Neonatal respiratory conditions are leading causes of mortality and morbidity during the neonatal period. This review evaluated 11 management interventions for respiratory distress syndrome (RDS), apnoea of prematurity (AOP), meconium aspiration syndrome (MAS), transient tachypnea of the newborn (TTN), as well as bronchopulmonary dysplasia (BPD) as a potential complication from respiratory care in low- and middle-income countries (LMICs). Two different methodological approaches were completed: (1) updating outdated reviews and pooling all LMIC studies and (2) re-analysis of LMIC studies from up-to-date reviews. Review updates were conducted between October 2022 and February 2023 and followed systematic methodology. A total of 50 studies were included across four review updates and seven review re-analyses. Findings indicate that bubble CPAP (RR 0.74, 95% CI 0.58 to 0.96) and prophylactic CPAP (RR 0.39, 95% CI 0.26 to 0.57) for RDS reduced the risk of treatment failure compared to other ventilation types or supportive care, respectively. Postnatal corticosteroids reduced BPD assessed as oxygen requirement at 36 weeks' postmenstrual age (RR 0.56, 95% CI 0.41 to 0.77). All other outcomes were found to be non-significant across remaining interventions. Our findings indicate that prophylactic and bubble CPAP may provide some benefit by reducing treatment failure compared to other pressure sources. The safety and efficacy of other management interventions for RDS, AOP, BPD, MAS, and TTN remains uncertain given limited evaluations in LMICs. Future research should conduct adequately powered trials in underrepresented LMIC regions, investigate long-term outcomes, and evaluate cost-effectiveness.

Introduction: Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). Methods: Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. Results: Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. Conclusion: The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.

Introduction: Hypoglycaemic neonates are usually admitted to neonatal intensive care for intravenous (IV) dextrose infusion if increased feeding and dextrose gel fail to restore normoglycaemia. However, the effectiveness of this intervention is uncertain. This review aimed to assess the evidence for the risks and benefits of IV dextrose for treatment of neonatal hypoglycaemia. Methods: Four databases and three clinical trial registries were searched from inception to October 5, 2023. Randomised controlled trials (RCTs), non-randomised studies of interventions, cohort studies, and before and after studies were considered for inclusion without language or publication date restrictions. Risk of bias was assessed using Cochrane’s Risk of Bias 2 tool or Risk of Bias in Non-Randomized Studies of Interventions tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Meta-analysis was planned but not carried out due to insufficient data. Results: Across 6 studies (two RCTs and four cohort), 711 participants were included. Evidence from one cohort study suggests IV dextrose treatment may not be associated with neurodevelopmental impairment at ≥18 months of age (no effect numbers, p > 0.2; very low certainty evidence; 60 infants). Evidence from one RCT suggests IV dextrose treatment may reduce the likelihood of repeated hypoglycaemia (risk ratio [RR]: 0.67 [95% CI: 0.20, 2.18], p = 0.5; low certainty evidence; 80 infants) compared to treatment with oral sucrose bolus. However, the risk of a hyperglycaemic episode may be increased (RR: 2.33 [95% CI: 0.65, 8.39], p = 0.19; 80 infants). Conclusion: More evidence is needed to clarify the benefits and risks of IV dextrose for treatment of neonatal hypoglycaemia.

Introduction: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection prevention interventions included strategies to reduce antimicrobial resistance (AMR), prevention of healthcare-associated infections (HAIs), clean birth kits (CBKs), chlorhexidine cleansing, topical emollients, and probiotic and synbiotic supplementation. Interventions to treat suspected neonatal infections included prophylactic systemic antifungal agents and community-based antibiotic delivery for possible serious bacterial infections (PSBIs). Methods: A descriptive review combining different methodological approaches was conducted. To provide the most suitable recommendations for real-world implementation, our analyses considered the impact of these interventions within three distinct health settings: facility, mixed, and community. Results: In facility settings, the strongest evidence supported the implementation of multimodal stewardship interventions for AMR reduction and device-associated infection prevention bundles for HAI prevention. Emollients in preterm newborns reduced the risk of invasive infection compared to routine skin care. Probiotics in preterm newborns reduced neonatal mortality, invasive infection, and necrotizing enterocolitis (NEC) risks compared to standard care or placebo. There was insufficient evidence for synbiotics and prophylactic systemic antifungals in LMICs. In mixed settings, CBKs reduced neonatal mortality risk compared to standard care. In community settings, chlorhexidine umbilical cord cleansing reduced omphalitis risk compared to dry cord care. For the treatment of PSBIs, purely domiciliary-based antibiotic delivery reduced the risk of all-cause neonatal mortality when compared to the standard hospital referral. Conclusion: Strategies for preventing HAIs and reducing AMR in healthcare facilities should be multimodal, and strategy selection should consider the feasibility of integration within existing newborn care programs. Probiotics are effective for facility-based use in preterm newborns; however, the establishment of high-quality, cost-effective mass production of standardized formulations is needed. Chlorhexidine cord cleansing is effective in community settings to prevent omphalitis in contexts where unhygienic cord applications are prevalent. Community-based antibiotic delivery of simplified regimens for PSBIs is a safe alternative when hospital-based care in LMICs is not possible or is declined by parents. More randomized trial evidence is needed to establish the effectiveness of CBKs, emollients, synbiotics, and prophylactic systemic antifungals in LMICs.

Background: Several interventions provided to newborns at birth or within 24 h after birth have been proven critical in improving neonatal survival and other birth outcomes. We aimed to provide an update on the effectiveness and safety of these interventions in low- and middle-income countries (LMICs). Summary: Following a comprehensive scoping of the literature, we updated or re-analyzed the LMIC-specific evidence for included topics. Ninety-four LMIC studies were identified. Delayed cord clamping with immediate neonatal care after cord clamping resulted in a lower risk of blood transfusion in newborns <32–34 gestational weeks and a lower occurrence of anemia in term newborns but did not have significant effect on neonatal mortality or other common morbidities both in preterm and term newborns. Immediate thermal care using plastic wrap/bag led to a 38% lower risk of hypothermia and a higher axillary temperature in preterm newborns without increasing the risk of hyperthermia. Kangaroo mother care initiated immediately (iKMC) or early after birth (eKMC, within 24 h) significantly reduced neonatal mortality and the occurrence of hypothermia in preterm or low-birth-weight neonates. For delayed first bath in newborns, no pooled estimate was generated due to high heterogeneity of included studies. Trials from high-income countries demonstrated anti-D’s effectiveness in lowering the incidence of Rhesus D alloimmunization in subsequent pregnancy if given within 72 h postpartum. Key Messages: We generated the most updated LMIC evidence for several immediate newborn care interventions. Despite their effectiveness and safety in improving some of the neonatal outcomes, further high-quality trials are necessary.

Introduction: Chimeric antigen receptor T cells (CAR-Ts) targeting CD19 represent a significant advance in treatment for patients with relapsed/refractory B-cell malignancies. Although a significant minority of recipients are women during their reproductive years, there is a paucity of data regarding pregnancy and neonatal outcomes in women previously treated with CAR-T. This is important as maternal T cells are known to cross the placenta and into breastmilk during pregnancy and breastfeeding, respectively. Case Presentation: Here we present two successful pregnancies following CAR-T therapy where both neonates were initially breastfed. These represent the first cases of neonates born following CAR-T therapy comprehensively described in medical literature. Conclusion: Pregnancy following CAR-T therapy does not appear to be associated with adverse neonatal outcomes. Further work is required to delineate the outcomes in this population.

Introduction: While a patent ductus arteriosus (PDA) helps offload the right ventricle in the acute congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension, its role on long-term outcomes in CDH has not been investigated. Our objective was to examine associations of the PDA with long-term clinical outcomes in CDH. Methods: A single-center retrospective descriptive study of 122 CDH patients dichotomized by duration with PDA, as ≤14 versus >14 postnatal days (PND) and ≤30 versus >30 PND. Fisher’s exact test, Wilcoxon rank-sum test, and multiple linear and logistic regression analyses were used for analyses. Results: In unadjusted and adjusted for CDH severity comparisons, patients with PDA >14 PND and >30 PND had a higher risk of death, longer length of stay, mechanical ventilation duration, and need for tracheostomy, diuretics, and PH medications at discharge. Conclusion: A PDA beyond the newborn period is associated with adverse outcomes in infants with CDH.

Introduction: Appropriate perinatal care provision and utilization is crucial to improve maternal and newborn survival and potentially meet Sustainable Development Goal 3. Ensuring availability of healthcare infrastructure as well as skilled personnel can potentially help improve maternal and neonatal outcomes globally as well as in resource-limited settings. Methods: A systematic review on effectiveness of perinatal care regionalization was updated, and a new review on facility-based interventions to improve postnatal care coverage and outcomes was conducted. The interventions were identified through literature reviews and included transport, mHealth, telemedicine, maternal education, capacity building, and incentive packages. Search was conducted in relevant databases and meta-analysis conducted on Review Manager 5.4. We conducted subgroup analysis for evidence from low- and middle-income countries (LMICs). Results: Implementation of regionalization programs significantly decreased maternal mortality in LMICs (OR: 0.43; 95% CI: 0.34–0.55, 2 studies), stillbirth overall (OR: 0.70; 95% CI: 0.54–0.89, 5 studies), perinatal mortality overall (OR: 0.54; 95% CI: 0.5–0.58, 2 studies), and LMICs (OR: 0.54; 95% CI: 0.50–0.58, 1 study). Transport-related interventions significantly decreased maternal mortality overall (OR: 0.55; 95% CI: 0.40–0.74, 1 study), neonatal mortality (RR: 0.76; 95% CI: 0.66–0.88, 1 study), perinatal mortality (RR: 0.86; 95% CI: 0.77–0.95, 1 study), and improved postnatal care coverage (OR: 6.89; 95% CI: 5.15–9.21, 1 study) in LMICs. Adding maternity homes/units significantly decreased stillbirth (OR: 0.75; 95% CI: 0.61–0.93, 1 study) in LMICs. Incentives for postnatal care significantly improved infant mortality (RR: 0.79; 95% CI: 0.65–0.96, 1 study), stillbirth (OR: 0.60; 95% CI: 0.44–0.83, 1 study), and postnatal care coverage (RR: 1.13; 95% CI: 1.03–1.25, 1 study) in LMICs. Telemedicine improved postnatal care coverage significantly in LMICs (RR: 2.54; 95% CI: 1.22–5.28, 3 studies) and decreased maternal mortality (OR: 0.46; 95% CI: 0.21–0.98, 1 study) and infant mortality (OR: 0.65; 95% CI: 0.45–0.95) in LMICs. Maternal education significantly decreased neonatal mortality (RR: 0.75; 95% CI: 0.66–0.84, 2 studies), perinatal mortality (RR: 0.86; 95% CI: 0.77–0.95, 1 study), infant mortality (RR: 0.79; 95% CI: 0.65–0.96, 1 study), and stillbirth (RR: 0.61; 95% CI: 0.45–0.82, 1 study). Capacity-building interventions significantly decreased maternal mortality in LMICs (OR: 0.37; 95% CI: 0.29–0.46, 5 studies), neonatal mortality overall (OR: 0.72; 95% CI: 0.53–0.98, 4 studies) and in LMICs (OR: 0.63; 95% CI: 0.54–0.74, 3 studies, and RR: 0.61; 95% CI: 0.48–0.79, 3 studies), perinatal mortality (OR: 0.53; 95% CI: 0.45–0.62, 2 studies, and RR: 0.86; 95% CI: 0.77–0.95, 1 study), infant mortality (OR: 0.50; 95% CI: 0.43–0.59, 1 study, and RR: 0.79; 95% CI: 0.65–0.96, 1 study), under-5 mortality (RR: 0.79; 95% CI: 0.66–0.94, 1 study), and stillbirth in LMICs (OR: 0.71; 95% CI: 0.62–0.82, 4 studies), and preterm birth overall (OR: 0.39; 95% CI: 0.19–0.81, 1 study). Conclusion: Perinatal regionalization and facility-based interventions have a positive impact on maternal and neonatal outcomes and calls for implementation in high burden settings but a better understanding of optimal interventions is needed through comprehensive trials in diverse settings.