73% did not require AED treatment. Based on MR volume measurements, greater brain volume was positively correlated with BSID II MDI (rs = 0.52, 95% CI 0.08-0.79) and negatively with GMFCS (rs = -0.69, 95% CI -0.85 to -0.42). Based on Bayesian logistic regression, AED treatment, the presence of comorbidities, and also cerebellar pathology could be identified as relevant risk factors for both neurodevelopmental outcomes, increasing the odds more than 2-fold-but with limited precision in estimation., Conclusions: Neuromotor outcome assessment after NEL is comparable to previously published drainage, irrigation, and fibrinolytic therapy (DRIFT) study results. A majority of NEL-treated patients showed independent mobility. Further validation of outcome measurements is warranted in an extended setup, as intended by the prospective international multicenter registry for treatment of posthemorrhagic hydrocephalus (TROPHY).

Background: Preterm birth implies an array of respiratory diseases including apnea of prematurity and bronchopulmonary dysplasia (BPD). Caffeine has been introduced to treat apneas but also appears to reduce rates of BPD. Oxygen is essential when treating preterm infants with respiratory problems but high oxygen exposure aggravates BPD. This experimental study is aimed at investigating the action of caffeine on inflammatory response and cell death in pulmonary tissue in a hyperoxia-based model of BPD in the newborn rat. Material/Methods . Lung injury was induced by hyperoxic exposure with 80% oxygen for three (P3) or five (P5) postnatal days with or without recovery in ambient air until postnatal day 15 (P15). Newborn Wistar rats were treated with PBS or caffeine (10 mg/kg) every two days beginning at the day of birth. The effects of caffeine on hyperoxic-induced pulmonary inflammatory response were examined at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR., Results: Treatment with caffeine significantly attenuated changes in hyperoxia-induced cell death and apoptosis-associated factors. There was a significant decrease in proinflammatory mediators and redox-sensitive transcription factor NF κ B in the hyperoxia-exposed lung tissue of the caffeine-treated group compared to the nontreated group. Moreover, treatment with caffeine under hyperoxia modulated the transcription of the adenosine receptor (Adora)1. Caffeine induced pulmonary chemokine and cytokine transcription followed by immune cell infiltration of alveolar macrophages as well as increased adenosine receptor (Adora1, 2a, and 2b) expression., Conclusions: The present study investigating the impact of caffeine on the inflammatory response, pulmonary cell degeneration and modulation of adenosine receptor expression, provides further evidence that caffeine acts as an antioxidative and anti-inflammatory drug for experimental oxygen-mediated lung injury. Experimental studies may broaden the understanding of therapeutic use of caffeine in modulating detrimental mechanisms involved in BPD development., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Stefanie Endesfelder et al.)

At the beginning of their career, civil servants in Germany can choose between the social health insurance (SHI) system and a private plan combined with a direct reimbursement of the government of up to 70 percent. Most civil servants chose the latter, not only but also because they have to cover all contributions in the social system themselves, while regular employees get nearly 50 percent from their employers. The city state of Hamburg decided to change the system by paying half of the contributions if civil servants choose the social plan. We use a stochastic microsimulation model to analyse which socio-economic types of civil servants could benefit from the Hamburg plan and if this changes the mix of insured persons in the SHI system. Our results show that low income and high morbidity types as well as families have a substantially higher incentive to choose SHI. This reform might thereby increase the adverse selection of high risk cases towards SHI., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The extensive use of antibiotics is reflected by an increasing prevalence of infections with multidrug-resistant bacteria, including third-generation cephalosporin-resistant bacteria (3GCRB). For neonatal intensive care units screening and enhanced barrier precautions are recommended to control the spread of multidrug-resistant Gram-negative bacteria, while evidence for efficacy of barrier precautions remains scarce in a non-outbreak setting., Objective: To determine the impact of a screening program for maternal 3GCRB colonization and the effects of contact precautions and cohort nursing, concerning the risk of neonatal late-onset sepsis (LOS) and antibiotic use rates (AURs)., Study Design: In a retrospective matched-pair cohort study, data of neonates exposed to maternal 3GCRB colonization were compared with findings in non-exposed neonates., Results: Of 3,144 neonates admitted, 184 neonates born to 3GCRB-positive mothers were eligible. Among them, 37 (20%) became 3GCRB positive during hospital stay. 3GCRB-exposed infants had a lower rate of LOS (6.5 vs. 14.1%, p=0.03) and lower AURs in that time period compared to controls (mean 0.009 vs. 0.025, p=0.006). When started within the first 72h after birth, days of therapy with meropenem were significantly lower in non-exposed vs. 3GCRB-exposed infants (mean 0.13 vs. 0.42; p=0.002). No invasive infections with 3GCRB occurred., Conclusions: Neonates of 3GCRB-positive mothers do not have an increased a priori risk for invasive 3GCRB infection and may benefit from enhanced contact precautions measures., Hintergrund: Der zunehmende Einsatz von Antibiotika führt zu einem Anstieg von Infektionen mit multiresistenten Erregern wie z. B. Drittgeneration Cephalosporin-resistenten Bakterien (3GCRB). Empfehlungen zu Screening- und Kohortierungsmaßnahmen auf neonatologischen Intensivstationen zielen auf die Prävention von horizontaler Transmission und invasiven Infektionen ab. Für Nicht-Ausbruchssituationen ist die Evidenz für Hygienemaßnahmen und Screeningprogrammen unzureichend. ZIEL: Evaluation eines Screening für mütterliche 3GCRB-Besiedlung mit nachfolgender Isolation bzw. Kohortenpflege des Neugeborenen (NG) unter Bezug auf das Risiko einer Late-Onset-Sepsis (LOS) und die Anzahl der Antibiotika-Tage (AUR)., Studiendesign: In einer retrospektiven Fall-Kontroll-Kohortenstudie wurden Daten von NG mit maternaler 3GCRB-Besiedelung im Vergleich zu einer Kontrollgruppe mit unauffälligem Screening analysiert., Ergebnisse: In einer Kohorte von 3144 NG fanden sich 184 NG von 3GCRB-besiedelten Müttern. Bei 37 (20%) wurde im Verlauf eine Besiedelung mit 3GCRB nachgewiesen. In der Gruppe der 3GCRB-exponierten NG kam es seltener zu einer LOS (6,5 vs. 14,1%, p=0,03). Zwischen dem 4. Lebenstag und der Entlassung hatten 3GCRB-exponierte NG eine niedrigere AUR (Mittelwert 0,009 vs. 0,025, p=0,006) als die Kontrollgruppe. Die Behandlungstage mit Meropenem (Start in den ersten 3 Lebenstagen), war in der Kontrollgruppe signifikant geringer als in der 3GCRB-exponierten Gruppe (Mittelwert 0,13 vs. 0,43 Tage; p=0,002). In beiden Gruppen trat keine invasive Infektion mit 3GCRB auf., Schlussfolgerung: Neugeborene, deren Mütter 3GCRB besiedelt sind, haben kein erhöhtes a priori Risiko für eine invasive Infektion mit 3GCRB Erregern und profitieren wahrscheinlich von erweiterten Kohortierungs- und Isolationsmaßnahmen., Competing Interests: C. Dame is member of the Neonatology Group of the Commission for Hospital Hygiene, Infection Prevention and Control (KRINKO) of the Federal Robert-Koch Institute (RKI), Berlin, Germany. All other authors report no conflict of interest relevant to this article., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown., Methods: In this observational study, counts of immature and mature platelets (=total platelet count - immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7., Results: Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus., Conclusion: During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

Background: To assess the postnatal rate of rise (ROR) of total serum bilirubin (TSB) in very low birth weight (VLBW) preterm infants, to determine risk factors associated with a rapid rise (>90th percentile), and to compare ROR and hour-specific TSB at postnatal 12-48 h with data of term infants retrieved from the literature., Methods: Retrospective analysis of 2430 routine TSB concentrations obtained between birth and initiation of phototherapy in 483 VLBW infants., Results: TSB increased by a median (interquartile range) ROR of 0.15 (0.11-0.19) mg/dL/h. The 50th percentile of TSB was below the 40th percentile of (near-)term counterparts at 12-48 h. TSB ROR correlated with the age at initiation (R S  = -0.687; p < 0.001) and the duration (R S  = 0.444; p < 0.001) of phototherapy. ROR >90th percentile (>0.25 mg/dL/h) was associated with lower gestational ages [27.2 (25.4-29.3) vs. 28.4 (26.4-30.4) weeks], lower birth weights [978 (665-1120) vs. 1045 (814-1300) g], and lower 5-min Apgar scores [7 (7-8) vs. 8 (7-9)]., Conclusion: ROR of TSB is an indicator for early and prolonged phototherapy. While hour-specific TSB and ROR at 12-48 h are lower than those reported for (near-)term infants, TSB appears to rise more rapidly in infants with low gestational age, low birth weight, and low 5-min Apgar score.

Introduction: The number of diseases covered by universal neonatal screening in Germany has risen steadily from 1 (phenylketonuria) in 1968 to 17 (with hearing impairment and congenital hip dysplasia) in 2018. Treatment, however, of disorders diagnosed by screening may harm children, as failed neuroblastoma screening has shown. There are several pilot studies to detect congenital cytomegalovirus (CMV) infection but no consensus as to the treatment of the infants identified., Methodology: Systematic search for studies investigating therapy of congenital CMV infection, using PubMed and the WHO International Clinical Trials Registry Platform (ICTRP)., Results: We found only one controlled trial that randomized infants with symptomatic congenital CMV infection (involving the central nervous system) to treatment (intravenous ganciclovir for 6 weeks) or no treatment. Treatment was associated with significantly less hearing deterioration. A second trial comparing 6 weeks vs. 6 months of treatment with valganciclovir, an oral prodrug of ganciclovir, found no benefit for hearing but modestly improved developmental outcomes associated with 6 months of treatment. In contrast, an open-label registry reported benefits for infants with congenital CMV infection and isolated hearing who received valganciclovir for 12 months, with hearing improvement in 2/3 of cases after a median follow-up of 4½ years., Conclusions: Antiviral treatment of neonates with congenital CMV infection and few symptoms including isolated hearing loss remains controversial. A generally accepted therapy, however, is pivotal before introducing universal or targeted screening for congenital CMV infection., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Exchange transfusion (ET) and intravenous immunoglobulin are potentially life-saving treatment options in newborns with gestational alloimmune liver disease (GALD). Since 2008, early ET has been the standard of care for symptomatic neonates with suspected GALD in our unit. The present study's aim was to investigate the outcomes of this approach., Methods: From 2008 to 2018, all neonates who received ET for suspected GALD were identified, and their clinical course and outcomes were analyzed in a descriptive cohort study. In survivors, liver function parameters before ET and maximum values after ET and at discharge were compared., Results: During the 11-year period, 12 infants received ET for suspected GALD at a median (range) chronological age of 11 (1-23) days and gestational age of 38 (32-40) weeks. Signs of impaired liver function, most frequently postnatal hypoglycemia, hyperferritinemia, direct hyperbilirubinemia, and coagulopathy, were present in all infants. Survival without a liver transplant in the overall cohort was 10 of 12 (83.3%) and 7 of 9 (78%) in those fulfilling the criteria of acute liver failure. Two patients died, one of them after liver transplantation. Direct bilirubin typically increased after ET, even in survivors. All survivors recovered and were discharged from the pediatric hepatology outpatient clinic after 8 (3-11) months of follow-up., Conclusions: In newborns with suspected GALD, a limited diagnostic work-up followed by early ET may lead to favorable outcomes. More data are required to develop an evidence-based clinical approach to GALD.

Neonatal infections are a major risk factor for neonatal mortality. A reliable diagnosis of early-onset sepsis (EOS) is hampered by the variable clinical presentations of the children. We hypothesized that changes in the Se or Cu status, or the biomarkers selenoprotein P (SELENOP) or ceruloplasmin (CP) alone or in combination may be informative of EOS. We generated a new human CP-specific non-competitive immunoassay (ELISA) suitable of analysing small sample volumes and validated the method with a commercial CP source. Using this novel CP assay, we analysed a case-control study of EOS (n = 19 control newborns, n = 18 suspected cases). Concentrations of Se, Cu, SELENOP, CP, interleukin-6 (IL-6), and C-reactive protein (CRP) along with the Cu/Se and CP/SELENOP ratios were evaluated by correlation analyses as biomarkers for EOS. Diagnostic value was estimated by receiver operating characteristic (ROC) curve analyses. The new CP-ELISA displayed a wide working range (0.10-6.78 mg CP/L) and low sample requirement (2 μL of serum, EDTA-, heparin- or citrate-plasma). Plasma CP correlated positively with Cu concentrations in the set of all samples (Pearson r = 0.8355, p < 0.0001). Three of the infected neonates displayed particularly high ratios of Cu/Se and CP/SELENOP, i.e., 3.8- to 6.9-fold higher than controls. Both the Cu/Se and the CP/SELENOP ratios correlated poorly with the early infection marker IL-6, but strongly and positively with the acute-phase protein CRP (Cu/Se-CRP: Spearman ϱ = 0.583, p = 0.011; CP/SELENOP-CRP: ϱ = 0.571, p = 0.013). The ROC curve analyses indicate that a combination of biomarkers for the Se and Cu status do not improve the early identification of EOS considerably. This study established a robust, highly precise, partly validated and scalable novel CP sandwich ELISA suitable for basic and clinical research, requiring minute amounts of sample. The ratio of circulating CP/SELENOP constitutes a promising new composite biomarker for detection of EOS, at least in a subset of severely diseased children., Competing Interests: Declaration of Competing Interest LS holds shares in selenOmed GmbH, a company involved in selenium status assessment and supplementation. JH, MW, LG-W, MW, MC, and CB have nothing to declare., (Copyright © 2019. Published by Elsevier GmbH.)

Intrauterine exposure to zidovudine-based combination antiretroviral therapy (cART) can cause severe anemia within the first weeks of life. Tenofovir disoproxil fumarate (TDF)-based regimens may have less hematologic side effects but may affect growth parameters. This study aimed to assess the safety of TDF for prevention of mother-to-child transmission (PMTCT) in HIV-exposed uninfected infants regarding early growth outcomes and hematologic side effects. Our retrospective observational cohort study included children born (n = 232) to HIV-infected mothers (n = 228) on cART. Blood counts were compared at birth, 4-6 weeks, and 3, 12 and 18 months of age. Growth parameters were measured at birth and 12 and 18 months of age. Data were analyzed according to treatment group (TDF and non-TDF cART regimes). The median hemoglobin (Hgb) was significantly lower in the non-TDF-based group at birth (15.4 g/dl vs. 16.9 g/dl; **p = 0.002) and at 4-6 weeks of age (9.9 g/dl vs. 10.4 g/dl; **p = 0.004). The mean corpuscular volume was higher in the non-TDF-based group (109 fl vs. 105 fl; ***p < 0.001) as well at 4-6 weeks (102 fl vs. 95 fl; ***p < 0.001). In the TDF-based group, a higher proportion of neutropenia (grade 2 and higher) compared to the non-TDF-group (21.4% vs. 11%; *p = 0.015) was observed at three months of age. This effect was transient. There was no difference in growth.Conclusions: TDF appears to have no major side effects in our cohort. Transient anemia was observed more commonly with non-TDF regimens. However, our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age.What is Known:• TDF is suspected to affect the growth of HIV-exposed uninfected infants.• Non-TDF-based cART regimes for prevention of mother-to-child transmission of HIV often result in transient anemia in the infant.What is New:• TDF appears to have no major side effects regarding the growth of HIV-exposed uninfected infants.• Our research suggests a potential delayed effect of TDF on neutrophils at 3 months of age in these infants.

Observational studies demonstrating reduced rates of infections, necrotizing enterocolitis (NEC), and mortality in preterm infants fed their own mother's milk, as opposed to formula, have prompted endeavors to achieve similar effects with the right choice of food and food additives. In a systematic review of meta-analyses and randomized controlled trials (RCTs), we considered nutritional interventions aimed at reducing the rates of infections, NEC, or mortality in very preterm infants. The overall effects of particular interventions were presented as risk ratios with 95% confidence intervals. In RCTs, pasteurized human donor milk, as opposed to formula, reduced NEC but not infections or mortality. No differences emerged between infants receiving human or bovine milk-based fortifiers. Pooled data of small trials and a recent large RCT suggested that bovine lactoferrin reduced rates of fungal sepsis without impact on other infections, NEC, or mortality. Pooled data of RCTs assessing the use of prebiotic oligosaccharides found reduced infection but not mortality. Enteral L-glutamine (six RCTs) lowered infection rates, and enteral L-arginine (three RCTs) reduced NEC. A meta-analysis sensitivity approach found multiple-strain (but not single-strain) probiotics to be highly effective in reducing NEC and mortality. Thus, selected food components may help to improve outcomes in preterm infants.

Background: Newborns with ductal-dependent congenital heart disease (CHD) are at increased risk for developing necrotizing enterocolitis (NEC)., Objectives: To investigate whether the use of dual-strain probiotics is beneficial for prevention of NEC in CHD patients, as demonstrated for premature infants., Study Design: Single-center retrospective cohort study of newborns with ductal-dependent CHD before and after implementation of oral dual-strain probiotics containing Bifidobacterium infantis and Lactobacillus acidophilus, on each day of exposure to prostaglandin E1 (PGE1)., Results: Birth weight, gestational age, and distribution of heart defects were similar in both cohorts. NEC occurred in 6 of 247 (2.4%) patients without probiotics, and in 3 of 242 (1.2%) patients who received probiotics (p = 0.504). NEC-related mortality (0.4 vs. 0.4%, p = 1.000) and overall mortality (11.0 vs. 8.7%, p = 0.448) were likewise not different. PGE1 exposure was 1,788 and 2,455 days, respectively. In subgroup analysis of 152 infants with aortic arch malformations, such as coarctation of the aorta and interrupted aortic arch, we observed a significant reduction of NEC frequency (5.6 vs. 0.0%, p = 0.048)., Conclusions: This is the first study to investigate the effect of a dual-strain probiotic on NEC in CHD patients. Infants with aortic arch malformations appear to benefit from dual-strain probiotics. Due to the scarcity of concurrence of ductal-dependent CHD and NEC, a clinical trial on probiotics to decrease risk of NEC in infants with ductal-dependent CHD would require several thousand infants., (© 2020 S. Karger AG, Basel.)

Objective: We aimed to investigate the clinical course and outcome of newborns with ductal-dependent congenital heart disease (CHD) who suffered from perinatal asphyxia., Study Design: Clinical data of 504 patients with ductal-dependent CHD and perinatal asphyxia were retrospectively analyzed over a 10-year period (2005-2014)., Result: Perinatal asphyxia was diagnosed in 17 (3.4%) patients, comprising two nonoverlapping groups: Five infants with intrauterine acidosis (umbilical artery pH < 7.0), and 12 infants with persistent or deteriorating postnatal depression (Apgar score <6 at 10 min of life). Preoperative (41.7%, p < 0.001) and overall mortality (50.0%, p = 0.001) were increased in infants with asphyxia caused by persistent or deteriorating postnatal depression. Apgar scores at 10 min were independently associated with preoperative (OR 0.479, 95% CI 0.342-0.672, p < 0.001) and overall death (OR 0.655, 95% CI 0.537-0.799, p < 0.001)., Conclusions: Asphyxia caused by postnatally deteriorating depression rather than fetal acidosis is associated with high mortality.

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met through a balanced, vegetable-based diet; however, due to their higher nutrient requirements per kilogramme of body weight, vegetarian children have a higher risk for developing nutrient deficiencies than adults. With a vegetarian diet, the mean intakes of some nutrients, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are lower than in omnivores or those eating fish. For other nutrients, such as iron and zinc, the bioavailability from vegetable foodstuffs is reduced when the intake of phytates and fibre is high; thus, the prevalence of iron deficiency can be increased despite high vitamin C intake. In addition, vitamin B12 is only found in animal-source foods. Vitamin B12 should be supplemented in people of all age groups who follow a strict vegan diet without consuming animal products. A vegetarian diet in childhood and adolescence requires good information and supervision by a paediatrician, if necessary, in cooperation with an appropriately trained dietary specialist.

The objective of this paper is to review current information regarding astrocytes function after a stroke in neonatal and adult brain. Based on the current literature, there are some molecular differences related to blood brain barrier (BBB) homeostasis disruption, inflammation and reactive oxygen species (ROS) mediated injury between the immature and mature brain after an ischemic event. In particular, astrocytes, the main glial cells in brain, play a different role in neonatal and adult brain after stroke, as time course of glial activation is strongly age dependent. Moreover, the present review provides further insight into the therapeutic approaches of using neonatal and adult astrocytes after stroke. More research will be needed in order to translate them into an effective treatment against stroke, the second main cause of death and disability worldwide., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures.

Palliative care concentrates on preventing and relieving suffering by reducing the severity of disease symptoms. Consistent treatment of pain and distress must therefore be an integral component of every palliative care concept. In this review non-pharmacological and pharmacological measures for pain and distress management in the context of palliative neonatal care are summarised. Furthermore, recommendations are given focusing on two special palliative neonatal care settings: compassionate extubation and withdrawing artificial nutrition and hydration., (© 2019 Elsevier Ltd. All rights reserved.)

Background: Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults., Aim: Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success., Methods: We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review., Results: We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed., Conclusion: Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.

Background: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats., Methods: Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR., Results: Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response., Conclusion: In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.

Background: Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below reference values, it is debated whether vitamin D should be supplemented after infancy., Methods: The effects of vitamin D supplementation in children > 2 years of age are analyzed based on a literature review of randomized controlled trials (RCTs)., Results: Vitamin D supplementation can potentially reduce the risk for influenza infections and improve asthma bronchiale exacerbation; however, it has no impact on asthma bronchiale severity. Vitamin D supplementation has no relevant effect on attention-deficit/hyperactivity disorders, cardiac failure, hypertension, or incidence of type II diabetes mellitus. Vitamin D supplementation has no effect on the rate of multiple sclerosis relapses, but on the number of new lesions detected by MRI. For other endpoints, RCTs are lacking., Conclusion: Based on currently available studies, routine vitamin D supplementation is not be recommended for children aged > 2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders.

Objectives: Patients with severe congenital heart disease and cardiac anomalies such as restrictive foramen ovale, intact atrial septum, or narrowing of ductus arteriosus are at risk for perinatal asphyxia, leading to hypoxic-ischemic encephalopathy. We hypothesize that therapeutic hypothermia can be applied to these patients and seek to investigate feasibility and safety of this method., Design: A retrospective observational study., Setting: The Department of Neonatology of Charité, University Hospital, Berlin, Germany., Patients: Newborns with severe congenital heart disease and perinatal asphyxia were retrospectively analyzed over a 6-year period., Interventions: Application of therapeutic hypothermia., Measurements and Main Results: Ten patients with perinatal asphyxia were enrolled in this study. All patients received low-dose prostaglandin E1 for ductal maintenance. Three patients without evidence for hypoxic-ischemic encephalopathy did not receive therapeutic hypothermia. One patient died at the age of 15 hours, and therapeutic hypothermia was discontinued after 19 hours in another patient with severe arterial hypotension. Adverse effects during hypothermia included respiratory insufficiency (100%), arterial hypotension (71%), the need for inotropic support (71%), and pulmonary hypertension (43%), the latter associated with prolonged postoperative inotropic support. No neurologic complications occurred before or after the surgery. Operative outcome of surviving patients was excellent. Early brain MRI scans were suggestive of good neurodevelopmental prognosis for most patients., Conclusions: Therapeutic hypothermia can be applied to patients with severe congenital heart disease and hypoxic-ischemic encephalopathy. Low-dose prostaglandin E1 infusions are safe for ductal maintenance during cooling, but cardiopulmonary adverse effects should be anticipated.

Objective: To investigate whether nasal high-frequency oscillatory ventilation (nHFOV) started immediately after extubation of mechanically ventilated very low birth weight infants reduces the partial pressure of carbon dioxide at 72 h after extubation in comparison with nasal continuous positive airway pressure. This randomised controlled single-centre trial aimed to include 68 preterm infants at high risk of extubation failure., Results: Implementation of the study protocol was feasible. However, from 2015 to 2017, only six patients could be recruited, leading to early termination of the trial. The slow recruitment was due to the introduction of new strategies to avoid endotracheal mechanical ventilation, which reduced the number of eligible infants. Moreover, the included infants failed their extubation more often than anticipated, thereby increasing the required sample size. Based on our single-centre experience, we provide information for study planning and discuss the specific requirements for future trial protocols on nHFOV. The extubation of high-risk infants into nHFOV could well be beneficial, but a multicentric approach is necessary to investigate this hypothesis. Trial Registration Clinicaltrials.gov NCT02340299, on 16 January 2015.

Introduction: Communication is essential to clinical routine, especially in NICUs with their vulnerable patients and the special team caring for them. Communication breakdowns and resulting treatment errors are described in the literature. The aim of this study is to provide an initial quantitative assessment of medical communication in a NICU., Methods: For task analysis, 15 Level III-NICU physicians were accompanied for 60 days in early and late shifts; each physician completed the COPSOQ questionnaire. Recorded tasks were assigned to main task categories and subcategories., Results: A total of 550 h of main and 100 h of secondary tasks were recorded, on average 9 h daily. The most time-consuming main activity was "Communication" (3 h), followed by "Indirect care/Administration" (2 h) and "Direct patient care" (1.5 h). "Communication" mainly consisted of discussions with colleagues and during early shifts. At 2 min, communication with nursing personnel during rounds was especially low. Communication showed a negative correlation to physician job satisfaction., Discussion: This work shows the suspected high proportion of communication in a NICU, especially among physicians themselves. The effectiveness of this communication is not assessable. However, a low proportion of communication with nursing staff is noticeable and reflects the variabiliy in team communication. Improvement of communication is necessary through training on and the application of existing techniques for handoffs and rounds., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To assess changes in attitudes of neonatologists regarding the care of extremely preterm infants and parental involvement over the last 20 years., Study Design: Internet-based survey (2016) involving 170 tertiary neonatal intensive care units in Austria, Switzerland, and Germany using the European Project on Parents' Information and Ethical Decision Making in Neonatal Intensive Care Units questionnaire (German edition) with minor modifications to the original survey from 1996 to 1997., Results: The 2016 survey included 104 respondents (52.5% response rate). In 2016, significantly more neonatologists reported having ever withheld intensive care treatment (99% vs 69%) and withdrawn mechanical ventilation (96% vs 61%) or life-saving drugs (99% vs 79%), compared with neonatologists surveyed in 1996-1997. Fewer considered limiting intensive care as a slippery slope possibly leading to abuse (18% vs 48%). In the situation of a deteriorating clinical condition despite all treatment, significantly more neonatologists would ask parental opinion about continuation of intensive care (49% vs 18%). In 2016, 21% of German neonatologists would resuscitate a hypothetical infant at the limits of viability, even against parental wishes., Conclusions: Withholding or withdrawing intensive care for extremely preterm infants at the limits of viability with parental involvement has become more acceptable than it was 20 years ago. However, resuscitating extremely preterm infants against parental wishes remains an option for up to one-fifth of the responding neonatologists in this survey., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Among children with hydrocephalus, neonates with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus (PH) are considered a group with one of the highest complication rates of treatment. Despite continued progress in neonatal care, a standardized and reliable guideline for surgical management is missing for this challenging condition. Thus, further research is warranted to compare common methods of surgical treatment. The introduction of neuroendoscopic lavage has precipitated the establishment of an international registry aimed at elaborating key elements of a standardized surgical treatment., Methods: The registry is designed as a multicenter, international, prospective data collection for neonates aged 41 weeks gestation, with an indication for surgical treatment for IVH with ventricular dilatation and progressive hydrocephalus. The following initial temporizing surgical interventions, each used as standard treatment at participating centers, will be compared: external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). Type of surgery, perioperative data including complications and mortality, subsequent shunt surgeries, ventricular size, and neurological outcome will be recorded at 6, 12, 36, and 60 months., Results: An online, password-protected website will be used to collect the prospective data in a synchronized manner. As a prospective registry, data collection will be ongoing, with no prespecified endpoint. A prespecified analysis will take place after a total of 100 patients in the NEL group have been entered. Analyses will be performed for safety (6 months), shunt dependency (12, 24 months), and neurological outcome (60 months)., Conclusion: The design and online platform of the TROPHY registry will enable the collection of prospective data on different surgical procedures for investigation of safety, efficacy, and neurodevelopmental outcome of neonates with IVH and hydrocephalus. The long-term goal is to provide valid data on NEL that is prospective, international, and multicenter. With the comparison of different surgical treatment modalities, we hope to develop better therapy guidelines for this complex neurosurgical condition.

Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods marketed in baby food pouches often have a high energy density and are predominantly extremely high in sugar content, with up to almost 90% of the total energy content. Regular consumption bears the risks of imbalanced nutrient provision and increased risks for dental caries and overweight. Complementary foods for infants and young children should have a balanced composition following the recommendations of the German Society of Pediatrics and Adolescent Medicine (DGKJ) and should contain only limited amounts of sugar. We discourage the feeding of pureed complementary foods from baby food pouches.

In preterm infants, the changes from fetal life to ex-utero conditions often coincide with reduced growth and white matter damage of the cerebellum. The premature increase in arterial oxygen tension caused by preterm birth may dysregulate cerebellar development. In a hyperoxia rat model of white matter damage to mimic a steep increase in oxygen levels by 24 h exposure to 80% O 2 from postnatal day 6 (P6) to day 7, we analyzed growth factor (GF) synthesis of cerebellar astrocytes. Determination of GF production was performed in astrocytes after Magnetic-activated cell sorting (MACS) isolation from cerebelli after hyperoxia exposure ex vivo, and also in astroglial cultures. Oligodendrocyte progenitor cell (OPC) function was analyzed in cerebellar OPCs isolated by MACS after hyperoxia. Administration of PDGFA from P6 to P11, during hyperoxia and during 4 days recovery, was finally tested for protection of oligodendroglia and myelination. As a result, expression of the GFs Pdgfa, Fgf2, and Bdnf was diminished in cerebellar astrocytes in vitro and in vivo. Gene expression of Olig1, Olig2, Sox9, Sox10, and Cnp was reduced in OPCs in vivo. Nasal PDGFA application improved oligodendroglial proliferation after hyperoxia at P7. However, this treatment effect vanished until P9. Impaired MBP expression after hyperoxia was attenuated by PDGFA treatment until P11, but not beyond when PDGFA supply was stopped. In this study on neonatal cerebellar injury, it is documented for the first time that improvement of oligodendroglial proliferation and of myelination can be achieved by PDGFA treatment. However, the treatment benefit is not maintained long term., (© 2019 Wiley Periodicals, Inc.)

Background: Milk curd obstruction as a cause of intestinal obstruction has been known since 1959, but has nearly disappeared. However, in recent years it has experienced a revival in small premature infants., Objective: The aim of this study was to evaluate the clinical characteristics of milk curd obstruction (lactobezoar) in preterm infants., Methods: Data of preterm infants with milk curd obstruction cared for at a large tertiary neonatal intensive care unit between 2012 and 2016 were retrieved from the electronic registry and paper records., Results: A total of 10 infants (2 girls, 8 boys) were identified: the median birth weight was 595 g (range 270-922), gestational age was 24.4 weeks (23.4-27.0), weight-for-gestational age percentile was 16 (0-62), and age at diagnosis was 28 days (16-64). Five infants (50%) were small for gestational age. All neonates had received fortified human milk (added protein 2.0 g/100 mL, range 0-2.8; added calcium 2,400 µmol/100 mL, range 0-6 844; added phosphate 2,400 µmol/100 mL, range 0-5,178). Seven neonates underwent surgery, and 2 infants died. Hyperechoic masses in extended bowel loops, visualised by abdominal ultrasound, and pale/acholic faeces were hallmarks of milk curd obstruction., Conclusions: In this study, milk curd obstruction occurred exclusively in infants with a birth weight < 1,000 g (2.2%) and < 28 weeks' gestational age (2.4%). Male and small for gestational age infants appeared to be at increased risk. Paying attention to the colour of the faeces of infants at risk might help to diagnose milk curd obstruction at an early stage., (© 2019 S. Karger AG, Basel.)

A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.

Sustained inflations and avoidance of endotracheal mechanical ventilation (eMV) are delivery room interventions aimed at preventing bronchopulmonary dysplasia (BPD). Their effectiveness is the subject of the present meta-analysis.The databases MEDLINE, EMBASE and CENTRAL were searched for randomised controlled trials (RCTs) of preterm infants that compared: 1) sustained inflations with intermittent positive-pressure ventilation; and 2) a non-intubated strategy of respiratory support with one that prescribed eMV at an earlier stage. Data extraction and analysis followed the standard methods of the Cochrane Collaboration. The primary outcome was death or BPD, defined as need for oxygen or positive pressure treatment at 36 weeks' postmenstrual age.Avoiding eMV (nine RCTs, 3486 infants) reduced the risk of death or BPD, with a risk ratio of 0.90 (95% CI 0.84-0.97) and a number needed to treat of 35. After sustained inflations (six RCTs, 854 infants), the risk ratio was 0.85 (95% CI 0.65-1.12). A current multicentre RCT of sustained inflations in very preterm infants was halted for increased early mortality in the sustained inflations arm.While strategies aimed at avoiding eMV had a small but significant impact on preventing BPD, sustained inflations had no effect and may even increase mortality in very preterm infants., Competing Interests: Conflict of interest: H.S. Fischer has nothing to disclose. Conflict of interest: G.M. Schmölzer has nothing to disclose. Conflict of interest: P-Y. Cheung has nothing to disclose. Conflict of interest: C. Bührer reports personal fees from Chiesi Pharmaceuticals (manufacturer of surfacant), outside the submitted work., (Copyright ©ERS 2018.)

Aim: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants., Methods: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development., Results: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28)., Conclusion: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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: Colonisation with Panton-Valentine Leukocidin expressing strains of Staphylococcus aureus (PVL + SA) is characterised by recurrent skin and soft tissue infections. While periorbital and orbital infections are common in children and frequently caused by S. aureus the role of PVL + SA in recurrent eye infections has not been studied. This study aimed to detect and report frequency and recurrence of periorbital or orbital infections as additional symptoms of PVL + SA colonisation in children., Methods: We conducted a retrospective cohort study of pediatric patients who were treated for PVL + SA skin and soft tissue infection in our in- and outpatient clinics in Berlin, Germany from January 2012 to January 2017. We identified cases with periorbital or orbital infections in the year prior to the first PVL + SA evidence. In these cases, we conducted follow-up interviews by phone to determine recurrence of symptoms after the completion of decolonisation procedures., Results: Fifty pediatric patients (age range: one week to 17 years) were evaluated and treated for PVL + SA infections in the reported time period. 19 patients (38%) reported periorbital infection or conjunctivitis, with recurrent hordeola as the most frequent finding (n = 9; 18%). Reappearance of hordeola (n = 5) was associated with recurrence of skin and soft tissue infections and/or de novo detection of PVL + SA. No further hordeola or other eye infections occurred after successful decolonisation., Conclusion: Our findings suggest a frequent involvement of periorbital skin in children with PVL + SA infections. Pediatric patients with recurrent periorbital infections might benefit from PVL + SA screening and consecutive decolonisation procedures.

Objective: Previous studies have described neuroendoscopic lavage (NEL) as a procedure for the treatment of posthemorrhagic hydrocephalus in newborn infants. This report describes complications and results in an extended case series from 2 separate hospitals., Methods: Patient records were screened for NEL procedures performed on infants with posthemorrhagic hydrocephalus between September 2010 and May 2016 (minimum follow-up period of 12 months). Efficacy of blood removal-as assessed with cerebral ultrasound, complications, eventual shunt placement rate, and subsequent shunt revisions-were recorded., Results: Fifty-six patients (35 male) underwent NEL at a postmenstrual median age of 31 weeks and 2 days (range, 26 weeks and 1 day to 52 weeks and 3 days) and a median weight of 1523 g (range, 734-4360 g). Median follow-up was 34 months (range, 12-80). Three patients died, and 31 patients required permanent ventriculoperitoneal shunting. There was no significant correlation between the need for ventriculoperitoneal shunting and gestational age (P = 0.05), birth weight (P = 0.07), age (P = 0.17), or weight (P = 0.59) after NEL. The median number of surgical interventions per patient was 2 (range, 1-7 interventions). Revision-free shunt survival was 63.6% at 12 and 56.2% at 24 months., Conclusions: NEL avoided shunt placement in 43% of newborn infants with posthemorrhagic hydrocephalus. In the shunted cohort, NEL may have also decreased the frequency of subsequent shunt revisions. The influence of NEL on neurodevelopment and safety remains to be investigated further in a multicenter setup., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although breast milk is the best diet in the first few months of life, risks can arise for the breast-fed infant. The article gives a comprehensive overview of possible risks regarding xenobiotics and pathogens in mother's milk, including medications, smoking, alcohol consumption, coffee consumption, persistent environmental contaminants and residues as well as infections.Where drug therapy is indicated, suitable medications are available for most conditions nowadays, so that prolonged nursing breaks or even weaning is not required. Long-term treatment, especially under combination therapy, needs to be examined on a case-by-case basis, however. Smoking and alcohol consumption should be avoided during the breastfeeding period, while moderate coffee consumption (up to 2 cups daily) is not of concern. The current levels of environmental contaminants and residues in breast milk are considered to be harmless to health; indeed, the body burden of dioxins considered to be critically high more than 20 years ago has been reduced by a factor of 10 to date. Among maternal infections, an human deficiency virus (HIV) infection is one of the few medical indications for weaning in countries with adequate hygiene standards.All in all, the risks of xenobiotics and pathogens in mother's milk are generally low in exclusively breastfed infants, so that there is usually no need for prolonged nursing breaks or even weaning. In only a small number of maternal conditions (certain medications, HIV infection), the infant should not be breastfed.

In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6. Phenobarbital treatment (50 mg/kg) resulted in a significant decrease of proliferative capacity in the dentate gyrus. Phenobarbital also reduced expression of neuronal markers (doublecortin (DCX), calretinin, NeuN), neuronal transcription factors (Pax6, Sox2, Tbr1/2, Prox1), and neurotrophins (NGF, BDNF, NT-3) up to 24 h after the last administration. The phenobarbital-mediated impairment of neurogenesis was largely ameliorated by preconditioning with caffeine (10 mg/kg). In contrast, caffeine alone reduced proliferative capacity and expression of the neuronal markers DCX and NeuN at 6 h, but increased expression of neurotrophins and neuronal transcription factors at 6 and 12 h. These results indicate that administration of phenobarbital during the vulnerable phase of brain development negatively interferes with neuronal development, which can be prevented in part by co-administration of caffeine.

In this case-control study, the erythropoietin (EPO) promoter variant s1617640, linked to high intravitreal EPO concentrations and increased risk of diabetic retinopathy, was not associated with severe retinopathy of prematurity. This finding was observed both in infants with and without recombinant EPO administration., (Copyright © 2018 Elsevier Inc. All rights reserved.)