Frontiers in Pediatrics

Background Despite cerebrospinal fluid (CSF) analysis being the gold standard for definitively diagnosing meningitis, its practical application has presented considerable difficulties, especially in environments with limited resources. Cranial ultrasound (CUS), while not a replacement for CSF analysis, provides rapid imaging to identify meningeal irregularities. Nevertheless, achieving a timely diagnosis of meningitis, particularly in its nascent stages, remains problematic, and healthcare professionals exhibit a notably low awareness of CUS's utility in diagnosing this condition. Methods This was a prospective cohort that recruited 273 term mother-neonate pairs. The neonates were initially divided into those with sepsis-meningitis (exposure group) and those with sepsis (non-exposure group) based on clinical assessment done by the admitting team. The research team further divided the participants into 4 diagnostic subgroups based on CUS findings: positive CUS for meningitis, positive clinical diagnosis for meningitis, positive CUS & clinical diagnosis for meningitis and those with negative CUS & clinical diagnosis for meningitis /sepsis only. Data on socio-demographics, clinical characteristics, blood works and CSF analysis reports, neurologic deficits and mortality outcomes were recorded for each neonate. Descriptive and inferential statistics were performed. Results The 4 diagnostic subgroups based on CUS findings were: positive CUS for meningitis (24.5%), positive clinical diagnosis for meningitis (4.4%), positive CUS & clinical diagnosis for meningitis (6.6%) and those with negative CUS & clinical diagnosis for meningitis /sepsis only (64.5%). Overall, duration of hospitalization was 11 days (range 2-45 days; interquartile range [IQR] 6,16) and the median chronological age of the neonates was 13 days (IQR 7, 21). Meningitis was suspected in 11% of neonates admitted with clinical sepsis. Uptake for lumbar puncture (LP) or ventricular tap (VT) was low at 4.4% (n = 12), underlining barriers to CSF-based diagnosis in this setting. Late-onset sepsis was associated with only 31.9% of NSM. The chronological age of the neonates at admission (p=0.002) and their duration of hospitalization (p=0.042) were significantly different across the 4 categories of neonates. Prominent sulci, hyperechoic brain lesions, ventriculitis, and lateral ventriculomegaly were the most common abnormal findings on CUS. Overall, neonates with meningitis presented later in age and stayed longer on the ward than those with sepsis: clinical meningitis diagnosis was likely to be made in older neonates and was associated with a shorter duration of hospitalization than CUS-diagnosed meningitis. Overall mortality rate was 2.2%. Mortality (16.7%) was highest amongst those with clinical & CUS diagnosed-NSM. Prevalence of Near-Miss cases of NSM was at least 27.6%. A neonate with clinical diagnosis of NSM was 3.94 times (95% CI 1.80, 8.62; p<0.001) more likely to have abnormal CUS at the time of admission. Percent agreement between the clinical and CUS diagnosis for NSM was 71.1%. Nine (75%) out of the 12 CSF reports was positive for meningitis; and the majority 55.6% (5) of the positive CSF report belonged to the category of neonates with sepsis only. Compared to CSF analysis, sensitivity of clinical diagnosis of NSM was 22.2%; specificity was 33.3%; positive predictive value (PPV) was 50%; negative predictive value (NPV) was 12.5% and likelihood ratio (LR) was 0.33. Whereas, sensitivity of CUS was 44.4%; specificity of CUS was 66.7%; PPV was 80%; NPV was 28.6% and LR was 1.33. Conclusion The CUS was only moderately effective at diagnosing meningitis whereas the presence of positive CSF among neonates with sepsis only within this study, further reaffirms the irreplaceability of CSF analysis in the diagnosis of NSM. Nevertheless, the integration of clinical assessment and CUS findings for diagnosing NSM emerged as possessing greater clinical significance in contexts characterized by limited resources. The systematic adoption of CUS for neonates exhibiting features suggestive of sepsis or meningitis (while exploring measures to improve on uptake of CSF analysis) could enhance the promptness of diagnosis, inform the selection of suitable therapeutic interventions, and potentially mitigate mortality rates and the occurrence of long-term neurological impairments, especially within environments facing resource limitations.

Objective: To compare self-weaning and dose-adjusted caffeine regimens in preterm infants discharged home on caffeine for apnea of prematurity (AOP). Design: A prospective cohort study. Setting: Tertiary neonatal unit and outpatient clinics, Karachi, Pakistan, April 2023 to July 2025. Patients: 204 preterm infants (<37 weeks' gestation) discharged home on caffeine for AOP; 94 self-weaning, 110 dose adjusted. Interventions: Self-weaning (absolute dose fixed, so mg/kg/day exposure declined with weight gain) versus dose-adjusted weaning (dose recalculated to current weight at each visit). Both were followed to 36 weeks postmenstrual age (PMA). Main outcome measures: Proportion continuing caffeine beyond 36 weeks PMA and caregiver-reported apnea after discontinuation. Results: Caffeine was continued beyond 36 weeks PMA in 68/94 self-weaning infants (72.3%) and 84/110 dose-adjusted infants (76.4%). No apnea was reported after discontinuation in either group, and all 204 infants survived to 36 weeks PMA. Apnea-related readmission on caffeine occurred in 1/94 (1.1%) versus 2/110 (1.8%). Weight at discontinuation was lower with self-weaning (1917 vs 2157g); the dose-adjusted group was more premature (mean 30.0 vs 30.7 weeks). After adjustment for gestational age and birth weight, regimen was not associated with continuation beyond 36 weeks (adjusted OR 0.82, 95% CI 0.43 to 1.57) or time to discontinuation (adjusted HR 1.21, 95% CI 0.91 to 1.60). Conclusions: Within a structured outpatient follow-up program, no post-discontinuation apnea was reported with either regimen,and apnea-related readmissions were infrequent. Self-weaning avoids repeated dose recalculation. A multicenter randomized trial with objective home monitoring is needed to determine the optimal timing of discontinuation.

Background: Infants <30 weeks gestational age (very preterm (VPT)), are at risk of experiencing multiple serious neonatal morbidities. These morbidities impart serious biological stress, which may be reflected in dysregulated protein expression even after the morbidities have resolved. Recent studies suggest that DNA methylation-based predictors of circulating proteins may reflect the molecular effects of neonatal adversity. The objective of this study is to examine associations between DNA methylation-derived EpiScores, which are externally trained methylation signatures that proxy circulating protein levels, and neonatal morbidity burden in children born VPT. Buccal DNA methylation was obtained at NICU discharge in 537 infants from the NOVI cohort. A total of 111 EpiScores were calculated and tested for association with multimorbidity (0-1 vs. [&ge;] 2 morbidities) using adjusted linear regression models. Cross-tissue analyses in an external paired blood-buccal dataset (n=21) were used to identify EpiScores with moderate-to-strong correlations across tissues. Results: Eighteen EpiScores were nominally associated with multimorbidity (p < 0.05), with Melanoma-derived growth regulatory protein (MIA) with FDR < 0.05 (beta = 0.0023, p = 0.0004). In cross-tissue analyses, 35 EpiScores yielded r > 0.50 (p<0.05), 11 of which showed nominal associations with multimorbidity, including MIA. Overall, the morbidity-associated EpiScores reflected immune, inflammatory, metabolic, and growth-related pathways. Conclusions: Buccal DNA methylation-derived EpiScores capture biological signatures associated with neonatal morbidity burden in very preterm infants.

Abstract Objective: Examine whether prenatal adversity is associated with Neonatal Opioid Withdrawal Syndrome (NOWS) severity and the need for pharmacological treatment in infants with prenatal opioid exposure. Study Design: Prospective cohort study of 235 infants from a multi-center study of infants with prenatal opioid exposure. Maternal factors were assessed using the electronic medical record and maternal questionnaires. Latent Class Analysis (LCA) was used to derive mutually exclusive prenatal adversity groups. Results: A 3-class LCA solution provided the best fit to the data and showed 3 distinct groups: one low adversity group (Class 3, 38.7%) and 2 high adversity groups. Infants born to mothers with elevated demographic, medical, polysubstance, and mental health risk factors (Class 1, 31.9%) were more likely to require pharmacological treatment for NOWS (OR=7.70, 95% CI: 3.65-17.14) and had higher NOWS severity, as indexed by longer length of stay ({beta} = 6.08, 95% CI: 4.09-8.07), and higher maximum Finnegan scores ({beta} = 2.62, 95% CI: 1.49-3.76). Infants born to mothers with elevated medical and polysubstance risk factors (Class 2, 29.4%) were also more likely to receive pharmacological treatment for NOWS (OR=3.22, 95% CI: 1.56-6.78) and had higher NOWS severity, as indexed by higher likelihood of receiving adjunctive medication (OR=3.62, 95% CI: 1.11-12.99). Conclusion: Maternal sociodemographic, mental health, substance use, and medical adversity may serve as an early marker of NOWS severity and may aid in the prediction of which neonates will require pharmacological treatment for NOWS. Early identification of infants at high risk for NOWS could lead to earlier treatment and the potential to reduce NOWS severity, length of stay, and associated healthcare costs.

Background. Many Indian special newborn care units (SNCUs) cannot offer amplitude-integrated EEG (aEEG) or early MRI, so bedside judgement decides which newborns receive closer neurological attention. Earlier work found that asphyxiated newborns cry with a higher pitch and shorter phonation than healthy newborns, and a meta-analysis reported higher fundamental frequency, dysphonation and atypical melody in infants with neurological dysfunction, with wide differences between studies. Aim. To determine whether basic acoustic features of a smartphone-recorded pain cry (following a heel prick) can differentiate term newborns with HIE from control newborns. Also, to track changes in cry acoustics over the first 72 hours of life and evaluate their association with the clinical severity and short-term outcomes of encephalopathy. Design. A prospective, single centre diagnostic accuracy and cohort study in a tertiary SNCU. Three groups of term newborns are recorded: newborns with HIE, healthy comparators, and sick comparators who do not have HIE. Every newborn is recorded after the same stimulus, the first clinically indicated heel-prick. Newborns with HIE and sick comparators are recorded again at 24 hours, 72 hours and before discharge. A cry that is late or absent counts as a result and not as a missing value. Three clinicians blinded to group also classify the cries by listening, so the phone-based measures can be compared with the human ear. Analysis. The primary outcome is the area under the ROC curve of a logistic model with five pre-specified acoustic predictors. The target is 180 analyzable newborns (70 with HIE and 110 comparators). Reporting follows STARD and TRIPOD+AI. Relevance. In a South Asian trial, cooling did not reduce death or disability at 18 months and increased death alone. A cry tool in this setting is therefore proposed to help prioritize EEG, seizure surveillance, closer observation and referral. It is not proposed as a trigger for cooling. Keywords: neonatal encephalopathy; infant cry; acoustic analysis; smartphone; diagnostic accuracy; low-resource setting.

Objective: To identify factors associated with predischarge morbidity and mortality among small for gestational age infants. Study Design: We conducted a retrospective single-center cohort study of small for gestational age infants admitted to a level IV neonatal intensive care unit. We determined the association of clinical characteristics, congenital anomalies, and genetic disorders with the primary outcome of predischarge morbidity or mortality and characterized morbidity and mortality across congenital anomaly subgroups. Results: Among 293 small for gestational age infants, 18 (6.1%) had a genetic disorder and 103 (35.2%) had a major congenital anomaly, with congenital heart disease (CHD) representing the largest subgroup. The primary outcome of morbidity or mortality occurred in 93 infants (31.7%); 74 infants (25.3%) experienced morbidity and 19 (6.5%) died. CHD (adjusted odds ratio [aOR]: 16.5, 95% CI 6.44-45.7) and multiple congenital anomalies (aOR: 17.8, 95% CI 4.64-71.1) were found to be strongly associated with morbidity or mortality, after accounting for sex, maternal race, and intubation > 7 days. Statistically significant associations were also found with the presence of musculoskeletal anomalies as well as genetic disorders in infants without congenital anomalies, though in limited sample sizes. CHD was the largest contributor to morbidity, whereas multiple congenital anomalies accounted for the greatest proportion of mortality. Infants with abdominal wall defects and central nervous system anomalies experienced no morbidity or mortality. Conclusion: Congenital heart disease and multiple congenital anomalies were strongly associated with morbidity and mortality among SGA infants, whereas the degree of SGA alone was not. These findings suggest that risk is not explained by the degree of SGA alone and may be more strongly associated with congenital disease and other underlying factors.

Background Neonatal sepsis remains a major cause of neonatal morbidity and mortality, particularly in low- and middle-income countries. Its management is increasingly complicated by antimicrobial resistance (AMR), while limited facility-specific data on causative bacterial pathogens and susceptibility patterns often necessitate empirical antibiotic treatment. This study assessed the prevalence of neonatal sepsis, bacterial pathogens and antimicrobial resistance patterns, and maternal, neonatal and clinical factors associated with neonatal sepsis among neonates admitted to the Neonatal Intensive Care Unit (NICU) at Livingstone University Teaching Hospital (LUTH), Zambia. Methods A retrospective cross-sectional record review was conducted among neonates admitted to the NICU at LUTH from 2020 to 2025. A total of 150 neonatal records were analysed. Neonatal, maternal, clinical, blood culture and antimicrobial susceptibility data were analysed using descriptive statistics, chi-square tests and logistic regression. Missing information was treated as missing and was not imputed; denominators were reported according to the records available for each analysis. Results Neonatal sepsis was identified in 52/150 neonates, giving a prevalence of 34.7% (95% CI: 27.5%-42.6%). Among the 52 sepsis cases, 20 had positive blood cultures, corresponding to a culture positivity rate of 38.5% (95% CI: 26.5%-52.0%); this represented 13.3% of the full study sample. Maternal fever during labour (aOR=6.822; 95% CI: 2.032-22.905; p=0.002) and caesarean delivery (aOR=2.245; 95% CI: 1.050-4.801; p=0.037) were independently associated with neonatal sepsis, while increasing birth weight was protective (aOR=0.891 per 100 g; 95% CI: 0.817-0.973; p=0.010). Escherichia coli was the most frequent isolate (5/20; 25.0%), followed by Klebsiella pneumoniae (4/20; 20.0%) and Staphylococcus aureus (4/20; 20.0%). Resistance was highest to ampicillin (15/19; 78.9%), followed by gentamicin and ceftriaxone (10/19; 52.6% each), while all 19 isolates tested against meropenem were susceptible. Conclusion The findings indicate that empirical management of neonatal sepsis at LUTH should be informed by local microbiological surveillance rather than reliance on historical first-line susceptibility assumptions. Routine blood culture and susceptibility testing, a regularly updated facility antibiogram, strengthened infection prevention and antimicrobial stewardship are required to improve treatment decisions and preserve effective antibiotics. Interpretation should consider the retrospective single-centre design, incomplete routine records and the small number of culture-positive isolates.

Introduction: Fighting the ventilator (FV) is characterized by a patients active counteraction of respiratory gas flow across multiple breaths during mechanical ventilation. An effective ventilation is prevented during such episodes. The objective of this exploratory study was to evaluate clinicians knowledge, perception and agreement regarding this condition. Methods: In a cross-sectional online survey, medical professionals with experience in intensive care medicine (mostly neonatal and pediatric patients) responded to 11 questions covering various clinical aspects of FV. Results: All respondents were familiar with the phenomenon and assessed it to be clinically relevant. Neonates were perceived to be predominantly affected. Promoting factors of FV included inadequate sedation and ventilation-associated factors. In clinical practice, the participants identified FV by clinical evaluation, analysis of ventilator waveforms and capnography and used both pharmacological and non-pharmacological intervention strategies. There was no consensus concerning the English terminology of the condition. Only few respondents were familiar with local guidelines to manage FV. Conclusion: Although there was consensus on the relevance of FV, diagnostics and management strategies were highly heterogeneous. Many participants agreed that poor patient-ventilator synchrony was an important cause of FV. Future work should focus on characterizing and generating evidence on FV.

Background: Risk adjustment for disease severity in pediatric intensive care research commonly relies on clinical organ dysfunction scores requiring detailed clinical and laboratory information, which is often unavailable in administrative healthcare datasets. We therefore evaluated the feasibility of a coding-based Pediatric Organ Dysfunction Index (PODI) derived from International Classification of Diseases (ICD-10) and Operation and Procedure System (OPS) codes, for approximating sepsis-related organ dysfunction and adjusting for disease severity, using the pediatric Sequential Organ Failure Assessment (pSOFA) score as a reference standard. Methods: In this retrospective single-center cohort study, pediatric sepsis episodes treated between November 2011 and November 2021 were identified. Discrimination for in-hospital mortality and calibration were assessed. Agreement between PODI and pSOFA was quantified using Spearman's rank correlation, and organ-specific agreement using sensitivity, specificity, and predictive values. An expanded PODI incorporating additional ICD-10 and OPS codes was evaluated in sensitivity analyses. Results: A total of 488 pediatric sepsis episodes were included, with an in-hospital mortality of 14.1%. The PODI showed good discrimination for in-hospital mortality (AUC 0.85, 95% CI 0.80-0.89), comparable to the maximum pSOFA (pSOFAmax) (AUC 0.78, 95% CI 0.72-0.83) and superior to pSOFA at sepsis onset (pSOFAonset) (AUC 0.73, 95% CI 0.67-0.80). Agreement between PODI and pSOFA organ-specific components varied considerably across organ systems, with the highest sensitivity to detect pulmonary dysfunction. Correlation between both scores was moderate (0.54 for pSOFAonset and 0.60 for pSOFAmax), indicating that comparable predictive performance does not render the scores interchangeable. The expanded PODI improved organ-level sensitivity for selected components but did not meaningfully improve mortality discrimination. Conclusions: The standard PODI may represent a practical approach to adjust for organ dysfunction and therapy intensity in administrative datasets with ICD-10 coding where clinical and laboratory information is unavailable. Given only moderate agreement with the pSOFA, the PODI should be understood as a covariate for risk adjustment at the group level rather than as a substitute for clinical organ dysfunction scores in individual patients. Further validation and refinement in non-sepsis cohorts are required before broader implementation in large-scale administrative research can be recommended.

Perinatal asphyxia is a leading cause of neonatal death in Mozambique and the main cause of early neonatal death in the referral hospitals of Gaza Province. Where blood gas analysis is unavailable, a low five-minute Apgar score remains a key marker of intrapartum compromise. This study aimed to identify maternal, obstetric, fetal and institutional factors associated with a low five-minute Apgar score at Xai-Xai Provincial Hospital, Mozambique. We conducted a secondary analysis of the records of 471 newborns delivered between January 2016 and December 2018, drawn from a matched case-control study of early neonatal death. The outcome was a five-minute Apgar score below 7. Associations were estimated with bivariate and multivariable conditional logistic regression and are reported as odds ratios with 95% confidence intervals. Of the 471 newborns, 76 (16.1%) had a low five-minute Apgar score. In the multivariable model, a gestational age of 42 weeks or more (adjusted odds ratio 4.04; 95% confidence interval 1.18-13.82) and ruptured membranes on admission (adjusted odds ratio 3.69; 95% confidence interval 1.37-9.96) were associated with higher odds of a low score, whereas partograph use during labour was associated with lower odds (adjusted odds ratio 0.07; 95% confidence interval 0.01-0.31). The association with preterm birth was attenuated after adjustment for birth weight. Post-term birth and ruptured membranes on admission were associated with a low five-minute Apgar score, and partograph use with lower odds. Because the sample was drawn from a study of early neonatal death, these associations should be confirmed in unselected birth cohorts. They nonetheless support strengthening intrapartum monitoring in Mozambican referral maternities.

ABSTRACT Breast milk is essential for optimal neonatal nutrition and survival, particularly among preterm and low-birth-weight infants. When a mothers own milk is unavailable, donor breast milk is the recommended alternative. However, Rwanda currently lacks accredited breast milk donation systems and milk banks, and little is known about healthcare providers perspectives on their potential implementation. The main objective of the study was to assess the acceptability of breast milk donation and explore the potential factors that could influence its adoption among healthcare providers in two Rwandan district hospitals. A convergent parallel design with a qualitative-dominant approach was conducted in the neonatology units of Kirehe District Hospital and Ruhengeri Level-II Teaching Hospital, Rwanda. Quantitative data were collected from 41 healthcare providers using structured questionnaires, including a six-item Likert scale (0=strongly disagree to4=strongly agree) to measure acceptability. Scores[&ge;]2.4 were interpreted as indicating high acceptability. Qualitative data were obtained through in-depth interviews with 10 healthcare providers and analyzed using inductive thematic analysis. Quantitative data were analyzed using descriptive statistics and non-parametric tests. The overall acceptability of breast milk donation was high, with 82.9% of healthcare providers expressing agreement (mean score: 2.83{+/-}1.10). Most participants (97.6%) perceived donor breast milk as beneficial for neonatal health. Key barriers included cultural resistance, limited maternal awareness, and inadequate infrastructure, while facilitators were staff training, institutional policies, and community engagement. Qualitative findings highlighted that providers were generally familiar with the concept of breast milk donation but noted the absence of formal programs in Rwanda. They emphasized that cultural concerns often stem from limited knowledge rather than entrenched opposition and strongly endorsed the benefits for infant health and maternal wellbeing. Providers stressed that successful implementation would depend on awareness-raising, trust in safety procedures, and institutional support through training and clear guidelines. Breast milk donation is highly acceptable among healthcare providers in Rwanda, with a mean score of 2.83{+/-}1.10 on the 0-4 Likert scale. Providers strongly recognized its benefits for vulnerable infants. Addressing gaps in awareness, infrastructure, and policy frameworks, alongside culturally sensitive community education, will be critical for successful implementation. These findings support the feasibility of introducing breast milk banking in Rwanda and provide evidence to guide policy and program development.

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

Abstract Background: Even though significant advances in diagnosis, treatment, and prevention strategies have been implemented, neonatal sepsis remains a common concern in clinical practice, especially in low-resource countries. It is one of the major causes of death during the first month of life. This study aimed to assess clinical outcomes and predictors of mortality among neonates with neonatal sepsis admitted to public hospitals in selected Hospitals in Addis Ababa, Ethiopia. Methods: A hospital-based prospective cohort study design was conducted among 466 neonates admitted with neonatal sepsis from September 2024 to January 2025. All neonates who were admitted to selected Hospitals of Addis Ababa city after being clinically or laboratory-diagnosed with neonatal sepsis by the attending physician were included in the study. Data were entered into EpiData 4.2 and analyzed by SPSS version 26. Bivariate and multivariate Cox regression were used to identify the relationship between dependent and independent variables. Finally, variables with p-value [&le;] 0.05 were taken as significant factors associated with poor clinical outcome. Results: The study was conducted among 466 neonates admitted with neonatal sepsis. Of all neonates admitted with neonatal sepsis, 372 (79.8%) were discharged with good outcomes, and 94 (20.2%) had a poor outcome/died. Duration of ruptured membrane being >12hr (AOR=7.02, 95 % (CI: 1.85, 26.57), marital status /divorced (AOR=3.12, 95 % (CI: 1.67, 7.45),rural residence (AOR= 6.05, 95 % (CI: 2.03-16.53), assisted instrumental delivery (AOR= 5.99, 95 % (CI: 1.46-17.11), meconium-stained amniotic fluid ((AOR= 9.48, 95 % (CI: 0.49-18.61)), no initiate exclusive breast feed within one hour (AOR= 3.20, 95 % (CI: 0.90-7.52), chest in drawing (AOR= 5.81, 95 % (CI: 1.75-11.23) were significantly associated with neonatal mortality. Conclusion: Neonatal mortality was moderately high. Meconium-stained amniotic fluid, prolonged duration of ruptured membrane (>12hr), Mode of delivery (instrumental delivery), and chest in drawing are among the predictors of neonatal mortality. Keywords: -Clinical outcome,Neonatal sepsis, Mortality, predictors, Ethiopia.

Abstract Background The globally low birth weight is estimated to account for about 15-20% of all births. Global annual preterm delivery is about fifteen million, more than 60% of which occurs in Asia and Sub-Saharan Africa. The Kenyan preterm birth rate is estimated to be 14 per 100 live births. Prematurity, the leading cause of low birth weight, and its associated complications account for a large proportion of neonatal and under 5 morbidity and mortality. Premature and low birth weight (LBW) infants have rapid growth with increased nutritional demands despite their inadequate nutrient stores. This predisposes them to post-natal growth restriction (PNGR). Timely and adequate nutrition is important to prevent PNGR that has been shown to have long term neurodevelopmental and growth consequences. Immaturity and clinical instability of these infants makes providing adequate nutrition for them a great challenge. This study was done to determine the prevalence of and factors associated with PNGR among LBW infants at discharge from a rural public referral hospital in Kenya. Methods This was a single center retrospective descriptive study, of infants with birth weight <1800g discharged between 1st January 2022 and 31st December 2023, done to determine the prevalence of and the factors associated with PNGR among these infants at discharge. PNGR was defined as poor growth after birth during the initial hospitalization period. Cross sectional PNGR was discharge weight less than 10th centile while longitudinal PNGR was a drop in centiles lines for weight at discharge. Moderate PNGR was discharge weight between 3rd and 10th centile while severe PNGR was discharge weight less than the 3rd centile. Weight at birth and discharge was obtained and presented as Z scores and centiles using the respective gender specific intergrowth 21 charts. Maternal, clinical and nutritional data were also obtained from the patient files and analyzed to determine their association with PNGR. Results Among the 143 LBW infants included in the study, the prevalence of PNGR was 63% (n=90) (severe 44.8%) and 53.2% (n=76) (severe 16.1%) for cross sectional and longitudinal PNGR respectively. Statistically significant associations for longitudinal PNGR were found in patients who received any supplements aOR(95%CI) 3.0(1.1-8.3) p=0.037, took 14 days or more to regain birth weight aOR (95%CI) 0.1(0.1-0.4) p=<0.01 and were admitted for 30 days or more aOR(95%CI) 0.3(0.1-0.9) p=0.025. Conclusion More than half of LBW infants in Nyeri County Referral Hospital are discharged with PNGR, a sizeable proportion with severe form. There is need to update local LBW infants feeding protocols to include breast milk fortification, parenteral nutrition and avail resources to support the high nutritional needs of this population.

Background: Cyclooxygenase (COX) inhibitors have been used to treat hemodynamically significant patent ductus arteriosus (PDA) in preterm infants. If the PDA remains hemodynamically significant after an initial course, additional courses of COX inhibitors or surgical intervention are considered. This systematic review evaluates PDA closure rates and safety after repeated courses of COX inhibitors in preterm infants. Methods: Embase, Medline, and two other databases were searched through April 2026 (pre-registered in PROSPERO [CRD42023454003]). Studies reporting PDA closure rates after two or more courses of COX inhibitors were included. Risk of bias was assessed using Joanna Briggs Institute tools. Meta-analyses with random-effects models were performed to calculate the proportions of PDA closure. Multilevel mixed-effects meta-regression was used to compare closure rates across treatment courses while accounting for within-study correlations. Results: A total of 33 studies were included. The PDA closure rates after the first, second, and third courses of COX inhibitors were 62% (95% confidence interval [CI] 57-67%), 46% (95% CI 40-52%; p < 0.001 vs the first course), and 38% (95% CI 27-51%; p = 0.001 vs the first course), respectively. Lower closure rates with repeated courses were also observed across most subgroups (extremely preterm/extremely low birth weight, ibuprofen, indomethacin, and intravenous administration), except for the second course of oral administration. Data on adverse events were limited, preventing meta-analysis. Conclusions: PDA closure rates after the second and third courses of COX inhibitors were lower than those after the first course in preterm infants. Evidence regarding the safety of repeated courses remains limited.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care utilization. A unique relationship between autism and GI dysfunction has been proposed, leading to a focus on autism in GI research, management guidelines, and clinical tool development. Leveraging >20 years of electronic health record data and a cohort of 42,204 cases with attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, or intellectual disability and 297,402 controls without NDDs, we quantified associations between NDDs and GI conditions in children. GI conditions were more common in cases than controls across all individual NDDs; intellectual disability and cerebral palsy were most strongly associated with having a GI condition. In this work, clinically recognized GI morbidity was elevated across all NDDs and not unique to autism, suggesting that a broader, transdiagnostic approach to GI dysfunction in children with NDDs is warranted.

Background/Objective: Seasonal upper respiratory tract infections (URTIs) are common in children and contribute to absenteeism and reduced quality of life. Over-the-counter treatments show limited efficacy and may cause adverse effects, thus warranting the need for natural alternatives. This study evaluated the efficacy of a whole-fruit supplement derived from boysenberry and apple (BerriQi) in reducing symptom severity and duration in school-aged children with URTIs using the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS - K). Methods: In this double-blind, randomised, placebo-controlled study, 84 children aged 5 -13 years with URTI-associated school absence were assigned to receive BerriQi or placebo (two chewable tablets daily) for 14 days. Outcomes included the severity and duration of global illness, composite symptom and function scores. Results: Both groups showed progressive reductions in global illness severity, symptom, and function score over 14 days. However, the BerriQi group consistently reported lower scores across all outcomes. While global illness severity did not differ significantly between groups, total symptom severity was significantly reduced with BerriQi (P=0.04), and functional scores showed a trend toward improvement (P=0.05). The BerriQi group experienced fewer sick days compared with placebo (8 vs. 11 days) and demonstrated a higher likelihood of functional recovery (HR = 1.79, 95% CI: 1.09 - 2.91; P=0.02). Conclusions: These findings suggest that BerriQi may serve as a promising natural paediatric supplement for alleviating respiratory illness symptoms and supporting faster functional recovery, potentially reducing school absenteeism associated with upper respiratory tract infections (URTIs).

Introduction: The TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) trial was a pan-European, multi-centre, phase II/III trial investigating the impact of prophylactic paracetamol (also known as acetaminophen) given during the first 5 days of life for children born before 29 weeks' gestational age (GA) on survival to 36 weeks' post-menstrual age without severe neonatal morbidities. However, due to time restrictions, long-term follow-up was not planned as part of the initial trial despite recommendations for neonatal trials to include endpoints measuring efficacy after discharge from the neonatal unit and on-going debate about the long-term effects of paracetamol in the neonatal period. This protocol describes a study to follow-up participants in the TREOCAPA trial at 2 years corrected age initiated after the trial's onset. Methods and analysis: The TREOCAPA Long Term (TREOCAPA-LT) study population consists of all children included in the TREOCAPA phase III trial in centres in countries participating in the follow-up study who are aged between 23.5 and 27.5 months corrected age during the study period. Families are contacted by the clinical teams and a parent or guardian is invited to complete an internet-based (online) questionnaire. The primary outcome is cognition, as measured by the non-verbal Cognitive Scale standard score from the Parent Report of Children's Abilities-Revised (PARCA-R) questionnaire. Secondary outcomes are moderate to severe neurodevelopment, health service use and costs. Data will be analysed according to the study groups to which children were randomised in the original TREOCAPA RCT. Ethics and Dissemination: The TREOCAPA-LT protocol was first approved by ethics' committees in France (the study's sponsor) and subsequently by all participating countries. Results from TREOCAPA-LT will be published in open access journals in accordance with the funder's regulations. Registration: https://clinicaltrials.gov/study/NCT06064825

Sepsis is a substantial contributor to neonatal mortality in Africa, with Klebsiella pneumoniae as the leading causative pathogen. Incorporating molecular tools such as whole genome sequencing (WGS) into routine surveillance of important bacterial pathogens, including those causing neonatal sepsis, can support targeted deployment of infection prevention and control measures and treatment interventions. This study aimed to understand the current practices and capacity for culture, identification and genomic analysis of bacterial pathogens in Africa, with a particular focus on K. pneumoniae, to support standardised genomic surveillance. A cross-sectional online survey was distributed to various clinician and scientist networks across Africa. All respondents completed a demographics section, while sections on laboratory test capacity, blood culture practices, WGS, and bioinformatics analysis were completed based on experience in these aspects. Responses were received from 52 institutions in 25 African countries. Among 51 institutions completing the laboratory test capacity section, 61% reported performing blood cultures, with the majority using manual commercial biochemical systems for species identification (71%) and manual disk diffusion for antibiotic susceptibility testing (82%). Participating institutions reported near-universal access to a -80{degrees}C freezer, centrifuge and thermocycler, but shaking incubators were less commonly available (67%). More than half of respondents (54%) indicated that they perform the entire WGS workflow (including DNA extraction, library preparation and WGS) internally, with most performing DNA extraction internally (88%) using column-based kits (70%). Outsourcing was progressively more common at later workflow stages. Infrastructure challenges that limit bioinformatics analysis capabilities were reported by all 23 respondents who completed this question, including limited access to high-performance computing and data storage space. This survey found sufficient capacity to support genomic surveillance of neonatal sepsis pathogens across participating African institutions. However, investments in blood culture, supply chains, sequencing, bioinformatics, and data dissemination capacity are needed to realise its full potential. These findings will support the development of standardised genomic surveillance protocols tailored to the diverse capacities of African laboratories.