Background: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants.Methods/design: SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using ‘opt-out’ or deferred consent). Exclusion criteria will be no parental informed consent (or if ‘opt-out’ is used, lack of a record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record of the parents’ decision to opt-out in the infant’s clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants.Discussion: Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates.Trial registration: ClinicalTrial.gov,NCT03770741. Registered 10 December 2018.

Objective: Automatic control (SPOC) of the fraction of inspired oxygen (FiO₂), based on continuous analysis of pulse oximeter saturation (SpO₂), improves the proportion of time preterm infants spend within a specified SpO₂-target range (Target%). We evaluated if a revised SPOC algorithm (SPOC_new, including an upper limit for FiO₂) compared to both routine manual control (RMC) and the previously tested algorithm (SPOC_old, unrestricted maximum FiO₂) increases Target%, and evaluated the effect of the pulse oximeter’s averaging time on controlling the SpO₂ signal during SPOC periods. Design: Unblinded, randomised controlled crossover study comparing 2 SPOC algorithms and 2 SpO₂ averaging times in random order: 12 hours SPOC_new and 12 hours SPOC_old (averaging time 2 s or 8 s for 6 hours each) were compared with 6-hour RMC. A generated list of random numbers was used for allocation sequence. Setting: University-affiliated tertiary neonatal intensive care unit, Germany Patients: Twenty-four infants on non-invasive respiratory support with FiO₂ >0.21 were analysed (median gestational age at birth, birth weight and age at randomisation were 25.3 weeks, 585 g and 30 days). Main outcome measure: Target%. Results: Mean (SD) [95% CI] Target% was 56% (9) [52, 59] for RMC versus 69% (9) [65, 72] for SPOC_old__2s, 70% (7) [67, 73] for SPOC_new__2s, 71% (8) [68, 74] for SPOC_old__8s and 72% (8) [69, 75] for SPOC_new__8s. Conclusions: Irrespective of SpO₂-averaging time, Target% was higher with both SPOC algorithms compared to RMC. Despite limiting the maximum FiO₂, SPOC_new remained significantly better at maintaining SpO₂ within target range compared to RMC. Trial registration: NCT03785899

Background and Objectives: Neonates and children are at high risk of medication errors (ME) with intravenous (IV) infusion therapies, particularly when strategies such as the “rule of six” with individualized, weight-based concentrations are used. Standard concentrations (SCs) have been proposed to reduce variability, improve safety, and facilitate the use of electronic prescribing and smart infusion technologies. The impact of SCs for continuous IV infusions on ME rates in neonatal and pediatric settings was systematically evaluated. Methods: A systematic review was conducted in MEDLINE, Embase and CINAHL (database inception-August 2025) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies implementing SCs for neonatal or pediatric IV infusions and measuring outcomes referring to ME rates were included. The relative risk reduction/increase in MEs was calculated. Results: Five uncontrolled before-after studies published between 2005 and 2020 were included. The relative risk reductions ranged from 41.2% to 95.1% for overall ME and from 49.7% to 100% for selected error types. In two studies, the relative risk for two error types (paper-generated prescriptions, administration) increased after implementing SCs. Reviewed benefits included decreased calculation and preparation errors, reduced medication process times, improved workflow efficiency and high staff satisfaction. Conclusions: SCs may contribute to safer IV infusion practice in the neonatal and pediatric setting, especially combined with smart technologies and training. However, current evidence is limited and heterogeneous. Larger, prospective experimental studies are needed to confirm their long-term impact on pediatric ME rates.

Background: The prone position is one of the most frequently used treatment options for infants with Robin sequence (RS), but its effect and its safety regarding the increased risk of sudden infant death syndrome are controversial. Methods: In a prospective randomized crossover study, we investigated the effects of the prone versus supine position on obstructive sleep apnea (OSA) using polygraphy. Infants with RS admitted to the University Hospital Tuebingen between 4/2021 and 5/2023 were analyzed for their obstructive apnea index (OAI), oxygen desaturation index < 80%, minimum and basal oxygen saturation, basal and highest transcutaneous carbon dioxide level, and respiratory and heart rate in both sleep positions. Results: A total of 29 children were analyzed. A total of 21/29 children were measured in both positions, while 6/29 children were only measured in the supine position and 2/29 only in the prone position. We found no significant difference in the OAI for the supine versus prone position in main effects analyses. In unadjusted linear model analysis, infants in the supine position had an OAI of 9.9 (95% CI, −2.4, 22.3) events/h higher than those in the prone position. A total of 13/21 infants benefitted from the prone position, whilst 8/21 had a worsening of their OSA. We found no evidence of a significant interaction between sleeping position and syndromic status. Conclusions: Prone positioning improves, but does not eliminate, OSA symptoms in infants with RS, and severe OSA may often persist. There are infants in whom a change to the prone position leads to a worsening of their OSA.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO₂) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO₂ to “back-up FiO₂” during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO₂ before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a “backup FiO₂” (which reflects FiO₂-requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www.clinicaltrials.gov under the registration no. NCT03785899. What is Known:• Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states.• Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range. What is New:• Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery.• FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots.

Background/Objectives: Medication errors remain a patient safety concern in neonatal intensive care units (NICU), mainly due to multiple dilution steps, a lack of standardized preparation instructions, and the frequent use of high-alert medications. While standard concentrations (SCs) for intravenous (iv) medication are recommended internationally, a national standard is missing for NICUs in Germany. The aim of this study was to evaluate a proposal for a national list of standardized iv medication concentrations to be used in German NICUs. Methods: In collaboration with the German Society for Neonatology and Pediatric Intensive Care (GNPI) and the Federal Association of German Hospital Pharmacists (ADKA), a multiprofessional expert team, including experts from the medication safety initiatives TELE-KASPER and Kinderformularium.DE and affiliated with seven German university hospitals, evaluated SCs for infusion medication administered to infants weighing 500 g to 5 kg. The evaluation process was based on international SCs lists, clinical practice, stability data, and handling aspects. Medication used in at least four of the seven hospitals was shortlisted. In the first round of the consensus process, an online survey submitted to the German Level-1 NICUs (n = 165) and their affiliated hospital pharmacies identified preferred SCs. In the second round of the consensus process, the expert team further evaluated the results of the survey. Results: The survey response rate was 52%. The consensus process resulted in a list encompassing 50 iv medications and 80 appropriate SCs. Ancillary information on preparation, stability, osmolarity, pH, and practical administration was added. Conclusions: The proposed SCs for infusion medication used in NICUs have the potential to reduce medication errors, simplify electronic prescribing, and improve workflow efficiency. Implementation aligns with international patient safety initiatives to improve medication safety in pediatric patients.