Background: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the survival and well-being of preterm infants. While initially the rationale behind delaying clamping was to facilitate increased placental transfusion, research has unveiled additional hemodynamic benefits. Summary: Experimental studies have demonstrated improved circulatory transition when clamping is postponed until the lungs are adequately aerated. This suggests that infants requiring assistance during the transition phase may benefit from stabilization while still attached to the cord. The Aeration, Breathing, and then Clamping (ABC) project aimed to translate these experimental findings into clinical practice. Key Message: In this review, we will discuss the insights gained and lessons learned from the project’s implementation.

Background: Inborn errors of immunity (IEI), formerly referred to as primary immunodeficiencies, manifest with a wide range of symptoms such as increased susceptibility to infections, immune dysregulation, and autoinflammation. Although most cases manifest in childhood, onset during the neonatal period is rare but potentially critical. Summary: In this review, we discuss the diverse clinical presentations of IEI and the specific challenges they pose to neonatologists. Rather than detailing every molecular defect, we focus on common clinical scenarios in neonates and young infants, providing practical diagnostic strategies to ensure timely and effective therapeutic interventions. Key Messages: Clinical presentations of IEI in neonates may include delayed separation of the umbilical cord, skin rashes such as eczema and erythroderma, and recurrent episodes of inflammation. We also highlight immunological emergencies that require urgent medical attention, such as hyperinflammatory activity mimicking acute neonatal liver failure, sometimes seen in hemophagocytic lymphohistiocytosis. We also discuss appropriate medical action in the case of a positive newborn screening for severe T-cell defects. Early medical intervention in such circumstances may significantly improve outcomes.

Introduction: In Canada, newborn morbidity far surpasses mortality. The neonatal adverse outcome indicator (NAOI) summarizes neonatal morbidity, but Canadian trend data are lacking. Methods: This Canada-wide retrospective cross-sectional study included hospital livebirths between 24 and 42 weeks’ gestation, from 2013 to 2022. Data were obtained from the Canadian Institute of Health Information’s Discharge Database, excluding Quebec. The NAOI included 15 newborn complications (e.g., birth trauma, intraventricular hemorrhage, or respiratory failure) and seven interventions (e.g., resuscitation by intubation and/or chest compressions), adapted from Australia’s NAOI. Rates of NAOI were calculated by gestational age. Unadjusted rate ratios (RR) and 95% confidence interval (CI) were calculated for neonatal mortality, neonatal intensive care unit (NICU) admission, and extended hospital stay, each in relation to the number of NAOI components present (0, 1, 2, 3, 4, or ≥5). Results: Among 2,821,671 newborns, the NAOI rate was 7.6%. NAOI increased from 7.3% in 2013 to 8.0% in 2022 (p < 0.01). NAOI prevalence was highest in the most preterm infants. Compared to no NAOI, RRs (95% CI) for mortality were 8.5 (7.6–9.5) with 1, 118.1 (108.4–128.4) with 3, and 395.3 (367.2–425.0) with ≥5 NAOI components. Respective RRs for NICU admission were 6.7 (6.6–6.7), 11.2 (10.9–11.3), and 11.9 (11.6–12.2), and RR for extended hospital stay were 6.6 (6.4–6.7), 12.2 (11.7–12.7), and 26.4 (25.2–27.5). International comparison suggested that Canada had a higher prevalence of NAOI. Conclusion: The Canadian NAOI captures neonatal morbidity using hospitalization data and is associated with neonatal mortality, NICU admission, and extended hospital stay. Newborn morbidity may be on the rise in recent years.

Background: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or bronchopulmonary dysplasia. However, with an ever-expanding variety of NIV modes available, there is much debate about which NIV modality should ideally be used, how, and when. The aims of this work were to summarise the evidence on different NIV modalities for both primary and secondary respiratory support: nCPAP, nasal high-flow therapy (nHFT), and nasal intermittent positive airway pressure ventilation (nIPPV), bi-level positive airway pressure (BiPAP), nasal high-frequency oscillatory ventilation (nHFOV), and nasally applied, non-invasive neurally adjusted ventilatory assist (NIV-NAVA) modes, with particular focus on their use in preterm infants. Summary: This is a narrative review with reference to published guidelines by European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. nCPAP is currently the most commonly used primary and secondary NIV modality for premature infants. However, there is increasing evidence on the superiority of nIPPV over nCPAP. No beneficial effect was found for BiPAP over nCPAP. For the use of nHFT, nHFOV, and NIV-NAVA, more studies are needed to establish their place in neonatal respiratory care. Key Messages: The superiority of nIPPV over nCPAP needs to be confirmed by contemporaneous trials comparing nCPAP to nIPPV at comparable mean airway pressures. Future trials should study NIV modalities in preterm infants with comparable respiratory pathology and indications, at comparable pressure settings and with different modes of synchronisation. Importantly, future trials should not exclude infants of the smallest gestational ages.

Background: Newborn resuscitation algorithms have since the turn of the century been more evidence-based. In this review, we discuss the development of American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR)’s algorithm for newborn resuscitation from 1992–2024. We have also aimed to identify the remaining gaps in non-evidenced practice. Summary: Of the 22 procedures reviewed in the 2020 ILCOR recommendations, the evidence was either low, very low, or non-existing. The strength of recommendation is weak or non-existing for most topics discussed. Several knowledge gaps are also summarized. The special challenge for low- and middle-income countries (LMIC) is discussed. Key Messages: Newborn resuscitation is still not evidence-based, although great progress has been achieved the recent years. We have identified several knowledge gaps which should be prioritized in future research. The challenge of obtaining evidence-based knowledge from LMIC should be focused on in future research.

Plain Language SummaryCongenital intrauterine infection occurs when mother-to-fetus transmission of infection occurs during pregnancy, disrupting fetal development. Intrauterine HSV infection is rare and difficult to diagnose because HSV needs to be detect in specimens collected within 48 h of birth. Here, we present the case of an infant with typical signs of intrauterine HSV infection, including the brain, eye, and skin lesions, diagnosed retrospectively at the age of 7 months using preserved dried umbilical cord. Additionally, we conducted a literature review of methods used for the diagnosis of intrauterine HSV infection. A female infant was born with the typical signs, but was not diagnosed during the neonatal period because skin and blood samples tested negative. She was referred to our hospital at the age of 7 months because of developmental delay and seizures. Polymerase chain reaction (PCR) of a preserved dried umbilical cord specimen detected HSV type 2, confirming the diagnosis of intrauterine HSV infection. In Japan, umbilical cords are traditionally dried and preserved at home after birth as a symbol of the mother-child bond. Detection of virus in umbilical cord specimens strongly suggests infection before birth. We reviewed 104 previously reported cases of congenital or intrauterine HSV infection, of which 28.8% had the typical triad (skin, brain, and eye lesions), and 50% were diagnosed using specimens collected after 48 h post-birth. To our knowledge, this is the first retrospective diagnosis of intrauterine HSV infection based on PCR testing of preserved dried umbilical cord, underscoring its diagnostic value.

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants. Methods: Cohort analysis of eligible preterm infants born <29 weeks’ gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88–93%) or high (90–95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). Conclusion: For neonates <29 weeks’ gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.

Background: Oxygen is crucial for life but too little (hypoxia) or too much (hyperoxia) may be fatal or cause lifelong morbidity. Summary: In this review, we discuss the challenges of balancing oxygen control in preterm infants during fetal development, the first few minutes after birth, in the neonatal intensive care unit and after hospital discharge, where intensive care monitoring and response to dangerous oxygen levels is more often than not, out of reach with current technologies and services. Key Messages: Appropriate oxygenation is critically important even from before birth, but at no time is the need to strike a balance more important than during the first few minutes after birth, when body physiology is changing at its most rapid pace. Preterm infants, in particular, have a poor control of oxygen balance. Underdeveloped organs, especially of the lungs, require supplemental oxygen to prevent hypoxia. However, they are also at risk of hyperoxia due to immature antioxidant defenses. Existing evidence demonstrate considerable challenges that need to be overcome before we can ensure safe treatment of preterm infants with one of the most commonly used drugs in newborn care, oxygen.