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.

Aims: The aim of this study was to examine the potential association of family‐centred care as perceived by parents during a NICU stay with parents’ depressive symptoms at discharge and at 4 months corrected for infant age.Design: A longitudinal, multicentre cohort study was conducted from 2018 to 2020 in 23 NICUs across 15 countries.Methods: Parents (n = 635 mothers, n = 466, fathers) of infants (n = 739) born before 35 weeks of gestation and admitted to the participating NICUs were enrolled to the study during the first weeks of their infants’ hospitalizations. They responded to Digi‐FCC daily text messages inquiring about their perception of family‐centred care provided by NICU staff. In addition, they completed a questionnaire assessing their overall perception of family‐centred care at discharge. Parents’ depressive symptoms were measured by the Edinburgh Postnatal Depression Scale at discharge and again after discharge when their infants were at 4 months corrected for age.Results: The mothers’ and the fathers’ perceptions of family‐centred care were associated with their depressive symptoms at discharge and at 4 months corrected age, controlling for gestational age, multiple birth, parent education and relationship status. Parents’ participation in infant care, care‐related decisions and emotional support provided to parents by staff explained the variation in the parents’ perceptions of family‐centred care. The factors facilitating the implementation of family‐centred care included unlimited access to the unit for the parents and for their significant others, as well as amenities for parents.Conclusions: Our study shows that family‐centred NICU care associates with parents’ depressive symptoms after a NICU stay.Impact: Depression is common in parents of preterm infants. The provision of family‐centred care may protect the mental well‐being of parents of preterm infants.

Background: Several genes and single nucleotide polymorphisms (SNPs) have been associated with early childhood caries. However, they are highly age- and population-dependent and the majority of existing caries prediction models are based on environmental and behavioral factors only and are scarce in infants. Methods: We examined 6 novel and previously analyzed 22 SNPs in the cohort of 95 Polish children (48 caries, 47 caries-free) aged 2–3 years. All polymorphisms were genotyped from DNA extracted from oral epithelium samples. We used Fisher’s exact test, receiver operator characteristic (ROC) curve and uni-/multi-variable logistic regression to test the association of SNPs with the disease, followed by the neural network (NN) analysis. Results: The logistic regression (LogReg) model showed 90% sensitivity and 96% specificity, overall accuracy of 93% (p < 0.0001), and the area under the curve (AUC) was 0.970 (95% CI: 0.912–0.994; p < 0.0001). We found 90.9–98.4% and 73.6–87.2% prediction accuracy in the test and validation predictions, respectively. The strongest predictors were: AMELX_rs17878486 and TUFT1_rs2337360 (in both LogReg and NN), MMP16_rs1042937 (in NN) and ENAM_rs12640848 (in LogReg). Conclusions: Neural network prediction model might be a substantial tool for screening/early preventive treatment of patients at high risk of caries development in the early childhood. The knowledge of potential risk status could allow early targeted training in oral hygiene and modifications of eating habits.

There are differences in the adoption rates of less invasive surfactant administration (LISA) worldwide. We aimed to describe and analyze the process of LISA introduction at the country level. A standardized training program (33 courses covering >500 neonatologists) was followed by a cohort study. Data regarding consecutive LISA procedures were acquired over 12 months in 31 tertiary neonatal centers, using a dedicated on-line platform. Of 500 LISA procedures, 75% were performed by specialists and 25% by residents. The mean percentage share of LISA in all surfactant therapies was 24%, which represents a 6-fold increase compared to previous years. After 12 months, 76% of the procedures were rated “easy/very easy” vs 59% at baseline (p<0.05). Surfactant re-treatment rate was 15%. Twenty-three percent of infants required mechanical ventilation within 72 hours of life. Oxygen desaturation and surfactant reflux were the most frequent complications. Unlike previous reports describing exclusive use of nasal continuous positive airway pressure (nCPAP) during LISA, majority of procedures (63%) were carried out using nasal intermittent positive pressure ventilation (NIPPV) or Bilevel Positive Airway Pressure (BiPAP). Efficacy of LISA with NIPPV or BiPAP was not significantly different from that with nCPAP (22.4% vs 24.5% of cases requiring intubation). Ventilation was provided with nasal cannulas or nasal masks (90%) and rarely with “RAM” cannulas or nasopharyngeal tubes. Rigid catheters were preferred (88.4%); tracheal insertion was successful at first attempt in 87% of cases. Majority of infants (79%) received no premedication prior to the procedure and almost all were given caffeine citrate. Median time of instillation was 1.5 minutes. The LISA procedure does not appear to be technically difficult to master. Training combining theory with practical exercises is an efficient implementation strategy. Variations in adoption rates indicate the need for additional, more personalized teachings in some centers.

Aim: To establish the impact of oxygen requirement before surfactant (SF) and time from birth to SF administration on treatment outcomes in neonatal respiratory distress syndrome (RDS).Methods: We conducted a post-hoc analysis of data from a prospective cohort study of 500 premature infants treated with less invasive surfactant administration (LISA). LISA failure was defined as the need for early (<72 h of life) mechanical ventilation (MV). Baseline clinical characteristic parameters, time to SF, and fraction of inspired oxygen (FiO₂) prior to SF were all included in the multifactorial logistic regression model that explained LISA failure.Results: LISA failed in 114 of 500 infants (22.8%). The median time to SF was 2.1 h (IQR: 0.8–6.7), and the median FiO₂ prior to SF was 0.40 (IQR: 0.35–0.50). Factors significantly associated with LISA failure were FiO₂ prior to SF (OR 1.03, 95% CI 1.01–1.04) and gestational age (OR 0.82, 95 CI 0.75–0.89); both p <0.001. Time to SF was not an independent risk factor for therapy failure (p = 0.528) or the need for MV at any time during hospitalization (p = 0.933).Conclusions: The FiO₂ before SF, but not time to SF, influences the need for MV in infants with RDS. While our findings support the relevance of FiO₂ in SF prescription, better adherence to the recommended FiO₂ threshold for SF (0.30) is required in daily practice.

Objective Despite lack of evidence supporting efficacy, prophylactic fresh frozen plasma and Octaplas transfusions may be administered to very preterm infants to reduce bleeding risk. International variation in plasma transfusion practices in neonatal intensive care units (NICUs) is poorly understood, therefore, we aimed to describe neonatal plasma transfusion practice in Europe. Design Prospective observational study. Setting 64 NICUs in 22 European countries, with a 6-week study period per centre between September 2022 and August 2023. Patients Preterm infants born below 32 weeks of gestational age. Interventions Admission to the NICU. Main outcome measures Plasma transfusion prevalence, cumulative incidence, indications, transfusion volumes and infusion rates and adverse effects. Results A total of 92 of 1143 infants included (8.0%) received plasma during the study period, collectively receiving 177 transfusions. Overall prevalence was 0.3 plasma transfusion days per 100 admission days, and rates varied substantially across Europe. By day 28 of life, 13.5% (95% CI 10.0% to 16.9%) of infants received at least one plasma transfusion, accounted for competing risks of death or discharge. Transfusions were given for a broad range of indications, including active bleeding (29.4%), abnormal coagulation screen results (23.7%) and volume replacement/hypotension (21.5%). Transfusion volumes and infusion rates varied significantly; the most common volume was 15 mL/kg (range: 5–30 mL/kg) and the most common duration was 2 hours (range: 30 min to 6 hours). Conclusions We found wide variation in plasma transfusion practices in Europe, highlighting the need for evidence to inform neonatologists in daily practice and guidelines, in particular for non-bleeding indications. Trial registration number ISRCTN17267090.