Human preterm colostrum stimulates outgrowth in neurogenic tissue.

BACKGROUND: The olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb. METHODS: Olfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry. RESULTS: Outgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity. CONCLUSIONS: A high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk. IMPACT: The hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk. In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed. Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk. A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue. Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life.

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.

Association of Administration of Surfactant Using Less Invasive Methods With Outcomes in Extremely Preterm Infants Less Than 27 Weeks of Gestation.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposure: Use of LISA within the first 72 hours of life. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Sensitive asprosin detection in clinical samples reveals serum/saliva correlation and indicates cartilage as source for serum asprosin.

The C-terminal pro-fibrillin-1 propeptide asprosin is described as white adipose tissue derived hormone that stimulates rapid hepatic glucose release and activates hunger-promoting hypothalamic neurons. Numerous studies proposed correlations of asprosin levels with clinical parameters. However, the enormous variability of reported serum and plasma asprosin levels illustrates the need for sensitive and reliable detection methods in clinical samples. Here we report on newly developed biochemical methods for asprosin concentration and detection in several body fluids including serum, plasma, saliva, breast milk, and urine. Since we found that glycosylation impacts human asprosin detection we analyzed its glycosylation profile. Employing a new sandwich ELISA revealed that serum and saliva asprosin correlate strongly, depend on biological sex, and feeding status. To investigate the contribution of connective tissue-derived asprosin to serum levels we screened two cohorts with described cartilage turnover. Serum asprosin correlated with COMP, a marker for cartilage degradation upon running exercise and after total hip replacement surgery. This together with our finding that asprosin is produced by primary human chondrocytes and expressed in human cartilage suggests a contribution of cartilage to serum asprosin. Furthermore, we determined asprosin levels in breast milk, and urine, for the first time, and propose saliva asprosin as an accessible clinical marker for future studies.

Privacy, Early Colostrum, and Gestational Age are Associated with Exclusive Breastfeeding in Preterm and Sick Term Infants.

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<0.001) and early colostrum (p=0.002) significantly increased exclusive breastfeeding. Conclusion Extremely immature and late preterm infants were least likely to be exclusively breastfed at discharge and need special support. Interventions such as privacy and early colostrum should be promoted to increase breastfeeding.

Primary anastomosis as a valid alternative for extremely low birth weight infants with spontaneous intestinal perforation.

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 < 1000 g and may have a positive impact on weight gain and length of hospitalization. However, further studies on selection criteria for PA are necessary. 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.

Reference values for N-terminal Pro-brain natriuretic peptide in premature infants during their first weeks of life.

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.

Delivery room skin-to-skin contact in preterm infants affects long-term expression of stress response genes.

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.

Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia-exposed HT22 murine hippocampal neurons.

Ketamine is a widely used drug in pediatric anesthesia, and both neurotoxic and neuroprotective effects have been associated with its use. There are only a few studies to date which have examined the effects of ketamine on neurons under hypoxic conditions, which may lead to severe brain damage and poor neurocognitive outcomes in neonates. In the present study, the effects of ketamine on cellular pathways associated with neurogenesis, extracellular matrix homeostasis and proliferation were examined in vitro in hypoxia-exposed neurons. Differentiated HT22 murine hippocampal neurons were treated with 1, 10 and 20 µM ketamine and cultured under hypoxic or normoxic conditions for 24 h followed by quantitative PCR analysis of relevant candidate genes. Ketamine treatment did not exert any notable effects on the mRNA expression levels of markers of neurogenesis (neuronal growth factor and syndecan 1), extracellular matrix homeostasis (matrix-metalloproteinase 2 and 9, tenascin C and tenascin R) or proliferation markers (Ki67 and proliferating cell nuclear antigen) compared with the respective untreated controls. However, there was a tendency towards downregulation of multiple cellular markers under hypoxic conditions and simultaneous ketamine treatment. No dose-dependent association was found in the ketamine treated groups for genetic markers of neurogenesis, extracellular matrix homeostasis or proliferation. Based on the results, ketamine may have increased the vulnerability of hippocampal neurons in vitro to hypoxia, independent of the dose. The results of the present study contribute to the ongoing discussion on the safety concerns around ketamine use in pediatric clinical practice from a laboratory perspective.

[Flap Reconstruction as Alternative Anastomosis Technique for the Surgery of Oesophageal Atresia with Distal Oesophagotracheal Fistula]. / Die Lappenplastik als alternative Anastomosentechnik für die operative Korrektur der Ösophagusatresie mit distaler ösophagotrachealer Fistel.

AIM: The creation of a primary anastomosis in newborns with oesophageal atresia and distal oesophageotracheal fistula (EA-DF) is technically challenging, especially in small children. The goal is to approximate the fragile oesophageal ends without suture disruption and to minimize the mobilisation of the lower segment. We describe an alternative anastomosis technique aiming at reducing the tension on the first sutures at the posterior wall. INDICATIONS: EA-DF was corrected in 13 newborns either by open (n = 11) or thoracoscopic (n = 2) surgery using this technique. METHOD: The anastomosis technique is based on creation of a dorsal flap of the upper oesophageal pouch and insertion in the spatulated lower oesophageal segment after the fistula has been separated. Subsequently, the first sutures of the posterior wall can be accomplished with reduced tension. Upon completion of the anastomosis, a diagonally shaped anastomotic plane results. CONCLUSION: The method is a helpful alternative to approximate the oesophageal stumps of newborns with EA and distal oesophagotracheal fistula. By this technique, the first stabilising sutures of the posterior wall can be accomplished with reduced tension. This results in reduced tensile stress on the individual sutures and simplifies the anastomisation in comparison to the conventional end-to-end anastomosis.

Intranasal breast milk for premature infants with severe intraventricular hemorrhage-an observation.

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.

Novel DRAQ5™/SYTOX® Blue Based Flow Cytometric Strategy to Identify and Characterize Stem Cells in Human Breast Milk.

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.

Peritoneal drainage in pneumoperitoneum in extremely low birth weight infants.

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. CONCLUSION: 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.

Prenatal parental decision-making and postnatal outcome in renal oligohydramnios.

BACKGROUND: Previous studies on renal oligohydramnios (ROH) report highly variable outcome and identify early onset of ROH and presence of extrarenal manifestations as predictors of adverse outcome in most cases. Data on termination of pregnancy (TOP) and associated parental decision-making processes are mostly missing, but context-sensitive for the interpretation of these findings. We provide here a comprehensive analysis on the diagnosis, prenatal decision-making and postnatal clinical course in all pregnancies with ROH at our medical centre over an 8-year period. METHODS: We report retrospective chart review data on 103 consecutive pregnancies from 2008 to 2015 with a median follow-up of 554 days. RESULTS: After ROH diagnosis, 38 families opted for TOP. This decision was associated with onset of ROH (p < 0.001), underlying renal disease (p = 0.001) and presence of extrarenal manifestations (p = 0.02). Eight infants died in utero and 8 cases were lost to follow-up. Of the 49 liveborn children, 11 received palliative and 38 underwent active care. Overall survival of the latter group was 84.2% (n = 32) corresponding to 31% of all pregnancies (32 out of 103) analysed. One third of the surviving infants needed renal replacement therapy during the first 6 weeks of life. CONCLUSIONS: Over one third of pregnancies with ROH were terminated and the parental decision was based on risk factors associated with adverse outcome. Neonatal death was rare in the actively treated infants and the overall outcome promising. Our study illustrates that only careful analysis of the whole process, from prenatal diagnosis via parental decision-making to postnatal outcome, allows sensible interpretation of outcome data.

An Echocardiographic Screening Program Helps to Identify Pulmonary Hypertension in Extremely Low Birthweight Infants with and without Bronchopulmonary Dysplasia: A Single-Center Experience.

BACKGROUND: Pulmonary hypertension (PH) affects 1 in 6 infants with a birthweight <1,000 g (extremely low birthweight; ELBW) and is frequently associated with bronchopulmonary dysplasia (BPD). If untreated, the mortality rates of the disease are high. 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.

Survival Among Infants Born at 22 or 23 Weeks' Gestation Following Active Prenatal and Postnatal Care.

IMPORTANCE: Rates of survival for infants born at the border of viability are still low and vary considerably among neonatal intensive care units. OBJECTIVE: To determine whether higher survival rates and better short-term outcomes for infants born at 22 or 23 weeks' gestation may be achieved by active prenatal and postnatal care. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 106 infants born at 22 or 23 weeks of gestation at a level III neonatal intensive care unit at the University of Cologne Medical Centre in Cologne, Germany, between January 1, 2010, and December 31, 2014. Data analysis was performed in June 2015. EXPOSURES: Active prenatal and postnatal care. MAIN OUTCOMES AND MEASURES: Survival until hospital discharge and survival without neonatal or short-term severe complications (defined as high-grade intraventricular hemorrhage, surgery for abdominal complications, bronchopulmonary dysplasia, or retinopathy of prematurity). RESULTS: Of 106 liveborn infants (45 born at 22 weeks and 61 born at 23 weeks and 6 days), 20 (19%) received palliative care (17 born at 22 weeks and 3 born at 23 weeks), and 86 (81%) received active care (28 born at 22 weeks and 58 born at 23 weeks). Of the 86 infants who received active care (mean [SD] maternal age, 32 [6] years), 58 (67%) survived until hospital discharge (17 born at 22 weeks and 41 born at 23 weeks). Eighty-five infants survived without severe complications, with 1 infant born at 22 weeks excluded because of missing data (6 of 27 [22%] born at 22 weeks, and 16 of 58 [28%] born at 23 weeks). Survival was predicted by the Apgar score after 5 minutes (odds ratio, 0.62 [95% CI, 0.46-0.84]) and birth weight (odds ratio, 0.001 [95% CI, 0.00-0.40]). CONCLUSIONS AND RELEVANCE: One in 4 infants born at the border of viability and offered active care survived without severe complications. This finding should be considered for individualized parental approaches and decision making. Active follow-up information is required to determine childhood outcomes.

Massive macroglossia after palatoplasty: case report and review of the literature.

UNLABELLED: Cleft palates are among the most common birth defects. Serious complications in perioperative airway management after palatoplasty are rare and mostly described in children with preexisting compromise of airway due to craniofacial anomalies. A very uncommon but typical and frightening complication is postoperative extreme, very rapid emergence, and life-threatening macroglossia. While macroglossia usually has its peak within 24-48 h after palatoplasty and resolves spontaneously, we report a patient with massive lingual swelling with complete obstruction of the upper airway on the fifth postoperative day requiring tracheotomy. Swelling only resolved after removing the endotracheal tube after tracheotomy. Next to the description of our case, we discuss standard care procedure in perioperative management of patients with cleft palate to prevent this life-threatening complication after palatoplasty. CONCLUSION: Macroglossia can occur even 3-5 days after surgery and can be maintained by the pressure of the endotracheal tube to the tongue ground. Knowledge and avoidance of these risk factors are as important as early treatment of respiratory compromise.