Introduction Maternal and newborn morbidity and mortality are a global concern. Understanding the epidemiology of post-discharge complications could identify opportunities for interventions. We aimed to quantify mortality, care-seeking events and readmission among mothers and newborns in Uganda following facility-based delivery.Methods This prospective observational study (Apr 2022-Sep 2023) enrolled women presenting for delivery at two regional referral hospitals in Uganda. Data were collected during admission and 6 weeks after delivery by phone.Results Overall, 7131 women delivered 7359 newborns, of whom 7129 (99%) women and 6968 (94%) newborns were discharged alive. The newborn mortality rate was 2.7% and 32% of deaths occurred post-discharge. Following discharge, 230 (3%) women and 287 (4%) newborns were readmitted. Suspected sepsis and infections were the most common reasons for readmission among mothers (62.2%) and newborns (89.9%). Caesarean delivery (OR:2·26 (1·75-2·93)) and perinatal death (OR:3·18 (2·09-4·69)) were associated with post-discharge maternal readmission. Both maternal and newborn readmission were associated with household food insecurity during pregnancy (maternal OR:1·56 (1·15-2·08); newborn OR: 1·73 (1·31-2·25)). Newborn resuscitation with oxygen was associated with maternal readmission (OR:2.24 (1.24–3·78)), newborn readmission (OR: 2·74 (1·54-4·56)) and newborn death (OR: 4·01 (1·73-8·21)). Although >99% of women had ≥1 antenatal care visit, only 511 (7%) had ≥1 routine postnatal care visit. There were no routine postnatal care visits among 211 (91·7%) readmitted mothers, 276 (96·2%) newborns and 57 (91·9%) newborns who died.Conclusion Post-discharge complications occur in a context of low routine postnatal care use. Risk-informed discharge planning, postnatal care and health education strategies may improve outcomes in mothers, newborns and their families.

BACKGROUND:Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in young children. Although passive immunization strategies are available for infants, the relationship between population immunity and epidemic intensity remains poorly understood. Measuring maternally derived RSV antibodies in newborns could provide a scalable sentinel approach to monitor population immunity. OBJECTIVE:To demonstrate the feasibility of using residual newborn dried blood spots (NDBS), collected universally, to quantify population-level RSV antibody immunity at birth. METHODS:We developed a method to quantify RSV antibody levels and function using residual NDBS from the British Columbia Newborn Screening Program. Assay performance and stability were first evaluated using adult dried blood spot (DBS) and serum controls, then applied to two NDBS sets. RESULTS:In adult DBS, IgG against RSV pre-fusion (pre-F) protein was stable for at least 30 days and ⁓20-fold lower than corresponding sera. In NDBS, pre-F IgG levels remained stable for 140 days at room temperature, correlated with viral neutralization titers (ρ=0.64, p < 0.0001; N = 159), and showed antigen specificity through competitive blocking with soluble post-F protein across multiple RSV antigens (pre-F, post-F, N, Ga, Gb). ⁓42% of samples were below the lower limit of quantification. CONCLUSIONS:RSV antibody immunity can be quantified from residual NDBS. This scalable approach enables population-level surveillance of RSV immunity and supports large-scale studies of seasonal RSV epidemiology and correlates of protection across regions.

The long-term health burden of SARS-CoV-2 infections remains poorly understood. In a cohort from Vancouver, Canada, we identified immune imprinting to endemic β-human coronaviruses (HCoVs), reflected by affinity-matured IgG responses that cross-reacted with the SARS-CoV-2 spike with low affinity, along with an early expansion of memory B cells recognizing HKU1 and the conserved S2 domain following the first dose of ancestral-strain vaccination. Vaccination also enhanced antibody-dependent cellular phagocytosis (ADCP), primarily directed against the HKU1 spike and SARS-CoV-2 S2 domains. In another cohort from the same region, higher HKU1 spike IgG levels and increased antibody-dependent complement deposition (ADCD) were associated with a greater likelihood of post-COVID symptoms, even though these individuals had experienced fewer SARS-CoV-2 infections at the one-year follow-up. Together, these findings suggest that β-HCoV-associated immune imprinting may simultaneously reduce infection risk and promote pathological Fc-mediated inflammation, potentially contributing to post-COVID conditions following infection with contemporary SARS-CoV-2 variants in individuals vaccinated against earlier strains.

Sepsis is a major cause of global neonatal mortality, affecting 1.3 to 1.9 million neonates worldwide. Accurate diagnoses and effective treatment of sepsis during the onset is essential to improve outcomes. Current efforts to develop sensitive molecular biomarkers, however, are limited by the lack of accurate diagnostic tests, particularly the lack of sensitive viral testing or blood culture methods with low blood inoculums from small neonates. Consequently, antibiotic treatments are often misused, contributing to antimicrobial resistance among neonates exposed to unnecessary antibiotics. To improve the management of neonatal sepsis, a thorough understanding of early neonatal immune development and the pathophysiology of the disease is required. In this review, we summarize the current understanding of the newborn’s immune system based on different gestational ages and describe its influence on molecular mechanisms characterizing neonatal sepsis. We also focus on current endeavors for neonatal sepsis diagnosis and new approaches using omics-based biomarkers, highlighting their limitations and future directions for clinical applications. Lastly, we will discuss how utilizing systems immunology provides mechanistic insights and potential avenues towards therapeutics.

Gargle sampling emerged as a novel method for diagnostic testing during the coronavirus disease 2019 (COVID-19) pandemic, yet uncertainty remained about its performance when compared with conventional sampling methods. To evaluate the performance of self-collected gargle samples compared to traditional healthcare worker (HCW)-collected upper respiratory tract swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection with nucleic acid amplification testing (NAAT). We conducted a systematic review (PROSPERO registration: CRD42022312628) to (1) estimate sensitivity of gargle sampling, (2) estimate the difference in sensitivity between gargle and swab methods, and (3) understand how various testing contexts may impact gargle sensitivity. MEDLINE, EMBASE, Web of Science, Global Index Medicus, and preprint servers were searched. Studies reporting primary data and investigating COVID-19 diagnostic performance of self-collected gargle samples compared to HCW-collected swabs tested using NAAT were included. Quality assessment was performed, and random effects meta-analysis was conducted to estimate the pooled gargle sensitivity and mean difference in sensitivity between gargle and swab methods. Searches identified 1453 results with 32 studies included. Meta-analysis pooled 34 gargle-swab comparisons. Gargle sensitivity was estimated to be 92.2

Oncostatin M (OSM) receptor beta (OSMRβ), encoded by OSMR, is a cytokine receptor subunit required for signaling by OSM and IL-31. We identified 10 affected individuals from seven unrelated families with germline biallelic loss-of-function variants in OSMR who shared a phenotype of early-onset, severe, widespread atopic dermatitis with peripheral eosinophilia and markedly elevated serum IgE. All patient-derived OSMRβ variants failed to localize to the cell surface, resulting in selective loss of OSM-dependent signaling. Patient cells showed markedly reduced OSM-induced phosphorylation of STAT1, STAT3, and STAT5, while signaling through other IL-6 family receptor complexes remained intact. Transcriptomic profiling of patient primary dermal fibroblasts revealed consistent downstream effects, including loss of interferon-responsive and inflammatory gene programs. Re-expression of wild-type OSMR restored receptor surface expression, STAT activation, and transcriptional responses, confirming a causal loss-of-function mechanism. Together, these findings establish biallelic OSMR deficiency as a novel primary atopic disorder.

In 2024, the National Advisory Committee on Immunization recommended universal RSV immunization across Canada, prioritizing infants in remote communities. However, in the absence of population-based data, programs may not effectively narrow health gaps in remote communities. Retrospective cohort study of all births in British Columbia (BC) from April 2013 to March 2024, followed for 1 year, using health administrative data. Main outcomes were hospitalizations for all-cause and RSV-lower respiratory tract infection (LRTI). Secondary outcomes were tertiary Pediatric Intensive Care Unit (PICU) admissions, length of stay, and air transport. Main exposures were community remoteness and social determinants of health. Incidence rates and incidence rate ratios (IRR) adjusted for sex, prematurity, and chronic conditions were estimated using Poisson generalized estimating equations. Among 472,623 infants, those living in remote communities (N=3636) had higher hospitalization risk for all-cause (IRR: 2.91, 95%CI 2.02-3.65) and RSV-LRTIs (IRR: 1.60, 95%CI 1.17-2.19) compared to metropolitan areas. Length of stay and PICU admission rates were similar by region. Almost half (48.8%) of children from remote areas hospitalized for all-cause LRTIs required air evacuation. Infants from remote communities remained at higher risk for all-cause (aIRR 2.84, 95% CI 2.22–3.63) and RSV-LRTI (aIRR 1.56, 95% CI 1.15–2.12) hospitalizations after adjusting for covariates. Infants in remote communities experienced a disproportionately high RSV-LRTI burden, supporting prioritized RSV interventions in these regions. The residual risk after accounting for known factors highlights the need to investigate additional drivers of vulnerability in remote areas.

This cohort study examines children in British Columbia, Canada, born between 2013 and 2024 to assess whether use of monoclonal antibodies for a second respiratory syncytial virus (RSV) season is warranted for extremely preterm infants.

Importance:The respiratory syncytial virus (RSV) bivalent prefusion F protein vaccine (RSVpreF) administered during pregnancy has demonstrated efficacy in protecting infants against early-life RSV disease in the pivotal clinical trial. Objective:To conduct a systematic review and meta-analysis to synthesize real-world evidence on the effectiveness of RSVpreF in preventing RSV-associated lower respiratory tract infection (LRTI) in infants. Data Sources:PubMed, Scopus, and Europe PMC were searched from January 1, 2020, through January 30, 2026. Study Selection:A total of 1144 studies were initially identified. Eligible were nonrandomized studies reporting the effectiveness of RSVpreF vaccine in pregnancy in the prevention of RSV-associated LRTI in infants. Data Extraction and Synthesis:All studies were screened independently by 2 reviewers. Data were extracted on RSV-associated outcomes among infants born to women who received RSVpreF vaccination during pregnancy and infants born to unvaccinated women. Main Outcomes and Measures:The primary outcome was RSV-associated LRTI hospitalization. Odds ratios (ORs) were pooled using random-effects meta-analysis with the Hartung-Knapp adjustment and Sidik-Jonkman estimator. Vaccine effectiveness against RSV-associated LRTI hospitalization was calculated as (1 - OR) × 100% and assessed in infants from birth to age 3 months and from birth to 6 months, separately. The limited available data precluded meta-analysis of effectiveness against the secondary outcomes of RSV-associated emergency department visits, intensive care unit admissions, and death. Results:A total of 7 studies were included, comprising 7112 infants, of whom 2684 were born to vaccinated mothers. The studies collected data from January 2024 through April 2025 from Argentina, the UK, and the US. Pooled vaccine effectiveness against RSV-associated LRTI hospitalization was 82% (95% CI, 81%-82%; 3 studies, 4397 participants; I2 = 0%) in infants from birth to 3 months and 78% (95% CI, 70%-84%; 6 studies, 3008 participants; I2 = 18.7%) in infants from birth to 6 months, when mothers were vaccinated 14 days or more before delivery. Conclusions and Relevance:The results of this systematic review and meta-analysis suggest that postimplementation data support the effectiveness of RSVpreF in pregnancy for the prevention of RSV-associated LRTI hospitalization during the first 6 months of life. The results support the introduction of RSVpreF into routine antenatal immunization programs.

Although clinical trials have shown that nirsevimab is safe, post-licensure safety data from routine clinical settings are lacking. This study describes parent-reported health events occurring within seven days of nirsevimab administration. Post-licensure, active, safety surveillance was conducted during the 2024-25 viral season in Canada, using parent-completed questionnaires distributed 8 days after immunization. Parents or caregivers of 1,559 children completed the survey. A third (454/1,559) of children had received nirsevimab co-administered with routine vaccines. Local injection-site reactions were reported in 140 children (9.0%), 79/454 (17.4%, [95%CI: 14.2-21.3]) when nirsevimab was co-administered and 61/1,105 (5.5% [95%CI: 4.3-7.1]) when nirsevimab was given alone. Injection-site reactions extending beyond the closest joint were uncommon (6/1,559, 0.4%). Health events that prevented daily activities or required healthcare consultation were reported in 38/1,105 (3.4%) cases with nirsevimab administered alone and 19/454 (4.2%) with nirsevimab co-administered. The most reported symptoms were rhinorrhea: 1.8%, cough: 1.7%, feeding/eating changes: 1.6%, fever: 1.6% and diarrhea or change in bowel habits: 1.5%. Rash occurred in 10 children (0.6%). No cases of anaphylaxis were reported. Overall, in this study nirsevimab was well tolerated, with low incidence of health events within seven days of immunization. Results after co-administration support the incorporation of nirsevimab into the routine vaccination schedule. Documenting parent-reported outcomes in post-licensure settings expands the safety data obtained from clinical trials and offers transparent, timely additional reassuring data to enhance parental confidence in RSV antibody interventions.

IntroductionThe intestinal epithelium of human infants is developmentally immature compared to that of adults. Exactly how this immaturity affects key epithelial functions and their interactions with nearby immune cells remains an understudied area of research, partly due to limited access to non-diseased infant gut tissues. Human intestinal organoids, or “mini guts” generated from tissue stem cells, are promising models for investigating intestinal biology and disease mechanisms. These three-dimensional structures closely mimic their tissue of origin, including cellular physiology and genetics. We have also previously shown that neonatal Th17 cells represent a distinct cell population with a cytokine profile skewed toward IL-22 production rather than IL-17A, as seen in adult Th17 cells.MethodsIn this study, we sought to model the impact of neonatal-derived Th17 cytokine, namely IL-22 and the intestinal epithelium using infant-derived ileal enteroids. We generated enteroids from ileal biopsies from infants (< 6 months old) and cultured them for seven days with standard organoid growth media, organoid media supplemented with conditioned media from cord-blood-derived Th17 cells, or media supplemented with recombinant IL-22. We assessed morphological changes and conducted transcriptomics profiling via RNAseq.ResultsExposing enteroids to neonatal Th17-cells-derived conditioned media led to enhanced growth, maturation, and differentiation as compared to control media. These effects were ablated when an IL-22 neutralizing antibody was used, while conversely, supplementing with recombinant IL-22 mimicked the Th17 effects, increasing intestinal epithelial cell proliferation and inducing marked differentiation of secretory cells. Our transcriptomic profiling similarly demonstrated significant changes in response to IL-22 with downregulation of Wnt and Notch signaling and upregulation of immune pathways, particularly interferon signaling. The transcriptomic data also suggested that IL-22 treatment led to changes in cell type composition with an increase in stem- and progenitor cells at the expense of enterocytes.ConclusionTaken together, our data suggests that early-life intestinal development is likely influenced by IL-22-dependent crosstalk between the infant epithelium and exposure to neighboring Th17 cells. This promotes epithelial cell maturation and immune readiness, reflected at both the morphological and molecular levels. Our work also provides a relevant framework for studying healthy infant gut development, which can be further leveraged to examine early-life gastrointestinal disorders, model complex human disease, and therapeutic testing while reducing reliance on animal models.

OBJECTIVES:Allogeneic haematopoietic cell transplant (alloHCT) and lung transplant (LT) recipients are at highest risk for severe respiratory syncytial virus (RSV) disease, even as compared to other immunocompromised groups. Notably, these groups were excluded from published RSV vaccine clinical trials. The aim of this study was to determine the safety and immunogenicity of adjuvanted RSVPreF3 vaccine in adult alloHCT and LT recipients. METHODS:Adult alloHCT (≥6 months posttransplant) and LT (≥3 months posttransplant) recipients were enrolled and administered a single dose of adjuvanted RSVPreF3 vaccine. Blood samples were collected at baseline and 4-6 weeks postimmunization to assess neutralizing antibodies (NAb), anti-RSVPreF-IgG antibody levels and RSV-specific polyfunctional T-cells. Safety was assessed through participant-led diaries and follow-up. RESULTS:Eighty-six participants (46 alloHCT, 40 LT) were enrolled, with median follow-up of 191 days (interquartile range [IQR] 170-248). The median age was 59 years (IQR 45.5-67.3) for LT and 64 years (IQR 59-69) for alloHCT recipients. NAb titres increased postvaccination in both groups (alloHCT: 1.3-fold, LT: 3.0-fold; p < 0.0001). Seroconversion by NAb occurred in 15 of 45 (33.3%) alloHCT and 19 of 39 (48.7%) LT recipients. IgG binding antibody levels increased significantly in both groups (3.3-fold in LT, p = 0.0018; 2.3-fold in alloHCT, p = 0.0015). CD4+ polyfunctional T-cell responses were detected in 30 of 42 (71.4%) alloHCT and 28/35 (80.0%) LT recipients postvaccination. CD8+ T-cell responses were lower, but frequencies increased in LT recipients after vaccination (p = 0.024). Overall, the vaccine was well tolerated with grade 1 pain the most reported adverse event (54/86, 62.8%). There was no study intervention-related withdrawal. Three LT recipients developed RSV infection postvaccination; two required hospitalization. CONCLUSIONS:The adjuvanted RSVPreF3 vaccine was immunogenic and well tolerated with modest seroconversion but robust CD4+ T-cell responses. These data support the benefit of RSV vaccination but underscore the need for further strategies to optimize NAb and CD8+ T-cell responses in this high-risk population.

BACKGROUND/OBJECTIVES:Severe acute respiratory syndrome (SARS-CoV-2) has had a profound global impact and continues to represent a health challenge worldwide. The durability of SARS-CoV-2 vaccine responses in pediatric inflammatory bowel disease (PIBD) patients receiving biologic therapies is unknown. This study aimed to quantify SARS-CoV-2 antibody responses post vaccination in these immunosuppressed patients over 12 months. METHODS:Prospective study comparing antibody responses against SARS-CoV-2 spike protein at 1, 3, 6, and 12 months in PIBD patients aged 5-18 years treated with anti-tumor necrosis factor alpha (anti-TNF) therapies with or without an immunomodulator (IM) versus vedolizumab. RESULTS:Between 1 May 2021 and 1 May 2022, 194 participants on anti-TNF monotherapy (n = 78), anti-TNF with IM (n = 83), vedolizumab (n = 15), and steroids (n = 18) were recruited. Anti-SARS-CoV-2 spike levels increased after the first vaccine and were further boosted 1 month after the second dose. Linear mixed-effects modelling showed antibody waning over time (effect difference -2509 IgG AU/mL per week [95%CI: -4998--20, p = 0.048]), counterbalanced by booster doses (effect difference 184,138 IgG AU/mL per additional vaccine dose [95%CI: 138,342-229,934, p < 0.001]). Receiving anti-TNF therapy contributed to reduced antibody responses compared to vedolizumab (anti-TNF monotherapy effect difference: -212,640 [95%CI: -336,928--88,351] p = 0.001; anti-TNF with IM: -151,880 [95%CI: -277,309--26,451] p = 0.018). Seroconversion and breakthrough infection rates were similar between groups, and all infections were mild, without hospitalizations. CONCLUSIONS:Although SARS-CoV-2 antibody responses were attenuated in PIBD patients receiving anti-TNF therapy compared with vedolizumab, this did not impact protection, as seroconversion and breakthrough infection rates were similar, with no hospitalizations. These data reinforce the importance of updating vaccines and, in particular, SARS-CoV-2 vaccines in immunosuppressed PIBD patients on advanced therapies.

Epigenetic modifications such as DNA methylation are both cell type and developmental age specific. Here, we show that the immunological maturation of blood cell types influences DNA methylation changes from naive cord blood to fully functional adult blood. Lymphoid cells in adult blood showed more variability than in cord blood suggesting an antigen-dependent maturation of DNA methylation in lymphoid cells throughout the lifespan. Fewer DNA methylation changes between cord and adult blood were observed in myeloid cells, particularly in monocytes, which demonstrated the least number of DNA methylation changes between cord and adult blood. We also noted differences in epigenetic ages by immune cell types within the same individuals, specifically in cord blood where monocytes were epigenetically oldest compared to the other cell types. In addition, we provide a publicly available resource to the community as an R Shiny web application to interactively explore epigenetic patterns between naive cord white blood cells and fully functional adult white blood cells for six immune cell types.

Importance:National Immunization Technical Advisory Groups recommend long-acting monoclonal antibody prophylaxis for the prevention of respiratory syncytial virus (RSV) disease for children at high risk in the first season, regardless of RSV vaccination during pregnancy, and for those who remain at increased risk in the second season. Objective:This study assessed which groups of children with chronic medical conditions (CMCs) are at higher risk of RSV hospitalization during their first and second RSV seasons. Design, Setting, and Participants:This retrospective, population-based, season-stratified cohort analysis was conducted among children who were born between April 1, 2013, and March 31, 2023, in British Columbia, Canada (population of 5.7 million in 2024), and were enrolled in the provincial medical service plan and followed up until the day before their third RSV season or April 1, 2024, whichever occurred first. Exposure:Any CMC diagnosed in the first 2 years of life. Main Outcomes and Measures:Respiratory syncytial virus-related hospitalizations. Results:The final cohort consisted of 431 937 children (32 959 [7.6%] born at <37 weeks' gestation; 222 207 boys [51.4%]) followed up for a median of 728 days (IQR, 642-729 days), including 25 452 children (5.9%) diagnosed with at least 1 of 1116 distinct CMCs. In total, 4567 children (1.1%) experienced a combined total of 4592 RSV hospitalizations, combining data from the first and second RSV seasons. In the first RSV season, the RSV hospitalization rate per 1000 person-years for children with CMCs was 15.9 (95% CI, 14.2-17.6) and for children without CMCs was 8.0 (95% CI, 7.7-8.3). In the second RSV season, the RSV hospitalization rate per 1000 person-years for children with CMCs was 7.8 (95% CI, 6.7-8.8) and for children without CMCs was 2.2 (95% CI, 2.1-2.3). Children with multisystem CMCs, particularly those affecting the respiratory, cardiovascular, or gastrointestinal systems, had second-season RSV hospitalization rates that were at least 2-fold higher than the rate among all children in the first season. Second-season rates among children with Down syndrome or those who were born prematurely (<28 weeks of gestation) were 5-fold higher than for all children in the first season. Conclusions and Relevance:This population-based retrospective cohort study identified specific groups of higher-risk children with CMCs who could most benefit from prophylaxis with long-acting monoclonal antibodies in their first and second RSV seasons. This study supports expanded eligibility criteria for long-acting monoclonal antibody prophylaxis.

INTRODUCTION:Neonatal sepsis remains a major contributor to morbidity and mortality worldwide, with the highest burden in low- and middle-income countries (LMICs). Generating accurate estimates of disease burden is critical for setting research priorities, informing health policy, and resource allocation. However, in many LMICs, limited access to timely and reliable diagnostic tools severely limits case detection, undermines epidemiological surveillance, and impedes efforts to improve clinical outcomes. AREAS COVERED:This review examines the clinical, scientific, and health system implications of misdiagnosing neonatal sepsis. We describe the challenges of accurate case identification and summarize findings from prospective, multicenter studies showing marked variability in incidence across different geographic and healthcare settings. We explore the sources of this variability and discuss its impact on patient care, clinical trials interpretation, and progress toward reducing the global burden of neonatal sepsis. EXPERT OPINION:The lack of standardized case definition hinders neonatal sepsis research and may contribute to the growing threat of antimicrobial resistance. Addressing this requires acknowledging the substantial uncertainty in current global incidence estimates. More importantly, it demands shifting focus from passive reporting of variability to actively investigating the methodological, sociodemographic, clinical, biological, and systemic drivers that shape sepsis detection and outcomes across diverse settings.

To explore whether prenatal conditions (i.e. chorioamnionitis, preeclampsia or small-for-gestational age (SGA)) affect the very preterm infant’s response to docosahexaenoic acid (DHA) on bronchopulmonary dysplasia (BPD), according to mode of delivery, an independent factor shown to modulate this association. Secondary exploratory analysis of the MOBYDIck randomized controlled trial (NCT02371460) evaluating the effect of a neonatal high-dose DHA supplementation through maternal breastmilk compared to placebo. Population was preterm infants born before 29 weeks of gestation in sixteen Canadian neonatal intensive care units. Primary outcome was physiological BPD based on pulse oximetry assessment. Secondary outcomes included “death or BPD”; “moderate-or-severe” BPD; severe BPD; death from any causes. Heterogeneity in the effect of DHA on outcomes was assessed by prenatal conditions and mode of delivery using generalized estimating equation logistic regression models. The trial intended to enroll 800 mothers but was stopped early for safety, likely making subgroup analysis underpowered. 230 mothers (271 infants) were included in DHA group and 226 mothers (252 infants) in placebo group. The association between high-dose DHA and BPD differed by chorioamnionitis status (heterogeneity P=0.04). In infants exposed to chorioamnionitis and vaginal delivery, DHA supplementation was associated with a reduced risk of physiological BPD (adjusted odds ratio, 0.18 [95

BACKGROUND:Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in young children and results in significant healthcare burden and costs. To reduce the impact of RSV in this population, the monoclonal antibody palivizumab has historically been used. Recently, new preventive options have become available, including a longer-acting monoclonal antibody (nirsevimab) and a maternal vaccine (RSVpreF). METHODS:We developed a discrete-event simulation model using epidemiological and cost data from British Columbia, Canada, and published efficacy estimates. The model simulated a cohort of 100,000 newborns and followed them up to 24 months. We conducted the analysis from a healthcare system perspective, evaluating five immunization strategies: (1) the historical palivizumab standard of care for high-risk children; (2) nirsevimab for high- and moderate-risk children; (3) in-season maternal RSVpreF vaccination combined with nirsevimab for high-risk children; (4) in-season maternal RSVpreF plus nirsevimab for high- and moderate-risk children; and (5) nirsevimab for all infants. We conducted a sequential cost-effectiveness analysis, ordering strategies by cost, excluding dominated or extendedly dominated options, and evaluating the remaining strategies stepwise. To support policy interpretation, we also performed a pairwise analysis comparing each strategy directly with the historical standard of care. RESULTS:In the sequential analysis, strategy 2 was the most cost-effective option. Strategy 4 provided additional health gains but was not cost-effective incrementally (ICER ≈ $119,000 per QALY vs strategy 2). Strategy 5 offered the greatest overall health benefits but was the least cost-effective option. When compared directly with the historical standard of care, however, strategy 4 was cost-effective (ICER ≈ $18,000 per QALY). INTERPRETATION:These findings support policy recommendations to prioritize nirsevimab for high- and moderate-risk infants as the most cost-effective strategy. Maternal RSVpreF vaccination offers added health benefits and is cost-effective compared with the historical standard of care, though not when considered incrementally.

Sepsis is responsible for about one third of neonatal deaths worldwide. Preterm infants are at higher risk of sepsis than term infants. However, contemporary population-based data are scarce and the risks of neonatal sepsis associated with gestational age at delivery are understudied. To determine the population-based incidence of neonatal sepsis in British Columbia (BC), Canada and to examine changes in the risk of sepsis by gestational age at delivery. A population-based retrospective cohort study including all children born in BC from 2004 to 2020, capturing hospital admissions up to the first 28 days of life. Data were obtained from the BC Perinatal Data Registry. The primary outcome was sepsis, identified by ICD-10 diagnostic codes or a confirmed positive blood culture abstracted from medical charts. Secondary outcomes included explicit sepsis (ICD-10 codes explicitly mentioning sepsis), implicit sepsis (cases of severe infection associated with an organ dysfunction ICD-10 code), culture-positive sepsis (bacterial or fungal blood culture), and septic shock. Incidence proportions were calculated as the number of sepsis cases per 1,000 live births, stratified by gestational age (in weeks) and birth year. Of the 722,264 live-born infants in the cohort, 3,537 had sepsis (4.86 per 1,000 live births). In preterm infants (<37 weeks), the incidence was 23.9 per 1,000 live births versus 2.8 per 1,000 in term infants. This difference highlights the increased vulnerability of preterm infants to sepsis, which may be due to their underdeveloped immune systems, organs, or other physiological factors. For secondary outcomes, there were 793 cases of culture-positive sepsis, 2,635 cases of explicit sepsis, 280 cases of implicit sepsis and 244 cases of septic shock. The incidence of all types of sepsis decreased with increasing gestational age (Figure 1). Bacterial sepsis was more common than viral or fungal sepsis (overall incidence of 3.5 cases per 1,000 live births). Fungal sepsis had higher incidence at <31 weeks (6.12 cases per 1,000 live births at 25 weeks). Since 2004, the incidence of sepsis has been decreasing in BC. This study found that the incidence of sepsis in preterm infants was lower than that reported in the literature, which tends to focus on NICU populations. The population-level incidence of sepsis was much higher in preterm compared with term infants. Therefore, targeted prevention strategies and early interventions for preterm infants are essential to reduce the burden of sepsis and improve neonatal outcomes at a population level.