Frontiers in Pediatrics

Background and ObjectivesCurrent potassium reference intervals for neonates fail to account for sampling method differences and prematurity-related factors, leading to unnecessary resampling and interventions. We aimed to establish sampling-specific potassium reference intervals for term and preterm neonates using comprehensive electronic health record data. MethodsWe analyzed 195 606 blood gas measurements from 10 290 neonates (2007-2024) at a tertiary neonatal intensive care unit. After ex-cluding values during severely impaired clinical conditions using integrated clinical metadata, we derived reference intervals for venous, arterial, and cap-illary samples. Multivariate analysis identified factors affecting potassium homeostasis. ResultsFrom 55 664 included values, capillary samples showed signif-icantly higher potassium levels than arterial or venous samples. Reference intervals (2.5th-97.5th percentiles) for neonates >7 days: venous [2.6, 5.5] mM, arterial [2.6, 5.9] mM, capillary [3.0, 6.3] mM. Time-matched analysis of 5403 paired samples showed capillary-specific intervals achieved 88% sensitivity and 94% specificity for detecting true hyperkalemia compared to arterial or venous controls. ConclusionCapillary blood gas potassium levels require distinct, higher reference intervals than venous or arterial samples in neonates. Implementa-tion of sampling-specific reference ranges may reduce false-positive results and unnecessary interventions in this vulnerable population. Article SummaryLarge EHR-based study defines sampling-specific neonatal potassium reference intervals; higher capillary ranges reduce false positives and maybe unnecessary interventions. Whats Known on This SubjectExisting neonatal potassium reference intervals often ignore sampling modality and prematurity, contributing to clinical uncertainty and unnecessary repeat testing in neonates. What This Study AddsProvides sampling-specific potassium reference intervals for neonates; capillary samples require distinct, higher ranges, improving discrimination of true hyperkalemia and reducing false positives. Contributors Statement PageRudolf G. Ascherl: Conceptualized and designed the study, coordinated data extraction, perfomed analysis and visualization, drafted and revised the initial manuscript. Benjamin W. Ackermann: Contributed to study design, assisted in revising the manuscript. Matthias Knupfer: Provided clinical oversight, interpreted findings, critically reviewed the manuscript. Equal contribution: Rudolf G. Ascherl and Benjamin W. Ackermann. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Severe neonatal hyperbilirubinaemia represents a considerable cause of mortality and long term-morbidity in neonates born in low resource settings. Early identification of risk factors, such as glucose-6-phosphate dehydrogenase (G6PD) status, has the potential to prevent severe hyperbilirubinaemia and improve the clinical outcomes. The primary aim of the study was to assess equivalency of cord blood and neonatal capillary blood for diagnosis of G6PD deficiency using the quantitative point-of-care "STANDARD G6PDTM" test (SD Biosensor, Korea). Additional secondary aims were to compare the "STANDARD G6PDTM" with gold standard spectrophotometry and to analyse changes in G6PD activity in the first 4 months of life. A total of 75 neonates born in Shoklo Malaria Research Unit (SMRU) clinics were selected based on their G6PD status assessed through routine cord blood screening using the "STANDARD G6PDTM" test. Using activity thresholds established before in this setting, 25 G6PD deficient, 25 G6PD intermediate and 25 G6PD normal neonates were identified and re-tested on capillary blood collected within 24 hours of life and at day 7. They were also followed-up at 1 and 4 months of age to study haematologic and G6PD activity changes over time. The results showed that the "STANDARD G6PDTM" can be used reliably up to one week of life for testing neonates using the same thresholds established in cord blood. Performance of the point-of-care test as compared to the gold standard spectrophotometry remained excellent at all sampling time-points. Nevertheless, G6PD activity assessed longitudinally in the same participants decreased over time, both at 1 month of age and at 4 months of age, and interpretation of results in female infants with intermediate activity might require different thresholds. The study demonstrated that the "STANDARD G6PDTM" can effectively support clinical care in neonates and infants in populations with prevalent G6PD deficiency at the primary care level and especially in low-resource settings.

BackgroundAntibodies against phosphorylcholine (anti-PC) are reported to protect against infection. However, the association between cord serum anti-PC and bacterial infection in neonates is yet to be investigated. This study aimed to investigate these associations among both singletons and twins. MethodsA total of 1007 neonates (329 singletons and 678 twins) within the hospital-based Shenzhen Baoan Birth & Twin cohort were included in this study. Levels of IgM anti-PC, IgG anti-PC, as well as IgM, IgG, and IgA in cord serum were measured by enzyme-linked immunosorbent assay. Diagnoses of bacterial infections were identified within 0-27 days after birth. Multivariable logistic regression with propensity score adjustment was performed to assess the associations between levels of antibodies and neonatal bacterial infections. ResultsThe mean (standard deviation) levels of IgM and IgG anti-PC were 46.68 (14.15) ng/ml and 73.68 (30.44) ng/ml, respectively. Neonatal bacterial infections were diagnosed in 24 singletons (7.29%) and 48 twins (7.08%). A higher level of IgM anti-PC was associated with a lower risk of neonatal bacterial infections in the analyses of singletons (Odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.41-0.99) or discordant twin pairs (concerning bacterial infection) (OR: 0.44, 95% CI: 0.20-0.95). Statistically significant association was also shown for IgG among singletons and the first-born twins, but not for IgG anti-PC, IgM, or IgA. ConclusionA higher cord serum level of IgM anti-PC is associated with a lower risk of bacterial infections in neonates. Key pointA higher level of IgM anti-PC in cord serum is associated with a lower risk of bacterial infection in both singleton and twin neonates.

BackgroundInhaled nitric oxide (iNO) is a standard treatment for neonatal pulmonary hypertension in high-resource settings. Yet, its efficacy and cost-effectiveness in low- and middle-income countries (LMICs) remain underexplored. This study aimed to evaluate the impact of iNO on neonatal outcomes within a resource-limited Neonatal Intensive Care Unit (NICU) setting in Manaus, Brazil, to inform public health strategies. MethodsWe conducted a multicenter, quasi-experimental study employing a historical control design. We compared outcomes in 12 prospective neonates receiving iNO for persistent pulmonary hypertension of the newborn (PPHN) secondary to perinatal asphyxia (March-August 2018) with 12 historical controls (December 2015-December 2016). Participants were at a gestational age of more than 34 weeks with echocardiographic evidence of PPHN. Main outcomes included oxygenation parameters, mortality, and length of hospital stay. ResultsThe prospective group demonstrated significant acute improvement in all key oxygenation parameters following initiation of iNO (p < 0.01 for PO2, O2 saturation, PO2/FiO2, and Oxygenation Index). However, iNO did not significantly reduce overall mortality (16.6% vs. 0%, p = 0.48) or NICU length of stay (21.3 vs. 13.2 days, p = 0.09). Notably, total hospital length of stay was significantly longer in the iNO group (37.1 vs. 23.08 days, p=0.03), with deaths primarily linked to systemic complications. ConclusionAlthough iNO acutely improves oxygenation in neonates with PPHN in this resource-limited setting, these physiological benefits did not result in reduced mortality or shorter NICU stays and were associated with increased overall hospitalization. The findings indicate that iNO sustains critically ill neonates who subsequently require extended care. Effective implementation of costly interventions in LMICs requires a comprehensive supportive infrastructure. Further context-specific research is crucial for informing resource allocation and enhancing neonatal care.v

ObjectiveTo compare clinical care and outcome of preterm infants born in a tertiary neonatal unit with those requiring early postnatal transport to the same unit, and analyze their trends over an 9-year period. Study DesignA retrospective study of infants born before 33 weeks gestation between 2013 and 2021. Inborn (n=913) and outborn (n=133) infants were compared using logistic regression and trend analysis. ResultOutborn infants more frequently required intubation in delivery room (59.4% vs. 32.3%, p<0.001) and mechanical ventilation (69.2% vs. 44.5 %, p<0.001). They more frequently had severe intraventricular haemorrhage (IVH, 15% vs. 8.1%, p=0.027) and had lower survival rate (88.7% vs. 91.9%, p=0.02). Birth outside a tertiary neonatal unit increased the risk of severe IVH [odds ratio: 2.4 (95% confidence interval: 1.3-4.3)]. Only inborn infants showed decreasing trends in delivery room intubation (annual percentage change, APC: -21.2%, p<0.001) and mechanical ventilation (APC: -8.3%, p=0.001). ConclusionOutborn infants continue to require more invasive respiratory support and experience worse outcomes.

BackgroundThe World Health Organization (WHO) has developed danger signs (DS) to help front-line health workers triage interventions in children with severe illnesses. Our objective was to evaluate the extent to which DS predict bacterial sepsis in young infants presenting with acute illness. Methodology/Principal FindingsThis prospective study evaluated nine DS in infants younger than 3 months with suspected sepsis in a large regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. The main outcomes were positive blood or cerebrospinal fluid (CSF) cultures and mortality. Blood (n=85/401) and CSF (n=2/204) cultures were positive in 21.2% and 1% of infants, respectively (N=401; gestational age mean {+/-} SD: 37.1{+/-}3.3 weeks, birth weight 2865{+/-}785 grams). In-hospital deaths occurred in 9.7% (N=39/401) of infants (61.5% within 48h of admission). In univariate analyses, all DS were associated with mortality except for temperature instability and tachypnea, whereas "infant was unable to feed" was the only DS significantly associated with bacterial sepsis. After co-variable adjustments, number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.16; p<0.001; AUC-ROC: 0.756) but not positive cultures (OR 1.08; 95%CI: 0.92-1.30; p=0.336). Whether potential bacterial contaminants were included or not did not change results meaningfully. Conclusion/SignificanceDS predicted fatal outcomes but not positive cultures in a large regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality are unlikely to be accurate based on clinical signs alone, in infants in LMIC settings.

Opioid use disorder (OUD) has been linked to cardiometabolic diseases in adults through reductions in adiponectin--an adipocytokine with insulin-sensitizing effects. Opioid use during pregnancy dysregulates neonatal growth and may predispose to adult-onset diseases, but the impact of maternal OUD on neonatal adiponectin has not been studied. We hypothesize that maternal OUD also reduces adiponectin level in offspring (primary outcome) and alters growth (secondary outcome). To test our hypothesis, we conducted a prospective, observational pilot study and compared the expression of salivary adiponectin receptor 1/ADIPOR1 and anthropometric and body composition (fat and fat-free mass) measurements between opioid-exposed and age-matched non-exposed neonates born at [&ge;]34 weeks gestation. Data were stratified by exposure and sex using a Students t-test. Significance was set at p<0.05. A total of 67 neonates (35 opioid-exposed, 32 non-exposed neonates) were enrolled. Compared to healthy, non-exposed neonates, the expression of ADIPOR1 was reduced in opioid-exposed neonates (0.27-fold, p<0.01), with the lowest expression in those requiring pharmacotherapy (0.048-fold, p<0.001). Despite the smaller anthropometric measurements in the exposed than non-exposed neonates (2915{+/-}625 grams vs. 3209{+/-}345 grams, p=0.02), opioid-exposed neonates had comparable adiposity to non-exposed neonates (8.60{+/-}4.52% vs. 8.53{+/-}4.00%, p=0.95). Less breast milk was used in the exposed than non-exposed group (25.7% vs. 71.9%, p<0.01). Maternal OUD may be associated with aberrant growth and excess adiposity in offspring through its effect on adiponectin signaling, predisposing these neonates to cardiometabolic risks.

ObjectiveDysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels. Study designWe conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured. ResultsIndividual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy. ConclusionOur findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy.

ObjectivesTo evaluate the impact of undernutrition in school-aged children born with type III esophageal atresia (EA), and to determine its potential risk factors, including their respiratory history and status assessed by pulmonary function tests. MethodsRetrospective multicentre cohort study encompassing patients born between 2008 and 2013 with type III EA included in a national registry. Baseline data, surgical history and outcomes of patients with or without undernutrition (body mass index (BMI) z-score < -2 SD) at the age of 6-9 years were compared. ResultsOf the 212 patients included in the study, 20 (9.4%) presented with undernutrition, with a mean BMI z-score of -2.5 +/- 0.4. At birth, 13 (65%) of them where preterm, twice as high as in the control group (34.9%, p = 0.013), but adjusted neonatal weights and associated malformations did not differ between groups. Surgical management of EA and other intestinal malformations, including gastrostomy and fundoplication, were comparable between groups, except for hernia/cryptorchidism occurrence (20% vs 5.2%, p = 0.03). On spirometry, 15 (75%) of these patients demonstrated restriction, as compared to 38% of normal weight patients (p=0.002), and 60% of them required pulmonary treatments (vs 32%, p=0.02). Multivariate analysis identified birth in a level 3 maternity (odds ratio OR=6.0), hernia/cryptorchidism surgery (OR=5.2), a restrictive syndrome (OR=3.3) and pulmonary crisis treatment use (OR=2.7) as risk factors for undernutrition. ConclusionsIn contrast to intestinal and esophageal surgeries, the respiratory status appears to be significantly associated with nutritional outcomes in children born with type III EA. Clinical trialNCT04136795. What is known- Undernutrition remains common in children operated on for esophageal atresia. - There are associations between prematurity and undernutrition in children with esophageal atresia. What is new- Undernutrition is associated with a restrictive ventilatory pattern and with the use of pulmonary crisis treatments in school-aged children with type III esophageal atresia; - On the contrary, in this population, associated malformative conditions including the digestive tract and esophageal surgeries secondary to esophageal repair do not predispose children to undernutrition.

Background and objectivesContinuous full-channel EEG is the gold standard for electrocortical activity assessment in critically ill children, but its implementation faces challenges, leading to a growing use of amplitude-integrated EEG (aEEG). While suppressed aEEG amplitudes have been linked to adverse outcomes in preterm infants and adults after cardiac arrest, evidence for critically ill children remains limited. This retrospective study aimed to evaluate the association between suppressed aEEG amplitudes in critically ill children and death or poor functional neurological outcomes. Methods235 EEGs derived from individual patients < 18 years in the pediatric intensive care unit (PICU) at the University Hospital Essen (Germany) between 04/2014 and 07/2021 were retrospectively converted into aEEGs and amplitudes analyzed with respect to previously defined age-specific percentiles. Adjusted odds ratios for death and poor functional outcome at hospital discharge in patients with bilateral upper or lower amplitude suppression below the 10th percentile were calculated accounting for neurological injuries, acute disease severity, sedation levels, and functional neurological status before acute critical illness. ResultsThe median time from neurological insult to EEG recording was 2 days. PICU admission occurred due to neurological reasons in 43 % and patients had high overall disease severity. Thirty-three (14 %) patients died and 68 (29 %) had poor outcomes. Amplitude depression below the 10th percentile was frequent (upper amplitude: 27 %, lower amplitude: 34 %) with suppression of only one amplitude less frequent than bilateral suppression. Multivariable regression analyses yielded odds between 6.63 and 15.22 for death, neurological death, and poor neurological outcomes if both upper or both lower amplitudes were suppressed. Model discrimination was excellent with areas under the curve above 0.92 for all models. DiscussionThis study found a high prevalence of suppressed aEEG amplitudes in critically ill children early after PICU admission, with suppression being highly associated with death and poor functional outcomes at hospital discharge. These findings emphasize the potential of early identification of high-risk PICU patients through aEEG monitoring if conventional EEG is unavailable, potentially guiding neuroprotective therapies and early neurorehabilitation.

BackgroundImmunizing infants with various vaccines, including Bacillus Calmette-Guerin (BCG), Diphtheria-Pertusis-Tetanus (DPT), and measles, aims to enhance immunity. In instances where vaccine responses have been reported to be compromised, individuals are prone to infection. The BCG vaccine, for example, induces strong type 1 immune responses, particularly interferon-gamma (IFN-{gamma}) expression, that are essential for protection against Mycobacterium tuberculosis (Mtb). However, there is scanty evidence on whether this effect is established or sustained when infants are exposed to Mtb either in utero or after birth. We compared TB-specific cytokine responses for IFN-{gamma}, interleukin (IL)-2 (IL-2), tumour necrosis factor-alpha (TNF-), IL-17A, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) using supernatants harvested from QFT-Plus Blood Collection Tubes. MethodsThis cross-sectional study compared 22 infants born to mothers with bacteriologically confirmed active tuberculosis (TB), defined as TB exposed or cases, to 20 infants born to mothers without active TB, defined as TB non-exposed or controls. Plasma harvested from the QFT-plus tubes (TB1 and TB2) was used to perform a 5-plex Luminex assay using the LX 100/200 Luminex machine and measured in pg/mL. Data was analysed using R (v.4.4.1). The Mann-Whitney U test was used to determine statistical significance at a p-value less than 0.05 and a 95% confidence interval. Data was expressed as median and interquartile ranges (IQR). ResultsTB-exposed infants showed IFN{gamma} responses were slightly higher among TB-exposed infants compared to non-exposed (Medians (IQR): 15.49 (14.58-16.49) versus 14.96 (14.60-16.60), p=0.68, respectively. There was a strong expression of total IL-17A among TB-exposed compared to non-exposed 11.91 (10.89-13.50) versus 10.69 (10.17-11.64), p=0.035. We observed no differences in IL-2, TNF, and GM-CSF responses. ConclusionTB exposure among infants slightly alters their Mtb-specific cytokine responses, especially IL-17A cytokine responses. This suggests possible ongoing Mtb infection among TB-exposed infants. Follow-up studies of such infants are necessary to assess their risk of future TB infection and disease and the potential need for TB chemoprophylaxis.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

BACKGROUND: Half of positive blood cultures in pediatric emergency departments (PEDs) represent contaminants, driving unnecessary hospitalization, antibiotic exposure, and repeat visits. A clinical decision rule derived at CHU Sainte-Justine showed 99% sensitivity and 60% specificity for distinguishing bacteremia from contaminants but had not been externally validated. We sought to validate this rule in an independent pediatric cohort. METHODS: This retrospective diagnostic study spanned from January 2015 to May 2025 at a tertiary PED in Switzerland, using positive blood cultures from patients younger than 16 years. The four predictors (Gram-negative organisms or Gram-positive cocci in pairs or chains; time to positivity <17 hours; indwelling device; suspected osteoarticular infection) classified each case as low, moderate, or high risk. The primary outcome was bacteremia, adjudicated by two independent reviewers, based on organism identity and infectious disease specialist's assessment. Diagnostic accuracy was assessed with 95% CIs. RESULTS: Of 130 children enrolled (median age 3.8 years [IQR 0.9-9.9]; 61.5% male), 78 (60.0%) had true bacteremia. The rule yielded a sensitivity of 97.4% (95% CI, 91.0-99.7), specificity of 69.2% (95% CI, 54.9-81.3), positive predictive value of 82.6% (95% CI, 73.3-89.7), and negative predictive value of 94.7% (95% CI, 82.3-99.4). Both false-negatives were immunocompetent children with methicillin-susceptible Staphylococcus aureus bacteremia without indwelling devices. Among contaminants, 71% received antibiotics under usual care versus 31% classified as moderate or high risk by the rule. CONCLUSIONS: This first external validation supports the Sainte-Justine rule in a distinct pediatric population, preserving sensitivity with higher specificity. Multicenter validation is warranted before adoption.

BackgroundRespiratory Distress Syndrome (RDS) remains a leading cause of morbidity and mortality among premature infants. Their immature lungs lack surfactant, making breathing difficult. These infants need close monitoring with arterial blood gas (ABG) checks to guide oxygen therapy. While gestational age is known to influence disease severity, locally relevant data on oxygen requirements and arterial blood gas (ABG) changes across gestational age groups remain scarce in Pakistan. ObjectiveTo evaluate gestational age-related variations in oxygen demand, ABG parameters, and respiratory support among preterm neonates with RDS, with the goal of identifying physiologic and management differences that may guide tailored interventions in low-resource NICU settings. MethodologyThis four-month cross-sectional study was conducted in the NICU of the University of Lahore Teaching Hospital, Pakistan. Sixty-five preterm neonates (28-36 weeks) with RDS were enrolled through consecutive sampling. Data on gestational age, oxygen requirement (FiO2), mode of respiratory support, and ABG parameters were collected before and after stabilization on respiratory support. Data were analysed in SPSS 27 using ANOVA, Kruskal-Wallis, Chi-square, paired t-tests, and Spearmans correlation. ResultsLower gestational age was linked to higher oxygen needs (FiO2 83% at 28-30 weeks vs. 55% at 34-36 weeks, p < 0.001) and more invasive ventilation (60% vs. 10%, p = 0.011). ABG parameters correlated significantly with gestational age: earlier gestations had lower pH, higher PaCO2, and lower PaO2 and SaO2 (all p < 0.05), while HCO3- showed no correlation (p = 0.316). Despite stabilization, SaO2 values remained below the target 90-94% range in all groups. ConclusionGestational age is a key predictor of oxygen needs, ABG derangements, and intensity of respiratory support in preterm neonates with RDS. This first locally relevant evidence from Pakistan underscores the need for gestation-specific oxygen protocols to improve care in resource-limited NICUs and similar low-resource settings worldwide. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSRespiratory distress syndrome is a leading cause of illness and death in preterm babies. Oxygen therapy and arterial blood gas monitoring are central to care, but both under- and over-treatment can cause harm. Gestational age strongly influences oxygen needs and outcomes, yet data from local NICUs remain limited. What this study addsThis study shows that babies born at lower gestational ages need higher FiO2 and more invasive support. Blood gas values such as pH, PaO2, PaCO2, and SaO2 vary significantly with gestational age, while HCO3- does not. It also provides locally relevant evidence from Pakistan to guide neonatal care. How this study might affect research, practice or policyThese findings highlight the need for gestation-specific oxygen therapy and monitoring strategies in NICUs. They support the development of standardized oxygen protocols in resource-limited settings. The results may also inform future research to improve outcomes and reduce preventable complications in preterm infants.

Data from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.

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.

PurposeBlood draws have been associated with significant discomfort, especially for individuals with sensory hypersensitivity, as is common in autism. This results in avoidance of medical appointments and creates difficulties for scientific studies recruiting from this population. Touch Activated Phlebotomy (TAP) is a novel capillary blood collection technique that reduces the discomfort of blood draws, and here we aimed to assess its tolerability to autistic adults. Our secondary aim was to assess whether capillary and venous blood provide equivalent measurements of Vitamin B6 concentrations. Methods23 participants (11 autistic: 12 non-autistic) were recruited, and two TAP devices were administered before providing pain ratings. Traditional venipuncture was also carried out in the non-autistic individuals, with the same pain measures reported. Enzyme Linked Immunosorbent Assays (ELISAs) were conducted to quantify concentrations of Vitamin B6. ResultsThe TAP device caused significantly less pain than the traditional venipuncture procedure. Furthermore, TAP pain ratings in autistic individuals did not differ meaningfully from non-autistic individuals. Vitamin B6 concentrations showed minimal bias and good agreement between capillary and venous blood, and high repeatability between repeated capillary samples. No clear difference in Vitamin B6 concentrations was observed between autistic and non-autistic participants. ConclusionTAP is a well-tolerated method of obtaining capillary blood samples from autistic adults for medical and research purposes, and this has the potential to reduce avoidance of medical appointments in this population. Like most analytes tested to date, measurement of Vitamin B6 in capillary blood is a valid and reliable alternative to traditional venous samples.

AimTo establish reference intervals (RI) for blood amino acids (AA) in healthy newborns of North Asia measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate their differences from respective reference values for newborns from other populations. ObjectivesA cross-sectional study of 381 healthy newborns was conducted. De-identified dried blood spots annotated by age, birth-weight, and sex were obtained from 381 healthy newborns aged 0-7 days. Data was collected from April to May of 2020. MethodsDried blood spots collected from filtered paper were used to analyze and measure of 13 derivatized amino acids using LC-MS/MS method. Nonparametric statistical approaches were used to generate 2.5th-97.5th percentile distributions for newborns in North Asia in accordance with CLSI EP28-A3c. ResultsReference intervals (RI) for phenylalanine, tyrosine, citrulline, alanine, ornithine, proline in North Asian newborns differ slightly from those of newborns in other countries around the world. This allows for the use of universal RI in the diagnosis of congenital metabolic disorders of the indicated amino acids (AA) in different populations around the world. The RI for branched-chain essential AA (valine, leucine, and isoleucine are metabolic criteria for maple syrup disease) are higher in North Asian infants as compared to infants in other populations. In addition, the RI for arginine, aspartic acid, and glutamic acid in North Asian newborns are higher than in newborns in other countries around the world. In our study, the RI for methionine in newborns were lower than in many countries worldwide [McHugh D, 2011]. For optimal clinical practice, RI for certain AA in newborns (valine, leucine, isoleucine, methionine, arginine, aspartic acid, glutamic acid) should be determined for specific populations-further augmenting the diagnosis of inborn errors of metabolism.

BackgroundDiagnosing sepsis in preterm neonates is a significant challenge, underscoring the urgent need for timely and accurate methods. Serum inflammatory protein signatures show promising potential for early and precise disease diagnosis. MethodsIn this study, a cohort of preterm neonates (n=50, 25-35 weeks gestation, female 40%) at the time of suspicion and follow-up were enrolled along with healthy neonates. Based on clinical presentation and blood culture or MALDI results, the sepsis suspicion cases were categorized into culture-positive (CP)/culture-negative (CN) sepsis (n=13 each) or no-sepsis (NS, n=12) and compared with healthy controls (HC, n=12) from similar settings. These sub-groups (CP, CN, and NS) were followed up till completion of antibiotic therapy. Serum inflammatory proteins and trace elementals (57Fe, 66Zn, 63Cu, 77Se, 44Ca, 24Mg) were profiled using the Olink(R) Target 96 inflammation panel and inductively coupled plasma mass spectrometry (ICP-MS), respectively. Serum proteins with log2fold changes>{+/-}1.3 and p<0.05 were identified as differentially expressed proteins (DEPs) and monitored in the follow-up samples receiving treatment. Elements showing significant differences (p<0.05) between the study groups were also identified for correlation analysis. ResultsSerum inflammatory protein levels showed group-specific trends. Significantly higher serum IL-6, IL-10, TNF- and LIF levels with low IFN-{gamma} and CCL28 were observed in the CP sepsis group compared to HC. CN group also showed reduced serum IFN-{gamma} along with CXCL10 and CCL11 levels when compared to HC. Also, the serum IL-6 level in CP cases was positively correlated with IFN-{gamma} and IL-10 levels (r<0.77, p<0.05), and an increased IL6:IFN-{gamma} was observed in the CP, CN and NS groups compared to the HC. Serum of NS patients showed higher FGF-23 levels with lower IFN-{gamma} and CCL11 than HC. Upon recovery, the serum IL-6 levels reached normal levels in CP, whereas the CN group showed IFN-{gamma}, CXCL10, and CCL11 levels returned to normal. Serum iron levels were significantly reduced in both the CP and CN groups, while serum selenium was low in the CP group and serum copper was lower in the CN group, with all levels returning to normal upon recovery. ConclusionsAbsolute levels of IL-6, IL-10, IFN-{gamma}, and TNF- in serum can be used as biosignatures for neonatal sepsis, offering the potential for early disease diagnosis and monitoring therapeutic response. Additionally, these markers implicated in disease resolution mechanisms might serve as therapeutic targets in sepsis treatment.

BackgroundGiven their immature immune system, neonates are highly susceptible to infection, a major cause of neonatal death. However, associations between immune-response-related proteins and risk of neonatal infection have yet been systematically investigated. MethodsWe conducted a nested case-control study of 149 twins (60 cases and 89 controls, including 34 pairs of discordant twins), within the Shenzhen Baoan Birth and Twin (SZBBTwin) cohort. Using proximity extension assay of Olink Proteomics, 92 immune-response-related proteins were measured in samples of cord plasma. All twins were followed for a diagnosis of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially expressed proteins (DEPs), and multivariable logistic regression was used to assess the associations of the levels of proteins with neonatal infection. The receiver operating characteristic curve was plotted to evaluate the predictive performance of DEPs. Enrichment analysis was performed to annotate potential functions and pathways of DEPs. ResultsFive DEPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection. A higher cord plasma level of integrin alpha 11 (ITGA11) was associated with a higher risk of neonatal infection in both the analyses of all twins and discordant twins. The area under the curve achieved 0.835 for the five DEPs. The identified DEPs were mainly involved in immune function and protein binding, and most of them were enriched in the nuclear factor kappa-B pathway. ConclusionMultiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection. Key pointIn this nested case-control study, 92 immune-response-related proteins were measured in cord plasma by proximity extension assay. A higher level of ITGA11 was associated with a higher risk of neonatal infection, in the analyses of all twins and discordant twins.