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.

High rate of insecure attachment patterns in preterm infants at early school age.

AIM: In preterm infants, insecure attachment is associated with behavioural and emotional problems but data on attachment beyond toddler age are scarce. This study assessed attachment security at 6-8 years in very and moderate or late preterm infants. The results were compared to a non-clinical full-term sample. METHODS: Attachment security of 38 very and 20 moderate or late preterm infants was assessed during a home visit with the German version of the Attachment Story Completion Task. Attachment patterns of 28 full-term controls were taken from a previous study. Primary outcomes were attachment security and attachment security score. Secondary outcomes for the preterm groups were infant behavioural problems, parental stress, perceived social support, maternal depressive symptoms, and infant development. RESULTS: Very preterm infants had the highest rate of insecure attachment (81%) compared to moderate or late preterm infants (60%) and full-term infants (47%); (p = 0.013). Attachment security scores differed significantly between very preterm and full-term infants (p = 0.001). Secondary outcomes were similar in very and moderate or late preterm cohorts. CONCLUSION: Prematurity was associated with an increased risk of insecure attachment at early school age. Interventions targeting attachment security are reasonable considering the high rate of behavioural problems following premature birth.

Use of Sotrovimab in 14 Children with COVID-19: A Single-center Experience.

Children affected by coronavirus disease 2019 (COVID-19) with preexisting comorbidities are at risk of complications. Monoclonal antibodies prevent severe COVID-19 courses in adults but data on children are scarce. Here we report on the use of Sotrovimab in 14 children at risk of severe disease treated at the University of Cologne Children's Hospital. Tolerability was good and no infusion-related reactions were seen.

Impact of a pediatric infectious disease consultation service on timely step-down to oral antibiotic treatment for bone and joint infections.

PURPOSE: In recent years an earlier step down to oral antibiotic therapy has been advocated for numerous infections. Trained infectious disease specialists regularly consulting their colleagues may speed up the implementation of such recommendations into clinical practice and thus may improve treatment. METHODS: We retrospectively analyzed bone and joint infections in children admitted to the University Hospital of Cologne between 2010 and 2021. We assessed clinical, imaging, and microbiological findings and treatment modalities. Additionally, we assessed both the impact of a newly implemented pediatric infectious diseases consultation service and publications on revised treatment recommendations by comparing antibiotic therapy in two periods (2010-2016 versus 2017 to 2021). RESULTS: In total, 29 children presented with osteomyelitis, 16 with bacterial arthritis and 7 with discitis. In period 2 (2017-2021) we observed shorter duration of intravenous treatment (p = 0.009) and a higher percentage of oral antibiotic treatment in relation to the total duration of antibiotics (25% versus 59%, p = 0.007) compared to period 1 (2010-2016). Yet, no differences were identified for the total length of antibiotic treatment. Additionally, biopsies or synovial fluid samples were retrieved and cultured in more children in period 2 (p = 0.077). The main pathogen identified in osteomyelitis and bacterial arthritis was Staphylococcus aureus (MSSA), diagnosis was confirmed predominantly with MRI. CONCLUSION: Recent guidelines addressing the safety of an earlier step-down (to oral) antibiotic therapy have influenced clinical practice in the treatment of bone and joint infections in our hospital. A newly implemented pediatric infectious diseases consultation service might have accelerated this progress resulting in a faster step down to oral treatment.

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.

What Do We Know about Spondylodiscitis in Children? A Retrospective Study.

Pediatric spondylodiscitis (PSD) is a rare disease with a major impact on mobility and functional status. Data concerning demographic and microbiological characteristics, clinical course, treatment, and outcome are scarce. Therefore, the aim of this study was to present clinical experiences of a third-level hospital (2009-2019) in PSD and compare these with adult spondylodiscitis (ASD). Of a total of 10 PSD patients, most of the infants presented with unspecific pain such as hip pain or a limping, misleading an adequate diagnosis of spine origin. Eight patients could be treated conservatively whereas surgery was performed in two cases with one case of tuberculous PSD (tPSD). The causative agent was detected in three of the patients. The diagnosis of PSD is often difficult since clinical symptoms are unspecific and causative pathogens often remain undetected. Nevertheless, empirical anti-infective therapy also seems to be effective. Based on recent studies, clinicians should be encouraged to keep the duration of anti-infective therapy in children short. Since comorbidities are not presented in PSD it is unclear which children suffer from PSD; thus, studies are necessary to identify predisposing factors for PSD. In our study, PSD differs from ASD in diagnostic and especially in therapeutic aspects. Therefore, specific guidelines for PSD would be desirable.

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.

Molds and More: Rare Fungal Infections in Preterm Infants <24 Weeks of Gestation.

BACKGROUND: Extreme immature infants are at an increased risk of fungal infection due to immaturity of the skin barrier and the immune system. Besides Candida infections, in particular, Aspergillus may cause life-threatening diseases in preterm infants. Frequently, Aspergillus primarily affects the skin and may cause extensive damage. METHODS: We searched our hospital database for fungal infections other than Candida in preterm infants treated between 2015 and 2020 at our level III neonatal intensive care unit of the University Hospital of Cologne. RESULTS: In total, 13 preterm infants were identified. Of these, 11 had cutaneous Aspergillosis, one infant had severe enterocolitis caused by Aspergillus and Rhizopus and one had invasive intraabdominal Trichosporon mucoides infection. All infants were born <24 weeks of gestation, were delivered due to premature labor or chorioamnionitis, and had received prenatal steroids and/or hydrocortisone. Voriconazole and liposomal Amphotericin B were first-line treatments and the length of treatment varied between 3 and 148 days. Two infants died associated with severe infection. Liver toxicity was observed in six infants treated with Voriconazole. Therapeutic drug management for Voriconazole was performed in four infants. Target levels were not achieved by the doses that are recommended. CONCLUSIONS: Rare fungal infections, predominantly cutaneous Aspergillosis affects the most immature preterm infants and may cause severe disease. Treatment with Voriconazole has a high rate of liver toxicity and target levels are difficult to achieve in extremely immature infants.

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.

Is it all MIS-C? Unusual findings in a series of nine German patients with multi-system inflammatory syndrome in children after SARS-CoV-2 infection.

OBJECTIVES: Multi-system inflammatory syndrome in children (MIS-C) is a post-viral inflammatory vasculopathy of children and adolescents following Covid-19 infection. Since the incidence of SARS-CoV-infections has been increasing in Germany since October 2020, we observe an increasing number of children presenting with MIS-C. DESIGN: We present detailed clinical characteristics of a cohort of nine children with MIS-C admitted to a tertiary PICU at the University Hospital of Cologne between March 2020 and February 2021. RESULTS: The clinical sings and symptoms are largely in line with recent reports. All but one patient had positive SARS-CoV-2 antibodies. Latency form infection to MIS-C was 4-6 weeks. Two children presented with unusual findings: A girl had encephalomyelitis and a boy developed MIS-C side to side with acute leukemia. CONCLUSION: MIS-C has been increasing in Germany paralell to SARS-CoV-2 infections. Rarely, unuasual findings may be associated with MIS-C.

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.

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.

Pain response to vaccination in newborn infants of diabetic mothers.

BACKGROUND: Response to pain is altered in infants who were exposed to pain- and stressful events in the neonatal period. Infants of diabetic mothers receive several heel sticks after birth for measuring blood glucose and thus may show changes in their behavioral and physiologic response to pain. Moreover, maternal hyperglycemia may alter activity of the hypothalamic pituitary adrenal (HPA) axis reactivity. STUDY DESIGN: In total, 43 infants of diabetic mothers and 30 control infants were included into the study. Response to pain was assessed at 3 months of age following two intramuscular injections for vaccination. We assessed behavioral (Bernese pain scale), physiologic (heart rate) and hormonal (salivary cortisol) pain response to vaccination as well as spinal sensitization (flexion withdrawal reflex). RESULTS: Infants of diabetic mothers received a median number of 5 [4-19] painful events compared to 1 [1-3] in the control group. Heart rate reactivity differed significantly between groups. Infants of diabetic mothers had higher peaks (p = 0.002) and needed more time to recover to baseline (p < 0.001). Moreover, infants of diabetic mothers showed higher peak cortisol (p = 0.001) and a higher relative cortisol increase (p = 0.015). Flexor withdrawal reflex thresholds were significantly lower in infants of diabetic mothers (p = 0.003). CONCLUSION: The increase of physiologic and hormonal responses to pain in infants of diabetic mothers is probably caused by repeated painful events and an altered metabolic profile.

Delivery room skin-to-skin contact for preterm infants-A randomized clinical trial.

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.