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BMJ Paediatrics Open

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Preprints posted in the last 30 days, ranked by how well they match BMJ Paediatrics Open's content profile, based on 24 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Uptake, reidentification and regret in pediatric gender care

Tollit, M. A.; Conabere, W.; Gray, K.; Sibley, C.; Ayub, I.; Pace, C. C.; Traill, A.; Russo-Batterham, T.; Cavve, B. S.; Ravipati, T.; Rayner, C.; Pang, K. C.

2026-09-24 pediatrics 10.64898/2026.09.17.26363359 medRxiv
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Background: Gender-affirming medical care (GAMC) for children and adolescents in Australia has become increasingly politicized, despite care being provided in accordance with latest evidence-based international guidelines. Critics of GAMC claim that current assessment and deliberation processes are insufficient, and that too many young people are accessing medical interventions, no longer identifying as trans, and expressing treatment regret. These claims have led to widespread bans on the provision of paediatric GAMC, despite growing evidence regarding harms caused by such bans. Aim: This study sought to describe the care journeys of the young people attending Australia's largest paediatric gender service, with a focus on reporting the rates at which young people commenced medical interventions, re-identified with their birth-assigned sex, and expressed regret about their treatment. Methods: The Royal Children's Hospital Gender Service (RCHGS) is a statewide service that provides individualised multidisciplinary care to trans and gender diverse young people in Victoria, Australia. An initial extended triage appointment explores the needs and goals of the young person and their family. Some proceed to receive individualised multidisciplinary care (MDC) at RCHGS which can include psychosocial assessment and management, family support, and medical interventions including pubertal suppression (PS) and gender-affirming hormonal therapy (GAHT). We undertook a retrospective file audit of all patients who had attended at least one RCHGS appointment and been discharged between 1/1/2017-31/12/2024. For each person, key data were extracted from their electronic medical record and recorded in REDCap. Results: 1,391 patients were discharged over the 8-year study period and many different care trajectories were observed. 814 (58.5%) did not access ongoing MDC. Of the remaining 577, 353 (25.4% of total cohort) started a medical intervention ((PS: n=64/1391 (4.6%); estradiol: n=97/1391 (7.0%); testosterone: n=244/1391 (17.5%)). For those who started these medical interventions, the median duration and number of sessions from first appointment until commencement of medications was 530 (IQR: 371-693) days and 9 (IQR: 7-13) sessions. 346 of these patients (98.0%) had data on gender identity at discharge and subsequent care pathways. 7 (2.0%) re-identified with their birth-registered sex and stopped treatment: 4 did so after commencing PS (4/61=6.6% of those starting PS), 2 did so after commencing testosterone, and 1 did so after commencing estradiol (3/341=0.9% of those starting GAHT). Just one of these patients, who had been on estradiol for 1 month, expressed treatment regret given concerns about initial breast budding and future fertility. Conclusion: This study highlights varied trajectories of those referred to paediatric gender services, directly challenges claims used to justify restrictions on paediatric GAMC and underscores the importance of a person-centred approach to care.

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A school-based trauma-informed care and social-emotional learning intervention for adolescents with adverse childhood experiences in India: Protocol for a sequential mixed-methods study with a single-arm quasi-experimental evaluation

Bharti, B.; Malhotra, N.; Virk, A.; Malhi, P.; Bharti, S.; Lamba, D.; Pandey, C.

2026-10-06 pediatrics 10.64898/2026.10.02.26364571 medRxiv
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Background Adverse childhood experiences are major determinants of mental disorders, health-risk behaviours and non-communicable diseases across the life course, but evidence from India remains limited. This study aims to estimate the prevalence and patterns of adverse childhood experiences among Indian adolescents, examine their associations with mental health and non-communicable disease risk factors, and evaluate a culturally adapted school-based intervention integrating trauma-informed care and social-emotional learning. Methods A sequential mixed-methods study will be conducted among approximately 1,632 adolescents in 16 public and private schools in Chandigarh and Mohali, India. Phase I is a cross-sectional survey of adverse childhood experiences, mental health, perceived stress, sleep, screen time and behavioural and biological risk factors for non-communicable diseases. Phase II comprises focus group discussions and key informant interviews with students, parents, teachers, counsellors and mental health professionals to inform intervention development. In Phase III, findings from both phases will guide development of the intervention using the ADDIE (Analysis, Design, Development, Implementation and Evaluation) instructional design framework. In Phase IV, adolescents reporting ACE exposure will participate in a school-based intervention delivered over 8-12 weeks by trained psychologists, comprising trauma-informed social-emotional learning sessions, individual counselling sessions for high-risk adolescents (at least six sessions), school-wide awareness activities and parental sensitization. Effectiveness will be evaluated using a quasi-experimental pre-post design. The primary outcome will be change in emotional and behavioural difficulties measured by the Strengths and Difficulties Questionnaire (SDQ). Secondary outcomes will include changes in depressive symptoms (Patient Health Questionnaire-9), perceived stress, sleep quality, school functioning, and behavioural risk factors for NCDs. Recruitment began in April 2026 and is ongoing; data collection is expected to be complete by June 2028, and no results have yet been generated.

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Heating On Transport WitH prEtErm and Low birth weight infants using servocontrol thermoregulation (HOTWHEELS): study protocol for a randomised controlled trial.

Chaudhary, V.; Watson, T.; Lee, M.; Ilagan, N.; Hodgson, G.; Wilson, A.; Batta, V.; Gardiner, J.; Cooper, M.; Davis, J. W.

2026-09-30 pediatrics 10.64898/2026.09.29.26364248 medRxiv
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Background Temperature instability during neonatal transport contributes to adverse outcomes in preterm and low birth weight infants. Hypothermia in this population is associated with increased risk of intraventricular haemorrhage (IVH), sepsis, and death. Current transport temperature management is reactive and manually controlled. The Heating On Transport WitH prEtErm and Low birth weight neonates using Servocontrol patient temperature management system (HOTWHEELS) trial aims to determine whether automated, servo-controlled thermoregulation provides superior thermal stability compared to standard care and reduces hypothermia-associated adverse outcomes. Methods This prospective, randomised, superiority trial is conducted by the Newborn Emergency Transport Service of Western Australia. Infants with a gestational age of less than or equal to 34 weeks and/or weight of 1500 g requiring transport are randomised to serve-controlled or standard thermal care. The primary outcome is the proportion of infants with a temperature between 36.5 and 37.5 degrees Celsius on arrival at the receiving neonatal unit. Secondary outcomes include the incidence of IVH in the first 7 days, mortality before discharge, the incidence of moderate (<36.0) and severe (<35.0) hypothermia for greater than 15 minutes and the temperature change during transport. Trial registration: ANZCTR12624000503527. Impact HOTWHEELS is the first randomised trial in neonatal transport to evaluate servo-controlled temperature control. We believe the findings will inform standards of temperature control during transport for preterm and low birth weight infants.

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Prognosis after a new episode of musculoskeletal pain in children and young people, 2005-21: population-based study

Mason, K. J.; Jordan, K. P.; Thomas, M. J.; Bailey, J.; Mughal, F.; Protheroe, J.; Jowett, S.; Saxne Jöud, A.; Snell, K. I.; Dunn, K. M.

2026-10-16 pediatrics 10.64898/2026.10.15.26365290 medRxiv
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Objective: to estimate reconsultation risk and trajectories after a new episode of musculoskeletal pain in children and young people (CYP), and to determine routinely recorded prognostic factors associated with reconsultation. Design: Population based retrospective cohort study. Setting: Clinical Practice Research Datalink (CPRD) Aurum, 2005-2021. Participants: CYP aged 8-18 years consulting primary care for a new musculoskeletal pain episode (no musculoskeletal consultation in prior 12-months). Main Outcome Measures: Musculoskeletal pain reconsultation within 12-months, and 3-year musculoskeletal reconsultation trajectories derived using latent class growth analysis. Prognostic factors selected from a literature search and two-year symptom histories (sample prevalence >1%) were examined using regression models (conditional logistic; multinomial). Results: Among 313,830 CYP with >12 months' follow-up, 32% reconsulted for musculoskeletal pain within 12 months. Among 240,384 CYP with >3 years' follow-up, three trajectories were observed: single episode (62%), early reconsultation (18%), and persistent reconsultation (20%). Older age; female gender; hip, knee, multisite and back pain on index; previous headache; previous abdominal pain; and analgesic prescribing were associated with higher reconsultation risk. Asian or Black ethnicity, and residing in more deprived areas, were associated with lower recorded reconsultation. Conclusion: Most CYP had no further recorded consultation, but 38% followed early or persistent reconsultation trajectories. Routinely recorded prognostic factors, particularly index pain side and prior pain/symptom history, may differentiate groups who could benefit from proactive follow-up. Lower recorded reconsultation among Asian and Black individuals, and living in more deprived areas, should not imply lower need and warrants equity-sensitive monitoring of access, health-seeking, and coding.

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Adiposity and the Prevalence, Incidence and Distribution of Refractive Errors in Urban Vietnamese Children

Ho, N. T.; Tran, K. P. M.

2026-09-23 pediatrics 10.64898/2026.09.17.26363286 medRxiv
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PurposeTo examine the association between BMI-for-age z-score (BAZ) and BMI status with refractive error prevalence, incidence, subtypes, and quantitative refraction in Vietnamese schoolchildren. MethodsWe retrospectively analyzed body mass index and refractive error data from annual school health checks in three Vietnamese cities, 2022 to 2024. The main analysis set was restricted to children age 6 and older (49,415 examinations, 31,522 children). Refractive error subtypes and quantitative refraction came from a Hanoi autorefractor sub-cohort (13,059 examinations). We used sex-stratified Poisson models with generalized estimating equations, adjusted for age, city, and year, plus linear mixed models for quantitative outcomes. ResultsAny refractive error followed a U shaped curve across BAZ in both sexes, significant in girls (prevalence ratio 1.01 per 1-SD BAZ, p = 0.027) but not boys (p = 0.099). Obesity was associated with higher any refractive error prevalence in girls (adjusted prevalence ratio 1.05, p = 0.017). Astigmatism was associated with BAZ in both sexes (p < 0.001), anisometropia in boys only (p < 0.001), with no association for myopia or hyperopia. Spherical equivalent shifted slightly toward hyperopia, not myopia, with higher BAZ. A supplementary check over 1 to 2 years found no evidence that prior BAZ predicted new refractive error onset (prevalence ratio 1.02, p > 0.6 in both sexes), and the nonlinear pattern did not reappear. ConclusionsAdiposity relates cross-sectionally to refractive error in a nonlinear, sex specific way concentrated in astigmatism and anisometropia rather than myopia, though this did not hold up short term.

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Socioeconomic position and cardiometabolic risk factors in children and adolescents with obesity: findings from the Bern Obesity in Childhood and Adolescence Biorepository (BOCAB)

Koch, A.; Giachino, C.; Agbaje, A. O.; Juonala, M.; Magnussen, C. G.; Burgner, D. P.; Longmore, D. K.; Leuenberger, L. M.; Kuehni, C. E.; Tschumi, S.; Kopp, M. V.; Janner, M.; Saner, C.

2026-09-27 pediatrics 10.64898/2026.09.24.26362616 medRxiv
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Purpose: In high-income countries, lower socioeconomic position (SEP) is linked to higher childhood obesity prevalence but its association with cardiometabolic risk in those presenting in pediatric weight management services remain underexplored. Methods: In the Bern Obesity in Childhood and Adolescence Biorepository (BOCAB), we used the Swiss neighborhood index of SEP (0-100, 100=highest SEP) to assess cross-sectional associations with obesity severity and cardiometabolic risk factors, mediation by behavioral lifestyle factors and longitudinal associations between SEP and percentage of the 95th BMI percentile (%BMIp95) and waist circumference-to-height ratio (WHtR), adjusted for age and sex. Results: Among 886 participants (52% male, mean age 11.2 years [SD 3.1]), mean %BMIp95 was 124% (SD 17%). A 10-unit higher SEP was associated with lower %BMIp95 ({beta} -2.57; 95% CI -3.84 to -1.31) and lower WHtR ({beta} -0.006; -0.010 to -0.001), both partially mediated by weekly physical activity and screen time. Higher SEP was also associated with lower odds of insulin resistance (OR 0.80; 0.65 to 0.98), low HDL-cholesterol (OR 0.81; 0.67 to 0.98), elevated non-HDL-cholesterol (OR 0.74; 0.59 to 0.92) and elevated triglycerides (OR 0.83; 0.70 to 0.98). Among 419 participants with longitudinal data, annual reduction in %BMIp95 and WHtR did not differ by SEP. Conclusion: Lower SEP is associated with greater obesity severity and cardiometabolic risk among children and adolescents with obesity presenting at specialized tertiary care. Screening and early referral of lower-SEP children and adolescents with obesity should be encouraged, before cardiometabolic risk accumulates, particularly since treatment response did not differ once enrolled.

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Vitamin D Supplementation For The Prevention Of Respiratory Infections In Childhood: A Systematic Review And Meta-Analysis

Sousa, H. K. P.; Siqueira, T. d. S.; Oliveira, M. A. M. d. C.; Carvalho, E. R. B. d.; Cavalcante, A. J. H.; Silva, J. B. T. d.; Viana, P. L. V.; Fidencio, G. S.; Costa, V. C. S.; Arnaud, L. M. L. B.; Matos, A. P. V.; Barbosa, J. M. R.

2026-10-13 pediatrics 10.64898/2026.10.11.26365254 medRxiv
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Background: Vitamin D modulates innate and adaptive immunity and has been investigated for preventing pediatric respiratory infections. Objective: To assess the effects of vitamin D supplementation on respiratory tract infections (RTIs), including upper RTIs, lower RTIs/recurrent pneumonia, and hospitalization/clinical severity in children and adolescents. Methods: Systematic review and random-effects meta-analysis of 16 publications, of which 13 contributed to quantitative synthesis. Twenty-four effect estimates were pooled, eight per outcome. The odds ratio (OR) was analyzed on its natural logarithmic scale (logOR), using restricted maximum likelihood (REML) estimation and Knapp-Hartung (KH) adjusted inference. Where necessary, risk ratios (RRs), hazard ratios (HRs), and incidence rate ratios (IRRs) were approximated on the logOR scale. Results: For respiratory infection/upper RTI, pooled logOR was -0.284 (KH-adjusted 95% confidence interval [CI]: -0.678 to 0.110; OR 0.753; p = 0.132; I2 = 97.2%). For lower RTI/recurrent pneumonia, logOR was -0.445 (95% CI: -0.987 to 0.097; OR 0.641; p = 0.093; I2 = 89.5%). For hospitalization/clinical severity, logOR was -0.609 (95% CI: -1.134 to -0.083; OR 0.544; p = 0.029; I2 = 78.3%). Conclusions: Pooled estimates favored supplementation in direction for all three groups, although confidence intervals included the null for the first two. Heterogeneity was substantial, and the results are limited by approximations among effect measures, clinically diverse endpoints, and potentially correlated effects from individual studies.

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Maternal Vitamin B12 Deficiency And Perinatal And Child Neurodevelopmental Outcomes: A Systematic Review And Meta-Analysis

Carvalho, E. R. B. d.; Sousa, H. K. P.; Siqueira, T. d. S.; Queiroz, R. R. d.; Silva, J. B. T. d.; Cavalcante, A. J. H.; Viana, P. L. V.; Magalhaes, M. E. A.; Fidencio, G. S.; Carvalho, A. R. B. d.

2026-10-09 pediatrics 10.64898/2026.10.07.26364974 medRxiv
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Background: Vitamin B12 is essential for one-carbon metabolism, deoxyribonucleic acid (DNA) synthesis, and myelination, and inadequate maternal status during pregnancy may influence fetal growth and child neurodevelopment. Objective: To evaluate the association between maternal vitamin B12 status and perinatal and child neurodevelopmental outcomes. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized clinical trials. The main outcomes were preterm birth, low birth weight, small for gestational age (SGA), and cognitive/global development. For binary outcomes, the natural logarithm of the relative risk (logRR) was the primary analytical effect measure; for neurodevelopment, Hedges g was used. Random-effects models were fitted, between-study variance was estimated by restricted maximum likelihood (REML), and inference used Knapp-Hartung (KH) adjustment. Results: For preterm birth, nine estimates yielded a pooled logRR of 0.190 (95% confidence interval [95% CI] KH: -0.046 to 0.427; p = 0.101; I2 = 19.2%). For low birth weight, nine estimates yielded a pooled logRR of 0.136 (95% CI KH: -0.013 to 0.286; p = 0.069; I2 = 4.8%). For SGA, six estimates yielded a pooled logRR of 0.047 (95% CI KH: -0.083 to 0.177; p = 0.397; I2 = 0%). Cognitive/global development, assessed in five independent studies, showed a pooled Hedges g of 0.266 (95% CI KH: 0.034 to 0.499; p = 0.034; I2 = 55.7%). Conclusions: logRR estimates for preterm birth and low birth weight were directionally compatible with higher risk among mothers with lower vitamin B12 availability, but their 95% CIs included the null. No consistent association was observed for SGA. Higher maternal vitamin B12 availability or supplementation was associated with a small favorable effect on cognitive/global development, with moderate heterogeneity.

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Evaluation of linkage between health, education and social care administrative data for 21 million children in England

Nguyen, V. G.; Lam, J.; Stone, T.; Blackburn, R.; Gilbert, R.; Ruiz Nishiki, M.; Harron, K.

2026-09-22 health informatics 10.64898/2026.09.16.26363127 medRxiv
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Background Population-level administrative data cohorts hold huge potential for generating evidence to improve child health. Understanding the quality of these data is critical to enabling us to fully realise this potential. We aimed to evaluate linkage between children's health, education and social care administrative records (ECHILD) to identify possible sources of bias. Methods We created four cohorts to understand the drivers of inclusion/exclusion within ECHILD. For each cohort, we calculated the linkage rate by counting the total number of eligible individuals who appeared in the ECHILD linkage spine and any of the corresponding hospital/school component datasets. We then assessed whether linkage rates varied according to sociodemographic characteristics (year of birth, sex, ethnicity, region). Results ECHILD currently captures 34.2 million patients and 25.3 million pupils born between September 1984 and March 2023, aged 0-38 years. Over 90% of children with hospital birth records linked to a school record (rising to 93% for those born from 2014 onwards); 88% of children attending school in 2001/02 linked to a patient record (rising to 96% for those born in 2019/20), resulting in a total of 21 million linked individuals. Substantial variation existed between sociodemographic groups, with those living in London, residing in more deprived areas, or with recorded ethnicity other than White being less likely to be included. Conclusions Population-level datasets such as ECHILD often under-represent specific groups. Irrespective of the mechanisms by which individuals are excluded (e.g. opt outs, linkage errors or not interacting with services), those in minoritised ethnic groups and those living in more deprived areas are most affected. Linkage evaluations are critical for understanding who is and who is not included in analyses of these data so that researchers can account for potential sources of bias within analyses.

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Long term Follow-up of the TREOCAPA (Prophylactic TREatment Of the duCtus Arteriosus in Preterm infants by Acetaminophen) Study (TREOCAPA-LT): protocol and statistical analysis plan

Morgan, A. S.; Roze, J.-C.; Ursino, M.; Alberti, C.; Desplebin, V.; Durox, M.; Hankard, R.; Hamrit, M.; Johnson, S. J.; Kemper, R.; Marcon, Y.; Michel, M.; Zeitlin, J.; Cambonie, G.

2026-10-05 pediatrics 10.64898/2026.09.30.26364424 medRxiv
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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

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The cry as a vital sign: A smartphone based study protocol of neonatal cry acoustics in hypoxic ischemic encephalopathy

Chakraborty, D.

2026-10-14 pediatrics 10.64898/2026.10.12.26365334 medRxiv
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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.

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Associations between prenatal (poly)phenol intake and cognitive outcomes in school-age children

Fiecke, C.; Bellando, J.; Whiteside, M.; Slaton, C.; Bimali, M.; Bao, M.; Williams, D. K.; van der Plas, E.; Kay, C. D.; Andres, A.

2026-10-11 pediatrics 10.64898/2026.10.08.26365020 medRxiv
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Background: (Poly)phenol intake is associated with improved cognitive function in adults, with emerging evidence suggesting benefits in children. However, the role of prenatal (poly)phenol exposures in cognitive development remains a gap in early-life nutrition research. Objective: This analysis of a longitudinal cohort tested the associations between prenatal (poly)phenol intakes and cognitive outcomes in school-age children at age 5 and 8 years. Methods: Participants included mother-child pairs enrolled in a prospective, longitudinal study during pregnancy and completed 5- and 8-year follow-up visits (N = 129). 3-day food records were used to estimate prenatal and child intakes of energy and 18 (poly)phenol subclasses using a database developed from Phenol-Explorer (v3.6). The analytical sample included children (N = 111) with completed assessments for academic achievement, language skills, and intelligence quotient (IQ) scores (Mean = 100, SD = 15). Regression models estimated associations between (poly)phenol intakes and cognitive outcomes, adjusted for breastfeeding duration, maternal IQ, pre-pregnancy BMI, gestational age, and infant sex. Results: Average prenatal total (poly)phenol intake was 716 mg/d. Prenatal (poly)phenol intakes were not associated with child academic achievement scores. Higher prenatal flavone intakes were associated with higher language ({beta}: 4.36, p = 0.045) and IQ ({beta}: 9.43, p = 0.002) scores. Higher flavonol ({beta}: -4.67, p = 0.022) or hydroxybenzoic acid intakes ({beta}: -3.88, p = 0.026) were associated with lower language scores. Major sources of flavones and lignans included coffee, orange juice, and herbal tea. Coffee, cranberry, black tea, okra, and tomato sauce provided flavonols and hydroxybenzoic acids. Conclusions: Associations between prenatal (poly)phenol intake and child cognitive outcomes were mixed and differed by subclass. Further investigation is needed to explore the role of co-occurring nutrients and other dietary components. These findings suggest that (poly)phenol subclasses derived from healthier plant-based foods, including citrus fruit and herbal tea, may associate with improved child cognitive outcomes.

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Conditional Growth References for Vietnamese Children: Quantile Regression of Growth Distributions and Phenotypes

Ho, N. T.

2026-09-24 pediatrics 10.64898/2026.09.23.26363771 medRxiv
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Background and objective. The WHO growth reference judges a child's height against the population at one age, without using the child's own earlier growth. This study built and validated a quantile regression based conditional growth reference predicting a child's future height for age distribution from early growth status. Methods. Using deidentified longitudinal annual school children health check data from three major cities in Vietnam, this study linked a baseline height and BMI for age Z score near age 6 to outcome visits near age 12 or 15 in 4,857 children. A linear quantile regression and a pooled quantile generalized additive model, fit by sex, were compared against a linear benchmark and a naive persistence model on a held out test set, using pinball loss, interval coverage, and width against the WHO 90% band. This study also tested adding growth phenotype and checked generalization across the three cities. Results. The pooled model outperformed the discrete quantile regression in every group. Every individualized 90% interval was narrower than the WHO band, by 34.6 to 54.5%. Growth phenotype improved accuracy in most groups. The model generalized well to a held out Hanoi or Haiphong but poorly to a held out Ho Chi Minh City, where coverage fell to between 0.35 and 0.52, though the all-city model stayed well calibrated for Ho Chi Minh City itself. Conclusion. Conditional quantile modeling gives individualized growth predictions markedly narrower than a fixed population reference and gains further from growth phenotype, but needs local validation before use at an unrepresented site.

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Antimicrobial Resistance Patterns Of Bacterial Isolates From Neonates With Sepsis At Livingstone University Teaching Hospital, Zambia

Siaciti, L.; Siacit, M.; SIMUTANDA, C.; Tembo, N. N.

2026-09-29 pediatrics 10.64898/2026.09.27.26364139 medRxiv
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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.

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Parental Health Information Needs, Child-Health Literacy, and Use of Generative AI Among Parents of Children Aged 0 to 4 Years in France: A Cross-Sectional Study

Gavaland, K.; Barascud, N.; Edstedt Bonamy, A.-K.; Martinot, P.

2026-10-21 health informatics 10.64898/2026.10.20.26365983 medRxiv
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Background: The first thousand days are a sensitive window for child health and social health inequalities. When routine care falls short, parents of young children turn to online sources and, recently, to generative artificial intelligence (AI). Evidence on their concerns, child-health literacy, and AI use is scarce. Objective: To describe health informational needs and concerns, child-health literacy, and use of AI for child-health questions, including differences by parental role and parity, among parents of young children. Methods: In this cross-sectional study, two anonymous self-administered online questionnaires were disseminated through a digital health application between May 12 and June 11, 2026, to French-speaking parents of at least one child aged 0 to 47 months in France. Questionnaire 1 covered unmet information needs, concerns across 16 topics, perceived intra-couple concordance, and confidence in routine care. Questionnaire 2 covered a four-item child-health literacy quiz and AI use (frequency, topics, 12-month trend, barriers, trust conditions, perceived effect on consultations, and disclosure). Results: In total, 12,634 parents responded (Questionnaire 1, n=5,410; Questionnaire 2, n=7,224), mostly mothers (94.6% and 92.9%). Most (61.8%) had searched for information without finding a clear, reliable answer, selecting a median of 4 (Interquartile range [IQR] 3-7) over 16 topics. Leading concerns were sleep (51.3%), nutrition (48.1%), and education (i.e., upbringing and behavior) (47.8%). Mothers were nearly twice as likely as fathers to select accident prevention (26.5% vs 16.3%) and parental mental health (38.7% vs 28.6%); first-time parents selected most topics more often than experienced parents, most markedly dental hygiene (43.8% vs 27.6%). The median child-health literacy score was 3 (IQR 3-4) on a 0-to-4 quiz, with 19.9% of parents scoring 2 or below; tooth-brushing age was the weakest item (68.4% correct). Mothers outscored fathers on every item. More than half of parents (54.2%) had used AI for a child-health question, 11.2% weekly; among those reporting a trend, 68.3% had increased AI use for child-health questions over the year and 6.2% decreased it. The main barriers to AI use were a preference for professionals (55.9%) and reliability concerns (48.7%); trust depended most on medical oversight of the tool (76.6%). AI use appeared additive, with 66.8% reporting no change in healthcare visit frequency. One third (35.5%) had told an AI something shared with neither a professional nor their network, rising to 64.1% among regular users. Conclusions: Parental informational needs were widespread and frequently unmet. AI has become a common and fast-rising source for child-health questions, at times a confidential one, used alongside rather than instead of professionals. Child-health literacy was generally high but uneven, with oral health the clearest gap. Strengths include the sample size and early-generative-AI timing; limitations include the cross-sectional design, self-report, digital-recruitment selection bias, and the small proportion of fathers.

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Factors Associated with Predischarge Morbidity and Mortality in Small for Gestational Age Infants: A Single-Center Retrospective Cohort Study

Cinkus-Rios, C.; Pickell, S.; Thompson, C.; Bomback, M.; Lyford, A.; Hays, T.

2026-10-09 pediatrics 10.64898/2026.10.07.26364995 medRxiv
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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.

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A Synbiotic Infant Formula Promotes Balanced Immune-Microbiome Interactions in Term Infants: A Randomized Controlled Trial

Chen, Q.; Chung, C. K.; Capeding, M. R. Z.; Trinidad-Aseron, M.; Tenorio-Quinones, V. M. R.; Barcenilla, H.; Gonzalez, L.; Johnsson, A.; Darwish, N.; Li, H.; Rasmussen, J. A.; Moll, J. M.; Stauch, W.; Schwenk, J.; Lakshmikanth, T.; Sprenger, N.; Hays, N. P.; Noti, M.; Brodin, P.

2026-10-07 pediatrics 10.64898/2026.10.05.26364773 medRxiv
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Formula-fed infants have altered gut microbiota and immune development relative to breastfed infants. Human milk oligosaccharides (HMOs) and microbes able to ferment these, like Bifidobacterium infantis, promote healthy immune-microbiome interactions in breastfed infants. In this randomized trial, 240 healthy term infants in the Philippines received a synbiotic blend formula (SynF; seven HMOs, bovine milk oligosaccharides, and B. infantis LMG11588) or control formula (CtrlF) for 6 months. SynF supported growth non-inferior to CtrlF and near universal B. infantis colonization (vs <10% in CtrlF). Markers of intestinal inflammation were lower in children fed SynF while secretory IgA was higher. SynF fed infants showed lower markers of systemic inflammation in plasma, slower immune cell maturation, and fewer upper respiratory tract infections (URTI) during their first 6 months of life. These findings suggest that synbiotic formula can dampen inflammatory responses to colonizing microbes and mild infections in fully formula-fed, term infants. Trial registration: NCT06073652.

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A comparison of mortality for neonates aged 35 versus 36 weeks gestational age with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia in the National Inpatient Sample.

Khan, J. Y.; Groh, J. M.; Dookeran, K. A.

2026-10-21 pediatrics 10.64898/2026.10.19.26365848 medRxiv
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Objectives: Using a nationally representative database of U.S. hospitalizations, we aimed to (1) characterize contemporary trends in hypoxic-ischemic encephalopathy (HIE) prevalence by severity, therapeutic hypothermia (TH) utilization, and associated in-hospital mortality; and (2) examine the association between TH and mortality by HIE severity and gestational age (GA), focusing on 35- and 36-weeks GA. Methods: We analyzed newborn hospitalizations from the National Inpatient Sample, 2016-2023. Unspecified, mild, moderate, and severe HIE were identified using ICD-10-CM diagnosis codes P91.60-P91.63; and 35- and 36-weeks GA using codes P07.38-P07.39. TH was identified using ICD-10-PCS codes 6A4Z0ZZ and 6A4Z1ZZ. Survey-weighted multivariable generalized linear models with marginal standardization were used to estimate adjusted mortality risk differences (RD) with surprisal (S) values, and assess whether associations between TH and mortality differed by HIE severity across GA strata. Results: Among 29,767,238 hospital discharges, HIE was identified in 66,535 neonates (2.24 per 1,000), and TH used in 19.2% of HIE cases. In-hospital mortality was 9.74% among all HIE cases and 6.65% among TH-treated neonates. From 2016-23, HIE prevalence nearly doubled (1.58 to 3.01 per 1,000; p-for-trend <0.001) and TH utilization more than doubled (0.33 to 0.74 per 1,000; p-for-trend <0.001), while TH use as a proportion of HIE remained stable (17.8%-20.8%; p-for-trend=0.39). HIE severity distribution was: mild (15%), moderate (29.4%), severe (18.3%), and unspecified (37.3%), with moderate HIE increasing over time (22.3%-33.5%). Crude mortality was consistently highest for severe HIE (range: 33.65%-35.25%). Among infants with severe HIE, TH was associated with reduced mortality overall (RD -10.12%; 95% CI -14.86, -5.39; p<0.001; S=15.12), and specifically at 36-weeks GA (RD -21.98%; 95% CI -35.85, -8.12; p=0.002; S=9.06), but not at 35-weeks (RD -1.83%; 95% CI -21.2, 17.55; p=0.86; S=0.22). Conclusions: TH was associated with mortality reduction in severe HIE overall and at 36-weeks GA, but this benefit remains uncertain at 35-weeks GA.

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Efficacy of Repeated-Dose Albendazole/ Mebendazole Regimens for Soil-Transmitted Helminth Infections in Paediatric Population: A Systematic Review and Meta-Analysis

Singh, N.; Sahu, P.; Singh, V.; Bharti, P. P.; Siddiqui, A. M.; Kumar, A.

2026-10-12 pediatrics 10.64898/2026.10.09.26365109 medRxiv
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Background: Preventive chemotherapy via single-dose benzimidazoles remains the core strategy for soil-transmitted helminth (STH) control. However, single-dose regimens often yield sub-optimal clearance against species such as Trichuris trichiura and hookworm. This systematic review and meta-analysis evaluated the comparative efficacy of repeated-dose versus standard single-dose albendazole or mebendazole regimens in paediatric populations. Methods: Registered prospectively on PROSPERO (CRD420261491616), a comprehensive search of PubMed, Embase, Cochrane Library, and Google Scholar identified clinical trials comparing repeated-dose against single-dose albendazole or mebendazole in paediatric STH infections. Primary outcomes were cure rate (CR) and egg reduction rate (ERR). Random-effects models synthesized pooled odds ratios (OR) and mean differences (MD). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Five randomized clinical trials (N = 1,718 participants) met the inclusion criteria. Overall, repeated dosing demonstrated significant superiority in cure rate (pooled OR = 4.47, 95% CI: 1.58-12.67; I{superscript 2} = 92%) and egg reduction rate (pooled MD = 0.17, 95% CI: 0.01-0.32; I{superscript 2} = 87%). Discussion: Repeated-dose benzimidazole regimens offer superior overall therapeutic efficacy compared to standard single-dose administration in children. However, this therapeutic advantage is drug-specific: multi-dose albendazole consistently enhances parasite clearance across trial settings, whereas multi-dose mebendazole exhibits variable performance and lacks conclusive superiority over single dosing. Conclusion: Transitioning to targeted, multi-dose albendazole protocols--rather than mebendazole--may serve as an effective public health intervention to eliminate residual parasite reservoirs in high-transmission endemic regions.

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Environmental exposures associated with behavioral outcomes and their link to endogenous metabolites in children born very preterm

Patel, P.; Tan, Y.; Liang, D.; Camerota, M.; Marsit, C.; Lester, B. M.; Everson, T.

2026-10-01 pediatrics 10.64898/2026.09.25.26364017 medRxiv
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Abstract: Background: Children born very preterm (VPT) are at elevated risk for adverse neurobehavioral outcomes and are vulnerable to environmental exposures. We used untargeted metabolomics analysis to identify environmentally relevant metabolites associated with childhood behavioral problems and to characterize related endogenous metabolic pathways. Methods: We studied 226 children born <30 weeks gestation in a multi-site cohort study. Urine collected at age 4 was profiled using untargeted ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Associations between 30 exogenous environmental metabolites and behavioral problems score at age 4 were evaluated cross-sectionally using multivariable linear regression, followed by metabolome-wide association and pathway enrichment analyses. Results: Three exogenous metabolites were nominally associated with child behavior problems. Specifically, 2-(Acetylamino)-3-( henylthiol)propanoic acid was positively associated with overall ({beta}=1.42, p=0.006), externalizing ({beta}=1.50, p=0.006), and internalizing ({beta}=1.34, p=0.021) behavior problems. Diethofencarb was positively associated with overall ({beta}=0.34, p=0.018) and externalizing ({beta}=0.39, p=0.010) behavior problems, while protocatechuic acid was inversely associated with internalizing problems ({beta}=-0.68, p=0.027). No associations remained significant after false discovery rate (FDR) correction. Nevertheless, these metabolites were associated with 151, 131, and 530 endogenous metabolic features, respectively, at FDR<0.05, highlighting perturbations in lipid metabolism, mitochondrial energetics, inflammatory signaling, amino acid metabolism, and neuroactive pathways. Conclusions: Environmental metabolites associated with behavior problems were linked to broad endogenous metabolic differences relevant to neurodevelopment. These findings highlight potentially modifiable environmental influences, including exposures related to combustion-derived pollutants, pesticides, and dietary sources, that may contribute to behavioral vulnerability among children born very preterm