LISA Eligibility and LISA Success in Extremely Preterm Infants: A Single-Center Experience.

INTRODUCTION: Less invasive surfactant application (LISA) is associated with improved short-term outcomes in preterm infants. Data on LISA eligibility and success for infants <28 weeks of gestation are lacking. METHODS: Preterm infants <28 weeks of gestation who were born and actively treated in our tertiary care center in 2018 were included in the retrospective study. We assessed baseline characteristics, delivery room (DR) management, LISA success and complications, and short-term outcome. RESULTS: In total, 57 infants received LISA in the DR. LISA eligibility was 73% at 22 weeks, 88% at 23 weeks, and >90% at gestational ages >24 weeks. LISA was successful in 63% of infants. LISA failure was associated with increased risk for high-grade IVH (OR 17.88), death (OR 10.94), and a reduced chance for survival without complications (OR 8.75). CONCLUSION: Our report justifies LISA as a mode for surfactant application in preterm infants. It contributes to the call for studies to define risk factors for LISA failure.

Wide use of broad-spectrum antibiotics in very low birth weight infants with spontaneous focal intestinal perforation-is it really justified?

PURPOSE: Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. METHODS: Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. RESULTS: In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)). CONCLUSION: The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs).

Low incidence of acute kidney injury in VLBW infants with restrictive use of mechanical ventilation.

BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.

Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial.

Importance: An extrauterine placental perfusion (EPP) approach for physiological-based cord clamping (PBCC) may support infants with very low birth weight (VLBW) during transition without delaying measures of support. Objective: To test whether EPP in resuscitation of infants with VLBW results in higher hematocrit levels, better oxygenation, or improved infant outcomes compared with delayed cord clamping (DCC). Design, Setting, and Participants: This nonblinded, single-center randomized clinical trial was conducted at a tertiary care neonatal intensive care unit. Infants with a gestational age greater than 23 weeks and birth weight less than 1500 g born by cesarean delivery between May 2019 and June 2021 were included. Data were analyzed from October through December 2021. Intervention: Prior to cesarean delivery, participants were allocated to receive EPP or DCC. In the EPP group, infant and placenta, connected by an intact umbilical cord, were detached from the uterus and transferred to the resuscitation unit. Respiratory support was initiated while holding the placenta over the infant. The umbilical cord was clamped when infants showed regular spontaneous breathing, stable heart rates greater than 100 beats/min, and adequate oxygen saturations. In the DCC group, cords were clamped 30 to 60 seconds after birth before infants were transferred to the resuscitation unit, where respiratory support was started. Main Outcomes and Measure: The primary outcome was the mean hematocrit level in the first 24 hours after birth. Secondary prespecified outcome parameters comprised oxygenation during transition and short-term neonatal outcome. Results: Among 60 infants randomized and included, 1 infant was excluded after randomization; there were 29 infants in the EPP group (mean [SD] gestational age, 27 weeks 6 days [15.0 days]; 14 females [48.3%]) and 30 infants in the DCC group (mean [SD] gestational age, 28 weeks 1 day [17.1 days]; 17 females [56.7%]). The mean (SD) birth weight was 982.8 (276.6) g and 970.2 (323.0) g in the EPP and DCC group, respectively. Intention-to-treat analysis revealed no significant difference in mean hematocrit level (mean difference [MD], 2.1 percentage points; [95% CI, -2.2 to 6.4 percentage points]). During transition, infants in the EPP group had significantly higher peripheral oxygen saturation as measured by pulse oximetry (adjusted MD at 5 minutes, 15.3 percentage points [95% CI, 2.0 to 28.6 percentage points]) and regional cerebral oxygen saturation (adjusted MD at 5 minutes, 11.3 percentage points [95% CI, 2.0 to 20.6 percentage points]). Neonatal outcome parameters were similar in the 2 groups. Conclusions and Relevance: This study found that EPP resulted in similar hematocrit levels as DCC, with improved cerebral and peripheral oxygenation during transition. These findings suggest that EPP may be an alternative procedure for PBCC in infants with VLBW. Trial Registration: ClinicalTrials.gov Identifier: NCT03916159.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Use of whole exome sequencing in the NICU: Case of an extremely low birth weight infant with syndromic features.

Single gene (Mendelian) disorders are one of the leading causes of neonatal morbidity and mortality. However, in the setting of preterm birth phenotypic features of genetic diseases are often undifferentiated and are clinically very difficult to interpret based on the wide range of differential diagnoses. We report an extremely low birth weight infant (ELBW) born prematurely at 23 + 0 gestational weeks after twin pregnancy with a novel clinical manifestation with persistent hyperglycaemia as well as the known manifestations of disease-associated hypokinesia, renal salt wasting, and multifocal atrial tachycardia. The patient died of heart failure on the 72nd day of life. Whole exome sequencing (WES) revealed a previously well established, disease-causing heterozygous likely pathogenic variant in the Harvey rat sarcoma viral oncogene homolog (HRAS)-gene (c.35G > C, p. G12A, rs104894230), which implied the clinical diagnosis of Costello syndrome (CS; OMIM#190020.0004). The twin brother merely had complications related to preterm birth and did not show any CS symptoms. In conclusion, our case illustrated that CS should be considered in ELBW infants showing a life-threatening combination of complex cardiac arrhythmia and hypokinesia. If a syndromic disorder is suspected in the neonatal intensive care unit (NICU) setting, rapid WES is a useful, non-invasive diagnostic tool in critically ill ELBW infants.

Mask Continuous Positive Airway Pressure Therapy with Simultaneous Extrauterine Placental Transfusion for Resuscitation of Preterm Infants - A Preliminary Study.

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.