Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 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 →Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Non-operative management of traumatic occipitocervical distraction injuries in children: a systematic review
PURPOSE: Existing guidelines for the management of atlanto-occipital dislocation (AOD) recommend occipitocervical fusion (OCF) for these low frequency, high-consequence injuries. Recent literature has questioned this guidance and provided case examples of successful non-operative management of a more inclusive and broadly defined spectrum of injuries to the occipitocervical junction (OCJ) termed occipitocervical distraction injuries (OCDI). A systematic review of existing literature on this topic would inform efforts to investigate the safety and efficacy of non-operative management of these injuries. METHODS: We performed a systematic review based on preferred reporting items for systematic reviews (PRISMA) guidelines of English language publications to define and map literature related to non-operative management of pediatric traumatic OCDI. RESULTS: We identified 40 patients in 21 manuscripts meeting defined inclusion and exclusion criteria. 82.5% of patients were successfully managed with non-operative management alone. No patient declined neurologically during orthotic treatment or in relation to crossover to surgical management through a minimum of 3-month follow-up. CONCLUSIONS: This review supports the contention that non-operative management is both safe and effective in the management of OCDI. Further research to develop standardized diagnostic and treatment protocols for non-operative management of OCDI through registries and multi-center research efforts is needed.
31 July 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 →Neurosurgical review
Mechanical thrombectomy for pediatric large-vessel occlusion: a systematic review and meta-analysis with post hoc analysis
OBJECTIVE: To investigate the outcome of pediatric large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). INTRODUCTION: Pediatric LVO is a rare subtype of ischemic stroke. In adults, MT is recommended; however, the efficacy and safety of MT in pediatric LVO are less explored. The available studies are mostly observational studies; yet, these studies show inconsistent findings. METHOD: This review adhered to the PRISMA 2020 guideline. Studies comparing MT with medical management in pediatric with LVO were included. The primary endpoint was the favourable outcome. The mortality rate was sought as well. Subgroup analysis compared MT with intravenous thrombolysis (IVT) and conservative management. Post hoc exploratory analyses comprised Bayesian inference and trial sequential analysis (TSA). RESULT: Six studies comprising a total of 230 MT-treated and 206 non-MT patients were included. In the primary analysis, favourable outcome did not differ significantly between the MT and medical management groups (OR 1.83; 95% CI 0.97-3.43), while supported by exploratory Bayesian inference (OR 1.75; 95% CrI 1.05-2.67; BF10 5.05). Subgroup analysis showed favourable outcomes of MT over IVT (OR 2.39; 95% CI 1.19-4.79) and conservative treatment (OR 2.22; 95% CI 1.41-3.51), although the Bayesian model did not support these findings. The available evidence was insufficient to detect or exclude a difference in mortality between MT and medical management (OR 1.32; 95% CI 0.45-3.89). TSA indicated that the required information size was not reached and that additional trials are needed to reach the minimum sample requirements. CONCLUSION: In this synthesis of observational data, the MT may be associated with favourable outcome in pediatric LVO, however, these findings are hypothesis-generating only. Adequately powered prospective studies are needed before MT can be recommended for pediatric LVO. CLINICAL TRIAL NUMBER: not applicable.
13 July 2026
Read appraisal →European journal of pediatrics
Pentoxifylline in children with acute encephalitis syndrome: a randomized control trial
Because of the excessive endogenous inflammatory mediators, acute encephalitis syndrome (AES) results in death, or sequelae in survivors. Pentoxifylline, a modulator of inflammation, can have beneficial role in AES. The primary objective was to assess the efficacy of pentoxifylline in terms of time taken for improvement in Glasgow coma scale (GCS) from baseline, in children with AES. The secondary objectives were adverse effects of pentoxifylline and frequency of sequelae among the survivors. This open-label randomized controlled trial (RCT) was conducted in a tertiary care teaching institution for 2 years (January 2022 to December 2023). Children aged 1 month to 14 years with a clinical diagnosis of AES were randomized to receive either standard treatment along with pentoxifylline or standard treatment alone. The data were recorded in case record forms. Forty-four children were randomized (median age, 77 months; male 72.7%). There was no significant difference in the time (median, IQR) taken for improvement of Glasgow coma scale (GCS) by 3 points or normalization between the pentoxifylline group [26 (19-50) hours] and control group [28 (16-52) hours] (p = 0.92). Other outcomes like requirement of mechanical ventilation, mortality, and sequalae were not significantly different between the two groups. The adverse event rate was also not different. Conclusion: Adjunctive pentoxifylline did not provide significant clinical benefit in children with AES, although it was safe and well tolerated. Larger, adequately powered multicenter trials with etiological stratification and biomarker integration are needed to identify potential subgroup benefits. What is Known: • Acute encephalitis syndrome (AES) is associated with high mortality and significant neurological sequelae, largely driven by host-mediated inflammatory responses. • No immunomodulatory adjunct therapy has yet shown proven benefit in pediatric AES. What is New: • Adjunctive pentoxifylline did not significantly improve neurological recovery or clinical outcomes in children with AES. • Pentoxifylline was safe and well tolerated, supporting further evaluation in larger, etiology-stratified trials.
29 May 2026
Read appraisal →BMJ paediatrics open
Prevalence of dysglycemia following paediatric cardiac surgery: a systematic review and meta-analysis
BACKGROUND: Postoperative dysglycemia is a common but under-recognised complication in paediatric cardiac surgery, driven by physiologic stress, hormonal changes and cardiopulmonary bypass. Reported prevalence varies widely, and no meta-analysis has synthesised the evidence. Therefore, this study aimed to estimate the pooled prevalence of postoperative dysglycaemia and describe associated postoperative outcomes, such as intensive care unit (ICU) stay and mechanical ventilation duration. METHODS: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines and the Joanna Briggs Institute (JBI) methodology for prevalence studies. Eligible studies included paediatric patients (≤18 years) undergoing cardiac surgery reporting postoperative dysglycaemia (hyperglycaemia or hypoglycaemia). A random-effects model was used to calculate pooled prevalence and 95%CIs, with logit transformation applied to prevalence proportions and heterogeneity assessed using I² statistics. Subgroup analyses were performed by region/continent, study design, age group and glycaemic threshold. All included studies were critically appraised using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised trials. The protocol was registered with PROSPERO (CRD420251161893). RESULTS: 22 studies involving 3864 patients were included. The pooled prevalence of postoperative dysglycemia was 68.6% (95% CI 52.8 to 81.0), with hyperglycaemia accounting for most cases (71.2%) and hypoglycaemia observed in 8.1%. Prevalence was higher in Asia and North America (~75%) than in Europe (45.2%), though not statistically significant. Studies using lower hyperglycaemia thresholds (126-139 mg/dL) reported significantly the highest prevalence (82.3%, p<0.032). The pooled mean ICU stay among dysglycemic patients was 180.3 hours (95% CI 82.3 to 279.3), and mean mechanical ventilation duration was 94.6 hours (95% CI 5.2 to 184.1). Sensitivity analyses showed that no single study disproportionately influenced the overall pooled estimates, and no publication bias was detected. The certainty of evidence assessed using the GRADE approach was moderate for overall dysglycemia prevalence. CONCLUSION: Dysglycaemia is highly prevalent following paediatric cardiac surgery, particularly hyperglycaemia, with prolonged ICU and mechanical ventilation times observed among affected patients. These findings underscore the need for vigilant perioperative glucose monitoring, standardised definitions of dysglycaemia, and evidence-based glycaemic management protocols. Future multicentre studies are warranted to establish optimal glycaemic thresholds and evaluate targeted interventions to improve postoperative outcomes in this vulnerable population.
15 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 →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 →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 →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
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