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The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values. Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known:• Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New:• Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life.• Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes.

This study examines the infant–father attachment in infants born preterm (

The inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing.To analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network.In this cohort study of data from 68 tertiary level neonatal intensive care units in Germany of infants born between 22 weeks 0 days to 26 weeks 6 days of gestation between April 1, 2009, and December 31, 2020, short-term outcomes among infants receiving LISA vs infants not receiving LISA were compared.Use of LISA within the first 72 hours of life.The main outcomes were rates of LISA use, use of mechanical ventilation within the first 72 hours (considered failure of LISA), and association of LISA with outcomes, including death from all causes, bronchopulmonary dysplasia (BPD), death and BPD combined, pneumothorax, retinopathy of prematurity, intracerebral hemorrhage, and periventricular leukomalacia. To address potential confounding factors, multivariate logistic regression models were used.A total of 6542 infants (3030 [46.3%] female and 3512 [53.7%] male; mean [SD] GA, 25.3 (1.1) weeks; mean [SD] birth weight, 715 [180] g) were analyzed; 2534 infants (38.7%) received LISA, which was most frequently given quasi-prophylactically during delivery room management. Among the infants who received LISA, 1357 (53.6%) did not require mechanical ventilation in the first 72 hours compared with 331 infants (8.3%) of 4008 who did not receive LISA. In a multivariate logistic regression model that adjusted for GA, small-for-GA status, sex, multiple birth, inborn status, antenatal steroid use, and maximum fraction of inspired oxygen in the first 12 hours of life, LISA was associated with reduced risks of all-cause death (odds ratio [OR], 0.74; 95% CI, 0.61-0.90; P = .002), BPD (OR, 0.69; 95% CI, 0.62-0.78; P .001), and BPD or death (OR, 0.64; 95% CI, 0.57-0.72; P .001) compared with infants without LISA exposure.The results of this long-term multicenter cohort study suggest that LISA may be associated with reduced risks of adverse outcomes in extremely preterm infants.

We explored whether subnormal forced expiratory volume within 1 s (FEVThe multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEVSpirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEVThe proportion of children aged 5-9 years with subnormal FEV

The aim was to assess the results of primary anastomosis (PA) compared to enterostomy (ES) in infants with spontaneous intestinal perforation (SIP) and a weight below 1000 g. Between 2014 and 2016, enterostomy was routinely carried out on extremely low birth weight (ELBW) patients with SIP. From 2016 until 2019, all patients underwent anastomosis without stoma formation. We compared outcome and complications in both groups. Forty-two patients with a median gestational age of 24.3 weeks and a birth weight of 640 g with SIP were included. Thirty patients underwent PA; ES was performed in 12 patients. Overall in-hospital mortality was 11.9% (PA: 13.3%, ES: 8.3%). Reoperations due to complications became necessary in 10/30 patients with PA and 4/12 patients with ES. Length of stay was 110.5 days in the PA group and 124 days in the ES group. Median weight at discharge was higher in the PA group (PA: 2258 g, ES: 1880 g, p = .036).Conclusion: Primary anastomosis is a feasible treatment option for SIP in infants What is Known:• Enterostomy (ES) and primary anastomosis (PA) are feasible treatment options in preterm infants with spontaneous intestinal perforation (SIP).• Stomal complications or failure to thrive due to poor food utilization can pose significant problems. What is New:• Primary anastomosis in case of SIP is equal to enterostomy in terms of mortality and revision rate; however, length of stay and weight gain can be presumably positively influenced.• Primary anastomosis is a valid treatment option even for patients weighing less than 1000 g.

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277–5200) during the first week of life, 463 ng/l (n = 26, IQR: 364–704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714–1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750–8972) than infants born ≥ 28 + 0–31 weeks GA (n = 18, median: 1528, IQR: 838–3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups.Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life. What is Known:• Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life.What is New:• This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life.• In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

AIM The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age. METHODS Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors. RESULTS In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI)

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment.Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect. What is Known:• LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation. What is New:• Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Our study was designed to assess the rates of exclusive breastfeeding (defined as direct breastfeeding) and the use of mother’s own milk (MOM) in preterm infants and sick term infants at discharge and to identify potential influencing factors such as gestational age, early colostrum, and privacy. The study was conducted at a German level III neonatal department. All preterm and sick term infants admitted to the neonatal intensive care unit, the pediatric intensive care unit, the intermediate care unit, and the low care ward were included in the study. Infants were recruited between March and October 2015 (phase 1) and April to July 2016 (phase 2). Due to an emergency evacuation, privacy was limited during the first phase. Breastfeeding and the use of MOM were assessed daily using a self-designed score. In total, 482 infants of 452 mothers were included. More than 90% initiated breastfeeding and one-third were exclusively breastfed at discharge. Extremely immature infants and late preterm infants were less likely to be exclusively breastfed at discharge. Privacy (p

Aim To investigate the effects of 60 minutes delivery room skin-to-skin contact (DR-SSC) compared with 5 minutes visual contact (VC) on mother-child interaction (MCI), salivary cortisol, maternal depression, stress and bonding at 6 months corrected age. Methods A single-centre randomized controlled trial conducted in a German level III NICU. Eighty-eight preterm infants (25-32 weeks of gestational age) were randomized after initial stabilization to either 60 minutes DR-SSC or 5 minutes VC. Forty-five infants were allocated to DR-SSC, 43 to VC. Results Delivery room skin-to-skin contact dyads showed a higher quantity of maternal motoric (18 vs 15, P = .030), infant's vocal (7 vs 5, P = .044) and motoric (20 vs 15, P = .032) responses. Moreover, the combined score of maternal and infant responsive behaviour was higher (86 vs 71, P = .041) in DR-SSC dyads. DR-SSC mothers had lower risk of both, early postpartum depression (15% vs 45%, P = .003) and impaired bonding (Score 3 vs 5, P = .031). Conclusion In addition to regular intermittent kangaroo mother care, DR-SSC promotes MCI and decreases risk of maternal depression and bonding problems. Thus, DR-SSC may have positive effects on preterm development.

ObjectiveThe aim of our study was to determine if a genetic background of high blood pressure is a survival factor in preterm infants.DesignProspective cohort study.SettingPatients were enrolled in 53 neonatal intensive care units.PatientsPreterm infants with a birth weight below 1500 g.ExposuresGenetic score blood pressure estimates were calculated based on adult data. We compared infants with high genetic blood pressure estimates (>75th percentile of the genetic score) to infants with low genetic blood pressure estimates (Main outcome measuresLowest blood pressure on the first day of life and mortality.Results5580 preterm infants with a mean gestational age of 28.1±2.2 weeks and a mean birth weight of 1022±299 g were genotyped and analysed. Infants with low genetic blood pressure estimates had significantly lower blood pressure if compared with infants with high genetic blood pressure estimates (27.3±6.2vs 27.9±6.4, p=0.009, t-test). Other risk factors for low blood pressure included low gestational age (−1.26 mm Hg/week) and mechanical ventilation (−2.24 mm Hg, pConclusionsOur study provides first evidence that a genetic background of high blood pressure may be beneficial with regard to survival of preterm infants.

Evakuierungen einer Intensivstation oder eines ganzen Krankenhauses sind augenscheinlich seltene Ereignisse. Trotz der Raritat solcher Ereignisse sind intensive Vorplanungen fur derartige Szenarien obligat, da sie im Falle des Eintretens ein hohes Gefahrdungspotenzial sowohl fur die Patienten als auch fur das Personal bedeuten. Evakuierungen neonatologischer Intensiveinheiten sind besonders risikobehaftet und aufgrund von meist mangelnden Ausweichmoglichkeiten erschwert. Am 19.09.2014 kam es zu einem schweren Wasserschaden auf der 3. Etage der Universitatsfrauenklinik Koln. Am schwersten betroffen waren die unmittelbar darunter lokalisierte neonatologische Intensivstation mit 10 Betten (Level 1) und die Intermediate-Care-Station (Fruhgeborenenstation) mit 16 Betten. Dieser Bereich wurde durch das durchtretende Wasser so stark in Mitleidenschaft gezogen, dass der gesamte Bereich evakuiert werden musste. Letztlich gelang es, alle 26 Neugeborenen innerhalb des Universitatsklinikums zu verlegen. 6 Kinder wurden auf die im selben Gebaude in der 6. Etage lokalisierte Sauglingsstation verlegt. Die verbliebenen 20 Patienten wurden uber unterirdische Verbindungsgange, die im Normalbetrieb nicht in Benutzung sind, in andere Gebaude auf dem Campus verlegt. Alle Patiententransporte verliefen ohne Zwischenfalle. Evakuierungsszenarien mussen Bestandteil eines Krankenhausalarmplans sein. Insbesondere fur Hochrisikobereiche, wie z. B. Intensivstationen, sollten die Grundzuge eines solchen Szenarios im Vorfeld geplant werden. Im Ernstfall ist es wichtig, auf eine vordefinierte Fuhrungsstruktur zuruckgreifen zu konnen.

Purpose: This study aims to provide insights into the impact of organizational family-centered care characteristics at German neonatal intensive care units (NICUs) on the satisfaction of parents of very low birthweight (VLBW) infants.Materials and methods: Using multilevel modeling, this study analyzed whether organizational characteristics of NICUs fostering parent-infant interaction (by way of the existence of a recreation room, possibility of rooming in, existence of unrestricted visiting hours for parents, existence of parental classes, and the connection to parent associations as well as the existence of standards on developmentally supportive care) increase the satisfaction of parents after the infants' high-intensive care phase within the NICU.Results: Nine hundred and twenty-three VLBW infants from 66 NICUs in Germany born between May and October 2013 were enrolled in this multicenter study. We retrieved 1493 questionnaires completed by 1277 parents. The existence of unrestricted visiting hours (adjusted odds ratio (AOR): 1.967; 95% CI [1.118, 3.459]) and standardized procedures for developmentally supportive care (AOR: 1.775; 95% CI [1.166, 2.704]) were positively associated with parental satisfaction.Conclusions: Fostering the parent-infant interaction through the provision of developmentally supportive care and unrestricted visiting hours for parents whose infants are hospitalized within an NICU significantly contributes to the satisfaction of parents.

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%). Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies.• Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects.• The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants. Electronic supplementary material The online version of this article (10.1007/s00431-018-3279-7) contains supplementary material, which is available to authorized users.

Fur reife Neugeborene wird nach Geburt ein unmittelbarer, kontinuierlicher und ununterbrochener Hautkontakt mit der Mutter empfohlen. Dieser fruhe Kontakt hat positive Effekte auf die Mutter-Kind-Interaktion und Bindung. Bei Fruhgeborenen ist haufig eine Trennung von Mutter und Kind nach Geburt notig, um die erfolgreiche Transition der unreifen Kinder zu uberwachen sowie auftretende Probleme (insbesondere Storungen der Atmung) fruhzeitig zu erkennen und entsprechend zu behandeln. Auch wenn Hautkontakt fur Fruhgeborene in Form der „intermittent kangaroo mother care“(iKMC)-Methode in den letzten Jahren als Standard in den westlichen neonatalen Intensivstationen etabliert wurde, findet dieser haufig erst nach Tagen oder Wochen statt. Zudem haben die ersten Stunden nach Geburt als sog. sensible Phase der Mutter-Kind-Interaktion eine besondere Bedeutung fur die Entwicklung einer sicheren Bindung. Erste Studien, die einen fruhen Hautkontakt bei Fruhgeborenen untersuchten, konnten zeigen, dass dieser fur moderate und spate, aber auch unreife Fruhgeborene machbar und sicher ist, wenn die entsprechenden Voraussetzungen geschaffen werden. Ebenso konnten positive Effekte auf die Mutter-Kind-Interaktion und die Bindung fur Fruhgeborene mit fruhem Hautkontakt nachgewiesen werden. Eine sichere Bindung stellt einen protektiven Faktor fur Verhaltensauffalligkeiten oder neurokognitive Entwicklungsstorungen dar. Ziel der zukunftigen Versorgung von Fruh- und Neugeborenen sollte sein, einen fruhen Kontakt von Mutter und Kind unter Berucksichtigung der medizinisch notwendigen Unterstutzung entsprechend der Unreife der Kinder zu ermoglichen.

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Genetic diseases are a major cause of neonatal morbidity and mortality. The clinical differential diagnosis in severely ill neonates, especially in premature infants, is challenging. Next generation sequencing (NGS) diagnostics is a valuable tool, but the turnaround time is often too long to provide a diagnosis in the time needed for clinical guidance in newborn intensive care units (NICU). To minimize turnaround time, we developed an ultra-rapid whole genome sequencing pipeline and tested it in clinical practice. Our pilot case, was a preterm infant presenting with several crises of dehydration, hypoglycaemia and hyponatremia together with nephrocalcinosis and hypertrophic cardiomyopathy. Whole genome sequencing was performed using a paired-end 2x75bp protocol. Sequencing data were exported after 50 sequencing cycles for a first analysis. After run completion, the rapid-sequencing protocol, a second analysis of the 2 x 75 paired-end run was performed. Both analyses comprised read-mapping and SNP-/indel calling on an on-site Edico Genome DRAGEN server, followed by functional annotation and pathogenicity prediction using in-house scripts. After the first analysis within 17 h, the emergency ultra-rapid protocol identified two novel compound heterozygous variants in the insulin receptor gene (INSR), pathogenic variants in which cause Donohue Syndrome. The genetic diagnosis could be confirmed by detection of hyperinsulinism and patient care adjusted. Nonetheless, we decided to pursue RNA studies, proving the functional effect of the novel splice variant and reduced expression levels of INSR in patients skin fibroblasts.

The outcome of extremely low-birth-weight (ELBW) and very low-birth-weight (VLBW) infants has substantially improved in recent years. As acute kidney injury is frequent in these infants due to various risk factors, there is an increasing demand for renal replacement therapy in these patients. Data on that topic, however, are scarce. We review the available literature on that topic and report our experience on temporary dialysis in three extremely immature infants (two ELBW and one VLBW) with acute kidney failure. Peritoneal dialysis (PD) was performed for 19, 23, and 44 days until recovery of native renal function. At recent follow-up of 18 and 24 months, two patients are in good clinical condition with chronic kidney disease stages 1 and 4, respectively. One patient deceased at the age of 12 months due to secondary liver failure. The dialysis regimen applied in our study differed significantly from older infants with extremely short dwell times and accordingly high numbers of daily cycles. The use of rigid acute PD catheters was associated with less catheter-related complications (leakage, dislocation, and obstruction) as compared to ascites drainage catheters. In summary, PD was technically feasible and effective also in extremely immature infants, but frequent adjustments of dialysis regimens and high numbers of daily cycles posed immense efforts on both, parents and medical staff.

Most very preterm infants have difficulty aerating their lungs and require respiratory support at birth. Currently in clinical practice, non-invasive ventilation in the form of continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) is applied via facemask. As most very preterm infants breathe weakly and unnoticed at birth, PPV is often administered. PPV is, however, frequently ineffective due to pressure settings, mask leak and airway obstruction. Meanwhile, high positive inspiratory pressures and spontaneous breathing coinciding with inflations can generate high tidal volumes. Evidence from preclinical studies demonstrates that high tidal volumes can be injurious to the lungs and brains of premature newborns. To reduce the need for PPV in the delivery room, it should be considered to optimise spontaneous breathing with CPAP. CPAP is recommended in guidelines and commonly used in the delivery room after a period of PPV, but little data is available on the ideal CPAP strategy and CPAP delivering devices and interfaces used in the delivery room. This narrative review summarises the currently available evidence for why PPV can be inadequate at birth and what is known about different CPAP strategies, devices and interfaces used the delivery room.

The aim of this study was to contribute further to existing randomized controlled trials and meta-analyses showing advantages in the outcome of less invasive surfactant administration (LISA)-treated infants and add new aspects concerning treatment and outcome data collected in the routine clinical setting. Four hundred seven very low birth weight infants who received surfactant via either LISA or intubation methods were enrolled in the observational cross-sectional multicenter study. To compare infants in terms of surfactant administration, we used an exact matching procedure (the same gestational age, severe perinatal depression (pH 7.10), birth weight 10th percentile, antenatal steroid treatment, and the same gender). To check for robustness, we performed repeated matching. LISA-treated infants required significantly less mechanical ventilation during hospital stay (p 0.001) and days with supplemental oxygen (p = 0.03). Analgesics and sedatives were used less often during the stay (p 0.001). Infants treated with LISA had significantly lower rates of bronchopulmonary dysplasia (p = 0.003). LISA failure infants were identified as more likely to be small for gestational age and more immature.Our study complements former results with advantages for LISA-treated infants in mechanical ventilation and bronchopulmonary dysplasia in the clinical routine.DRKS00004589 What is Known: • According to existing literature, LISA-treated infants seem to have some favors in terms of treatment and outcome data. Observational studies in routine clinical setting are missing. What is New: • Data of 407 VLBW infants collected in routine clinical setting showed that LISA-treated infants needed less mechanical ventilation and fewer days with supplemental oxygen and less analgesics and sedatives. A reduced risk of BPD could be showed. SGA infants seem to have higher risks of LISA failure.

The aim was to determine if peritoneal drainage (PD) is a suitable treatment for pneumoperitoneum in extremely low birth weight (ELBW) infants. A retrospective chart review of 42 ELBW infants with pneumoperitoneum at the University Hospital of Cologne between November 2014 and April 2017 was performed. Forty-two infants with a median birth weight of 645 g (interquartile range (IQR) 550, 806) and a median gestational age of 24.3 weeks (IQR 23.2, 25.6) were treated for pneumoperitoneum. Twenty-six (62%) received PD, and in ten (38%), the drain could be removed without further intervention. Infants in the PD group were of significantly lower birth weight (622g vs. 750 g), age (4.5 vs. 10.0 days), and weight at diagnosis (538 vs. 778 g). The mortality in the PD group was 15% at 90 days of life, but no patient deceased in the primary laparotomy group.We suggest PD with close evaluation of drainage and clinical course as an alternative treatment for pneumoperitoneum in ELBW infants allowing bridging the vulnerable first days of life until these infants are in a more stable condition. Despite not reaching statistical significance in our series, PD showed the trend towards higher mortality. What is known: • Pneumoperitoneum is traditionally treated with laparotomy, but placement of peritoneal drainage (PD) is a valuable treatment option. • Previous randomized controlled trials have shown no significant differences in mortality for PD versus laparotomy. What is new: • In our cohort, 38% of the infants with PD could be saved from secondary laparotomy, but in the PD group there was a trend towards higher mortality. • PD allows bridging the vulnerable first days of life until ELBW infants are in a more stable condition for possible laparotomy.

Background: Pulmonary hypertension (PH) affects 1 in 6 infants with a birthweight Objectives: The aim of this study was to characterize risk factors for PH in ELBW infants and to describe the timing of onset of the disease by setting up a screening program. Methods: ELBW infants treated at the Department of Neonatology (level III neonatal intensive care unit at the University of Cologne Medical Centre, Germany) between January 2010 and March 2015 were included. Echocardiography screening for PH was performed either before discharge or if BPD was diagnosed. Additionally, infants had at least 1 echocardiographic scan after discharge. Survival with PH, age at diagnosis of PH, and risk factors associated with PH were assessed. Results: In total, 34/188 (18%) infants had PH. Of these, 14 (41%) were identified after discharge. Another 11 (32%) were diagnosed with PH without suffering from moderate or severe BPD. The risk factors for diagnosis of PH were moderate (odds ratio, OR 4 [2-8]) or severe BPD (OR 13 [2-71]), prolonged rupture of membranes >7 days (OR 5 [1-19]), and birthweight below the 3rd percentile (OR 3 [1-9]). All infants with PH before discharge and 50% diagnosed after discharge were treated with sildenafil (2.0 mg/kg/day). PH resolved and sildenafil was discontinued in all patients after a median duration of 13 months (IQR 8-20). Conclusions: An echocardiographic screening program may help to identify infants with PH. Examinations should include all ELBW infants irrespective of the presence of BPD and be continued after discharge.

Aim: Our aim was to study the development of the cutaneous flexion withdrawal reflex among premature infants admitted to the neonatal intensive care unit of the Children's Hospital, University of Cologne, in 2013.Methodology: This longitudinal cohort study explored the development of spinal cord excitability of 19 premature infants born at 22-26 weeks of gestation. We performed five investigations per subject and studied changes in the reflex threshold with increasing postnatal age at different behavioural states. The premature infants were stimulated with von Frey filaments on the plantar surface of the foot near the first metatarsophalangeal joint during the first 3 days of life and at postnatal ages of 10-14 days, 21-28 days, 4959 days and a corrected gestational age of 37-40 weeks.Results: The mean gestational age of the premature infants included in the study was 24 weeks. Premature infants with a gestational age of less than 26 weeks presented a flexion withdrawal reflex with a low threshold (0.5-2.85 milli-Newton) in the first 72 hours of life.Conclusion: The flexion withdrawal reflex among premature infants born at less than 26 weeks showed a continuous threshold increase with increasing postnatal age, reflecting changes in spinal cord excitability.

Premature birth is a traumatic event that puts mother and child at risk for subsequent psychopathology. Skin-to-skin contact in the form of intermittent kangaroo mother care has been shown to positively affect the infant's stress response and cognitive development, but underlying mechanisms remain unclear. Moreover, first skin-to-skin contact is usually delayed for days after birth. In the delivery room skin-to-skin study (DR-SSC), a prospective randomized controlled trial conducted from 2/2012 to 7/2015, we set out to assess the effect of delivery room skin-to-skin contact on the infant's mRNA expression of six key molecules involved in stress response and neurobehavioral development at hospital discharge. 88 firstborn, singleton preterm infants (born at 25-32 weeks of gestational age) were included. In the delivery room after initial stabilization, infants were randomized to either 60 min of skin-to-skin or 5 min of visual contact with their mother. In this explorative add-on study on the original DR-SSC study, we determined the expression of six important stress response genes (CRHR1 and CRHR2, AVP, NR3C1, HTR2A, and SLC6A4) in peripheral white blood cells of infants during routine blood sampling upon hospital discharge (corrected gestational age of 40 weeks). Infants were followed up to six months corrected age. Relative mRNA expression of the corticotropin releasing hormone receptor 2 (CRH R2), the glucocorticoid receptor gene (NR3C1), and the serotonin transporter gene (SLC6A4) was significantly reduced in the delivery room SSC infants. Additionally, gene expression of CRH R2 showed a correlation with HPA axis reactivity and parameters of mother-child interaction at six months corrected age. Our results highlight the importance of delivery room mother-child skin-to-skin contact and underline the urgent need for in-depth studies on the underlying molecular mechanisms.

ObjectiveTo determine if survival rates of preterm infants receiving active perinatal care improve over time.DesignThe German Neonatal Network is a cohort study of preterm infants with birth weight Setting43 German level III neonatal intensive care units (NICUs).Patients8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care.InterventionsParticipating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25–P75) and low (Main outcome measuresDeath by any cause before discharge.ResultsTotal survival increased from 85.8% in 2011–2013 to 87.4% in 2014–2016. This increase was due to reduced mortality of NICUs with low survival rates in 2011–2013. Survival increased in these centres from 53% to 64% in the 22–24 weeks strata and from 73% to 84% in the 25–26 weeks strata.ConclusionsOur data support previous reports that active perinatal care of very immature infants improves outcomes at the border of viability and survival rates at higher gestational ages. The high total number of surviving infants below 24 weeks of gestation challenges national recommendations exclusively referring to gestational age as the single criterion for providing active care. However, more data are needed before recommendations for parental counselling should be reconsidered.Trial registrationApproval by the local institutional review board for research in human subjects of the University of Lübeck (file number 08–022) and by the local ethic committees of all participating centres has been given.

Background Nosocomial infections are a serious problem in the treatment of extremely low birth weight infants (ELBW,1 000 g). In these patients, effective skin antisepsis is critical to prevent hospital-acquired infections and their sequelae. However, serious side effects of topical antiseptics have been repeatedly reported in extremely preterm infants and no agreement has been reached on the best product in this population. Therefore, we conducted a survey of the German NICUs aiming to investigate current practices and safety of topical antiseptics in ELBW neonates.We sent anonymized questionnaires to 166 German NICUs with the highest level of care.Usable questionnaires were returned by 64 NICUs (39%). These NICUs had treated a total of 2130 patients with a birth weight1 000 g in 2012. Octenidine without phenoxyethanol (OwPh) and Octenisept(®) were the predominantly used skin antiseptics for intensive-care procedures. At least one skin complication was reported by 27% (n=17) of the NICUs. In 9 cases Octenisept(®) was used, and in 6 cases octenidine was used.According to our knowledge, this is the first study surveying practices and safety of skin antisepsis in ELBWs in the German NICUs. Most German NICUs use octenidine, however, in different preparations. Skin complications including blistering, necrosis and scarring were seen with all octenidine products, a fact which has not been previously reported.

During recent decades, non-invasive respiratory support has become popular for treating neonates with respiratory failure. Several prospective randomized controlled trials have been performed to compare use of continuous positive airway pressure (CPAP) as primary respiratory support in preterm infants with respiratory distress syndrome (RDS) to endotracheal intubation, mechanical ventilation and surfactant therapy. Systematic reviews of these studies suggest that routine CPAP at delivery is efficacious in decreasing bronchopulmonary dysplasia (BPD), death, or both. This led to the recommendation to consider CPAP to avoid endotracheal intubation. As surfactant therapy is known to reduce BPD and death, several ways to combine CPAP with surfactant have been described. With the increasing use of CPAP immediately after birth, the early use of caffeine to stimulate respiration has become a point of discussion. This review focuses on different modes of surfactant application during CPAP and on the early use of caffeine as ancillary therapies to enhance CPAP success.

BACKGROUND NOD2 loss-of-function mutations, that is, R702W [rs2066844], G908R [rs2066845], and Leu1007fsinsC [rs5743293], have been linked to inflammatory bowel diseases. It is yet unknown whether these variants are also associated with necrotizing enterocolitis (NEC) or focal intestinal perforation (FIP) in infants of very low birth weight (VLBW). METHODS To test this hypothesis, we genotyped 9082 VLBW infants with European ancestry enrolled in a prospective, population-based cohort study of the German Neonatal Network. We assessed the effect of the NOD2 gene variants on the risk for major morbidities of the gastrointestinal tract, that is, NEC/FIP requiring surgery in multivariable logistic regression analyses. RESULTS In the whole cohort of VLBW infants, carriers of ≥ 2 NOD2 variant alleles had an increased risk for NEC requiring surgery (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.27-10.04; P = 0.03) and NEC or FIP requiring surgery (OR, 3.81; 95% CI, 1.70-8.51; P = 0.004) as compared with wild-type genotypes. In a multivariable logistic regression analysis including gestational age, birth weight, gender, multiple birth, and inborn delivery, the association between ≥ 2 NOD2 variant alleles and NEC surgery (OR, 4.14; 95% CI, 1.41-12.12; P = 0.009), FIP surgery (OR, 3.50; 95% CI, 1.02-12.04; P = 0.047), and NEC or FIP surgery (OR, 4.10; 95% CI, 1.74-9.73; P = 0.001) proved to be independent. We also performed a regression analysis in the subgroup of infants with available information on Lactobacillus acidophilus/Bifidobacterium infantis probiotic supplementation (n = 3638). Although probiotics had a protective effect on NEC and NEC or FIP requiring surgery, the NOD2 variants had no significant impact in this subgroup. CONCLUSIONS VLBW infants carrying ≥ 2 NOD2 genetic risk factors of inflammatory bowel disease in adults have an increased risk for severe gastrointestinal complications, such as NEC requiring surgery. Therefore, infants might benefit from NOD2 genotyping followed by supplementation with probiotics. Replication studies are needed along with genome-wide arrays to allow risk-adapted prevention and therapeutic strategies.

BACKGROUND Human breast milk could be an important stem cell source for the development of newborn and preterm infants, but quantitative data on the stem cell content in breast milk at various gestational stages are needed to determine the clinical value of breast milk as a source of stem cells. Breast milk also contains milk fat globules, lipid droplets of different sizes, debris and dead cells and these components hamper flow cytometry analysis of human breast milk samples. METHODS Here, we originally used standard protocols for flow cytometry to characterize cell populations in human breast milk but failed to discriminate between cells and noncellular components. We then applied a centrifugation protocol to separate cream and skim milk from the cell-containing pellet and used a novel staining protocol with DRAQ5™ and SYTOX® blue dye as well as antibodies to characterize cells within the pellet fraction. RESULTS Flow cytometry analysis identified viable DRAQ5™+ /SYTOX® Blue- cells and determined the content of CD11b+ monocytes and TRA-1-81+ putative stem cells in human breast milk samples. CONCLUSIONS Hence, we developed a novel and reliable flow cytometry based-approach to quantify subpopulation of cells in human breast milk with a high content of milk fat globules, lipid droplets, and particles. This approach will improve the identification and quantification of breast milk cells and allow standardizing the flow cytometry-based evaluation of the stem cell content. © 2018 International Clinical Cytometry Society.

Background: Delayed cord clamping or cord milking improves cardiovascular stability and outcome of preterm infants. However, both techniques may delay initiation of respiratory support. To allow lung aeration during cord blood transfusion, we implemented an extrauterine placental transfusion (EPT) approach. This study aimed to provide a detailed description of the EPT procedure and to evaluate its impact on the outcome of infants. Methods: A retrospective analysis was performed comprising 60 preterm infants (220/7 to 316/7 weeks of gestation). Of these, 40 were transferred to the resuscitation unit with the placenta still connected to the infant. In this EPT group, continuous positive airway pressure support was initiated while, simultaneously, placental blood was transfused by holding the placenta 40–50 cm above the infant’s heart. The cords of another 20 infants were clamped before respiratory support was started (standard group). Data on the infants’ outcome were compared retrospectively. In a subgroup of 22 infants (n = 14 EPT, n = 8 standard), respiratory function monitor recordings were performed and both heart rates and SpO2 levels in the first 10 min of life were compared between groups. Results: Although infants in the EPT group were lighter (EPT: 875 ± 355 g, standard: 1,117 ± 389 g; p = 0.02) and younger (266/7 weeks ± 19 days vs. 282/7 weeks ± 18 days; p = 0.045), there was no difference in neonatal outcome, including the incidence of intraventricular hemorrhage, bronchopulmonary disease, and red blood cell transfusions (all p > 0.1). Moreover, no differences in SpO2 levels and heart rates were observed in the infants whose resuscitations were recorded using a respiratory function monitor. Conclusions: In this retrospective analysis, EPT had no negative effects on the outcome of the infants, which warrants further evaluation in prospective randomized studies.

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51–0.84), p

Aim Providing less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA-treated infants and controls. Methods Infants receiving LISA, who were born before 32 gestational weeks and enrolled in the German Neonatal Network, were matched to control infants by gestational age, umbilical cord pH, Apgar-score at 5 min, small for gestational age status, antenatal treatment with steroids, gender and highest supplemental oxygen during the first 12 h of life. Outcome data were compared with chi-square and Mann–Whitney U-tests and adjusted for multiple comparisons. Results Between 2009 and 2012, 1103 infants were treated with LISA at 37 centres. LISA infants had lower rates of mechanical ventilation (41% versus 62%, p

To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants. We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009–2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death. Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99–1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model. This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants.