AIM:Doxapram is used as an additional therapy for apnea of prematurity when standard treatments such as caffeine or continuous positive airway pressure are insufficient, but its impact on long-term neurodevelopment remains uncertain. This study evaluated the association between Doxapram exposure and neurodevelopmental outcomes in very low birth weight infants (VLBWI), with a focus on potential dose-dependent effects. METHODS:In this monocentric retrospective cohort study, VLBWI with gestational age ≤ 32 weeks were included. Infants treated with Doxapram (n = 140) were compared to untreated controls (n = 280) matched by year of birth. Exposure was stratified by cumulative dose. The primary outcome was neurodevelopment at 24 months corrected age assessed by the mental development index or global development quotient (MDI/GDQ). Secondary outcomes included mortality, growth parameters and neurological outcomes. Multivariable logistic regression adjusted for confounders. RESULTS:Neurodevelopment did not differ between groups (MDI/GDQ: 94.2 ± 21.2 vs. 97.7 ± 14.8; p = 0.1), nor did mortality (5.0% vs. 6.8%; p = 0.53). No dose-dependent associations were observed. Secondary outcomes were comparable. CONCLUSIONS:Doxapram exposure was not associated with adverse neurodevelopmental outcomes in VLBWI within the investigated dosage range, although definitive conclusions on drug safety cannot be drawn from medium-sized cohorts and confirmation in prospective randomised studies is required.

This study aimed to assess frequency and causes of neonatal intensive care unit (NICU) admissions in neonates with shoulder dystocia (SD). A retrospective analysis of 116 SD cases at a tertiary perinatal center was performed (2007 – 2023). Maternal and neonatal parameters were evaluated in relation to NICU admission. Seventeen neonates (14.7

Accurate ultrasound assessment of abdominal organ size in preterm infants is essential for evaluating growth and detecting abnormalities. However, standardized reference intervals for liver, spleen, and kidney dimensions in preterms below 40 cm body length are lacking. This study aimed to establish reference intervals for these organs. 57 eutrophic preterm infants with a body length below 40 cm (gestational age: 23 4/7—31 5/7 weeks; birth length: 29—39.5 cm) were prospectively examined using a standardized ultrasound protocol recommended by the German Society for Ultrasound in Medicine (DEGUM). Craniocaudal liver length, spleen length, and renal volume were measured and correlated with corrected gestational age, body weight, and body length. Reference intervals were calculated from log-transformed data with 95

Abstract Background Klebsiella pneumoniae complex (Kp) is a relevant neonatal pathogen colonizing preterm infants. While outbreak investigations often focus on multidrug-resistant strains, the epidemiology and genomic dynamics of wild-type Kp in nonoutbreak neonatal intensive care unit (NICU) settings remain elusive. Methods We conducted a 30-month (October 2021 to March 2024) cohort study with weekly active, unselective colonization surveillance of all NICU patients to identify risk factors for nosocomial Kp acquisition and drivers of transmission in a tertiary 21-bed NICU/intermediate care unit (IMC) in Germany. Results Among 936 patients, 8.7% carried Kp, of which 70.4% were nosocomial. Very low birth weight (VLBW; < 1500 g) was the only independent risk factor for nosocomial acquisition (adjusted odds ratio [aOR], 3.42; 95% CI, 1.29–9.32). Kp infections occurred in three Kp carriers (3.7%). Genomic analyses of at least the first isolate per patient (83 in total) revealed an oligoclonal population structure, with ten distinct sequence types (STs) underlying temporally overlapping clusters. Ten genomic clusters (median size, four patients) were identified, with markedly higher odds in VLBW infants (aOR, 8.76; 95% CI, 2.45–34.16). Nosocomial cluster-assigned cases had higher rates and longer durations of noninvasive ventilation and peripheral venous catheter use. Cluster prevalence showed climate-associated variation, with a six-feature extreme gradient boosting (XGBoost) model identifying temperature and humidity among the strongest predictors. Conclusions Patient- and climate-associated parameters are main drivers of nosocomial wild-type Kp acquisition and cluster occurrence. Comprehensive surveillance and risk-adapted infection prevention and control support sustainable Kp control in VLBW infants.

Background Ultrasound (US) is among the most commonly used imaging modalities in neonatology due to its non-invasiveness and bedside applicability. Its frequent use may place additional demands on nurses, who already face considerable challenges in neonatal intensive care units (NICUs). However, there is no investigation into how US examinations affect nursing workflows and whether they are perceived as an additional burden. Aim This survey study aims to assess the impact of US examinations on NICU nurses’ daily work, identify challenges, and explore strategies for better integration into clinical practice. Material and methods In March 2025, nurses in a level III NICU completed a newly developed 38-item questionnaire assessing general attitudes toward US, its impact on workflow, and optimization options (4-point Likert scale), along with five free-text questions. Quantitative data were analyzed descriptively; conventional qualitative content analysis was applied to open-ended responses. Results 59 of 70 nurses participated (response rate: 84 %). While 98 % rated US as improving patient care, 42 % reported workflow interruptions, and 49 % noted reduced time for other nursing activities. Additionally, 61 % called for better interprofessional communication and coordination, while 81 % considered theoretical education beneficial for improving US integration and interpretation. Conclusion US is essential in neonatal diagnostics, but challenges nursing workflows. A 5-point plan was developed to improve integration, focusing on structured scheduling, enhanced interprofessional communication, streamlining US examinations, focused education, and greater parental involvement. These measures aim to enhance efficiency and minimize additional stress, ensuring that US supports rather than complicates nurses’ already demanding routines.

AIM:Cardiorespiratory events such as apnea, bradycardia and hypoxemia are common in preterm infants and may contribute to an impaired neurodevelopmental outcome. We hypothesised a significant reduction in the incidence of hypoxemia, bradycardia and gastric residuals in the prone position. METHODS:In this monocentric, prospective, randomised, two-arm crossover trial, at a tertiary university hospital, 48 preterm infants with a gestational age of < 32 weeks and a postmenstrual age of < 34 weeks were randomised to either a prone-supine or a supine-prone sequence of cardiorespiratory monitoring over a period of 24 h. The primary outcome parameter was the cumulative frequency of hypoxemias and bradycardias; secondary parameters comprised evaluation of basal parameters, hypoxemias, bradycardias and the amount of gastric residuals. RESULTS:The cumulative frequency of hypoxemias and bradycardias and the number of severe hypoxemias (peripheral oxygen saturation [SpO2] < 80%) were halved in the prone position (p = 0.03). Median basal SpO2 was significantly higher (p = 0.01) and gastric residuals were significantly lower (p = 0.0002) in the prone position. The frequency of apneas (> 10 s) was significantly increased in the prone position (p = 0.01). CONCLUSION:Prone positioning of preterm infants significantly reduces the cumulative frequency of hypoxemias and bradycardias, severe hypoxemias and gastric residuals while increasing basal SpO2.

Necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP) and meconium-related ileus (MI) requiring surgical intervention are associated with a high risk of severe short- and long-term complications in very-low-birth-weight (VLBW) infants including poor growth, cholestasis and neurodevelopmental impairment. This retrospective study aimed to identify risk factors for such complications in a cohort of 55 VLBW preterm infants requiring surgery with enterostomy creation due to NEC, SIP or MI. Long-term follow-up was available for 43 (78%) infants. Multiple regression analyses revealed that the duration of inflammation and longitudinal growth determined the risk of cholestasis and neurodevelopmental outcome at 2 years corrected age independent of the aetiology of the intestinal complication. Direct bilirubin increased by 4.9 μmol/L (95%CI 0.26–9.5), 1.4 μmol/L (95%CI 0.6–2.2) and 0.8 μmol/L (95%CI 0.22–1.13) with every day of elevated (Interleukin-6) IL-6, (C-reactive protein) CrP and parenteral nutrition. The mental development index at 2 years corrected age decreased by 3.8 (95%CI −7.3–−0.36), 0.4 (95%CI 0.07–0.80) and 0.3 (95%CI 0.08–0.57) with every day of elevated IL-6 and every 1 point decrease in weight percentile at discharge and 2 years. These data stress the importance of optimal timing for the initial surgery in order to prevent prolonged inflammation and an early reversal of the enterostomy in case of poor growth or insufficient enteral nutrition.

Background:After enterostomy creation, the distal bowel to the ostomy is excluded from the physiologic passage of stool, nutrient uptake, and growth of this intestinal section. Those infants frequently require long-term parenteral nutrition, continued after enterostomy reversal due to the notable diameter discrepancy of the proximal and distal bowel. Previous studies have shown that mucous fistula refeeding (MFR) results in faster weight gain in infants. The aim of the randomized multicenter open-label controlled MUCous FIstula REfeeding ("MUC-FIRE") trial is to demonstrate that MFR between enterostomy creation and reversal reduces the time to full enteral feeds after enterostomy closure compared to controls, resulting in shorter hospital stay and less adverse effects of parenteral nutrition. Methods/Design: A total of 120 infants will be included in the MUC-FIRE trial. Following enterostomy creation, infants will be randomized to either an intervention or a non-intervention group.In the intervention group, perioperative MFR between enterostomy creation and reversal will be performed. The control group receives standard care without MFR.The primary efficacy endpoint of the study is the time to full enteral feeds. Secondary endpoints include first postoperative bowel movement after stoma reversal, postoperative weight gain, and days of postoperative parenteral nutrition. In addition adverse events will be analyzed.Discussion:The MUC-FIRE trial will be the first prospective randomized trial to investigate the benefits and disadvantages of MFR in infants. The results of the trial are expected to provide an evidence-based foundation for guidelines in pediatric surgical centers worldwide.Trial registration:The trial has been registered at clinicaltrials.gov (number: NCT03469609, date of registration: March 19, 2018; last update: January 20, 2023, https://clinicaltrials.gov/ct2/show/NCT03469609?term=NCT03469609&draw=2&rank=1).

In preterm and term infants who require intermediate or intensive care Methicillin-resistant Staphylococcus aureus (MRSA) infection can lead to significant morbidity. In this study MRSA colonization and infection were assessed in a mixed tertiary neonatal intensive and intermediate care unit in Germany over an 8-year period (2013-2020). We investigated patient-related factors, associated with nosocomial MRSA acquisition, and we discuss our infection control concept for MRSA. Of 3488 patients treated during the study period, 24 were MRSA positive patients, corresponding to 26 patient hospital stays. The incidence was 0.7 MRSA patients per 100 patients. The incidence density was 0.4 MRSA patient hospital stays per 1000 patient days. Twelve patients (50%) acquired MRSA in the hospital. One patient developed a hospital acquired MRSA bloodstream infection 9 days after birth (i.e., 0.03% of all patients on the ward during the study period). A total of 122 patients had to be screened to detect one MRSA positive patient. In a logistic regression model, the use of 3rd generation intravenous cephalosporin (cefotaxim) was associated with nosocomial MRSA acquisition compared with matched control patients who did not acquire MRSA. In sum, the burden of MRSA colonization and infection in the ward was low during the study period. A comprehensive infection control concept that included microbiologic colonization screening, prospective infection surveillance together with isolation and emphasis on basic hygiene measures is essential to handle MRSA in this specialized setting.

We measured free and proteinic concentrations of native and modified amino acids from post-translational modifications (PTMs) and correlated them with the activity of SIRT1 and SIRT3 in the pellet and aqueous phases of human breast milk samples of ten lactating women during the neonatal period. SIRT1 and SIRT3 correlated directly with citrullination, asymmetric dimethylation and glycation of L-arginine, hydroxylation and glycation of L-lysine. SIRT1 and SIRT3 correlated inversely with the hydroxylation of L-proline. SIRT1 and SITR3 tended to correlate inversely with oxidative stress measured as malondialdehyde. Our study suggests that SIRT1 and SIRT3 may modulate PTMs in human breast milk cells.

Background: Serratia marcescens is a well-known and challenging pathogen in neonatal intensive care units. It is responsible for severe infections and can cause nosocomial outbreaks. Methods: We present the infection control response to a Serratia marcescens cluster which occurred in a tertiary neonatal intensive care unit. Results and conclusions: The presented comprehensive and decisive hygiene management response starting with the very first case aims especially at early detection and immediate interruption of nosocomial transmission. Frequent and sensitive microbiological screening, rigorous spatial isolation of colonized infants, and reinforcing adherence to hand hygiene are essential in this response, which comprises eight measures. It prevented a full-blown outbreak.

Breast feeding is regarded as the preferred nutrition modality for children during the first few months of life. It not only furthers growth and development but also is supposed to impact later life. The first 1000 days are regarded as a critical window for development, even beyond infancy. The physiological basis underlying this beneficial effect is not clear. Sirtuins are important regulatory proteins of metabolism and are supposed to play a critical role in ageing and longevity as well as in diseases. In the present study, we developed novel methods to assay sirtuin 1 and sirtuin 3 at enzyme activity (via fluorometry) and protein levels (by Western blot) in the aqueous phase and in the cell pellet of human breast milk and assessed the impact of ongoing lactation during the neonatal period. Sirtuin activities in the aqueous phase were negatively correlated with the duration of lactation in the neonatal period. There was no correlation of sirtuin activities in the cell pellet with the duration of lactation. The amounts of sirtuin 1 and sirtuin 3 measured by Western blot were negatively correlated with the lactation period.

Due to frequent cardiorespiratory events (CREs) in response to the first routine immunization (rIM), current guidelines recommend readmitting and monitoring extremely preterm infants after the second rIM, though evidence on CREs in response to the second rIM is weak. In a prospective observational study, preterm infants with an increase in CREs after the first rIM were monitored for CREs before and after the second rIM. Seventy-one infants with a median gestational age of 26.4 weeks and a median weight of 820 g at birth were investigated at a median postnatal age of 94 days. All but seven infants showed an increase in CREs after the second rIM. The frequency of hypoxemias (p < 0.0001), apneas (p = 0.0003) and cardiorespiratory events requiring tactile stimulation (CRE-ts) (p = 0.0034) increased significantly. The 25 infants (35%) presenting with CRE-ts were significantly more likely to have been continuously hospitalized since birth (p = 0.001) and to receive analeptic therapy at the first rIM (p = 0.002) or some kind of respiratory support at the first (p = 0.005) and second rIM (p < 0.0001). At a postmenstruational age of 43.5 weeks, CRE-ts ceased. Our data support the recommendation to monitor infants who fulfil the above-mentioned criteria during the second rIM up to a postmenstruational age of 44 weeks.

Background Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. Methods In this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH 2 O) or a lower (3–5 cmH 2 O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO 2 (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO 2 > 0.5 for > 1 h or pCO 2 ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). Discussion Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH 2 O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. Trial registration drks.de DRKS00019940 . Registered on March 13, 2020

Home oxygen therapy is increasingly prescribed for various conditions in the neonatal period, particularly for infants with bronchopulmonary dysplasia. Due to limited evidence on indication, minimal target oxygen saturation, monitoring, application and discontinuation of home oxygen therapy clinical practice varies widely throughout the world. International guidelines provide recommendations mostly on the basis of nonsystematic clinical observations. Most relevant points for the clinical management of home oxygen therapy include a minimal target oxygen saturation of equal to or greater than 93%, the provision of a home monitoring of oxygen saturation ideally with a memory function, and the conduct of continuous overnight oximetry or polysomnography during weaning from supplemental oxygen. This review summarizes relevant literature as well as existing guidelines and recommendations on home oxygen therapy to aid clinicians in the management of these patients and identifies areas for future research.

AIM:This study compiled percentiles for cardiorespiratory parameters in healthy term neonates during quiet sleep.METHODS:We enrolled 215 healthy term neonates born at Hannover Medical School, Germany, between October 2011 and March 2013. They were prospectively observed on the maternity ward at a median age of two days using six-hour recordings of pulse oximeter plethysmography, oxygen saturation, thoracic breathing movements and electrocardiogram during sleep in a supine position. We examined their heart rate, respiratory rate and oxygen saturation during quiet sleep, plus bradycardias, apnoeas lasting at least four-seconds and desaturations below 85%.RESULTS:The 3rd, 50th and 97th percentiles were calculated as follows: heart rate 87, 112 and 133 beats per minute, respiratory rate 32, 44 and 57 per minute and oxygen saturation 94, 98 and 100%. Desaturations, apnoeas and bradycardias below 80 beats per minute were common and recorded in 54%, 98% and 30% of participants. In contrast, only 7% experienced bradycardias of less than two-thirds of the baseline heart rate and 5% experienced apnoeas exceeding 15 seconds.CONCLUSION:Our results will facilitate the evidence-based valuation of cardiorespiratory parameters in term neonates and help validate the significance of cardiorespiratory events in preterm infants at discharge.

Objectives This article aims to investigate the impact of prenatal counseling on subsequent parents' experiences during in-patient care of their infant(s) and whether feelings of parents with deceased infants are different in principle.Study Design A questionnaire was sent to 99 families with a child born less than 26 weeks' gestational age at Medical School Hanover 2000-2008. Statistical analysis was performed using Fisher exact t test and chi-square tests in IBM SPSS Statistics for Windows, Version 20.0.Results Response rate was 73%. Parents with solely surviving children significantly more often answered the questionnaire (p < 0.001). Regardless of the infants' outcome, parents who felt well involved in prenatal decision making significantly more often also felt adequately involved in postnatal treatment of their child (p = 0.006) and would again decide on life-sustaining treatment of an extremely premature infant (p = 0.007). Furthermore, they were significantly less dubious about the treatment of their baby (p = 0.013) than parents not feeling sufficiently involved. Significantly fewer parents with only surviving child(ren) decided to have another baby later than parents with at least one deceased child (p = 0.004).Conclusion This study stresses the impact of prenatal counseling and shows that, regardless of outcome, the course of a trusting relationship between parents and health care team is already set before birth.

Objective. There is no consensus on prescription of home oxygen therapy to infants in Germany. We hypothesized that this causes considerable variability in prescribing home oxygen to infants. Study Design. A structured questionnaire involving management of home oxygen therapy was sent to all German pediatric departments (n = 293). Results. Response rate was 84% (247/293). SpO(2) cutoff values below which oxygen therapy was considered indicated showed a wide range (80% to 94%, mean 90%). Respondents admitting >50 very low birth weight infants annually significantly more frequently prescribed home oxygen (P < .001) and aimed for SpO(2) levels closer to the physiological range than those admitting less very low birth weight infants (P = .046). Conclusion. Management of pediatric home oxygen therapy is diverse in Germany. Optimal SpO(2) targets have to be further investigated by controlled studies and German guidelines should be established. Until then practice should abide by existing foreign guidelines.

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)’ study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400–999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants.

Background: Endotracheal suctioning, which is frequently necessary in mechanically ventilated patients, might cause complications, especially in patients with compromised lung function such as extremely low-birth-weight (ELBW) neonates. Objectives: To investigate whether closed endotracheal suctioning (CS) reduces the frequency of hypoxemia and bradycardia in ELBW neonates compared to open suctioning (OS). Methods: In a randomized, crossover trial, 15 ventilated ELBW neonates (mean birth weight 655 g) underwent suctioning with both techniques. Data on oxygen saturation (Spo2), heart rate (HR), arterial blood pressure, arterial blood gases, duration of the suctioning procedure and recovery time were collected. Statistical analysis was done using the SPSS t test for paired samples. Results: The mean frequency of hypoxemia <85% was significantly decreased (p = 0.012) during CS (0.5) versus OS (1.1). The mean minimum Spo2 was significantly higher (p = 0.012) during CS (87%) compared to OS (84%), and a significantly less steep drop in mean Spo2 (p = 0.007) (CS: –5%, OS: –8%) was found. Mean arterial Po2 (p = 0.035; CS: 59 mm Hg, OS: 53 mm Hg) and mean oxygenation ratio (p = 0.016; CS: 197, OS: 171) were significantly higher after CS. No significant differences were found in HR, incidence or duration of bradycardia, recovery time, arterial blood pressure, duration of suctioning, number of complications, or duration of hypoxemia. Conclusion: CS was superior to OS on oxygenation values. To prove its overall superiority, further research is required. So, in this group of patients, CS should currently be administered on an individual basis.