Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 61 appraisals
Seminars in fetal & neonatal medicine
Intraventricular hemorrhage in preterm infants: A systematic review of risk- and outcome-prediction models
Intraventricular hemorrhage (IVH) is a major complication of prematurity and one of the top causes of mortality and neurodevelopmental impairment. We conducted a systematic review of PubMed, Scopus, and Web of Science (From 1980 to 2025), identifying 40 studies evaluating prediction models (regression and machine learning) for risk of IVH occurrence and short- and long-term outcomes in preterm infants with IVH. Across these published studies, IVH risk prediction models included combinations of perinatal clinical variables, physiologic and hemodynamic indices, and serum biomarkers. Outcome-prediction models likewise varied. IVH grade was commonly included, with varying inclusion of comorbidities and neuroimaging-based injury markers. Most models performed acceptably, with machine-learning models showing better discrimination in larger datasets. However, the generalizability of the models is limited by heterogeneity in predictors, limited sample sizes, and inconsistent timing of predictor measurements. IVH severity remained the most consistent predictor across all outcome-prediction models. Despite promising performance assessments, clinical relevance is limited due to the infrequent reporting of model calibration, internal validation, and external validation. Future research that standardizes predictor definitions, leverages multicenter cohorts, and ensures thorough validation can advance early IVH risk and outcome-prediction models, thereby meaningfully improving clinical relevance and neonatal care.
2 Aug 2026
Read appraisal →Indian journal of pediatrics
Emerging Applications of Artificial Intelligence in Pediatric Care
Artificial intelligence (AI) technologies such as machine learning (ML), deep learning (DL), predictive analytics and other tools are rapidly changing pediatric health care, using large amounts of health data. AI tools aid in triage, real-time monitoring and risk stratification in acute care settings, towards improving overall outcomes and fewer complications. During newborn resuscitation, AI analyses real-time data, can guide decisions and enhance training. Computer vision systems with AI tools can generate reliable neonatal bilirubin estimates without the need for blood sampling. AI technology is also being used in the management of necrotising enterocolitis, respiratory distress syndrome, and screening and early diagnosis of retinopathy of prematurity. ML models assist in detecting brain injuries on MRI for conditions such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage; MRI biomarkers can be analyzed using AI to predict neurodevelopmental outcomes. AI-based clinical decision support systems have been deployed to enhance workflows and outcomes by early detection of disease, reducing medication errors and help clinicians improve decision-making. However, there remain ethical and practical challenges in the use of AI including data privacy, the need for high-quality pediatric datasets, rigorous clinical validation and transparency, to ensure that AI strengthens clinical judgement and is trustworthy.
2 Aug 2026
Read appraisal →JAMA
Prone Positioning in Infants With Acute Bronchiolitis: The PROPOSITIS Randomized Clinical Trial
IMPORTANCE: Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. OBJECTIVE: To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). INTERVENTIONS: Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. MAIN OUTCOMES AND MEASURES: The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. RESULTS: Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. CONCLUSIONS AND RELEVANCE: Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03976895.
30 July 2026
Read appraisal →Pediatric surgery international
ARM in ARM? Investigating the co-occurrence of anorectal malformations and labioscrotal anomalies.
Anorectal malformations (ARMs) are known to be associated with other defects, however there is no evidence addressing the co-occurrence of ARMs with anomalies of structures derived from the labioscrotal folds. We performed a systematic review (Prospero: CRD420251013945) aiming at investigating correlations and patterns between ARMs and labioscrotal anomalies (LSAs), when presenting simultaneously. Our search identified 1642 articles. After abstract screening, 344 full texts were assessed and 144 met the inclusion criteria. In total, these reported on 319 individual cases with both ARM and LSA. Individuals with complex ARMs had proportionally the most LSAs associated with their ARM - 58.4% of these were associated with only a single LSA. For 'high' and 'low' ARMs, 66.0% and 77.0% of cases were associated with a single LSA respectively. As data reporting prevalence of each type of ARM lacks information about LSAs, the potential to predict the presence of LSAs according to type of ARM is limited. Nevertheless, this review demonstrates a frequent association of ARMs with LSAs, that has not been previously described. This evidence highlights the importance of early screening and timely management of LSAs in patients with any type of ARM, with close collaboration between paediatric surgeons, urologists and other clinicians.
20 July 2026
Read appraisal →Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Genetics versus environment in the pathophysiology of sagittal synostosis
PURPOSE: This systematic review aims to provide an updated overview of the relative contribution of germline genetic and environmental factors to the pathophysiology of sagittal craniosynostosis (sCS). METHODS: Using the PubMed database in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, relevant studies addressing genetic and/or environmental determinants of sCS in paediatric patients were systematically reviewed. RESULTS: A total of 1238 records were identified, of which 97 studies met inclusion criteria after full-text review. Overall, 25,877 patients were included, with 11,086 diagnosed with sCS (42.8%). Germline genetic variants potentially associated with craniosynostosis were reported in 251 patients, accounting for 12.6% of genetically tested individuals with sCS. Identified variants were distributed across 125 genes, with recurrent findings in 25 genes. Environmental and perinatal factors were more consistently reported across large population-based and case-control studies. Frequently associated factors included male sex, advanced maternal age, maternal smoking, thyroid dysfunction, fertility treatments, foetal constraint, prematurity, and abnormal birth weight, although effect sizes varied across studies. CONCLUSION: Identifiable germline genetic causes appear to account for only a minority of sCS cases, whereas epidemiological evidence suggests that environmental and perinatal influences may also contribute to disease pathogenesis. Nevertheless, most cases lack identifiable germline mutations in key signalling pathways, and the available evidence does not support either genetic or environmental factors as individually deterministic drivers of disease development. Overall, the evidence synthesized in this review supports a multifactorial model for sCS, in which rare genetic susceptibility and non-genetic influences likely interact in the etiopathogenesis of the condition rather than reflecting a single dominant aetiology. However, heterogeneity across studies, differences in genetic testing methodologies, potential bias in exposure assessment, and the limited availability of integrative analyses restrict definitive conclusions regarding the relative contribution of these factors.
19 July 2026
Read appraisal →Pediatric surgery international
Single-stage versus staged reconstruction for high and intermediate anorectal malformations in neonates: a systematic review and meta-analysis
The surgical approach to high and intermediate anorectal malformations remains controversial. This systematic review compared continence and infection outcomes between the two approaches. MEDLINE, Embase, and Cochrane CENTRAL were searched per a registered protocol (PROSPERO CRD420261291319). Comparative studies of single-stage versus staged repair in neonates with high or intermediate anorectal malformations were included. Risk of bias was assessed using ROBINS-I. Random-effects meta-analysis with prediction intervals was performed. Four comparative studies (746 patients: 399 single-stage, 347 staged) were included. Pooled analysis showed no significant difference in incontinence outcomes (RR 0.93, 95% CI: 0.52-1.66, p = 0.80; 95% prediction interval: 0.28-3.08) with substantial heterogeneity (I²=83%). Infection data could not be pooled due to methodological concerns in outcome reporting. All included studies demonstrated moderate to serious risk of bias. GRADE certainty was LOW for incontinence and VERY LOW for infection. Current evidence does not demonstrate superiority of either approach for bowel continence (LOW certainty). Infection evidence was insufficient for synthesis (VERY LOW). Wide prediction intervals indicate substantial uncertainty; available data cannot confirm or refute inferior outcomes after single-stage repair. Prospective studies with standardized outcomes are needed. Protocol registration: PROSPERO CRD420261291319.
17 July 2026
Read appraisal →European journal of pediatrics
Efficacy and safety of procedural sedation-analgesia during laser photocoagulation for retinopathy of prematurity: a systematic review
UNLABELLED: Laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants causes significant procedural pain. Although general anaesthesia (GA) is the standard of care, many settings frequently rely on inadequate sedation-analgesia or topical anaesthesia alone, exposing neonates to considerable pain and clinical instability. This systematic review aimed to evaluate the efficacy and safety of procedural sedation-analgesia during laser photocoagulation for ROP. We searched MEDLINE, Embase, and Cochrane CENTRAL for trials investigating sedation-analgesic agents during laser photocoagulation. Primary outcome was analgesic efficacy (pain score reduction, rescue analgesics required). Additional outcomes included adverse effects (e.g., apnea, oxygen requirement). Two reviewers extracted relevant information and assessed risk-of-bias using ROB2 and evidence certainty using GRADE methodology. Of 540 articles screened, four relevant RCTs were identified (n = 265). These RCTs compared varying combinations of agents (oral dextrose vs. no dextrose, fentanyl vs. oral sucrose, fentanyl vs. ketamine, ketamine-propofol vs. GA). Three RCTs evaluating pain-related outcomes (PIPP-R score and intra-procedural crying duration) suggested that the investigated non-general anaesthetic regimens may provide inadequate procedural analgesia (low to very low-certainty evidence). The evidence is very uncertain about the effect of ketamine-propofol on post-procedure ventilation requirement compared with general anaesthesia. Apnea was the commonest adverse effect (three studies), especially with high-dose fentanyl (30%). Three studies had a low risk-of-bias, while one had some concerns (randomisation, outcome measurement). CONCLUSION: Overall, the included studies were small RCTs evaluating varying combinations of interventions, precluding concrete conclusions about the superiority of any analgesic regimen during laser photocoagulation. Further high-quality studies are needed to identify safe and effective analgesia for settings where GA is unavailable. REVIEW REGISTRATION: Prospectively registered on PROSPERO (CRD420251070146). WHAT IS KNOWN: • Laser photocoagulation procedure for retinopathy of prematurity is immensely painful. • Despite general anaesthesia being the standard, most neonates undergo the procedure under inadequate analgesia, particularly in high-burden settings. Optimal analgesic regimen for the laser procedure, in settings where general anaesthesia is unavailable, is unknown. WHAT IS NEW: • This systematic review of trials investigating analgesic agents for laser procedure for ROP found four RCTs with significant heterogeneity in intervention agents. • Low- to very low-certainty evidence suggests that none of the evaluated sedo-analgesic regimens consistently achieved optimal analgesia, and most infants continued to experience moderate-to-severe procedural pain.
13 July 2026
Read appraisal →JMIR mHealth and uHealth
Safer Sleep Guidance in Standalone UK Smartphone Apps for Parents of Newborns and Infants: Systematic mHealth App Review
BACKGROUND: Parents are increasingly using smartphone apps to help guide decision-making around aspects of caregiving, including safer sleep. However, it remains unclear whether the guidance provided aligns with best practice guidelines. OBJECTIVE: This review aimed to identify smartphone apps that provide safer sleep guidance and to assess their content, technical features, functionality, and quality. A secondary aim was to make recommendations on the improvements that existing and future apps can make to provide safer sleep guidance. METHODS: In January 2026, we searched the UK Google Play Store and Apple App Store for safer sleep guidance apps for parents and caregivers of newborns and infants (babies aged ≤12 months). Information regarding content, technical features, and functional features was extracted and summarized descriptively. Each app was evaluated by 2 raters using the Mobile App Rating Scale (MARS) and the IMS Institute for Healthcare Informatics functionality score. Adherence to best practice sleep guidance was assessed using bespoke criteria. Interrater reliability was calculated. RESULTS: A total of 1345 apps were identified, with 12 meeting the inclusion criteria. All were free to download, with 42% (5/12) containing in-app purchases. Only 17% (2/12) were affiliated with a professional health, medical, clinical, or government body. All 12 apps contained some information regarding safer sleep practices, although this was addressed and named differently (eg, calling it cot death, sudden infant death syndrome, or safe sleep). Of the 9 criteria relating to safer sleep best practice guidance, the apps mentioned an average of 6.75 (SD 1.71; range 3-9) criteria. Some promoted unsafe sleep practices (ie, around swaddling and cosleeping). The apps included an average of 5.4 of the 11 IMS functionality criteria (SD 2.5; range 2-9). The mean MARS score was 3.7 out of 5 (SD 0.43; range 2.92-4.13), and most (11/12, 92%) had a minimum acceptability score of 3 or above. Two had been formally trialed or tested. Although the language used was considered accessible (easy to understand), none of the apps allowed the language to be changed (beyond English), and very few (3/12, 25%) enabled users to change to night/dark mode, which would be considered essential when using these apps at night. CONCLUSIONS: Several apps about safer baby sleep exist. Few discuss safer sleep guidance comprehensively or raise awareness about sudden infant death syndrome and its links with unsafe sleep. All the reviewed apps met the minimum acceptability criteria for quality; however, not many were formally trialed or tested. More long-term research should be conducted on the effectiveness of safer sleep apps on adherence to safer sleep guidance. We recommend that apps relating to infant and baby safety in general include information on realistic safer sleep practices that are informed by best practice guidelines and take a risk minimization approach.
11 July 2026
Read appraisal →Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners
Systematic Review of Studies Investigating Infant Feeding Difficulties: Focus on Machine Learning Applications
INTRODUCTION: This study aims to systematically review studies using machine learning for infant feeding difficulties and identify the clinical applicability and limitations of such approaches. METHODS: A literature search was conducted in accordance with the PRISMA guidelines. Studies on the use of machine learning for infants with feeding difficulties were analyzed. RESULTS: We screened 1,104 studies, and 10 were eligible for inclusion. These studies applied machine learning to measure physiological signals during feeding, such as the number of sucking, swallowing and breathing events, to classify or predict feeding difficulties. The most common algorithms in the analyzed studies included support vector machines (SVMs), k-nearest neighbors (KNNs), and decision trees (DTs), which generally achieved high classification accuracy. DISCUSSION: Although all included studies used sensor-based data, only four directly applied machine learning models. Future research should expand the direct applications of machine learning, standardize measurements, and validate algorithms to improve clinical utility.
2 July 2026
Read appraisal →Biomedical physics & engineering express
Transformer imputation in CTG: a length-dependent evaluation of reconstruction methods
Objective.Computer and artificial intelligence (AI) analyses are being increasingly used in intrapartum cardiotocography (CTG). However, fetal heart rate (FHR) signal loss, which frequently occurs in clinical practice, hinders visual interpretation and reduces accuracy. Although the impact is well recognized, there is no consensus on the maximum continuous gap length that can be reliably reconstructed under clinical conditions. Therefore, we aim to identify suitable imputation methods and clarify the clinical limits of valid missing-segment lengths.Methods.Using an open FHR dataset (CTU-UHB), we extracted continuous segments and artificially introduced Removed data of varying lengths. Using performance metrics such as difference and similarity, we compared the performance among a Transformer-based model and linear and spline interpolation. Additionally, we quantified the similarity between the Pre-impute and removed data to assess task difficulty.Results.We analyzed 2727 segments from 552 cases across multiple gap lengths. In terms of numerical accuracy root mean square error (RMSE), spline consistently performed significantly worse than others. The Transformer generally maintained a better mean accuracy than linear interpolation, although significant differences were observed only under specific conditions. Conversely, for waveform preservation (correlation), the Transformer consistently outperformed linear interpolation. Notably, in highly complex imputation tasks, the Transformer proved most robust, yielding the lowest RMSE and highest correlation. However, performance systematically degraded for all methods as gap lengths increased.Conclusion.The Transformer provides an effective baseline for FHR imputation under clinical conditions, achieving a favorable balance between waveform and numerical accuracy. By clarifying the clinical limits of valid missing-segment lengths-specifically the decline in reliability beyond 30 s-this study provides guidance for standardizing preprocessing in future CTG AI research and clinical implementation.Significance.For imputing intrapartum FHR data, the Transformer generally improves waveform reproducibility over linear interpolation for short-to-moderate gaps. Defining the reliability limit provides a crucial baseline for future CTG AI.
29 June 2026
Read appraisal →ACS sensors
Machine Learning-Enabled Gas Sensor Based on MOF-Derived In2O3-CuO for Exhaled CO Detection
Noninvasive, precise breath analysis holds significant importance for the screening and monitoring of neonatal jaundice, with its core challenge lying in the specific detection of the key biomarker carbon monoxide (CO) within complex breath matrices. This research employed a controlled process to fabricate five sets of In2O3-CuO sensors derived from bimetallic metal-organic frameworks (Bi MOFs). These were assembled into a microsensor array, and by incorporating a linear discriminant analysis algorithm, an electronic nose system was constructed. This approach utilizes thermodynamic feature engineering to enhance data validity and optimize algorithm selection, thereby reducing reliance on large-scale data and computational resources. By integrating thermodynamically feature-driven machine learning, the electronic nose system-comprising merely five In2O3-CuO sensors-ultimately achieved accurate discrimination between CO and acetone. Concurrently, the single 3In2O3-CuO sensor exhibits excellent reproducibility, moisture resistance, and stability, with a low detection limit of 1 ppm and relatively rapid response/recovery times (5/21 s). By introducing machine learning algorithms to analyze the multidimensional response signals from the sensor array, the study successfully addressed the cross-sensitivity issue between CO and coexisting interfering gas C3H6O in clinical environments, achieving qualitative identification of CO ranging from 1 to 50 ppm (cross-validation accuracy reached 82%), providing a highly reliable technical platform for noninvasive screening of neonatal bilirubin metabolic abnormalities.
29 June 2026
Read appraisal →European journal of pediatrics
Congenital cytomegalovirus screening by dried blood spot: a systematic review
UNLABELLED: Congenital human cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss and neurological sequelae in children. Although newborn screening strategies remain controversial, dried blood spots (DBS) collected for routine metabolic screening have been proposed as a low-cost method for large-scale detection. This systematic review assessed studies that evaluated the accuracy of DBS testing for screening newborns for cCMV infection. A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and reported in accordance with PRISMA-DTA. The PIRT strategy included the following: Population (newborns undergoing screening for cCMV), Index test (detection of cCMV using DBS samples), Reference standard (confirmatory testing using saliva or urine PCR collected within 21 days of life), Target condition (cCMV infection). Searches were performed in PubMed/MEDLINE, Scopus, Bireme, Embase, LILACS, SciELO, and CENTRAL. The search identified 365 articles; after removing 210 duplicates, 155 were screened by title and abstract, and 9 studies were included. The included studies tested between 1174 and 551,034 DBS samples each. Confirmatory testing used PCR in urine (seven studies) or saliva (two studies). Three studies used paired samples for screening; sensitivity ranged from 28.3% to 79.3%, specificity from 99.9% to 100%. Positive predictive value (PPV) ranged from 39 to 100%, and negative predictive value (NPV) from 99.6% to 99.9%. CONCLUSION: Neonatal screening for congenital cytomegalovirus using DBS samples is promising, since it would allow early identification for timely interventions to reduce sequelae. WHAT IS KNOWN: • Congenital CMV is a leading cause of sensorineural hearing loss and neurodevelopmental sequelae, with many cases asymptomatic at birth. Diagnosis relies on early viral detection, and while saliva/urine PCR is sensitive, newborn screening lacks consensus and feasibility is unknown in many settings. WHAT IS NEW: • DBS PCR emerges as a scalable, feasible low-cost screening alternative for cCMV screening. A few states in the USA and provinces in Canada have implemented newborn cCMV screening programs using DBS, but the sensitivity appears lower than in research studies. Improving DNA extraction and PCR methods are required as well as assessing feasibility of using other specimens (e.g., urine or saliva) for screening.
28 June 2026
Read appraisal →PloS one
Long-term effects following prenatal cocaine exposure: A systematic review.
Cocaine use represents a global public-health concern, and children's exposure to this substance is receiving growing attention. Despite the importance of this phenomenon, efforts to isolate cocaine-specific long-term effects are affected by the limited availability of human cohorts followed into adulthood and by the influence of environmental factors and co-exposures. Addressing ongoing debates in the literature, this systematic review synthesizes human evidence on long-term outcomes following prenatal cocaine exposure (PCE), from infancy to early adulthood. A comprehensive search of PubMed and Scopus from inception to August 2025 identified 26 eligible studies. Results suggest that across maturational stages, PCE is consistently associated with early developmental effects (including smaller head circumference and motor delays), deficits in visuospatial, language and executive functions, focal neuroimaging alterations (white-matter microstructure and task-related functional recruitment), growth deficits, and elevated externalizing behaviours. However, evidence is characterised by heterogeneity in exposure assessment, frequent prenatal polysubstance exposure, socioeconomic confounding, caregiving instability and small neuroimaging samples. Overall, this review suggests that PCE is linked to a broad spectrum of detrimental effects and that some biological vulnerabilities associated with PCE may persist. Nonetheless, supportive postnatal environments may mitigate developmental disadvantages and promote better trajectories for affected children. These findings underscore the need for integrated public-health and clinical strategies that combine prevention of prenatal substance use with family-focused postnatal supports.
28 June 2026
Read appraisal →Environmental research
Air pollution and adverse birth outcomes: A systematic review of fine critical windows
Epidemiological studies have reported associations between prenatal exposure to outdoor air pollution and adverse pregnancy outcomes. However, most analyses assessed exposure over the entire pregnancy or by trimester, potentially missing specific critical windows of vulnerability that recent statistical methods can identify. The objective of this study was to summarise studies examining critical windows of exposure to outdoor air pollution in relation to adverse pregnancy outcomes. This systematic review (PROSPERO-CRD42024523345) followed PRISMA recommendations using PubMed, Embase and CENTRAL databases. The search was performed on April 2024 and udpated on February 2025. Eligible studies analysed critical windows of association between air pollutants (PM2.5, PM10, NO2, O3) and the following outcomes: prematurity, low birth weight, intrahepatic cholestasis of pregnancy, gestational diabetes, pre-eclampsia, eclampsia, gestational hypertension and stillbirth. Two independent reviewers screened titles, abstracts and full texts. Results were synthesised narratively. Out of 3631 articles, 20 studies were included. All were conducted in China or the United States and relied almost exclusively on distributed lag models (DLM or DLNM). Heterogeneity was observed across pathologies and between studies addressing the same outcome. The most consistent finding concerned preterm birth, for which the end of the second trimester (weeks 17-28) was often identified as a critical window. No studies addressed intrahepatic cholestasis of pregnancy or stillbirth. Conclusions. The variability in results reflects distinct pathophysiological mechanisms, differences in exposure levels, or individual characteristics. Precisely identifying critical windows of environmental exposure during pregnancy appears essential to improve perinatal environmental prevention and guide public health action.
15 June 2026
Read appraisal →Journal of hazardous materials
Prenatal 6:2 Cl-PFESA exposure and birth weight: A systematic review and meta-analysis
Most existing systematic reviews and meta-analyses on PFAS have focused on legacy compounds, yet with less attention on PFAS alternatives and mixtures. Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) have been introduced as PFOS alternatives. Among these, 6:2 Cl-PFESA has accumulated persistent environmental residues and has recently emerged as a significant health concern. We aim to evaluate the association between prenatal 6:2 Cl-PFESA exposure and birth weight using a meta-analysis. A systematic review identified 12 studies reporting birth weight in relation to 6:2 Cl-PFESA biomarker measures, including maternal serum and umbilical cord samples. Risk of bias and study sensitivity were assessed, and overall effects were estimated by random-effects model. Stratified analyses were conducted by study confidence, sample size, and exposure level. The overall pooled estimate showed no statistically significant association between 6:2 Cl-PFESA exposure and birth weight. However, subgroup analyses revealed a consistent reduction in birth weight per ln-unit increase in 6:2 Cl-PFESA in studies with large sample sizes (β = -20.05 g; 95% CI: -33.13, -6.97), high methodological confidence (β = -16.74 g; 95% CI: -26.42, -7.06), or higher exposure levels (β = -16.15 g; 95% CI: -25.43, -6.87), all showing low between-study heterogeneity. Sensitivity analysis excluding the study contributing most to heterogeneity indicated a 15.57 g decrease in birth weight per ln ng/mL increase in 6:2 Cl-PFESA (95% CI: -24.74, -6.40). Although current evidence suggests that prenatal 6:2 Cl-PFESA exposure may adversely affect fetal growth, well-designed prospective studies with standardized exposure assessments are needed to confirm this potential risk.
15 June 2026
Read appraisal →Pediatric surgery international
Early vs. delayed feeding after pediatric gastrointestinal surgery: a systematic review and meta-analysis
BACKGROUND: The adoption of early feeding after pediatric gastrointestinal surgery remains inconsistent due to concerns regarding anastomotic safety. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted comparing early enteral feeding (initiation within 48 h) with delayed feeding in patients < 18 years undergoing intestinal anastomosis or stoma reversal. RESULTS: Eight trials comprising 704 patients (323 early feeding, 381 delayed) were included across neonatal and pediatric elective surgical populations. Early feeding significantly shortened hospital length of stay (mean difference - 3.53 days; 95% CI - 4.35 to - 2.71) and reduced time to full feeds (mean difference - 3.15 days; 95% CI - 3.89 to - 2.40). There was no significant difference in anastomotic leakage (log risk ratio - 0.36; 95% CI - 1.23 to 0.51; I²=0%) or postoperative vomiting (log risk ratio - 0.02; 95% CI - 0.41 to 0.38). Early feeding was also associated with fewer wound infections (log risk ratio - 0.85; 95% CI - 1.48 to - 0.22). CONCLUSIONS: Overall, early enteral feeding after pediatric gastrointestinal surgery appears safe and confers clinically meaningful benefits by accelerating nutritional recovery, reducing infectious complications, and shortening hospitalization, supporting its incorporation into pediatric postoperative care pathways.
13 June 2026
Read appraisal →Journal of tropical pediatrics
A randomized controlled trial to evaluate the efficacy and safety of a double-walled incubator compared to a radiant warmer in the care of extremely low-birth-weight infants
This study compared the safety and efficacy of double-walled incubators versus radiant warmers in extremely low-birth weight (ELBW: birth weight < 1000 g) preterm infants, hypothesizing that incubator care would reduce the time to regain birth weight compared with radiant warmer care. In this single-center, nonblinded, randomized controlled trial, ELBW infants with gestational age ≥25 to ≤32 weeks were randomized shortly after birth to stay in either an incubator or a radiant warmer for the first week of life, followed by radiant warmer care for all infants. The primary outcome was time to regain birth weight. Secondary outcomes included fluid intake, sodium levels, hypernatremia, and other neonatal outcomes. One hundred ELBW infants were enrolled. The median time to regain birth weight did not significantly differ between the incubator and radiant warmer groups: 12.00 (IQR 7.00, 17.75) days versus 11.50 (IQR 7.25, 15.75) days, respectively, with an effect size of median difference 0.0 (95% CI -4.0 to 4.0, P = .89). There were no significant differences in any other secondary outcomes. The study lacked sufficient power to detect differences in these outcomes. Either a double-walled incubator or a radiant warmer can be considered similarly safe and effective for thermoregulation and for achieving time to regain birth weight in ELBW infants. Radiant warmers may be preferable in low- and middle-income countries because they are less costly than double-walled incubators.
12 June 2026
Read appraisal →Placenta
Recent advances in multimodal approaches for investigating placental development and related diseases
The placenta is a vital organ that supports fetal growth and pregnancy maintenance. Its dysfunction is associated with severe complications, including preeclampsia, fetal growth restriction, and placenta accreta spectrum disorders. Traditional approaches to placental research have provided valuable insights but are limited in capturing the complexity of this dynamic organ. In recent years, multimodal approaches-integrating advanced imaging, single-cell and spatial omics, and artificial intelligence (AI)-have enabled comprehensive analyses of placental development and disease. These strategies offer improved diagnostic accuracy, deeper molecular understanding, and real-time assessment of placental function. This review summarizes recent advances in multimodal placental research, highlighting key technologies such as ultrasound and MRI, single-cell transcriptomics, spatial profiling, and AI-based prediction models. Particular emphasis is placed on contributions from Chinese research teams, who have developed novel platforms, atlases, and clinically relevant tools. We also discuss ongoing challenges, including data standardization, interpretability of AI models, and ethical considerations. Looking ahead, the integration of multimodal data with AI and wearable technologies holds promise for precision obstetrics and individualized pregnancy care. Together, these innovations are advancing both scientific understanding and clinical management of placenta-related disorders.
12 June 2026
Read appraisal →Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Primary Intracranial High Grade Congenital Glial Lesions (PIHGCL): A systematic review of case reports from 1985 to 2025
BACKGROUND: Among congenital intracranial space-occupying lesions, teratomas, gliomas, and neuroblastomas are more frequently reported. However, primary congenital glioblastoma (cGBM) and congenital anaplastic astrocytoma (cAA) are underrecognized entities. Their detection remains challenging due to nonspecific prenatal findings and limited awareness among pediatricians and obstetric care providers, contributing to delayed diagnosis and worsened outcomes. OBJECTIVE: To summarize the clinical presentations, diagnostic imaging characteristics, reported cases, histopathological features, and neuro-oncological management strategies of primary intracranial high grade congenital glial lesions (PIHGCL). MATERIALS AND METHODS: A comprehensive literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in 2025 over PubMed and Google Scholar using keywords and Boolean operators, retrieving 35 studies (44 patients) with PIHGCL published 1985 to 2025. Quality assessment was done using Joanna Briggs Institute (JBI) tool. The data was analyzed descriptively as well as analytically to determine survival outcomes in treatment groups. RESULTS: A total of 28 studies (37 patients) discussed cGBM, and 7 studies (7 patients) described the occurrence of cAA. Most of the patients were infants i.e., 65.9% (29), presenting with macrocephaly in 27.7% (10) patients. Most of the lesions were intracerebral, 72.7% (32), lateralized equally to both sides, i.e., 46.5% (20). Surgical excision alone was done in 29.5% (13) patients, surgical excision with adjuvant chemotherapy was given to 43.2% (19) patients, chemotherapy alone in 6.8% (3) patients whereas 20.5% (9) underwent only conservative treatment. Kaplan Meir-analysis revealed a significant difference in survival in patients who received adjuvant treatment along with surgical excision in contrast to other treatment groups (χ2 = 7.83, df = 3, p = 0.05). CONCLUSION: PIHGCL presents during fetal or neonatal period with clinicopathological features distinct from adult and pediatric glioblastomas with distinct genetic etiology. Extent of resection is not a reliable marker of treatment outcomes in PIHGCL due to anatomical and physiological variations at the age of presentations. Adjuvant chemotherapy along with surgical resection results in improved patient survival.
11 June 2026
Read appraisal →BMJ paediatrics open
The efficacy of oral sucrose for relieving lumbar puncture pain in neonates: a randomised clinical trial
OBJECTIVE: To evaluate the analgesic efficacy and physiological effects of oral sucrose during lumbar puncture (LP) in term neonates. STUDY DESIGN: This double-blind, randomised trial enrolled 60 full-term neonates undergoing LP. Participants were randomly given 2 mL of 25% oral sucrose or sterile water 2 min before the procedure. The primary outcome was pain score change from baseline via the Neonatal Infant Pain Scale (NIPS). Secondary outcomes included changes in heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO₂). Measurements were taken at baseline, 1 min, and 3 min post-LP. RESULTS: The sucrose group showed significantly smaller changes in NIPS scores at 1 min (1.0 vs 5.0, p<0.001) and 3 min (0.0 vs 4.0, p<0.001), along with smaller HR increases (p=0.012) and SpO₂ decreases (p=0.023) at 1 min post-procedure. Clinically significant tachycardia (HR >160 bpm) occurred in 40% of controls vs 13.3% of sucrose-treated infants (p=0.045), and desaturation (SpO₂ <90%) in 26.7% of controls vs 6.7% of the sucrose group (p=0.038). CONCLUSION: A 2 mL dose of 25% oral sucrose administered 2 min prior to LP is a safe and effective intervention that significantly reduces behavioural and physiological markers of pain in term neonates during the immediate post-procedural period.
1 June 2026
Read appraisal →BMJ open
Birth outcomes for women with pre-existing mental health problems: a systematic review and meta-analysis
OBJECTIVES: To synthesise evidence on the association between any diagnosed or self-reported mental health problems prior to pregnancy (pre-existing mental health problems) and birth outcomes including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), neonatal unit (NNU) admission and mode of birth (instrumental birth, planned or unplanned caesarean section). METHODS: Systematic searches were conducted in MEDLINE, CINAHL, Embase and PsycINFO in December 2024 for studies examining the association between any pre-existing mental health problems and PTB, LBW, SGA, NNU admission and mode of birth. Only articles published in English were included with no restriction on year of publication. Two reviewers independently screened studies and extracted data. Study quality was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute checklists. Random-effects meta-analyses were conducted to pool crude and adjusted ORs (aORs) and risk ratios (aRR) with 95% CIs. ORs and RRs were analysed separately. Between-study heterogeneity was quantified using the I2 statistic. RESULTS: Of 15 467 records screened, 33 studies met the inclusion criteria. Women with any pre-existing mental health problems had higher odds and risks of adverse birth outcomes, including PTB (aOR 1.41, 95% CI 1.27 to 1.56) (aRR 1.36, 95% CI 1.21 to 1.51), LBW (aOR 1.28, 95% CI 1.22 to 1.33) (aRR 1.32, 95% CI 1.04 to 1.68), SGA (aOR 1.27, 95% CI 1.07 to 1.51) (aRR 1.34, 95% CI 1.19 to 1.51) and NNU admission (aOR 1.44, 95% CI 1.19 to 1.74). Adjusted estimates were based on multivariable models that commonly controlled for maternal age, parity and socio-demographic factors. No consistent associations were observed between pre-existing mental health problems and mode of birth. CONCLUSIONS: Pre-existing mental health problems were associated with increased risks and odds of several adverse birth outcomes. These findings highlight the importance of early identification and targeted support for women with mental health problems before pregnancy to strengthen preconception and maternity care planning. PROSPERO REGISTRATION NUMBER: CRD42023485834.
31 May 2026
Read appraisal →Journal of perinatal medicine
Functional neurobehaviour of the human fetus: a comprehensive framework for prenatal assessment using 4D ultrasound and AI
OBJECTIVES: To evaluate current evidence on prenatal neurobehavioural assessment using four-dimensional ultrasound (4D-US), structured scoring systems, and emerging artificial intelligence (AI) platforms, and to develop an integrated framework for early identification of neurodevelopmental vulnerability. METHODS: A narrative review of the literature from 2000 to 2025 was conducted following PRISMA-guided organisational principles to enhance transparency. Studies were eligible if they used 3D/4D ultrasound to assess fetal neurobehaviour, including spontaneous motor activity, facial expressions, or behavioural transitions. Specific tools examined included the Kurjak Antenatal Neurodevelopmental Test (KANET), prenatal General Movements Assessment (GMA), and AI-assisted behavioural analysis systems. Methodological quality was appraised using the Newcastle-Ottawa Scale and the Joanna Briggs Institute checklist. Data extraction focused on imaging protocols, behavioural parameters, scoring systems, and associations with neonatal neurological outcomes. RESULTS: Fifty eligible studies demonstrated that fetal motor sequences, movement variability, and facial expressions exhibit hierarchical maturation consistent with developmental progression of brainstem, subcortical, and cortical neural circuits. KANET parameters showed reproducible scoring and meaningful correlation with neonatal neurodevelopment, particularly in high-risk pregnancies. Prenatal general movement patterns displayed continuity with postnatal repertoires and contributed to early neurological prediction. AI-based classifiers provided objective quantification of fetal movement and facial activity, supporting automated or semi-automated assessment workflows. CONCLUSIONS: Functional neurobehavioural assessment using 4D-US, structured scoring tools, and AI-enhanced analysis is feasible, reproducible, and clinically informative. Integrating behavioural markers with neurosonographic findings and computational modelling may strengthen early detection of neurological risk and improve long-term neurodevelopmental care pathways.
27 May 2026
Read appraisal →Zeitschrift fur Naturforschung. C, Journal of biosciences
Exploring the potency of 6-bromo-3-methylquinoline analogues as prostaglandin F2α inhibitors
Prostaglandin F2α (PGF2α) is associated with preterm labor and preterm birth. PGF2α inhibitors have thus proven to be a promising target in the development of lead compounds to prevent preterm birth. In this work, Quantitative Structural Activity Relationship (QSAR) was implemented on a dataset of 77 compounds of 6-bromo-3-methylquinoline analogues using statistical approach and random selection in the QSARINS software. The Genetic Algorithm-Multiple Linear Regression (GA-MLR) approach was used to predict the best model (R 2 = 0.8943 and Q 2 LOO = 0.8836). The inclusion of descriptors FNSA-2 and WV.mass resulted in a well-fitted and highly predictable model. Artificial neural network (ANN) analysis was also carried out to validate the model effectiveness. Twenty eight new molecules with better predicted biological activity (pIC50) were designed. The binding energy from the docking study of seven compounds have shown higher binding activity than P10 into prostaglandin F synthase protein (PDB ID: 2F38). The stability of protein-ligand complex was further validated by 100 ns molecular dynamics simulation and MM-PBSA binding free energy. DFT and ADME-toxicity analysis also confirmed their drug-likeness properties. Collectively, our findings highlight novel quinoline derivatives as promising lead candidates, warranting further validation through collaborative in vitro and in vivo studies.
27 May 2026
Read appraisal →Journal of perinatal medicine
Effect of preterm birth on neonatal, infant, child, young adult and adult mortality: a systematic review and meta-analysis
OBJECTIVES: Preterm birth is associated with a higher risk of mortality. In 2020, the global incidence of preterm births was reported at 9.9 per 100 live births. This meta-analysis was undertaken to evaluate the effect of preterm birth on mortality among various age groups. METHODS: A thorough search was done on four electronic databases: "PubMed, Scopus, Web of Science, and Embase". Adhering to PRISMA 2020 guidelines, observational analytical studies published till 4th December 2024 were included. Screening of the studies was done by two independent reviewers in two stages: title/abstract, followed by full text review of the advanced articles. It was followed by data extraction. Study quality was assessed with the Newcastle Ottawa Scale. Meta-analysis using a random-effects model was done in R Studio. PROSPERO ID: CRD42024622282. RESULTS: Database search yielded 1775 unique studies. 23 studies met the final predefined eligibility criteria. Preterm babies showed an increased risk of mortality compared to term babies with a pooled relative risk of 6.12 (95 % CI: 3.16-11.84) for neonatal mortality, 11.84 (95 % CI: 6.88-20.37) for infant mortality and 1.88 (95 % CI: 1.24-2.83) for 1-5 year. However, it was similar in adult mortality with a pooled relative risk of 1.21 (95 % CI: 0.07-20.12). CONCLUSIONS: Preterm birth is strongly associated with increased risks of childhood mortality, especially in extreme and very preterm infants, but the risk persists even for late preterms.
27 May 2026
Read appraisal →Journal of perinatal medicine
Oral adjuvants supplemented to phototherapy as a therapeutic strategy for neonatal hyperbilirubinemia: a systematic review
INTRODUCTION: Neonatal jaundice is a common condition characterized by elevated serum bilirubin levels. Although usually benign, inadequate management may result in severe complications such as bilirubin encephalopathy and kernicterus. Phototherapy is the standard treatment; however, concerns regarding potential short- and long-term adverse effects have motivated the investigation of oral adjuvants as complementary therapies to accelerate bilirubin clearance and reduce phototherapy exposure. CONTENT: This systematic review followed PRISMA guidelines and was registered in PROSPERO (CRD420251071886). Randomized controlled trials published between 2010 and 2025 were included, evaluating full-term neonates (35-42 weeks, 2-4 kg) without Rh incompatibility. Searches were conducted in PubMed, Cochrane Central, Embase, and Web of Science. Of 193 identified records, 18 RCTs met eligibility criteria. The oral adjuvants assessed included probiotics, phenobarbital, ursodeoxycholic acid (UDCA), oral calcium, zinc sulfate, fenofibrate, and clofibrate. Lactobacillus reuteri demonstrated greater 24-hour reductions in total serum bilirubin (TSB) compared to controls, whereas Bifidobacterium strains primarily reduced phototherapy duration. Phenobarbital did not outperform phototherapy alone and was associated with longer hospitalization. UDCA showed substantial bilirubin reductions, although findings were heterogeneous. Zinc supplementation did not demonstrate consistent significant benefit. Fenofibrate produced statistically significant decreases in TSB across trials and showed the most consistent efficacy. Clofibrate also reduced bilirubin levels but with methodological variability and limited comparative data. SUMMARY: Oral adjuvants combined with phototherapy may enhance bilirubin reduction in term neonates, particularly fenofibrate. OUTLOOK: However, heterogeneity and potential bias limit definitive conclusions, emphasizing the need for large, multicenter randomized trials.
27 May 2026
Read appraisal →Journal of perinatal medicine
Early kangaroo care in preterm ≤32 weeks and very low birth weight infants: a systematic review and meta-analysis
OBJECTIVES: Kangaroo care (KC), involving skin-to-skin contact, early breastfeeding and early discharge, demonstrated benefits in improving outcomes for preterm and low birth weight infants. This systematic review and meta-analysis aimed to evaluate the effectiveness of early KC (initiated within the first 24 h) vs. conventional neonatal care in very preterm infants (≤32 weeks) and/or very low birth weight (VLBW) infants (<1,500 g). METHODS: A comprehensive search of MEDLINE, SCOPUS, Web of Science, and CENTRAL databases was conducted. Randomized controlled trials (RCTs) comparing early KC to conventional care in very preterm and/or VLBW infants were included. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analysis was conducted using R, with relative risks (RR) and 95 % confidence intervals (CI) calculated. RESULTS: Four RCTs, encompassing 1,679 newborns, were included. Meta-analysis revealed a significant reduction in mortality risk (RR=0.81, 95 % CI: 0.67-0.98) with early KC. The pooled RR for infection risk was 0.89 (95 % CI: 0.77-1.02). The impact on hypothermia was mixed, with moderate heterogeneity observed. CONCLUSIONS: Early KC may reduce mortality and morbidity in very preterm and VLBW infants although its effects on hypothermia vary by severity. Further studies are required to assess its effects on infants weighing <1,000 g or born before 28 weeks of gestation.
26 May 2026
Read appraisal →European journal of pediatrics
Associations of socioeconomic status and nurturing environment with developmental outcomes in very preterm children without sensorimotor impairment: a secondary analysis of the INTACT study
UNLABELLED: The objective of this study is to retrospectively evaluate the associations between socioeconomic status (SES), including nurturing environment, and developmental quotients (DQ) at age 3 in children born very preterm with birth weight ≤ 1500 g. This secondary analysis used follow-up data from the Improvement of NICU Practices and Team Approach Cluster Randomized Controlled Trial. Participants born < 32 weeks' gestation without major sensorimotor impairments were stratified into three groups: 22-24, 25-27, and 28-31 weeks. Multiple linear regression evaluated the associations between prenatal SES and DQ scores of the Kyoto Scale of Psychological Development (KSPD), adjusted for sex, parity, gestational age, small for gestational age, multiple births, and facilities. Post-discharge SES variables were subsequently added to assess associations with nurturing environment. Of 2148 eligible survivors, 1978 underwent KSPD testing and 1846 caregivers completed SES questionnaires. Higher parental education was positively associated with total DQ across all groups: 22-24 weeks (β = 2.246, 95% CI 0.015-4.477), 25-27 weeks (β = 1.589, 95% CI 0.408-2.770), and 28-31 weeks (β = 1.299, 95% CI 0.315-2.282). Group childcare utilization was associated with higher total DQ: 22-24 weeks (β = 3.397, 95% CI 0.893-5.901), 25-27 weeks (β = 1.851, 95% CI 0.591-3.111), and 28-31 weeks (β = 2.617, 95% CI 1.613-3.620). These associations remained after adjustments for postnatal morbidities. CONCLUSION: Among children born very preterm without major sensorimotor impairments, parental education and group childcare utilization were independently associated with more favorable cognitive outcomes at age 3. These results suggest the importance of socioeconomic and environmental support in optimizing developmental outcomes for this vulnerable population. WHAT IS KNOWN: • Prenatal and postnatal SES are associated with developmental outcomes in both preterm and term children. In addition, daily group childcare environments influence child development in the general population. WHAT IS NEW: • Among very preterm children without major sensorimotor impairments, including those born at 22-24 weeks' gestation, parental education and group childcare utilization are independently associated with more favorable cognitive and language outcomes at age 3.
25 May 2026
Read appraisal →Annals of medicine
Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis
BACKGROUND: No systematic review has evaluated the existing evidence regarding the association between packed red blood cell (pRBC) transfusion and clinical worsening of necrotizing enterocolitis (NEC) in neonates. This systematic review and meta-analysis was conducted to address this knowledge gap. MATERIALS AND METHODS: We searched the Cochrane Library, EBSCO, Embase, Web of Science, Google Scholar, and PubMed for studies on pRBC transfusion and NEC published before May 10, 2025. Relevant articles were selected through title, abstract, and full-text screening. English-language case-control studies or cohort studies, or randomized controlled trials involving newborns with NEC that compared pRBC transfusion with no transfusion and reported changes in NEC clinical status were included. Review articles, systematic reviews, case reports, editorials, animal studies, duplicate publications, and studies with incomplete data were excluded. RESULTS: Five studies involving 971 neonates with NEC were included. The pooled analysis demonstrated a potential association between pRBC transfusion and clinical deterioration of NEC in neonates (odds ratio: 6.05, 95% confidence interval: 3.02-12.14). CONCLUSIONS: pRBC transfusion was associated with an exacerbation of NEC in neonates. However, these findings should be interpreted cautiously because of the small number of eligible studies included in this meta-analysis, and future large-scale, well-designed studies are needed to confirm the observed association. Published studies have identified an association between pRBC transfusion and NEC progression; however, whether this association is causal remains unclear.Despite consistent evidence from observational studies suggesting a potential association between pRBC transfusion and NEC progression, the overall quality of the evidence is low because of the lack of randomized controlled trials to determine causality.
25 May 2026
Read appraisal →The Cochrane database of systematic reviews
Early erythropoiesis-stimulating agents in preterm or low-birthweight infants
RATIONALE: Preterm and low-birthweight infants are at risk of anemia due to a variety of factors, including low levels of erythropoietin. They may therefore benefit from erythropoiesis-stimulating agents (ESAs). However, controversy remains about their effectiveness and safety, not only in reducing blood transfusions but also in improving clinical outcomes. OBJECTIVES: To assess the benefits and harms of early administration of ESAs in preterm or low-birthweight infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Scopus, DOAJ, and trial registries to 31 March 2025, and checked the reference lists of studies and systematic reviews for potentially relevant studies. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) comparing early (initiated before eight days of life) ESAs (erythropoietin or darbepoetin) to placebo or no intervention among preterm (< 37 weeks' gestation) or low-birthweight (< 2500 g) infants. OUTCOMES: Outcomes included mortality during initial hospital stay (all-cause mortality), moderate to severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age, proportion of infants exposed to one or more red blood cell (RBC) transfusions, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and severe intraventricular hemorrhage (sIVH). RISK OF BIAS: We used the Cochrane RoB 1 tool to assess risk of bias. SYNTHESIS METHODS: We performed data collection and analyses according to the methods of Cochrane Neonatal (fixed-effect meta-analysis using the inverse-variance method). We analyzed categorical data using risk ratio (RR) and continuous data using mean difference (MD), and reported the 95% confidence interval (CI) on all estimates. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included 37 studies (n = 6724), five (n = 3052) of which are new. Two studies (n = 752) investigated darbepoetin, and 35 studies (n = 5972) investigated erythropoietin. SYNTHESIS OF RESULTS: ESAs compared to placebo or no intervention Mortality: ESAs probably result in little to no difference in mortality during initial hospital stay (RR 0.93, 95% CI 0.80 to 1.09; I² = 0%; 24 studies, 5217 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably results in little to no difference in mortality (RR 0.91, 95% CI 0.77 to 1.09; I² = 0%; 23 studies, 4505 participants), and early use of darbepoetin probably results in little to no difference in mortality (RR 1.00, 95% CI 0.71 to 1.43; I² = 0%; 2 studies, 712 participants). NDI: ESAs may reduce moderate to severe NDI at 18 to 26 months' corrected age (RR 0.81, 95% CI 0.68 to 0.95; I² = 86%; 3 studies, 1707 participants; low-certainty evidence). Subgroup analysis suggests that early use of erythropoietin may reduce moderate to severe NDI at 18 to 26 months' corrected age (RR 0.79, 95% CI 0.66 to 0.95; I² = 93%; 2 studies, 1239 participants), while early use of darbepoetin may result in little to no difference in moderate to severe NDI at 18 to 26 months' corrected age (RR 0.87, 95% CI 0.59 to 1.28; I² not applicable; 1 study, 468 participants). Transfusions: ESAs may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.79, 95% CI 0.76 to 0.83; I² = 56%; 21 studies, 3507 participants; low-certainty evidence). Subgroup analysis suggests that erythropoietin may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.80, 95% CI 0.76 to 0.84; I² = 56%; 20 studies, 2795 participants); darbepoetin may reduce the proportion of infants exposed to one or more RBC transfusions (RR 0.75, 95% CI 0.68 to 0.84; I² = 0%; 2 studies, 712 participants). ROP (any stage): ESAs result in little to no difference in incidence of ROP (RR 0.91, 95% CI 0.83 to 1.00; I² = 0%; 14 studies, 3844 participants; high-certainty evidence). Subgroup analysis suggests the use of either erythropoietin (RR 0.92, 95% CI 0.84 to 1.02; I² = 0%; 13 studies, 3230 participants) or darbepoetin (RR 0.83, 95% CI 0.58 to 1.17; I² = 0%; 2 studies, 614 participants) results in little to no difference in incidence of ROP. NEC (any stage): ESAs probably reduce the incidence of NEC (RR 0.74, 95% CI 0.62 to 0.87; I² = 0%; 20 studies, 5749 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably reduces the incidence of NEC (RR 0.72, 95% CI 0.61 to 0.85; I² = 0%; 19 studies, 5041 participants), while early use of darbepoetin probably results in little to no difference in incidence of NEC (RR 1.08, 95% CI 0.54 to 2.15; I² = 0%; 2 studies, 708 participants). sIVH (grade ≥ 3): ESAs probably reduce the incidence of sIVH (RR 0.70, 95% CI 0.56 to 0.89; I² = 43%; 9 studies, 2458 participants; moderate-certainty evidence). Subgroup analysis suggests that early use of erythropoietin probably reduces the incidence of sIVH (RR 0.72, 95% CI 0.57 to 0.91; I² = 47%; 9 studies, 2396 participants), while early use of darbepoetin probably results in little to no difference in incidence of sIVH (RR 0.40, 95% CI 0.11 to 1.41; I² not applicable; 1 study, 62 participants). Of note, the test for subgroup differences between erythropoietin and darbepoetin revealed no evidence of a difference for the outcomes of mortality, moderate to severe NDI, NEC, sIVH, ROP, and the proportion of infants exposed to RBC transfusion. We downgraded the certainty of evidence for inconsistency, imprecision, and high risk of bias in the included studies. AUTHORS' CONCLUSIONS: Early use of ESAs probably results in little to no difference in mortality (moderate-certainty evidence); may reduce moderate to severe NDI at 18 to 26 months' corrected age (low-certainty evidence); has little to no effect on ROP (high-certainty evidence); may reduce the proportion of infants exposed to one or more RBC transfusions (low-certainty evidence); and probably reduces both NEC and sIVH (moderate-certainty evidence). Given the benefits of ESAs, future research should focus on cost-effectiveness, equity, feasibility of implementation, and acceptability to different stakeholders of the routine use of erythropoietin or darbepoetin among preterm or low-birthweight infants. FUNDING: No funding was received for this review. REGISTRATION: Protocol (and previous versions) available via 10.1002/14651858.CD004863; 10.1002/14651858.CD004863.pub2; 10.1002/14651858.CD004863.pub3; 10.1002/14651858.CD004863.pub4; 10.1002/14651858.cd004863.pub5; 10.1002/14651858.CD004863.pub6.
25 May 2026
Read appraisal →European journal of pediatrics
Application of machine learning to predict bronchiolitis severity in children: a single-centre retrospective cohort study
UNLABELLED: Several severity scores have been developed to assess disease severity in infants with bronchiolitis, but they often lack objectivity and may not reliably reflect clinical outcomes. We performed a single-centre retrospective cohort study including infants younger than 12 months admitted with a clinical diagnosis of bronchiolitis over three epidemic seasons (2021-2024). Cluster analysis was applied to identify groups of infants with similar clinical patterns, which were subsequently mapped to severity levels. A machine learning (ML) model was then trained to predict these severity levels using anamnestic and clinical variables available at admission. For comparison, the bronchiolitis risk of admission score (BRAS) and the respiratory severity score-heart rate (RSS-HR) were also calculated at admission. A total of 112 infants were included, and three severity levels were identified. Mild bronchiolitis corresponded to infants not requiring NICU admission or supplementary ventilation. Moderate cases involved infants needing supplementary ventilation without NICU admission. Severe bronchiolitis was associated with both NICU admission and supplementary ventilation. BRAS showed only a weak association with the newly defined clinical severity score (τ = 0.354, p < 0.001), while RSS-HR showed no significant correlation. In contrast, the ML model demonstrated strong predictive performance (τ = 0.731, p < 0.001 in the test set). A simplified decision tree based on three admission variables-age, retractions, and oxygen saturation-also showed good predictive ability (τ = 0.654, p < 0.001). CONCLUSIONS: A new dynamic approach for assessing bronchiolitis severity at hospital admission, capable of robust and adaptable prediction across clinical settings, has been elaborated. WHAT IS KNOWN: • Several bronchiolitis severity scores exist, but many lack validation, are subjective, and have limited applicability across settings, making early and accurate severity prediction difficult. WHAT IS NEW: • Our study introduces a three-level, outcome-based severity score and a dynamic ML tool, plus a simplified ARS decision tree, all outperforming conventional scores in predicting severity at admission.
23 May 2026
Read appraisal →Journal of global health
Impact of travel time to health facilities on perinatal outcomes: a systematic review with narrative synthesis and meta-analysis
BACKGROUND: Evidence-based global guidance on safe travel time for small or sick newborns who require transfer to health facilities after birth is lacking. A two-hour threshold is frequently cited in low- and middle-income countries (LMICs), while 30 minutes is commonly used in high-income countries (HICs). Although these thresholds are widely referenced, their empirical basis and consistency across levels of newborn care and journey types have not been systematically examined. This study synthesises the evidence linking travel time and perinatal outcomes. METHODS: We conducted a systematic review with narrative synthesis and meta-analysis to assess the impact of travel time or distance (home-to-facility or interfacility) on stillbirth, perinatal mortality, and neonatal mortality. We searched Embase, MEDLINE, and Cochrane Central Register of Controlled Trials for published studies from 2014 to 2023. Given substantial methodological heterogeneity, we used narrative synthesis as the primary analytical approach and conducted random-effects meta-analyses where studies were sufficiently comparable (≥2 with similar definitions and outcome windows), pooling effect estimates for travel time thresholds of 30 minutes, 1 hour, or 2 hours and travel distances of 5, 10, and 15 km. We assessed bias using the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS: Of 8317 screened records, 166 were eligible for full-text review, with 37 studies meeting the inclusion criteria- All but two had low or moderate risk of bias. Most studies (n = 26) came from LMICs and documented higher perinatal survival with shorter journeys. Studies from HICs demonstrated lower out-of-hospital birth, lower morbidity, and lower mortality with shorter journeys though associations were weaker. Across the narrative synthesis, shorter travel times were consistently associated with better outcomes. Exploratory pooling suggested a greater than 3-fold higher odds of survival for interfacility journeys under 30 minutes (odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.90-5.57) and over 2-fold higher odds of survival for journeys from any location to hospitals at all thresholds (OR = 2.06; 95% CI = 1.60-2.65 for 2 hours; OR = 2.20; 95% CI = 1.46-3.33 for 1 hour; OR = 1.92; 95% CI = 1.10-3.34 for 30 minutes), though prediction intervals were wide, reflecting methodological and contextual diversity. CONCLUSIONS: We found that shorter journeys were associated with better perinatal outcomes, with the highest survival rates observed for journeys under 30 minutes to the hospital. Due to substantial contextual and methodological heterogeneity, pooled estimates should be interpreted as illustrative, rather than definitive. A travel time norm of 30 minutes or one hour is preferable to the two-hour threshold currently used in LMICs. To safeguard perinatal survival rates, any travel-time standard should be balanced with corresponding quality of care standards. REGISTRATION: PROSPERO: CRD42023460423.
16 May 2026
Read appraisal →BMJ open
Mapping the evidence on stillbirth prevention across the reproductive continuum: an umbrella review
OBJECTIVES: To collate and appraise evidence from existing systematic reviews and meta-analyses on interventions to prevent stillbirth and reduce perinatal mortality across the reproductive continuum, including preconception, antenatal, intrapartum and immediate newborn periods. DESIGN: Umbrella review synthesising evidence from systematic reviews, including meta-analyses where available. DATA SOURCES: A comprehensive search was conducted in CENTRAL (via Cochrane Register of Studies Online), PubMed, Embase and Web of Science, along with trial registries (WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ISRCTN Registry), from inception to 12 January 2026. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses synthesising randomised controlled trials or quasi-experimental studies that reported stillbirth, perinatal mortality, fetal loss or fetal death were included. Reviews focused exclusively on predefined high-risk populations were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed methodological quality using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) certainty ratings were extracted as reported by the original review authors. Evidence synthesis followed a structured framework adapted from Ota et al, integrating direction of effect and certainty of evidence based on pooled estimates and GRADE assessments. Publication overlap was assessed using the Corrected Covered Area index where relevant. RESULTS: A total of 116 systematic reviews were included, synthesising evidence from randomised controlled and quasi-experimental studies across preconception, antenatal, intrapartum and immediate newborn periods. Evidence from individual reviews showed clear benefit for several interventions, including balanced energy-protein supplementation, home visits by community health workers, birth preparedness interventions, labour induction at or beyond 37 weeks of gestation and skilled or community-based intrapartum care, primarily for reducing perinatal mortality. Reduced antenatal visit schedules compared with standard care were associated with a possible increase in stillbirth or perinatal mortality, indicating potential harm. Many interventions-such as group antenatal care (ANC), nutritional education, case-note provision, routine ultrasound or Doppler monitoring, antibiotic treatment for bacterial vaginosis, antiretroviral therapy in pregnancy and several pharmacological or hormonal interventions-demonstrated unknown or inconclusive effects on stillbirth or perinatal mortality, largely due to imprecision and heterogeneity. CONCLUSIONS: This umbrella review identifies a range of interventions with evidence of effectiveness across the reproductive continuum, particularly those addressing maternal nutrition, continuity of ANC and quality intrapartum and newborn care. However, substantial evidence gaps remain, especially for interventions widely implemented without strong supporting evidence. These findings highlight the need for context-specific implementation research and prioritisation of proven strategies in low- and middle-income countries, where the burden of stillbirth remains highest. PROSPERO REGISTRATION NUMBER: CRD42024531100.
14 May 2026
Read appraisal →Journal of investigative surgery : the official journal of the Academy of Surgical Research
Vascular and Wound-Healing Implications of Single-Stage Versus Multistage Repair of Anorectal Malformations: A Systematic Review and Meta-Analysis
BACKGROUND: Anorectal malformations (ARMs) are managed using either single-stage or multistage surgical repair. However, concerns persist regarding wound-related complications and long-term functional outcomes, which remain inconsistently reported across surgical approaches. OBJECTIVE: To compare wound-related complications and long-term functional outcomes following single-stage versus multistage repair of ARMs, with emphasis on wound perfusion, dehiscence, and vascular healing dynamics. METHODS: A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251006245). PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between 2000 and 2024 comparing single-stage and staged ARM repair in neonates and infants. Outcomes included wound dehiscence, surgical site infection (SSI), stenosis, prolapse, redo surgery, constipation, soiling, and voluntary bowel movements. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: Nineteen studies involving 1,972 patients were included. Single-stage repair was associated with a significantly higher risk of wound dehiscence (OR 3.31; 95% CI 1.90-5.79; p < 0.0001), while no significant differences were observed for SSI, stenosis, prolapse, redo surgery, constipation, soiling, or voluntary bowel movements. Moderate to high heterogeneity was noted for selected outcomes. CONCLUSIONS: Single-stage repair provides comparable infection rates and long-term functional outcomes to multistage surgery but carries an increased risk of wound dehiscence. Optimizing tissue perfusion and minimizing tension are essential to improve outcomes. This study highlights the important role of vascular and wound-healing mechanisms in determining outcomes after anorectal malformation (ARM) repair. While single-stage surgery reduces the burden of multiple procedures, it exposes perineal tissues to fecal contamination and potential microvascular stress, which may increase the risk of wound complications.An understanding of tissue perfusion, venous drainage, and local tissue tension is critical during neonatal reconstructive surgery. Incorporating techniques that preserve vascular integrity, minimize tension, and protect the surgical site can help optimize postoperative healing and reduce the risk of wound dehiscence.
13 May 2026
Read appraisal →PloS one
Maternal body mass index and the risk of early-onset Group B Streptococcus disease in newborns: A systematic review and meta-analysis
BACKGROUND: Early-onset group B Streptococcus disease (EOGBS) remains a leading cause of neonatal morbidity and mortality. The incidence can be substantially reduced by intrapartum antibiotic prophylaxis in women with defined risk factors. However, the role of high prepregnancy body mass index (BMI) as a risk factor remains unclear. This systematic review and meta-analysis therefore aimed to evaluate the association between maternal BMI and the risk of EOGBS, as well as related proxy outcomes, including intrapartum vaginal GBS colonization and rectovaginal or urinary GBS colonization before term. METHODS: We systematically searched MEDLINE, Embase, and Cochrane CENTRAL on the 28th of January 2026, for studies examining the relationship between pregestational BMI and EOGBS or its proxy outcomes. Eligible studies included observational and interventional designs but not case reports and conference abstracts. Risk of bias was assessed using the QUIPS tool. Random-effects meta-regression and sensitivity analyses were performed. RESULTS: We identified 19 eligible observational studies reporting data from a total of 3,707,047 women, encompassing 277,887 cases. For the risk of EOGBS and its proxy outcomes, assuming a log-linear association, our meta-regression showed a 2.4% increase in the odds ratio (OR) per unit increase in BMI. This corresponds to an OR of 1.4 (95% CI 1.1-1.6) for a BMI of 35 and 1.7 (95% CI 1.3-2.3) for a BMI of 45, compared to a normal BMI of 22.3. One very large study on 1,971,346 live singleton births with 780 EOGBS cases, found a hazard ratio of 2.4 (95% CI 1.7-3.4) for a BMI of 35.0-39.9 compared to normal BMI (18.5-24.9). CONCLUSIONS: Although the overall association appears modest, incorporating BMI may improve prevention strategies for EOGBS .
13 May 2026
Read appraisal →Vaccine
Effect of neonatal BCG vaccination on oral herpes in early childhood: A nested study within a randomised controlled trial
BACKGROUND: Bacille Calmette-Guérin (BCG) vaccine, primarily used against tuberculosis, has off-target (non-specific) immunomodulatory effects, including potential protection against recurrences of latent herpes simplex virus (HSV) infections. Recurrent episodes of HSV herpes labialis (oral 'cold sores') affect a substantial proportion of the population, including young children, and there is currently no effective preventive intervention. METHODS: This pilot study, nested within the MIS BAIR randomised controlled trial (RCT), explored whether neonatal BCG vaccination, compared with no BCG vaccination, reduces the incidence and recurrence of herpes labialis during the first five years of life. FINDINGS: Among the 563 children (44% of 1272 randomised) who completed the 5-year follow-up, children in the BCG group were less likely to develop herpes labialis, compared with the control group (5% vs 8%; 38% relative risk reduction, p = 0.1). Risk of recurrence was significantly lower in the BCG group (33% vs. 71%; 53% relative risk reduction, p = 0.02). BCG-vaccinated children also reported a later onset of symptoms and a reduced impact on fluid intake during episodes. INTERPRETATION: This exploratory study suggests a protective role for neonatal BCG against HSV in children. However, its limitations, including its sample size, incomplete follow up and lack of virological confirmation, mean further studies are needed to confirm these findings. FUNDING: National Health and Medical Research Council (NHMRC) of Australia and others, as detailed in the acknowledgements.
12 May 2026
Read appraisal →European journal of pediatrics
Post-asphyxia acute kidney injury in neonates: a systematic review
UNLABELLED: Perinatal asphyxia is a major cause of neonatal morbidity and mortality globally. It affects multi-systems and has significant renal consequences. Acute kidney injury (AKI) is a frequent complication of perinatal asphyxia; however, its burden, diagnosis, and outcomes remain variably characterized. This study employed a scoping review approach to map and synthesize the existing evidence on post-asphyxia AKI in neonates. A total of 30 studies published between 1995 and 2025 were included, encompassing different geographic regions, study designs, and diagnostic criteria. The review demonstrates a clear growth in scholarly attention to post-asphyxia AKI, particularly in the last 25 years, coinciding with the introduction of neonatal-modified KDIGO definitions and advances in neonatal nephrology. Reported incidence of AKI varied widely, ranging from 20% to over 60%, reflecting non-homogeneity in study populations, differing case definitions of acute kidney injury in neonates, the severities of hypoxic-ischemic encephalopathy, and varied methodological approaches. Findings consistently indicate that AKI is strongly associated with severe forms of perinatal asphyxia, the presence of multi-organ dysfunction, prolonged neonatal intensive care stay, and mortality. CONCLUSION: Despite emerging interest in novel biomarkers and standard definitions, important gaps persist in early detection, long-term renal outcome data, and evidence from low- and middle-income countries. Addressing these gaps through standardized monitoring, biomarker validation, and longitudinal follow-up will improve renal survival in neonates affected by perinatal asphyxia. WHAT IS KNOWN: • The newborn kidneys are susceptible to the hemodynamic changes that follow ischemia/asphyxia due to a poor functioning capacity and oftentimes an inadequate structural potential. • Neonatal AKI is closely linked to severe forms of asphyxia, increased length of hospital stay and increased mortality. its reported incidence is widely varied. WHAT IS NEW: • The emergence of novel biomarkers in the identification and diagnosis of neonatal AKI, and the uptake and application of standard definitions (modified neonatal KDIGO) in the identification of neonatal AKI. • The availabiltiy of specialized kidney support therapy (continuous kidney replacement therapy; the carpadiem) in the management of neonatal AKI.
11 May 2026
Read appraisal →European journal of pediatrics
Prognosis of neonates receiving invasive mechanical ventilation in low-resource settings: a systematic review and prognostic meta-analysis
Provision of invasive mechanical ventilation (IMV) in the neonatal intensive care has seen a steady rise in low-esource settings (LRS). However, outcomes among those exposed to IMV remain under-reported, with the current evidence base being restricted to single-centre observational studies, thus limiting comparative analyses and effective healthcare planning. This study aims to estimate the pooled proportion of mortality and morbidity among neonates exposed to IMV in low-resource settings. Medline, Embase, and CENTRAL were searched until 22 August 2025. Randomised and non-randomised studies were included. Two reviewers, blinded to each other, extracted data independently. Proportion-based meta-analyses using random-effects model were performed. Risk of bias was assessed using ROBINS-E, and evidence-certainty was evaluated using the GRADE approach. One hundred of 117 studies were included, with most conducted in South Asia. In-hospital mortality was reported in 68 studies (7193 neonates), with a pooled estimate of 45% (39%-50%), evidence-certainty being very low. Among the secondary outcomes, the pooled rates were as follows: bronchopulmonary dysplasia, 10% (5%-18%); intraventricular haemorrhage (any grade), 10% (5%-19%); necrotising enterocolitis (any stage), 14% (6%-31%); retinopathy of prematurity (any stage), 33% (22%-46%); ventilator-associated pneumonia, 21% (14%-29%); sepsis, 32% (25%-40%) and pulmonary haemorrhage, 9% (6%-14%). Evidence-certainty for all the secondary outcomes was also very low. Subgroup analysis comparing two distinct time epochs revealed a significant difference in mortality, 43% (36%-50%) (I2 = 93.5%) in the post-2010 epoch compared to 55% (48%-63%) (I2 = 82.9%) in the pre-2010 epoch (p = 0.004). Heterogeneous outcome definitions and predominance of unadjusted analyses across studies limit the existing evidence.Conclusions: In LRS, the mortality and morbidity rates among neonates receiving IMV remain substantially high with a modest improvement in survival in the past decade. Improving outcomes mandates moving beyond access to the provision of IMV to investing in comprehensive training and scaling up critical auxiliary resources. Future research must adopt standardised outcome definitions and adjusted analyses to precisely quantify the impact of IMV in LRS.
11 May 2026
Read appraisal →Molecular omics
Placental metabolomics for assessment of pregnancy complications: a systematic review
Metabolomics is a powerful tool for understanding biological function at the cellular level. While this omics technology has found application in areas ranging from toxicology to cancer, its potential for the study of human pregnancy complications is in its infancy. Proper placental function is critical for a healthy pregnancy and assessing placental metabolism offers a direct window into placental physiology. This review aims to analyse placental metabolomics in pregnancy complications in humans. A systematic search was completed using PubMed and Google Scholar, and the Covidence software was used for the screening process. Following title and abstract screening and full-text review, 32 articles remained and were included in this review. Multiple articles performed metabolomics using mass spectrometry and/or nuclear magnetic resonance to study pre-eclampsia, gestational hypertension, foetal growth restriction, maternal obesity, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and preterm birth. A subset of pregnancy complications was investigated in only a single study each (human immunodeficiency virus in pregnancy, neural tube defects, chromosomal disorders, chronic hypoxia, and recurrent pregnancy loss). Univariate analyses identified potential biomarkers of pregnancy complications. Multivariate analyses demonstrated that the placental global metabolic profiles could separate healthy and complicated pregnancies and identified metabolic pathways (e.g. amino acid metabolism, lipid and phospholipid metabolism) to explain pathogenesis and the mechanisms of disease. We highlight knowledge gaps and future directions, emphasizing the need for data replication and inclusion of variables such as biological sex in the field of placental metabolomics.
11 May 2026
Read appraisal →European journal of pediatrics
Oral dextrose gel vs standard care for the treatment of hypoglycemia in high-risk neonates: an open-label randomized controlled trial
UNLABELLED: To determine whether 40% dextrose gel with oral feeds reduces NICU admission for asymptomatic hypoglycemia compared with standard care with oral feeds in at-risk neonates within 48 h of life. Secondary objectives were to assess rebound and recurrent hypoglycemia, hyperglycemia, and exclusive breastfeeding at discharge and at 6 weeks. Open-label randomized controlled trial conducted at a tertiary hospital in South India between April 2023 and May 2024. Neonates born at ≥ 35 weeks of gestation with asymptomatic hypoglycemia within the first 48 h of life were randomly assigned to receive either 200 mg/kg of oral 40% dextrose gel with oral feeds or standard care with oral feeds alone. The primary outcome was NICU admission for hypoglycemia. A total of 193 neonates were enrolled, with 98 in the standard care group and 95 in the gel group. Baseline characteristics were comparable. NICU admission for hypoglycemia occurred in 4.2% in gel group and 12.2% in standard care group (RR 0.34, 95% CI 0.11-1.03; p = 0.06), with a number needed to treat of 13. Exclusive breastfeeding was higher in gel group at discharge (97% vs 76%; p < 0.001) and at 6 weeks (90% vs 69%; p < 0.001). Rebound hypoglycemia, recurrent hypoglycemia, and hyperglycemia were similar between groups. CONCLUSION: Oral dextrose gel was associated with fewer NICU admissions, but the primary outcome did not reach statistical significance. Improved breastfeeding rates were observed as secondary outcomes. These findings should be interpreted cautiously and confirmed in adequately powered studies. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI/2023/02/050027). WHAT'S KNOWN: • Oral 40% dextrose gel is an eff ective fi rst-line treatment for neonatal hypoglycemia and has been shown to reduce treatment failure and intravenous glucose use in previous trials. • Existing evidence is predominantly from high-income settings, with limited randomized data from low- and middle-income countries assessing pragmatic outcomes such as NICU admission. WHAT IS NEW: • In this open-label randomized controlled trial, oral dextrose gel was associated with fewer NICU admissions for hypoglycemia (4.2% vs 12.2%) and higher exclusive breastfeeding rates at discharge and 6 weeks compared with standard care. • These fi ndings support the potential utility of dextrose gel as a simple, low-cost intervention for managing neonatal hypoglycemia in resource-limited settings.
11 May 2026
Read appraisal →The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
The effect of maternal scent-infused blanket on the stress level, crying duration and physiological parameters of premature newborns
BACKGROUND: Olfactory cues from the mother may soothe distress in premature infants in the Neonatal Intensive Care Unit (NICU). This study evaluated the effect of a maternal scent-infused blanket on stress, crying duration, and physiological parameters in premature newborns. METHODS: This double-blind randomized clinical trial included 69 premature infants who were randomly assigned to one of three groups: maternal scent-infused blanket, unscented blanket, or control (no blanket) group. Infants were covered with the assigned blanket for 60 min daily for 3 consecutive days. The maternal scent was obtained by placing a clean blanket in contact with the mother's bare chest overnight prior to each day's exposure, with fragrance-free cleansing products used and a new blanket for each session. Primary outcomes were stress level (Newborn Stress Scale, NSS), crying duration (chronometer), and Secondary outcomes were physiological parameters (heart rate, respiratory rate, oxygen saturation, and body temperature). Measurements were collected at 5 min before intervention, immediately after, and at 15, 30, 45, and 60 min during intervention, plus 5 min after intervention, each day for three consecutive days. Data were analyzed using one-way ANOVA and ANCOVA adjusting for baseline values; p < 0.05 denoted significance. RESULTS: Stress scores and crying duration differed significantly among groups during the intervention, with the maternal scent-infused blanket group showing lower NSS scores and shorter crying times than the unscented and no-blanket groups (p < 0.001). During exposure, heart rate, oxygen saturation, and body temperature differed among groups (significant at multiple time points, p < 0.001); by contrast, respiratory rate did not differ significantly (p > 0.05). Differences were not observed at baseline or immediately after the intervention for these physiological measures. CONCLUSION: The maternal scent-infused blanket may reduce stress and crying duration, with transient improvements in some physiological parameters during exposure. Maternal olfactory cues could serve as a feasible non-pharmacological adjunct to support comfort and well-being in vulnerable newborns, emphasizing parental involvement in neonatal care.
10 May 2026
Read appraisal →Journal of wound care
Incidence and risk factors of medical adhesive-related skin injury among ICU patients: a systematic review and meta-analysis
OBJECTIVE: To summarise the evidence regarding the incidence and risk factors of medical adhesive-related skin injury (MARSI) among patients in the intensive care unit (ICU). METHOD: A systematic review and meta-analysis was undertaken using articles available in nine databases: PubMed; the Cochrane Library; Web of Science; Embase; CINAHL; Chinese Biomedical Literature Database; China National Knowledge Infrastructure Database; Wanfang Database; and Weipu Database, from inception until 30 June 2024. Additional studies were identified by examining the references of relevant articles. The Stata 16.0 statistical platform (StataCorp LLC, US) was used for analysis. Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality standards. RESULTS: Of 14,743 titles screened, 19 studies involving 5218 patients were included in the systematic review. The pooled incidence of MARSI was 21% (95% confidence interval (CI): 14%, 28%), and the incidence of MARSI among neonatal ICU, paediatric ICU and adult ICU was 15% (95% CI: 6%, 26%), 48% (95% CI: 35%, 60%) and 16% (95% CI: 11%, 22%), respectively. Significant risk factors in adult ICUs included oedema (odds ratio (OR): 8.144; 95%CI: 3.267, 20.304), Braden scale score (OR: 0.733; 95%CI: 0.641, 0.837), length of ICU stay (OR: 1.072; 95%CI: 1.026, 1.120), mechanical ventilation (OR: 3.698; 95%CI: 1.900, 7.199), sedative use (OR: 6.022; 95%CI: 2.859, 12.687), Nutritional Risk Screening 2002 score (OR: 4.241; 95%CI: 1.984, 9.065) and hypoalbuminaemia (OR: 4.321; 95%CI: 1.967, 9.488). CONCLUSION: This study found that MARSI is prevalent among ICU patients and is associated with multiple risk factors. Improved strategies for identifying and clinically managing MARSI in ICU patients are needed. Nevertheless, large-sample and multicentre studies are still warranted to validate the present study's findings.
10 May 2026
Read appraisal →Neurosurgical review
The efficacy of ventriculosubgaleal shunt in managing neonatal hydrocephalus due to intraventricular hemorrhage: a systematic review and meta-analysis
Intraventricular hemorrhage (IVH) is a severe complication in premature neonates, occurring in 25%-30% of cases and often leading to posthemorrhagic hydrocephalus (PHH). When blood clots in the cerebrospinal fluid (CSF), preventing permanent shunt placement, temporary interventions are considered. Ventriculosubgaleal shunt (VSGS) utilizes the subgaleal space to absorb and drain excess CSF, reducing infection risk and allowing hydrocephalus control until the neonate reaches an appropriate weight and CSF clarity. This systematic review and meta-analysis evaluate the safety and efficacy of VSGS in treating neonatal PHH. A systematic review was conducted using Medline, Embase, and Web of Science following Cochrane and PRISMA guidelines. Eligible studies included those with ≥ 4 neonates. The primary outcomes analyzed were VSGS-related infection, VSGS revision, VSGS catheter migration, catheter obstruction, VSGS-related CSF leakage, permanent ventriculoperitoneal shunt (VPS) placement, overall mortality, and procedure-related mortality. A total of nineteen studies, encompassing 562 neonates, were included in our analysis. The pooled VSGS-related infection rate was 9% (95%CI: 5% to 12%). The need for VSGS revision was observed in 4% of cases (95%CI: 0% to 8%). The catheter obstruction rate was 2% (95% CI: 0% to 5%), while VSGS catheter migration occurred in 1% of cases (95%CI: 0% to 5%). VSGS-related CSF leakage was reported in 6% of neonates (95%CI: 3% to 9%). Permanent VPS placement was required in 75% of patients (95%CI: 67% to 82%). The overall mortality rate was 10% (95%CI: 4% to 16%), and the procedure-related mortality rate was 1% (95%CI: 0% to 2%). This systematic review and meta-analysis identified VSGS as a safe and effective option for treating hydrocephalus caused by IVH in premature neonates.
10 May 2026
Read appraisal →Journal of neonatal-perinatal medicine
Machine learning demonstrates normal fetal Doppler velocimetry associated with reduced risk of necrotizing enterocolitis among preterm infants with growth restriction
BackgroundNecrotizing enterocolitis (NEC) is an intestinal ischemic disease that affects preterm infants with fetal growth restriction (FGR). The role of fetal Dopplers in stratifying risk for developing NEC is unclear but the innovative use of machine learning technology may aid in identifying their contribution.MethodsThis is a single center retrospective cohort of 164 infants born before 33 weeks' gestation with FGR from 2016 to 2019. We used machine learning to classify NEC and to evaluate the predictive values of gestational age (GA), birth weight (BW), and the presence of abnormal umbilical artery (UA) Dopplers before delivery.ResultsEarly GA and lower BW strongly predicted NEC. The presence of normal fetal UA Dopplers was heavily weighted in classifying infants unlikely to develop NEC. Fetal UA Dopplers had a 95% specificity (15% sensitivity) for NEC.ConclusionsIf validated, normal fetal UA Doppler studies may identify infants with FGR at low risk for NEC who may avoid conservative NEC-prevention strategies.
9 May 2026
Read appraisal →Biomedical physics & engineering express
Impact of multimodal information on the estimation of fetal growth indicators using machine learning regression models
Accurate estimation of fetal growth indicators such as birth weight, birth length, and gestational age at birth is essential for monitoring pregnancy outcomes and guiding clinical decisions. Traditional predictive models typically rely on ultrasound-based fetometric data to estimate fetal weight or length. While valuable, these models provide estimates only at the time of measurement, rather than predicting values at birth, and may overlook important clinical and sociodemographic factors that also influence fetal growth. This study aimed to evaluate whether incorporating echographic, clinical, and sociodemographic features could improve the accuracy of predicting fetal growth indicators at birth and to quantify the contribution of each variable. Data from 154 cases were collected and processed for model development (61.5% for training and 38.5% for testing), divided into three feature sets: fetometric, clinical-sociodemographic, and combined clinical, echographic, and sociodemographic data. Six regression models were developed to predict three fetal growth indicators: birth weight, birth length, and gestational age at birth. Model performances were assessed usingR2, mean absolute error (MAE), and mean absolute percentage error (MAPE). The multimodal models significantly outperformed those relying only on fetometric or clinical-sociodemographic data, with the random forest achieving the best performance for birth weightR2: 0.8991; MAE: 255.08 g; MAPE: 8.46%, birth lengthR2: 0.8679; MAE: 7.21 cm; MAPE: 2.73%, and gestational age at birthR2: 0.8886; MAE: 1.34 d; MAPE: 2.76%. Feature relevance analysis revealed that variables such as maternal height, maternal weight, placenta location, and alcohol consumption played substantial roles in prediction accuracy, alongside classic fetometric measurements such as head circumference. These findings highlight the multifactorial nature of fetal growth and demonstrate that integrating clinical and sociodemographic information enhances the performance of fetal growth prediction models, ultimately supporting improved perinatal care.
25 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Cerebral fuels within the first week of life in very preterm infants: a cohort study
BACKGROUND: Ketones and lactate may contribute towards overall cerebral fuel availability in term infants, yet the availability of such cerebral fuels in very preterm infants is unclear. We undertook a prespecified substudy to explore ketone and lactate concentrations in the first week of life in infants recruited to the REACT trial (real-time continuous glucose monitoring in the newborn): an international multicentre randomised controlled trial of 182 very low birth weight infants investigating the use of continuous glucose monitoring in glycaemic care. METHODS: Ketone and lactate measurements were prospectively collected over the first week of life using the Nova Biomedical point-of-care meter. A longitudinal analysis was undertaken to explore lactate and ketone concentration trends across time and their relationships with blood glucose, baseline demographics, nutritional support and insulin treatment. RESULTS: Data were available for 168 infants (85 females) including 2902 blood glucose, 2084 ketone and 2017 lactate samples. The mean (SD) gestational age was 27.4 (2.0) weeks. Lactate concentrations were higher initially, with mean (SD) 1.72 (1.26) mmol/L on day 2 and lowered to 1.19 (1.1) mmol/L on day 7. Ketone concentrations remained consistently low at 0.1 mmol/L. Neither simultaneous blood glucose concentrations, macronutrient intake nor receipt of insulin was consistently related to ketone or lactate concentrations. CONCLUSION: In this cohort of very preterm infants, there were persistently low concentrations of ketones and relatively higher concentrations of lactate throughout the first week of life. Future research should evaluate changes in these metabolites during episodes of acute hypoglycaemia or hyperglycaemia over more prolonged periods of neonatal intensive care.
20 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Duration of apnoea before start of backup ventilation during nCPAP in extremely preterm infants and time spent within the SpO2 target: a randomised cross-over study
OBJECTIVE: Central apnoea due to immaturity of the respiratory drive constitutes the main cause of frequent and prolonged desaturations in extremely preterm (EPT) infants <28 weeks. We investigated the impact of varying the duration of apnoea before backup ventilation (BUV) on the measures of oxygenation in EPT infants during nasal continuous positive airway pressure (nCPAP) therapy. DESIGN: Single-centre randomised cross-over trial. SETTING: Level 3 neonatal intensive care unit. PATIENTS: 24 EPT infants on nCPAP with BUV. MAIN OUTCOME MEASURES: The primary outcome was the time spent within a predefined oxygen saturation (SpO2) target (88%-95% or ≥88% with fraction of inspired oxygen (FiO2) =0.21) during start of BUV after 4 s of apnoea duration (AD 4) or 16 s of apnoea duration (AD 16) RESULTS: The study was successfully completed in 22 children (median gestational age 24+5 weeks, birth weight 628 g, postnatal age 48 days). Mean time spent within the SpO2 target didn't differ between AD 4 and AD 16 (66.9% vs 67.2%, p=0.88). There were no differences in the time below or above the SpO2 target, prolonged (>30 s, >60 s, >120 s) and severe (<80%, <70%) episodes of hypoxaemias and cerebral tissue oxygenation. Mean FiO2, mean airway pressure, transcutaneous carbon dioxide pressure, heart rate and respiratory frequency did not differ while the rate of BUV was significantly higher during AD 4. CONCLUSION: Reducing the time of apnoea until start of BUV didn't improve the time spent within the SpO2 target in respiratory unstable EPT infants. Our data demand intensified efforts to specify these settings of non-invasive respiratory support that better achieve this important clinical goal. TRIAL REGISTRATION NUMBER: DRKS00031911.
20 Apr 2026
Read appraisal →PloS one
Impact of prophylactic oral azithromycin during labor on Azithromycin Resistance (AMR) in nasal Staphylococcus aureus and Streptococcus pneumoniae in women and infants in the multi-country Azithromycin Prevention in Labor Use Study (A-PLUS)
BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,. METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery. RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret. CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.
20 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Cost-consequence analysis of early full milk feeding versus gradual feeding with intravenous support in preterm infants: results from the FEED1 trial
OBJECTIVE: To assess the economic consequences of initiating full milk feeds from birth compared with intravenous fluids with gradual feeding in infants born preterm. DESIGN: Within-trial economic evaluation alongside a prospective, multicentre, randomised controlled trial (Fluids Exclusively Enteral from Day 1). A cost-consequence approach was used (revised from the planned cost-effectiveness analysis to avoid double counting length of stay within costs). SETTING: 46 UK National Health Service (NHS) neonatal units. PATIENTS: Preterm infants born at 30+0to 32+6 weeks' gestation. INTERVENTIONS: Infants were allocated to either full milk feeds or gradual feeding with intravenous support within 3 hours of birth. MAIN OUTCOME MEASURE: Resource use and costs were captured from birth to 6 weeks' corrected age. Costs were assessed from an NHS and personal social services perspective. The primary clinical outcome was length of hospital stay. RESULTS: 2088 infants were enrolled. There was no statistically significant difference in mean (95% CI) length of hospital stay between groups (-0.050 days (-0.638 to 0.538)). Mean total costs were £670 lower in the full milk group (95% CI: -£1562 to £223; p=0.141). Subgroup analyses suggested lower costs among infants born at 30 weeks' gestation and those below the 10th birth weight centile; no evidence of interaction was found. CONCLUSIONS: Initiating full milk feeds from birth was associated with a modest reduction in costs compared with gradual feeding. While overall hospital stays and costs were not significantly reduced, early full feeding may offer economic advantages in selected subgroups. Further research is needed to assess long-term outcomes. TRIAL REGISTRATION NUMBER: ISRCTN89654042.
19 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Umbilical cord management strategies and risk of intraventricular haemorrhage in preterm neonates: a systematic review and meta-analysis
OBJECTIVES: To assess the comparative effectiveness of different umbilical cord management strategies for preventing intraventricular haemorrhage (IVH) in preterm neonates. DESIGN: A systematic review and meta-analysis. STUDY SOURCES: PubMed, Scopus and Web of Science were searched from inception to March 2025 for relevant randomised controlled trials. PARTICIPANTS: All preterm neonates born <37+0 weeks of gestation. INTERVENTIONS: All umbilical cord management strategies, including immediate cord clamping (ICC), delayed cord clamping (DCC), intact umbilical cord milking (I-UCM), cut umbilical cord milking (C-UCM), intact cord stabilisation (ICS), physiology-based cord clamping and extrauterine placental perfusion. MAIN OUTCOME MEASURES: Any grade IVH (grades I-IV) and severe IVH (grades III-IV). DATA SYNTHESIS: Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% CIs. Analyses were stratified for very preterm (<32 weeks) and extremely preterm neonates (<28 weeks). RESULTS: Forty-nine studies with 8706 neonates were included. Thirty-five direct comparisons between strategies were made, but no clear evidence of benefit or harm emerged. Certainty of evidence ranged from moderate to very low, often downgraded due to imprecision, risk of bias and inconsistency. The most frequent comparison was DCC versus ICC, with 14 studies (RR 0.90, CI 0.65 to 1.26) for any grade IVH and 11 studies (RR 1.14, CI 0.69 to 1.87) for severe IVH. The second most common comparison, DCC versus I-UCM, showed no benefit: RR 1.03 (CI 0.80 to 1.32; eight studies, 2200 participants) and RR 0.77 (CI 0.35 to 1.66; seven studies, 2032 participants). ICS versus DCC was the only comparison which was rated as moderate certainty of evidence for both, any grade IVH (RR 0.96, CI 0.82 to 1.13) and severe IVH (RR 0.91, CI 0.62 to 1.35). CONCLUSIONS: No umbilical cord management strategy was clearly associated with increased or decreased IVH risk. Evidence certainty was generally low to very low, primarily due to bias and imprecision.
19 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Closed-loop automated oxygen control in preterm ventilated infants: a randomised controlled trial
OBJECTIVE: To compare the duration of mechanical ventilation between preterm infants receiving closed-loop automated oxygen control (CLAC) or manual oxygen control. DESIGN: Randomised controlled trial. SETTING: Tertiary neonatal unit in London, UK. PATIENTS: Infants (n=69) with a median (IQR) gestational age of 27.0 (25.6-29.0) weeks studied at a corrected postmenstrual age of 27.6 (25.9-29.1) weeks. INTERVENTIONS: Infants were randomised to CLAC or manual oxygen control within 48 hours of initiation of mechanical ventilation if less than 7 days of age until successful extubation. MAIN OUTCOME MEASURES: Duration of mechanical ventilation. RESULTS: The CLAC infants (n=34) compared with those who received manual control had a shorter duration of mechanical ventilation (median (range): 11 (1-57) vs 40 (3-134) days, p=0.027), a shorter duration of supplemental oxygen (median (range): 33 (0-100) vs 47 (3-335) days, p=0.031), a lower incidence of bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (55% vs 83.9%, p=0.015) and fewer required home oxygen (26.5% vs 51.4%, p=0.016). In the CLAC infants, the time spent in the target oxygen range (91%-95%) was increased (p<0.001) and the times spent in hypoxaemia (peripheral oxygen saturation level (SpO2)<85%) and hyperoxaemia (SpO2>95%) were reduced (p<0.001). CONCLUSIONS: Use of CLAC in preterm, ventilated infants was associated with improved achievement of oxygen saturation targets, shorter durations of mechanical ventilation and supplemental oxygen treatment and a lower incidence of BPD. These results need to be replicated in larger multicentre studies before any change in routine practice could be recommended. TRIAL REGISTRATION NUMBER: NCT05030337.
19 Apr 2026
Read appraisal →Archives of disease in childhood. Fetal and neonatal edition
Intermittent hypoxia and caffeine in infants born preterm: the ICAF Randomized Clinical Trial
OBJECTIVE: To determine whether extending caffeine therapy through 43 weeks' postmenstrual age (PMA) decreases intermittent hypoxia (IH) in convalescing preterm infants. Secondary objectives were to assess caffeine effects on changes in inflammation-related plasma biomarkers and brain MRI. DESIGN: Multicentre masked randomised trial. SETTING: 16 US hospitals. PATIENTS: Infants at <30 weeks + 6 days gestational age on caffeine between 32 weeks and 36+5 days PMA in room air with routine caffeine discontinuation prior to 36 weeks +6 days. INTERVENTION: Randomisation to caffeine or placebo and treated through 42 completed weeks. Pulse oximetry was recorded from enrolment through 1 week after stopping study drug. Blood for 12 inflammation-related biomarkers obtained at enrolment and 38 weeks' PMA and brain imaging after enrolment or <3 days of randomisation, and study end. MAIN OUTCOME MEASURE: Seconds/hour of oxygen saturation <90% from randomisation to study end. RESULTS: Randomised 160 subjects, 78 placebo, 82 caffeine. IH was less at every PMA with caffeine treatment from 34 (172.7 (123.4, 241.7); 84.7 (64.4, 111.4, p<0.01) through 41 weeks (73.0 (51.3, 103.7); 26.6 (18.5, 38.2, p<0.001). Adjusted TNF-α levels were 23% lower at follow-up in the caffeine group compared with placebo (p<0.02), without other biomarker differences. Paired brain imaging found no significant differences. CONCLUSIONS: Extended caffeine reduced the burden of IH in very preterm infants and may reduce inflammation. Further study is needed to determine if this effect of caffeine is associated with reduced risk of adverse outcomes. TRIAL REGISTRATION NUMBER: NCT03321734.
19 Apr 2026
Read appraisal →Sleep
Fetal sleep: a cross-species review of physiology, measurement, and classification
STUDY OBJECTIVES: Fetal sleep is a vital yet underexplored aspect of prenatal neurodevelopment. Its cyclic organization reflects the maturation of central neural circuits, and disturbances in these patterns may offer some of the earliest detectable signs of neurological compromise. This is the first review to integrate more than seven decades of research into a unified, cross-species synthesis of fetal sleep. We examine: (1) Physiology and Ontogeny-comparing human fetuses with animal models; and (2) Methodological Evolution-transitioning from invasive neurophysiology to non-invasive monitoring and deep learning frameworks. METHODS: A structured narrative synthesis was guided by a systematic literature search across four databases (PubMed, Scopus, IEEE Xplore, and Google Scholar). From 2925 identified records, 169 studies involving fetal sleep-related physiology, sleep-state classification, or signal-based monitoring were included in this review. RESULTS: Across the 169 studies, fetal sleep states become clearly observable as the brain matures. In fetal sheep and baboons, organized cycling between active and quiet sleep emerges at approximately 80%-90% gestation. In humans, this differentiation occurs later, around 95% gestation, with full maturation reached near term. Despite extensive animal research, no unified, clinically validated framework exists for defining fetal sleep states, limiting translation into routine obstetric practice. CONCLUSIONS: By integrating evidence across species, methodologies, and clinical contexts, this review provides the scientific foundation for developing objective, multimodal, and non-invasive fetal sleep monitoring technologies-tools that may ultimately support earlier detection of neurological compromise and guide timely prenatal intervention.
17 Apr 2026
Read appraisal →Journal of the American College of Surgeons
Effect of Adhesion Barrier Use During Ladd Procedure for Intestinal Malrotation on Postoperative Midgut Volvulus and Postoperative Small-Bowel Obstruction: A Retrospective Cohort Study Using a National Inpatient Database
BACKGROUND: Postoperative midgut volvulus is a life-threatening complication after the Ladd procedure. An adhesion barrier to prevent postoperative small-bowel obstruction could increase postoperative midgut volvulus incidence due to reduced adhesions. We aimed to examine the effect of adhesion barrier use during Ladd procedures on postoperative midgut volvulus and postoperative small-bowel obstruction. STUDY DESIGN: We retrospectively identified patients younger than 18 years who underwent the Ladd procedure between July 2010 and March 2021, using a Japanese nationwide inpatient database. We used propensity score overlap-weighting analyses to compare reoperation for midgut volvulus, rehospitalization, and operation for small-bowel obstruction, mortality, total rehospitalization length, and total rehospitalization cost within 1 year after the Ladd procedure between patients in whom adhesion barrier was used (barrier group) and patients in whom it was not used (nonbarrier group). RESULTS: Of the 1,159 eligible patients, adhesion barrier was used in 314 and not used in 845 patients. The proportion of reoperations for midgut volvulus did not differ between the barrier and nonbarrier groups (3.5% vs 2.7%; risk difference 0.8%, 95% CI -1.9 to 3.5). The proportion of rehospitalization due to small-bowel obstruction was lower in the barrier group than in the nonbarrier group (2.6% vs 6.3%; risk difference -3.6%, 95% CI -6.6 to -0.8). No significant differences were observed in operation for small-bowel obstruction, mortality, and total length and cost of rehospitalization. CONCLUSIONS: The use of adhesion barrier during the Ladd procedure can prevent rehospitalization due to postoperative small-bowel obstruction without increasing the incidence of postoperative midgut volvulus.
17 Apr 2026
Read appraisal →European journal of pediatrics
Effect of intranasal breast milk administration on cerebral oxygenation, vital signs, and transition time to full oral feeding in preterm infants: a randomized controlled study
UNLABELLED: This study examined the effects of intranasal breast milk administration on cerebral oxygenation, vital signs, and time to transition to full oral feeding in preterm infants. This assessor-blinded, randomized controlled trial included 40 preterm infants with gestational ages between 28+0 and 36+6 weeks. Infants in the intervention group received 0.2 mL of fresh breast milk intranasally three times daily for 3 days. The control group continued to receive routine clinical care. During each intervention period, cerebral oxygenation and vital signs were recorded at baseline (T0), 5 (T1), 15 (T2), and 30 (T3) minutes after the intervention. The time required for preterm infants to achieve full oral feeding was monitored until discharge. Cerebral oxygenation levels of preterm infants who received intranasal breast milk were significantly higher than the control group and respiratory rate was lower at some measurement times. No significant differences were found between groups in oxygen saturation, heart rate, time to full oral feeding, length of hospital stay, vomiting frequency and defecation frequency. CONCLUSION: Intranasal breast milk administration has the potential to increase cerebral oxygenation in preterm infants. The maintenance of oxygen saturation and heart rate, along with good tolerance of the procedure, suggests that this intervention may be safe and feasible. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov on 21 May 2024 (Identifier: NCT06706115). WHAT IS KNOWN: • Intranasal breast milk administration has been reported to have therapeutic potential in improving brain injury in preterm infants. • Intranasal administration of breast milk is known not to cause significant side effects in preterm infants diagnosed with intraventricular hemorrhage. WHAT IS NEW: • Intranasal breast milk administration may increase cerebral rSO₂ in preterm infants. • Intranasal breast milk administration did not affect preterm infants' heart rate, SpO₂ levels, time to transition to full oral feeding, length of hospital stay, daily vomiting, and stooling frequency.
17 Apr 2026
Read appraisal →European journal of pediatrics
7-days versus 14-days antibiotic therapy in uncomplicated culture proven neonatal sepsis: a randomized control assessor-blinded trial
UNLABELLED: The trial aimed to establish the non-inferiority of a 7-day antibiotic therapy for uncomplicated neonatal sepsis when compared to the standard 14-day therapy. This study was a parallel-group, randomized non-inferiority assessor-blinded trial conducted in a tertiary Neonatal Intensive Care Unit in Central India. Neonates weighing ≥ 1000 g with suspected sepsis were screened and those meeting criteria were enrolled. Exclusions included babies with CNS (central nervous system) infections, septic arthritis, and life-threatening congenital malformations. Participants were observed for 7 days on antibiotics and re-evaluated; those with positive blood cultures were then randomized to receive either 7 or 14 days of antibiotics. The primary outcome was the relapse of sepsis, and a sample size of 70 in each arm was calculated based on a non-inferiority margin. Follow-ups were conducted for 48 h post-antibiotic treatment and weekly for 35 days to monitor any recurrence of illness. During the study, 917 babies with suspected sepsis were admitted, of which 256 had culture-positive sepsis. After excluding those with meningitis, staphylococcus, and fungal infections, 140 babies showed improvement at day 5 and were randomized into two groups: one receiving antibiotics for 7 days and the other for 14 days, each consisting of 70 babies. Klebsiella pneumoniae was the prevalent organism. The 7-day group had a shorter hospital stay (p < 0.05) and less respiratory support (p < 0.05). Outcomes revealed a low incidence of probable relapse in both groups, with no fatalities or definitive relapses recorded. CONCLUSIONS: A 7-day antibiotic regimen for uncomplicated neonatal sepsis is not inferior to a 14-day regimen. WHAT IS KNOWN: • Unregulated use of antibiotics can lead to a myriad of problems, especially in neonates. • There is some evidence that uncomplicated neonatal sepsis can be treated with short-course antibiotics. WHAT IS NEW: • Data is lacking-especially from Central India. • This trial checks if it is possible to reduce the duration of antibiotic therapy in uncomplicated neonatal sepsis.
16 Apr 2026
Read appraisal →The Cochrane database of systematic reviews
Insulin-like growth factor-1 for the prevention or treatment of retinopathy of prematurity
RATIONALE: Retinopathy of prematurity (ROP) is a disorder of the developing retina in which abnormal proliferation of retinal blood vessels may lead to severe visual compromise or retinal detachment in infants born preterm. Insulin-like growth factor-1 (IGF-1) promotes normal retinal vessel growth in utero; however, IGF-1 levels fall substantially following preterm birth. By returning IGF-1 to in utero levels, postnatal treatment with IGF-1 may interrupt ROP pathogenesis, preventing disease or reducing its severity. OBJECTIVES: To compare treatment with IGF-1 to standard care or placebo for the prevention of retinopathy of prematurity or treatment of early retinopathy of prematurity. SEARCH METHODS: We used CENTRAL, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Issue 3, 2025, in the Cochrane Library, CINAHL Plus with Full Text (EBSCOhost), Epistemonikos, clinical trials registries (US National Library of Medicine Clinicaltrials.gov, World Health Organization's International Trials Registry Platform, and ISRCTN Registry), together with reference checking and citation searching to identify studies that are included in this review. The latest search date was 10 March 2025. ELIGIBILITY CRITERIA: We considered all randomized controlled trials (RCTs), cluster-RCTs, and quasi-RCTs comparing IGF-1 with standard care or placebo for the prevention of ROP or treatment of early ROP in preterm infants. We planned to exclude cross-over randomized trials. OUTCOMES: Our outcomes of interest were: • Development of Type 1 ROP, defined as ROP requiring treatment at any time during the birth hospitalization or outpatient follow-up • Development of ROP ≥ stage 3 at any time during the birth hospitalization or outpatient follow-up • Development of ROP of any severity at any time during the birth hospitalization or outpatient follow-up • Occurrence of one or more serious adverse events (SAEs) at any time during the birth hospitalization • Mortality during the birth hospitalization • Hypoglycemia during the birth hospitalization RISK OF BIAS: We used the original Cochrane Risk of Bias 1 tool (RoB 1) to assess possible bias in the included studies. SYNTHESIS METHODS: Dichotomous data were reported using risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Where possible, we synthesized results for each outcome using meta-analysis with fixed-effect models. We used GRADE to assess the certainty of evidence for each outcome. INCLUDED STUDIES: We included two studies totaling 140 participants. Both included studies were parallel-group RCTs performed between 2011 and 2016 enrolling extremely preterm infants in well-resourced settings in Europe and North America. The two published primary study references describe a two-center RCT (n = 19) and a 20-center RCT (n = 121) comparing treatment starting on the first day of life with intravenous IGF-1 (as mecasermin rinfabate) to standard care for prevention of ROP in newborn infants at 23 weeks' to 27 weeks plus six days' gestational age with follow-up through 40 weeks' postmenstrual age. SYNTHESIS OF RESULTS: Type 1 ROP/ROP requiring treatment Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of Type 1 ROP/ROP requiring treatment (RR 0.94, 95% CI 0.38 to 2.35; P = 0.90; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP ≥ stage 3 Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of severe ROP (RR 1.27, 95% CI 0.61 to 2.65; P = 0.52; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP of any severity Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of ROP of any severity (RR 1.30, 95% CI 0.94 to 1.80; P = 0.12; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). SAEs during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the occurrence of one or more SAEs during the birth hospitalization in preterm infants (RR 1.18, 95% CI 0.94 to 1.47; P = 0.15; I2 = 65%; 2 studies, 140 infants; very low-certainty evidence). Post-hoc sensitivity analysis including only the larger RCT demonstrated an increased risk of experiencing one or more SAEs with IGF-1 compared to controls (RR 1.28, 95% CI 1.01 to 1.62, P = 0.05; RD 0.17, 95% CI 0.01 to 0.33, P = 0.04; number needed to treat for an additional harmful outcome (NNTH) 5.9; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). All-cause mortality during the birth hospitalization Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo on all-cause mortality during the birth hospitalization in preterm infants (RR 1.69, 95% CI 0.71 to 3.99; P = 0.23; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). Hypoglycemia during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the incidence of hypoglycemia in preterm infants during the birth hospitalization (RR 1.00, 95% CI 0.62 to 1.63; P = 0.99; I2 = 0%; 2 RCTs, 140 infants; very low-certainty evidence). We assessed all results to be of very low certainty due to small total enrollment and substantial risk of bias. Both included studies had a high risk of bias in two domains. In addition, both were funded by industry. AUTHORS' CONCLUSIONS: The available data are of very low certainty, and so we are not able to draw conclusions about the effects of treatment with IGF-1 in preterm infants for preventing or treating ROP, or about its effects on risk of serious adverse events, mortality, or hypoglycemia in this population. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD013216.
16 Apr 2026
Read appraisal →European journal of pediatrics
Multi-directional phototherapy vs. unidirectional phototherapy from below for severe neonatal jaundice: a randomized pilot trial in home phototherapy
UNLABELLED: Severe neonatal jaundice is a common problem, carrying a risk of neurologic toxicity. Phototherapy has become the standard treatment for jaundiced infants, eliminating the need for exchange transfusion and the risk of neurotoxicity. We hypothesized that treatment with multi-directional phototherapy would be more rapid than with single-direction, high-intensity treatment from below (unidirectional) in the home setting. We performed a prospective, randomized, pilot trial comparing high-intensity multi-directional phototherapy to high-intensity unidirectional treatment in the home setting. Treatment time was determined from device timers. Serum bilirubin levels were obtained daily and as ordered by the pediatrician, serving as a basis for estimating the bilirubin reduction rates. Eight infants were treated with multi-directional phototherapy; nine were treated with unidirectional phototherapy. Multi-directional treatment was more rapid with treatment time of 15.1 ± 6.4 h vs. 25.1 ± 11.8 h; p = 0.05. The estimated rate of bilirubin reduction was more rapid with multi-directional phototherapy 0.40 ± 0.21 vs. 0.14 ± 0.10 mg/dL/h; p < 0.02. CONCLUSION: Multi-directional phototherapy was more rapid than treatment with unidirectional phototherapy in the home setting. TRIAL REGISTRATION: ISRCTN88608924 29 January 2026, retrospectively registered. WHAT IS KNOWN: •Home phototherapy for hyperbilirubinemia is safe and effective. •Treatment times with fiberoptic and wearable devices in the home setting can be lengthy and complicated by overheating and readmission. WHAT IS NEW: •Home phototherapy with multidirectional illumination is more effective than unidirectional undersurface phototherapy. •Multidirectional home phototherapy can lower bilirubin levels at a rate comparable to hospital devices.
15 Apr 2026
Read appraisal →European journal of pediatrics
Randomised crossover trial of neurally adjusted ventilatory assist (NAVA) for neonates with congenital diaphragmatic hernias: the NAN-C study
Retrospective studies comparing NAVA to assist control ventilation (ACV) in neonates with congenital diaphragmatic hernia (CDH) have shown that ventilatory mode may improve respiratory parameters. The aim of this study is to determine if infants with CDH studied post-operatively had a lower oxygenation index (OI) on NAVA compared to ACV. This dual-centre randomised cross-over trial compared post-operative NAVA with ACV in infants with CDH. Infants were randomised to receive either NAVA or ACV first in a 1:1 ratio for a 4-h period. At the end of each 4-h period, blood gas analysis was performed and the OI calculated. The inspired oxygen concentration (FiO2), the peak inflation (PIP), and mean airway pressure (MAP) were averaged from the last 5 min on each mode. Eleven infants were randomised. Nine infants completed the trial. with median gestational age of 38 (range 34.6-39.3) weeks and median postnatal age of 7 (range 5-36) days. Eight had left-sided CDH, six had patch repair and two had thoracoscopic repair. The mean OI after 4 h on NAVA was 3.9 ± 1.8 compared to 5.9 ± 1.61 on ACV (p = 0.008). The peak Edi (6.05 ± 4.5 versus 9.86 ± 7.3 µV, p = 0.028), PIP (17 ± 6.3 versus 22 ± 5.3 cmH2O, p = 0.017), and MAP (8.7 ± 2.6 versus 11.1 ± 1.8 cmH2O, p = 0.008), expiratory tidal volume (5.06 ± 0.71 versus 9.86 ± 1.29 ml/kg, p = 0.043) were lower on NAVA versus ACV. Two infants were randomised, but the trial was stopped due to a low Edi signal.Conclusion: NAVA compared to ACV improved oxygenation postoperatively in infants with CDH. On NAVA, infants had lower oxygen indices, peak Edi, expiratory tidal volume and peak and mean airway pressures.
10 Apr 2026
Read appraisal →BMJ paediatrics open
Impact of parent education programmes on confidence and self-efficacy in parents of preterm infants: a systematic review
OBJECTIVE: Families of preterm infants can experience high stress during neonatal intensive care unit (NICU) hospitalisation, which interferes with the development of parenting confidence and self-efficacy through active engagement with their infants. Parent NICU support programmes provide guidance and education to build this connection. This systematic review examined the effects of parent education programmes on confidence and self-efficacy among parents of preterm infants. DESIGN: Systematic review in PubMed/Medline, PsycINFO, CINAHL, Google Scholar and Web of Science. SETTING: NICU. PARTICIPANTS: Parents of preterm infants. INTERVENTION: Education programmes offered to parents in the NICU. MAIN OUTCOME MEASURES: Quantitative surveys measuring parent confidence or self-efficacy. RESULTS: 14 studies met inclusion criteria from an initial 220 identified. Five were randomised controlled trials and nine were non-randomised studies. Programmes combining information delivery with opportunities for parent-infant engagement were most effective. Infant access and time to practise skills were key factors in transferring programme knowledge to increase parent confidence and self-efficacy. While 6 of the 14 studies did not show statistically significant differences between groups, all interventions demonstrated improvements in parental confidence or self-efficacy from baseline. Vast variability in duration of intervention, proper descriptions of facilitator trainings, methodological limitations and potential confounding factors reduced the overall quality of evidence to a low level. CONCLUSION: Both unit-specific programmes developed within individual NICUs and commercially available, copyrighted parent education programmes hold value. They are generally effective in building parent confidence and self-efficacy among parents of preterm infants. Integrating either type of programme into standard NICU care may hold promise for strengthening parental competence and promoting family-centred outcomes. Clarity on content/topics of programmes, duration and level of facilitator trainings can strengthen the process of supporting parents in the NICU, even in low resource settings. PROSPERO REGISTRATION NUMBER: CRD42024524063.
4 Apr 2026
Read appraisal →Developmental cognitive neuroscience
Deep learning in fetal, infant, and toddler neuroimaging research.
Artificial intelligence (AI) is increasingly being integrated into everyday tasks and work environments. However, its adoption in medical image analysis has progressed more slowly due to high clinical stakes, limited availability of labeled data, and substantial variability in imaging protocols and population. These challenges are further pronounced in the field of fetal, infant, and toddler (FIT) neuroimaging, where datasets are especially scarce and subject to large amounts of anatomical variability. However, deep learning (DL), a specific method within machine learning, which is itself a subfield of AI, has emerged as a powerful framework to adapt to the challenges of medical image analysis. This review is written for the broad FIT research community, including clinicians, neuroscientists, and develop mental scientists who may not have formal training in AI. To make the material accessible, we provide a concise overview of DL concepts before reviewing a selected, and non-exhaustive, list of applications of DL in FIT neuroimaging, including structural image analysis, enhancement of data acquisition, modeling of cognitive and perceptual processes, and automated video tagging. In closing, we discuss best practices for data curation, ongoing challenges, and opportunities for future research.
4 Apr 2026
Read appraisal →Nat Med
Feasibility and clinical utility of expanded genomic newborn screening in the Early Check program
Although genomic sequencing presents groundbreaking newborn screening (NBS) opportunities, critical feasibility and utility questions remain. Here we present initial results from the Early Check program-an observational study assessing the feasibility and clinical utility of genomic NBS in North Carolina. Recruitment was statewide through mailed letters with electronic consent. Genome sequencing with analysis of 169 high actionability genes (plus 29 optional lower actionability genes) was performed using residual NBS dried blood spots. In 8 months, 1,979 newborns were screened, with 50 (2.5%) screen positives. Negative results were returned electronically, positive results by genetic counselors. Twenty-eight results (55%) were true positives, all received anticipatory guidance, surveillance and management recommendations, and referral to specialists as appropriate. We report technical feasibility and preliminary clinical utility finding, along with interpretation and follow-up challenges that hinder public health implementation. We propose standardized terminology to facilitate cross-study comparisons and accurate characterization of genomic NBS outcomes.
1 Nov 2025
Read appraisal →