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Frontiers in Pediatrics

Frontiers Media SA

Preprints posted in the last 90 days, ranked by how well they match Frontiers in Pediatrics's content profile, based on 32 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit.

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External validation of a decision rule for bacteremia vs contaminants in pediatric blood cultures

DAmours-Gravel, M.; Charvet, A.; Ibanez Miguel, C.; Rouxel, N.; Fontaine, C.; Besson, J.; Jiguet, L.; Karara, L.; Pozzi, L.; Teixeira, C.; Henoud-Bertaina, C.; Alves, C.; Cherkaoui, A.; Courvoisier, D. S.; Siebert, J. N.

2026-07-20 emergency medicine 10.64898/2026.07.17.26358300 medRxiv
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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.

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Use of cranial ultrasonography to improve prompt and early diagnosis of meningitis at the Neonatal Centre of Excellence, University Teaching Hospitals, Lusaka, Zambia.

OGAH, A. O.; Hamer, D. H.

2026-07-30 pediatrics 10.64898/2026.07.29.26359192 medRxiv
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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.

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Alcohol consumption during pregnancy dysregulates maternofetal angiogenic and inflammatory factors with sex specificities

Sautreuil, C.; Lesueur, C.; Pinto Cardoso, G.; Bruel, H.; Biran, V.; Muller, J.-B.; Duigou, A.-L.; Datin-Dorriere, V.; Verspyck, E.; Marguet, F.; Laquerriere, A.; Gressens, P.; Gonzalez, B.; Marret, S.

2026-07-17 pediatrics 10.64898/2026.07.15.26357094 medRxiv
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Prenatal alcohol exposure (PAE) is a major cause of neurodevelopmental disorders, yet most children are diagnosed late or misdiagnosed. Neuroplacentology suggest that placental factors released into maternal and/or umbilical cord blood contribute to fetal brain development. Consistently, a preclinical inter-organ transcriptomic database revealed that PAE disrupts the expression ratio of angiogenic and inflammatory factors suggesting an angio-inflammatory response. This study aimed i) to assay, by multiplex immunoassay, angiogenic and inflammatory factors in maternal and umbilical cord blood from alcohol-consuming women and ii) to perform a maternofetal analysis according to neonatal sex. Afterwards, dysregulated factors from mothers who gave birth to females or males were submitted to STRING and ShinyGO analyses. Results showed that PAE differently altered the distribution profiles of dysregulated angiogenic and inflammatory factors in maternal and umbilical cord blood. Moreover, sex-specific differences were observed, with 36% of dysregulated proteins specific to males, 48% to females, and 16% common to both. STRING analysis revealed robust functional protein-protein interactions linking together inflammatory and angiogenic clusters while the ShinyGO analysis identified enriched pathways related to vascular shear stress. These findings provide the first maternofetal analysis of combined angiogenic and inflammatory factors from alcohol-consuming mothers.

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Long-Term Brain White Matter Outcomes Following Neonatal Acute Kidney Injury

Ward, R. C.; Steinbach, E. J.; Nopoulos, P. C.; van der Plas, E.; Hopkins, L.; Soranno, D. E.; Conrad, A. L.; Harshman, L. A.

2026-07-01 pediatrics 10.64898/2026.06.24.26356471 medRxiv
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Acute kidney injury (AKI) is common among neonates in the intensive care unit and has been linked to abnormal neurodevelopment, yet long-term effects on brain structure remain uncharacterized. In this secondary analysis, we compared brain white matter integrity, measured by fractional anisotropy (FA) on 3T MRI, in children ages 5 to 12 years born preterm with (n=5) versus without (n=10) a history of neonatal AKI. Contrary to our hypothesis, children with prior neonatal AKI showed higher FA across seven white matter regions in unadjusted analyses. After adjustment for sex, birth weight, and age at MRI, the AKI group retained significantly greater FA in the corticospinal tract ({beta}=0.7, 95% CI 0.09-1.31) and superior frontooccipital fasciculus ({beta}=0.68, 95% CI 0.02-1.34). Because elevated FA may reflect compensatory glial responses rather than improved neurological function, these findings suggest neonatal AKI may have lasting, complex effects on white matter microstructure. Larger studies pairing neuroimaging with neurocognitive assessment are needed.

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Multi-modal recruitment efficiency in ScreenPlus, a large-scale consented pilot NBS program

Clarke, M. J.; Paleologos, K.; Kelly, N. R.; Bailey, S. M.; Joseph, M.; Kupchik, G. S.; Lumba, R.; Ganesh, J. J.; Stroustrup, A.; Orsini, J.; Goldenberg, A. J.; Wasserstein, M. P.

2026-07-02 pediatrics 10.64898/2026.06.30.26356857 medRxiv
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ScreenPlus is a consented pilot program that aims to screen 100,000 babies for a panel of rare disorders. Given its size, ScreenPlus provides a unique opportunity to learn about optimal recruitment practices. ScreenPlus recruitment strategy includes recruiter-initiated Active and Hybrid modes and parent-initiated Independent mode. Active recruitment occurs in-person at the postpartum bedside, whereas Hybrid recruitment includes other attempt types. In Independent recruitment, parents access online educational and e-consent forms. Analysis of 47,642 completed recruitment profiles from May 2021 through April 2025 showed that Active recruitment was used in 72.2% and had the highest percentage of parents consenting (65.5%) in an average of 1.2 days. Hybrid recruitment was used in 27.1% of profiles and resulted in a 44.5% consent rate in an average of 8.6 days, with electronic medical record messaging being the attempt type most likely to lead to a consent. Independent recruitment was used in less than 1% of profiles. In Active and Hybrid Recruitment, non-English speakers were more likely to consent compared with English speakers. Collectively, these findings emphasize that although optimal pilot NBS recruitment is multi-modal, direct communication between parents and study team has the highest consent yield.

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Cortisol Stress Response is Associated with Iron Status in Pregnancy

Reid, B. M.; Celestin, G. F.; Georgieff, M. K.; Mbayiwa, K.; Keenan, K.

2026-06-24 nutrition 10.64898/2026.06.22.26356237 medRxiv
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Background: Iron deficiency (ID) affects up to 40% of pregnant women in the third trimester, even in highly resourced and iron-supplemented populations, with adverse consequences for maternal health and long-term offspring development. Psychological stress may compromise iron status through hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation and inflammation, but no study has directly examined cortisol in relation to iron status across human pregnancy. Objective: This longitudinal study examined associations between HPA function and maternal iron status across pregnancy and tested whether IL-6 and CRP mediated the relationship between cortisol and ferritin across gestation. Methods: One hundred sixty-eight pregnant Black women with Medicaid insurance completed up to four laboratory assessments across pregnancy. Salivary cortisol was measured before and in response to the Trier Social Stress Test, yielding basal and reactive cortisol indices. Serum ferritin, IL-6, and CRP were collected at each visit. Trimester-specific regression models examined cortisol reactivity in relation to ferritin; linear mixed-effects models with moderated mediation tested whether basal cortisol predicted ferritin via inflammation. Results: Higher cortisol reactivity was associated with lower ferritin specifically in the third trimester (std. {beta} = -0.197, p = .004). Higher basal cortisol predicted a steeper IL-6 rise across gestation (p = .002), and IL-6 was positively associated with ferritin (b = 0.236, p = .006), consistent with inflammatory iron sequestration. The indirect effect of basal cortisol on ferritin via IL-6 was statistically significant, and higher basal cortisol was negatively associated with cortisol reactivity in the third trimester. No pathway was observed through CRP. Conclusion: Greater cortisol reactivity predicted lower third-trimester ferritin, a pattern that suggests cumulative iron depletion, atypically sustained HPA reactivity in late pregnancy, or both. To our knowledge, this is the first prospective study linking cortisol reactivity to iron status across human pregnancy, identifying maternal stress physiology as a novel target for understanding and addressing gestational iron deficiency.

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Asthma diagnosis in school-age children: a survey among Swiss physicians

Guerra Buezo, B.; Sasaki, M.; Leuenberger, L. M.; Glick, S.; Gaillard, E. A.; Moeller, A.; Regamey, N.; Sutter, O.; Goutaki, M.; Kuehni, C. E.

2026-07-16 pediatrics 10.64898/2026.07.13.26357724 medRxiv
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Background: Clinical guidelines recommend objective tests to diagnose asthma in school-age children, but their availability and use in routine practice remain uncertain. We evaluated asthma diagnostic practices in Switzerland, focusing on first-line tests (spirometry, bronchodilator reversibility testing, and fractional exhaled nitric oxide [FeNO]). Methods: Cross-sectional, nationwide online survey of primary care paediatricians (PCPs) and respiratory specialists. We assessed access to and use of diagnostic tests, focusing on first-line tests, and examined reasons for non-use, referral practices, and guideline consultation. We used multivariable logistic regression to identified factors associated with spirometry access among PCPs. Results: Of 1,055 respondents, 625 diagnosed asthma in children, including 419 PCPs. Among PCPs, 50% (95% confidence interval [CI] 45-55) reported no access to spirometry and 95% (95% CI 92-97) no access to FeNO, whereas all paediatric respiratory specialists and almost all adult respiratory specialists had access to both tests. Barriers to first-line testing among PCPs included economic constraints and difficulties interpreting test results. Spirometry access was lower in French- and Italian-speaking regions than in German-speaking regions (adjusted odds ratio [aOR] 0.09, 95% CI 0.05-0.15), but higher among PCPs working full-time (aOR 2.04, 95% CI 1.11-3.82) and those using Swiss asthma guidelines (aOR 1.71, 95% CI 1.01-2.92). PCPs without spirometry access more frequently referred children to specialists for diagnostic confirmation (89% versus 80%; p=0.019). Conclusion: Many PCPs in Switzerland lack access to guideline-recommended tests. Improving access, reimbursement, and training in test interpretation may help reduce the gap between guidelines and clinical practice.

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Determinants of severe adverse outcomes among low-birth-weight neonates admitted to a county referral hospital in Kenya: a mixed-methods cross-sectional study

Cheptoo, J.; Shisanya, M. S.; Mukthar, V.; Morema, E. N.

2026-07-21 pediatrics 10.64898/2026.07.20.26358516 medRxiv
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Abstract Background. Low-birth-weight (LBW) neonates carry a disproportionate burden of morbidity and mortality in resource-limited newborn units, yet facility-level evidence on the determinants of severe in-hospital outcomes at county referral level in Kenya is limited. We determined the maternal, neonatal and care-related determinants of severe adverse outcomes among LBW neonates admitted to Kericho County Referral Hospital (KCRH) and used healthcare-provider perspectives to explain the quantitative findings. Methods. We conducted a facility-based, convergent mixed-methods cross-sectional study. Quantitative data were obtained from 169 LBW neonate-mother pairs through structured maternal interviews and clinical-record abstraction; qualitative data came from nine key informant interviews with newborn-unit healthcare workers. A severe adverse outcome was defined as the occurrence of at least one of respiratory distress, sepsis, hypothermia, hypoglycaemia, prolonged neonatal unit stay ([&ge;]7 days) or neonatal death. Associations were examined using bivariate tests and a multivariable binary logistic regression model entering 13 candidate predictors simultaneously, with multicollinearity, calibration and discrimination diagnostics. Interviews were analysed thematically and integrated with the quantitative results in a joint display. Results. A severe adverse outcome occurred in 136 of 169 neonates (80.5%); respiratory distress was the most common single complication (69.8%), and neonates experienced a mean of 2.46 (SD 1.31) adverse outcomes. In the adjusted model (omnibus {chi}{superscript 2}(13) = 57.70, p < 0.001; Nagelkerke R{superscript 2} = 0.46; area under the receiver-operating-characteristic curve = 0.879), three factors independently predicted severe adverse outcome: lower birth weight (adjusted odds ratio [AOR] 0.997 per gram, 95% CI 0.995-0.999, p = 0.012), maternal pregnancy-induced hypertension (AOR 18.49, 95% CI 1.87-182.47, p = 0.013) and warm-chain care (AOR 10.94, 95% CI 1.40-85.41, p = 0.023; a direction consistent with confounding by indication). Providers emphasised the fragile first hour of stabilisation, staffing and workload, warm-chain maintenance, infection prevention, commodity availability and referral coordination. Conclusions. Severe adverse outcomes were near-universal among LBW neonates at KCRH and were driven by neonatal biological vulnerability, maternal hypertensive disease and the readiness of newborn-unit care. Improving outcomes requires early, birth-weight-based risk stratification of the smallest neonates alongside strengthening of antenatal detection of hypertension and reliable, timely newborn-unit care processes.

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Early Joint Trajectories of Liver-Related Laboratory Biomarkers and 60-Day Mortality in Sepsis-Associated Liver Injury

Qi, Y.-n.; Zhou, T.; Zhao, Q.; Liu, C.

2026-07-01 emergency medicine 10.64898/2026.06.27.26356734 medRxiv
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Background: Sepsis-associated liver injury (SALI) is commonly assessed using static laboratory values, although liver dysfunction during sepsis is dynamic.Methods: This retrospective cohort study included 162 ICU patients with SALI. Early trajectories of alanine aminotransferase, total bilirubin, and albumin during the first 7 days after ICU admission were identified using group-based multi-trajectory modeling. Landmark analysis and Cox regression were used to evaluate 60-day mortality.Results: Twenty-five patients died within 60 days. Four trajectory classes were identified. Between-class separation was driven mainly by alanine aminotransferase and total bilirubin, whereas albumin showed limited short-term variation. After the landmark time point, Class 3 (HR, 4.374; 95% CI, 1.960-9.759; P <0 .001) and Class 4 (HR, 7.451; 95% CI, 3.649-15.212; P <0 .001) had higher mortality risk than Class 1.Conclusions: Early joint trajectories of liver-related laboratory biomarkers may identify clinically meaningful SALI subphenotypes and support risk stratification in critically ill patients.

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Feasibility of adjusting for sepsis-related organ dysfunction in pediatric patients using administrative healthcare data

Ravichandrajah, H.; Fischer, A.; Tiago Gomez, A.; Hojeij, R.; Goretzki, S. C.; Felderhoff-Mueser, U.; Park, H.-J.; Kernan, K.; Carcillo, J. A.; Dohna-Schwake, C.; Bruns, N.

2026-08-13 pediatrics 10.64898/2026.08.12.26360255 medRxiv
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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.

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Neonatal critical illness is associated with pancytopenia development in childhood

Dulmovits, B. M.; Goldstein Novick, N. P.; Devine, M.; Thom, C. S.

2026-07-23 pediatrics 10.64898/2026.07.21.26358620 medRxiv
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Objectives. Perinatal illness and preterm birth carry lifelong multiorgan complications and are associated with hematologic derangements during neonatal intensive care unit (NICU) admission. Despite this, long term hematologic morbidities following neonatal critical illness remain undefined. Our objective was to identify associations between prematurity, perinatal critical illness, and later hematologic dysfunction. Study design. Single neonatal care network retrospective cohort study with cohorts divided by gestational age and the presence of critical illness markers. The association between hematologic dysfunction, critical illness, and prematurity was investigated using multivariate logistic regression. Results. Among 13073 infants, critical illness or prematurity was found to increase the odds of developing pancytopenia post-NICU discharge. Subsequent analyses stratified on prematurity demonstrate that a diagnosis of shock or sepsis was associated with pancytopenia. Conclusions. Our findings suggest that perinatal insults are associated with hematopoietic system dysfunction and long term morbidity. Importantly, critical illness, not prematurity itself, may drive this association in preterm infants.

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Rising rate of non-receipt of vitamin K prophylaxis for newborns, January 2019 - June 2026

Masters, N. B.; Farrar, K. G.; Holler, E.; Lancaster, J. M.

2026-09-02 pediatrics 10.64898/2026.08.31.26361837 medRxiv
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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.

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Clinical outcomes and its determinants among neonates with neonatal sepsis admitted to selected Governmental hospitals in Addis Ababa, Ethiopia.

Gutema, R. M.; Namara, G. T.

2026-08-12 pediatrics 10.64898/2026.08.10.26360094 medRxiv
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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.

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Levels and tracking of Lipoprotein (a) serum concentrations from infancy to adolescence

Jumpponen, T.; Juonala, M.; Salo, P.; Lisinen, I.; Laitinen, T. T.; Pahkala, K.; Rovio, S. P.; Viikari, J. S. A.; Rönnemaa, T.; Niinikoski, H.; Routi, T.; Jula, A. M.; Nuotio, J.; Raitakari, O. T.; Mykkänen, J.

2026-06-29 cardiovascular medicine 10.64898/2026.06.25.26356629 medRxiv
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Background and aims: Longitudinal data and tracking of serum lipoprotein(a) (Lp(a)) concentrations through childhood?s development from infancy to adolescence are lacking. We aimed to establish the strength of the tracking phenomenon from early infancy to adolescence and to examine whether a heart-healthy dietary intervention and individual dietary components influence serum concentrations of Lp(a). Methods: 1062 healthy children aged 7 months were recruited and randomized into control (N=522) and intervention (N=540) groups in the Special Turku Coronary Risk Factor Intervention Project (STRIP). Serum Lp(a) concentration was measured at 10 age points (0.7, 1.3, 2, 3, 4, 5, 9, 11, 13, and 15 years) and median serum Lp(a) levels were studied longitudinally. Tracking across age points was studied using Spearman's rank-order correlation. Sex differences and the effects of the dietary intervention and individual dietary components were analyzed with linear mixed-effects models for repeated measures. Results: A total of 7018 Lp(a) measurements were analyzed. Median serum Lp(a) concentrations increased from infancy until approximately age 13 years. After age 13, median Lp(a) declined in boys (-15.1%) but was largely unchanged in girls. Girls had higher Lp(a) concentrations at all age points (P=0.01). Spearman's correlation analysis indicated a strong tracking between age points in both sexes (r=0.854-0.956). Achievement of at least one dietary fat quality goal of the intervention corresponded to a 2.5% increase in serum Lp(a) concentration (P=0.0004). Higher sucrose intake was associated with modestly higher Lp(a), whereas fiber intake showed no association. At age 15 years, 16.2% of all participants with available measurements had elevated Lp(a) ([&ge;] 30mg/dL). Conclusions: A rising trend was observed in median serum Lp(a) concentrations from infancy to adolescence. Due to strong tracking, these findings suggest that early-life measurements may provide valuable insight for longitudinal cardiovascular risk assessment. Heart-healthy diet does not meaningfully influence serum Lp(a).

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Identifying the risk profile of anemia subtypes and hemodynamic obstetric complications in relation to peripartum cardiomyopathy

Sompel, K.; Shalowitz, E.; Davis, M.; Kudron, E.; Son, S. L.; Kao, D. P.

2026-06-15 cardiovascular medicine 10.64898/2026.06.11.26355493 medRxiv
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Background: Peripartum cardiomyopathy (PPCM) is a leading cause of maternal mortality worldwide, with worse outcomes associated with African Ancestry and delayed presentation. However, the mechanisms underlying PPCM are incompletely understood. Objective: Use a large, nationwide cohort to explore associations between PPCM and underexplored perinatal risk factors and complications of childbirth. Methods: Public hospital discharge data were obtained from eleven U.S. states between 2003-2019. Delivery hospitalizations, patient characteristics and obstetric complications were identified using ICD-9 and -10 CM codes. Only cases with unique patient identifiers enabling readmission analysis were included. The primary outcome was incident PPCM coded between 30 days antepartum and 150 days postpartum. Results: Of 7,424,916 delivering patients, 5,488 patients were diagnosed with PPCM. Patients with PPCM had higher rates of anemia, anemia of chronic disease (ACD), iron deficiency anemia (IDA), sickle cell disease (SCD), sickle cell trait (SCT), red blood cell (RBC) transfusion, and postpartum hemorrhage (PPH) (p<0.001 for all). Transfusion was associated with increased risk of postpartum PPCM both with PPH (OR 2.16) and without PPH (OR 1.92). In multivariable analysis antepartum diagnosis was more common in the setting of anemia (OR 2.5, p<0.001), ACD (OR 16.31 p<0.006), SCD (9.11, p=0.002) and SCT (OR 2.96 p=0.021), while IDA was associated with peripartum and postpartum PPCM (OR 2.04 p<0.001). Conclusion: Anemia subtypes, RBC transfusion, and PPH were associated with an increased risk for PPCM. The magnitude of risk varied by race and timing of presentation. Further study of peripartum interventions directed at these risk factors is warranted.

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prevalence and Factors associated with post-natal growth restriction among low-birth-weight infants at a rural county referral hospital, Kenya: A retrospective observational study

Lyanda, L. N.; Ochieng, R.; Keter, A.

2026-08-05 pediatrics 10.64898/2026.08.04.26359674 medRxiv
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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.

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Electronic health data exploring cardiorespiratory responses of transfusions in preterm infants: An international multicenter cohort study

Honore, A.; Rech, T.; Scrivens, A.; Binotto, I.; Zandvoort, C. S.; van der Staaij, H.; Peck, M.; Zivanovic, S.; Stanworth, S. J.; Hartley, C.; Dame, C.; Deschmann, E.; the Neonatal Transfusion Network,

2026-09-03 pediatrics 10.64898/2026.09.01.26361418 medRxiv
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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.

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Elevated Rates of Gastrointestinal Dysfunction in Children with Neurodevelopmental Disabilities: Not Just an Autism Issue

Savatt, J. M.; Nixon, M. P.; Berry, A. S. F.; Johns, A.; Walsh, L. K.; Martin, C. L.; Ledbetter, D. H.; Challman, T. D.; Myers, S. M.

2026-08-19 pediatrics 10.64898/2026.08.17.26360370 medRxiv
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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.

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Effect of Boysenberry apple powder blend (BerriQi) on reducing symptom severity in children with Upper respiratory tract infection

Shrestha, A.; Graham, E.; Mckeen, S.

2026-08-03 nutrition 10.64898/2026.07.26.26358747 medRxiv
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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).

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Hepatitis B cell-free DNA in non-invasive prenatal testing as an early biomarker of viral infectivity

Dao, V. N.; Nguyen, P. T.; Tran, T. N.; Nguyen, N. H.; Tang, H.-S.; Boni, M. F.; Giang, H.; Phan, D. M.

2026-08-17 genetic and genomic medicine 10.64898/2026.08.15.26360031 medRxiv
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Non-invasive prenatal testing (NIPT) was initially developed to detect chromosomal abnormalities in fetuses through the analysis of cell-free fetal DNA in maternal blood. Recent advancements have expanded NIPT's applications to include the detection of viral infections during pregnancy. However, interpreting pathogen-derived cell-free DNA (cf-DNA) remains clinically complex. This study explores the clinical relevance of hepatitis B virus (HBV) cf-DNA using a dataset of approximately 500,000 NIPT visits and an independent validation cohort of 582 pregnant women (40 HBV-infected), aligned with HBV epidemiology from both population and individual perspectives. Our analysis reveals that HBV cf-DNA is a strong biomarker of high viral infectivity rather than a general marker of infection, suggesting its potential to identify pregnant women at heightened risk of vertical transmission by the end of the first trimester. Additionally, HBV-positive women showed a small but consistent reduction in fetal fraction relative to HBV-negative women across gestational weeks 9 - 17, an association compatible with an early effect of HBV on the placental contribution to cell-free DNA, although the observational design and unmeasured maternal covariates preclude causal inference.