Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Use and Impact of Pessary, Cerclage, and Progesterone for the Secondary Prevention of Preterm Birth: Data from the German Neonatal Network.

BACKGROUND: To evaluate the use and effect of cervical stitch cerclage, pessary, and progesterone on pregnancy outcome in mothers of very low birth weight infants (VLBWI) born<32 weeks of gestation in the German Neonatal Network (GNN). METHODS: The GNN is a population-based cohort study enrolling VLBWI since 2009. We included 575 neonates from 424 mothers into our analysis, who were born between 2015 and 2019, after prenatal intervention with cerclage, pessary, progesterone or a combination between 20/0 to 25/0 weeks of gestation to prevent preterm birth. Median intervention-to-birth interval was the primary endpoint. RESULTS: 231 of 424 pregnant women had a cerclage only (54.5%), 76 women a pessary only (17.9%), and 27 were prescribed progesterone only (15.3%). The most common combination treatment (>1 intervention group) was cerclage plus progesterone (n=27), followed by cerclage plus pessary (n=13). The median intervention-to-birth interval for the whole cohort was 24 days (IQR 19.0 days). The earlier the intervention was started, the longer the intervention-to-birth interval lasted: When started at 20 weeks, the interval was 34 days in contrast to 11.5 days, when started at 25 weeks. The >1 group was born at a significantly higher median GA with 27.0 weeks (IQR 2.9 weeks) and a higher median birth weight of 980 g (IQR 394 g) accordingly. CONCLUSION: We propose that the earliest possible start of intervention leads to the most efficient pregnancy prolongation.

Umbilical venous catheter- and peripherally inserted central catheter-associated complications in preterm infants with birth weight < 1250 g : Results from a survey in Austria and Germany.

BACKGROUND AND OBJECTIVE: Umbilical venous catheters (UVC) and peripherally inserted central catheters (PICC) are commonly used in preterm infants but have been associated with a number of serious complications. We performed a survey in Austria and Germany to assess the use of UVCs and PICCs in preterm infants with a birth weight < 1250 g and associated rates of catheter-related adverse events. METHODS: Electronic survey of participating centers of the NeoVitaA trial. Main outcome parameter was the reported rates of UVC- and PICC-associated complications (infection, thrombosis, emboli, organ injury, arrhythmia, dislocation, miscellaneous). RESULTS: In total, 20 neonatal intensive care units (NICU) providing maximal intensive care in Austria and Germany (level I) were contacted, with a senior neonatologist response rate of 12/20 (60%). The reported rates for UVC with a dwell time of 1-10 days were bacterial infection: 4.2 ± 3.4% (range 0-10%); thrombosis: 7.3 ± 7.1% (0-20%); emboli: 0.9 ± 2.0% (0-5%); organ injury: 1.1 ± 1.9% (0-5%); cardiac arrhythmia: 2.2 ± 2.5% (0-5%); and dislocation: 5.4 ± 8.7% (0-30%); and for PICCs with a dwell time of 1-14 days bacterial infection: 15.0 ± 3.4% (range 2.5-30%); thrombosis; 4.3 ± 3.5% (0-10%); emboli: 0.8 ± 1.6% (0-5%); organ injury: 1.5 ± 2.3% (0-5%); cardiac arrhythmia: 1.5 ± 2.3% (0-5%), and dislocation: 8.5 ± 4.6% (0-30%). CONCLUSION: The catheter-related complication rates reported in this survey differed between UVCs and PICCs and were higher than those reported in the literature. To generate more reliable data on this clinically important issue, we plan to perform a large prospective multicenter randomized controlled trial investigating the non-inferiority of a prolonged UVC dwell time (up to 10 days) against the early change (up to 5 days) to a PICC.

Lactoferrin and Human Neutrophil Protein (HNP) 1-3 Levels During the Neonatal Period in Preterm Infants.

Antimicrobial polypeptides (APPs) are part of the innate immune system, but their specific role in the context of preterm birth is not yet understood. The aim of this investigation was to determine the systemic expression of APPs, i.e., lactoferrin (LF) and human neutrophil protein (HNP) 1-3 in preterm infants in the period of highest vulnerability for infection and to correlate these biomarkers with short-term outcome. We therefore conducted a prospective two-center study including plasma samples of 278 preterm infants and 78 corresponding mothers. APP levels were analyzed on day 1, 3, 7, and 21 of life via enzyme-linked immunosorbent assay (ELISA). The levels of LF and HNP1-3 remained stable during the first 21 days of life and were not influenced by maternal levels. Elevated APP levels were found at day 1 in infants born to mothers with amniotic infection syndrome (AIS vs. no AIS, mean ± SD in ng/ml: LF 199.8 ± 300 vs. 124.1 ± 216.8, HNP 1-3 16,819 ± 36,124 vs. 8,701 ± 11,840; p = 0.021, n = 179). We found no elevated levels of APPs before the onset of sepsis episodes or in association with other short-term outcomes that are in part mediated by inflammation such as necrotizing enterocolitis (NEC) or retinopathy of prematurity (ROP). Interestingly, infants developing bronchopulmonary dysplasia (BPD) showed higher levels of HNP1-3 on day 21 than infants without BPD (13,473 ± 16,135 vs. 8,388 ± 15,938, n = 111, p = 0.008). In infants born without amniotic infection, levels of the measured APPs correlated with gestational age and birth weight. In our longitudinal study, systemic levels of LF and HNP 1-3 were not associated with postnatal infection and adverse short-term outcomes in preterm infants.

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.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The 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 FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis.

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Developmental outcome of extremely preterm infants is improved after less invasive surfactant application: Developmental outcome after LISA.

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) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008). CONCLUSION: At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior.

Iatrogenic severe hyperglycemia due to parenteral administration of glucose in children - a case series.

BACKGROUND: Iatrogenic severe hyperglycemia (ISH) caused by glucose-containing i.v. solution is a potentially fatal treatment error. The objective of this study was to investigate the causes, circumstances, course of disease, and complications of ISH > 300 mg/dl (16.7 mmol/l) in neonates and children. METHODS: We emailed a survey to 105 neonatal and pediatric intensive care units in Germany, Austria, and Switzerland, asking to retrospectively report cases of ISH. RESULTS: We received 11 reports about premature infants to children. Four patients (36%) had poor outcome: 2 died and 2 suffered persistent sequelae. The highest observed blood glucose was at median 983 mg/dl (54.6 mmol/l) (range 594-2240 mg/dl; 33.0-124.3 mmol/l) and median time to normoglycemia was 7 h (range 2-23). Blood glucose was higher and time to normoglycemia longer in patients with poor outcome. Invasive therapy was required in 73% (mechanical ventilation) and 50% (vasopressor therapy) of patients, respectively. Administration of insulin did not differ between outcome groups. Patients with poor outcome showed coma (100% vs. 40%) and seizures (75% vs. 29%) more frequently than those with good outcome. CONCLUSIONS: ISH is a severe condition with high morbidity and mortality. Further research to amplify the understanding of this condition is needed, but focus should largely be held on its prevention.

Hydrocortisone to treat early bronchopulmonary dysplasia in very preterm infants: study protocol for a randomized controlled trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is still a common complication in very premature infants. At present, there is no effective treatment for BPD. Glucocorticoids are drugs commonly used to prevent or treat BPD before and after birth. In very premature infants with high risk factors for BPD, early use of dexamethasone can reduce the rate of death and/or BPD but may cause long-term adverse neurodevelopmental outcomes. Hydrocortisone (HC), as an alternative drug to dexamethasone, has been increasingly used to prevent BPD. However, no study has reported the efficacy and safety of HC to treat early BPD diagnosed at postnatal day (PND) 28. METHODS: This study protocol is for a multicenter double-blind randomized controlled trial of low-dose HC in the treatment of early BPD. Early BPD infants will be randomly assigned to the HC treatment group or control group. Infants in the HC group will receive 0.5 mg/kg HC twice a day for 7 days and then 0.5 mg/kg HC once a day for 3 days. The control group will be given the same volume of placebo and no intervention on the basis of routine treatment. The primary outcome is survival without moderate or severe BPD at 36 weeks postmenstrual age. Secondary outcomes are the short- and long-term effects on growth, metabolism, neurodevelopment, and other possible complications. DISCUSSION: This trial will determine the efficacy and safety of low-dose HC administration compared to placebo for the reduction of moderate or severe BPD at 36 weeks postmenstrual age in very preterm infants with early BPD. TRIAL REGISTRATION: China Clinical Trial Registration Center ChiCTR1900021854 . Registered on 13 March 2019.

Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk.

Objective: To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth. METHODS: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727). The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted in linear/logistic regression models. RESULTS: 5954 (76.5%) infants received L. acidophilus/B. infantis prophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size B = 0.224; 95% CI: 2.82-4.35; p < 0.001) but not in the F group (effect size B = -0.06; 95% CI: -3.05-0.28; p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation proved to be protective against clinical sepsis (OR 0.69; 95% CI: 0.59-0.79; p < 0.001). CONCLUSION: Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive effect, probiotics seem to require human milk.

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study.

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.

The effect of less invasive surfactant administration on cerebral oxygenation in preterm infants.

AIM: To determine the regional cerebral tissue oxygenation saturation (rcSO2 ) in a group of infants requiring less invasive surfactant administration (LISA) as compared to infants with continuous positive airway pressure (CPAP) only. METHODS: In preterm infants with a gestational age 26 0/7-31 6/7 weeks, we conducted an observational study using near-infrared spectroscopy (NIRS) in the first 120 hours of life. RESULTS: We analysed the data of 22 infants who never received surfactant (CPAP), 22 infants had LISA and CPAP (LISA) and 6 infants received surfactant via endotracheal tube (ETT). Four infants had both surfactant application modes including six LISA applications. In total, there were 32 successful LISA applications but 44 attempts; 13/44 (30%) of LISA attempts resulted in a 20% decrease of rcSO2 . During the first 120 hours of life, rcSO2 values of CPAP were similar to those of infants in the LISA group, that is median rcSO2 values 90% vs 85%, respectively (P = .126). Episodes with rcSO2 values <65% were 0.4% in the CPAP group as compared to 4.8% in the LISA group (P < .001). CONCLUSION: Our observational data indicate that rcSO2 values of infants in the LISA group were similar to the CPAP group.

Active perinatal care of preterm infants in the German Neonatal Network.

OBJECTIVE: To determine if survival rates of preterm infants receiving active perinatal care improve over time. DESIGN: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016. SETTING: 43 German level III neonatal intensive care units (NICUs). PATIENTS: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. INTERVENTIONS: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (

Associations between Neonatal Serum Bilirubin and Childhood Obesity in Term Infants.

Inverse correlations between serum bilirubin level and obesity had been reported in adults. We aimed to investigate the associations between neonatal hyperbilirubinemia and childhood obesity. Data was obtained from the U.S. Collaborative Perinatal Project (CPP), a multicenter study from 1959 to 1976. Data of serum bilirubin in term newborns were used to observe the association with obesity at age of 7 years. Logistic regression models were performed to calculate adjusted odds ratios (aORs) for obesity. For children from the same mother sharing similar factors, Generalized Estimating Equation (GEE) model was used to correct for intracluster correlation. Relative to newborns with total serum bilirubin (TSB) < 3 mg/dl, there are lower risks for obesity in those with 3 mg/dl ≤ TSB < 6 mg/dl (aOR 0.91; 95%CI 0.81, 1.02), 6 mg/dl ≤ TSB < 9 mg/dl (aOR 0.88; 95%CI 0.78, 0.99), 9 mg/dl ≤ TSB<13 mg/dl (aOR 0.83; 95%CI 0.71, 0.98). By stratifying for subtypes of bilirubin, the inverse correlations only existed in exposure to unconjugated bilirubin. By using the GEE model correcting for intracluster correlations, the results are consistent. In summary, exposure to bilirubin up to 13 mg/dl is inversely associated with obesity at the age of 7 years in term infants.

Positional treatment without mechanical ventilation in a very preterm infant with unilateral pulmonary interstitial emphysema: case report and review of the literature.

BACKGROUND: Pulmonary interstitial emphysema (PIE) in very low birth weight infants is a rare but severe complication. Although most of these air leaks develop in mechanically ventilated infants, they have also been reported in infants exposed only to nasal continuous positive airway pressure (CPAP). The optimal treatment for PIE is still under discussion and includes different approaches such as unilateral intubation, high frequency oscillation ventilation and even surgical lobectomy. However, as yet, there has been no report on complete resolution of unilateral PIE by positioning therapy without mechanical ventilation. CASE PRESENTATION: We report the case of a 28+1gestational week twin, 990 g birth weight, Apgar 9-10-10. After stabilization with nasal CPAP the baby received surfactant by less invasive surfactant application (LISA) technique in the delivery room after 35 min of life, and continued respiratory support with nasal CPAP. At day 5 X-ray presented unilateral PIE, while pCO2 increased from 40 mmHg to 55 mmHg and FiO2 from 0.21 to 0.28 to achieve SpO2 in the target range of 89-94%. The baby was treated by strict positioning on the affected hemithorax in a special splint while spontaneously breathing on High Flow Nasal Cannula (HFNC). Complete resolution of the unilateral PIE was observed after 96 h. No chronic lung disease developed. CONCLUSION: For unilateral PIE in very preterm infants, positioning on the affected hemithorax without mechanical ventilation is a therapeutic option.

Mannose-binding lectin and mannose-binding protein-associated serine protease 2 levels and infection in very-low-birth-weight infants.

OBJECTIVE: The aim of this study was to explore the role of the lectin pathway in neonatal sepsis through the study of MBL and MASP2 levels and their relationship with infection in a cohort of very-low-birth-weight infants (VLBWI). METHODS: MBL and MASP2 were measured in plasma samples of n = 89 VLBWI using ELISA and correlated with clinical parameters. MBL plasma levels were aligned with genotyping data of mbl2 exon 1 polymorphisms, rs1800450, rs1800451, and rs5030737. RESULTS: MBL levels were clearly determined by MBL genotype, i.e., AA individuals had tenfold higher MBL levels than AO individuals. MBL and MASP2 levels did not correlate with gestational age, apart from MASP2 levels on day 7. During the first 21 days of life, we noted a gradual increase in both MBL and MASP2 levels. On day 7 of life, MASP2 levels in infants developing late-onset sepsis measured before the onset of symptoms were found to be lower, as compared to non-LOS infants. CONCLUSIONS: In our cohort of VLBWI, MBL levels were genetically determined, but not associated with gestational age or sepsis in the first 21 days of life. Lower MASP2 levels on day 7 may indicate increased risk for late-onset infection.

Less invasive surfactant administration and complications of preterm birth.

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 < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49-0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48-0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45-0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14-1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born <26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants <26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup.

IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.

Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections. The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies. This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants. It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants. In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA. Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography. Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants. Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD). However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns. Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age. Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern. The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.

Neonatal blood rheological parameters at delivery in healthy neonates and in those with morbidities.

Rheological blood parameters of neonates are different form those of adults. Many authors have studied changes in blood rheology in neonates in different clinical disorders. To-date, no one set the normal values for blood rheological parameters in healthy neonates. The aim of this study is to set the norm for rheological blood parameters in healthy newborns and to describe the changes in those parameters in common clinical disorders that affect the newborns. We recruited all the neonates born to mothers experiencing un eventful pregnancies, blood was taken from the umbilical cord right after the delivery. In this time period we recruited 4985 neonate. From this huge database we were able to set the standards for blood rheology in neonates, namely plasma viscosity of 1.06±0.072 mPa, erythrocyte aggregation at stasis of 2.41±2.74 s-1 and erythrocyte aggregation under low shear forces of 8.51±6.38 s-1. These values changed significantly in some diseased neonates. This is the largest study investigating normal rheological parameters and deviations from the norm in common clinical disorders occurring in this early stage of life.