Acute Kidney Injury in Neonates: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: There is a paucity of pooled synthesized data on the epidemiology of neonatal acute kidney injury (AKI). Our objective with this study is to systematically assess the worldwide incidence of AKI in neonates. METHODS: We searched 3 electronic databases (Embase, PubMed, Web of Sciences) from January 2004 to December 2022 without language restrictions. We included cohort and cross-sectional studies that reported the incidence of AKI or associated mortality in neonates. Eligible studies had at least 10 participants and used standard criteria (Acute Kidney Injury Network/Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE)/ Kidney Disease Improving Global Outcomes) to define AKI. Two authors independently retrieved data on demographic characteristics, clinical setting, and outcomes (incidence and AKI-associated mortality) using a semi-structured proforma and assessed the risk of bias. We used a random-effects meta-analysis to calculate pooled estimates with 95% confidence intervals. RESULTS: We included 201 studies (98 228 participants) from 45 countries. The incidence of any stage AKI was 30% (95% confidence interval 28-32), and that of severe AKI was 15% (14-16). Overall, AKI-associated mortality was 30% (27-33). The odds of mortality were higher (odds ratio 3.4; 2.9-4.0) in neonates with AKI compared with those without AKI. We found that perinatal asphyxia, sepsis, patent ductus arteriosus, necrotizing enterocolitis, and nephrotoxic medications were significant risk factors for AKI. Significant heterogeneity in the pooled estimates was a limitation of this study. CONCLUSIONS: AKI was observed in one-third of the neonates and was associated with increased risk of mortality. The incidence of AKI was almost similar in neonates with perinatal asphyxia and sepsis, but mortality was higher in the former group.

Imparting child nutritional assessment skills among medical students using hybrid problem-based learning approach in a community setting.

Background: Malnutrition affects up to a third of children in India, with severe and acute malnutrition prevalent among under five children. Nutritional assessment skills for detecting malnutrition in children in primary care settings are vital. Hybrid problem-based learning (HPBL) is an innovative, collaborative, and adaptable instructional learning strategy that can be used to teach medical students clinical skills in a community setting. Methods: A two-month quasi-experimental study was undertaken in a rural setting with third-year medical students. Faculty members were sensitized and subject experts developed a training module addressing the knowledge, attitude, communication, and practice domains. The students underwent a 3-week training module where pre-testing, case presentation, and group formation in first week, an anchoring lecture, tutorial and self-directed learning and role-play by students in subsequent week, and in last week, case discussion, post-testing, and feedback rounds were done. Results: In all domains, knowledge (3.8, 0.01), practice (4.3, 0.01), attitude and communication (3.7, 0.01), and proportional satisfactory responses, the HPBL approach resulted in a significant improvement in nutritional assessment competency. Teachers preferred the practical and engaging character of the approach, stating that doubts and questions were better addressed and that they would use it to teach similar topics. Conclusion: HPBL is an excellent teaching method for clinical skills, like nutritional assessment in simulated/field settings. The novel teaching-learning approach was well received by students and faculty members. Learning outcomes and satisfaction rates enhanced in students and faculty were encouraged to apply the approach to other topics.

Role of nebulised magnesium sulfate in treating acute asthma in children: a systematic review and meta-analysis.

OBJECTIVES: To review the efficacy of nebulised magnesium sulfate (MgSO4) in acute asthma in children. METHODS: The authors searched Medline, Embase, Web of Science and Cochrane Library for randomised controlled trials (RCTs) published until 15 December 2023. RCTs were included if they compared the efficacy and safety of nebulised MgSO4 as a second-line agent in children presenting with acute asthma exacerbation. A random-effects meta-analysis was performed, and the Risk of Bias V.2 tool was used to assess the biases among them. RESULTS: 10 RCTs enrolling 2301 children with acute asthma were included. All trials were placebo controlled and administered nebulised MgSO4/placebo and salbutamol (±ipratropium bromide). There was no significant difference in Composite Asthma Severity Score between the two groups (6 RCTs, 1953 participants; standardised mean difference: -0.09; 95% CI: -0.2 to +0.02, I2=21%). Children in the MgSO4 group have significantly better peak expiratory flow rate (% predicted) than the control group (2 RCTs, 145 participants; mean difference: 19.3; 95% CI: 8.9 to 29.8; I2=0%). There was no difference in the need for hospitalisation, intensive care unit admission or duration of hospital stay. Adverse events were minor, infrequent (7.3%) and similar among the two groups. CONCLUSIONS: There is low-certainty evidence that nebulised MgSO4 as an add-on second-line therapy for acute asthma in children does not reduce asthma severity or a need for hospitalisation. However, it was associated with slightly better lung functions. The current evidence does not support the routine use of nebulised MgSO4 in paediatric acute asthma management. PROSPERO REGISTRATION NUMBER: CRD42022373692.

The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

Management of Urinary Tract Infections and Vesicoureteric Reflux: Key Updates From Revised Indian Society of Pediatric Nephrology Guidelines 2023.

Non-specific symptoms and difficulty in collecting urine specimens make the diagnosis of urinary tract infection (UTI) challenging in children. However, timely diagnosis and initiation of therapy are essential to prevent complications. Children with recurrent UTIs require detailed evaluation and follow-up for optimal management. We report key updates from the revised evidence-based practice guidelines of the Indian Society of Pediatric Nephrology for UTIs and primary vesicoureteric reflux.

Effect of oropharyngeal colostrum therapy on neonatal sepsis in preterm neonates: A systematic review and meta-analysis.

Various studies have shown that oropharyngeal colostrum application (OPCA) is beneficial to preterm neonates. We performed a systematic review and meta-analysis to assess whether OPCA reduces the incidence of culture-proven neonatal sepsis in preterm neonates. Randomized controlled trials comparing OPCA with placebo or standard care in preterm neonates were included. Medline, Embase, Web of Science, Cumulated Index to Nursing and Allied Health Literature, Scopus, and CENTRAL were searched for studies published up to June 15, 2023. We used the Cochrane Risk of Bias tool, version 2, for risk of bias assessment, the random-effects model (RevMan 5.4) for meta-analysis, and Gradepro software for assessing the certainty of evidence. Twenty-one studies involving 2393 participants were included in this meta-analysis. Four studies had a low risk of bias, whereas seven had a high risk. Oropharyngeal colostrum significantly reduced the incidence of culture-proven sepsis (18 studies, 1990 neonates, risk ratio [RR]: 0.78, 95% confidence interval [95% CI]: 0.65, 0.94), mortality (18 studies, 2117 neonates, RR: 0.73, 95% CI: 0.59, 0.90), necrotizing enterocolitis (NEC) (17 studies, 1692 neonates, RR: 0.59, 95% CI: 0.43, 0.82), feeding intolerance episodes (four studies, 445 neonates, RR: 0.59, 95% CI: 0.38, 0.92), and the time to full enteral feeding (19 studies, 2142 neonates, mean difference: -2 to 21 days, 95% CI: -3.44, -0.99 days). There was no reduction in intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, ventilator-associated pneumonia, neurodevelopmental abnormalities, hospital stay duration, time to full oral feeding, weight at discharge, pneumonia, and duration of antibiotic therapy. The certainty of the evidence was high for the outcomes of culture-positive sepsis and mortality, moderate for NEC, low for time to full enteral feeding, and very low for feeding intolerance. OPCA reduces culture-positive sepsis and mortality (high certainty), NEC (moderate certainty), and time to full enteral feeding (low certainty) in preterm neonates. However, scarcity of data from extremely premature infants limits the generalizability of these results to this population.

Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance.

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as 5-fluorouracil-resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil-resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.

Evidence-based clinical practice guideline for management of urinary tract infection and primary vesicoureteric reflux.

We present updated, evidence-based clinical practice guidelines from the Indian Society of Pediatric Nephrology (ISPN) for the management of urinary tract infection (UTI) and primary vesicoureteric reflux (VUR) in children. These guidelines conform to international standards; Institute of Medicine and AGREE checklists were used to ensure transparency, rigor, and thoroughness in the guideline development. In view of the robust methodology, these guidelines are applicable globally for the management of UTI and VUR. Seventeen recommendations and 18 clinical practice points have been formulated. Some of the key recommendations and practice points are as follows. Urine culture with > 104 colony forming units/mL is considered significant for the diagnosis of UTI in an infant if the clinical suspicion is strong. Urine leukocyte esterase and nitrite can be used as an alternative screening test to urine microscopy in a child with suspected UTI. Acute pyelonephritis can be treated with oral antibiotics in a non-toxic infant for 7-10 days. An acute-phase DMSA scan is not recommended in the evaluation of UTI. Micturating cystourethrography (MCU) is indicated in children with recurrent UTI, abnormal kidney ultrasound, and in patients below 2 years of age with non-E. coli UTI. Dimercaptosuccinic acid scan (DMSA scan) is indicated only in children with recurrent UTI and high-grade (3-5) VUR. Antibiotic prophylaxis is not indicated in children with a normal urinary tract after UTI. Prophylaxis is recommended to prevent UTI in children with bladder bowel dysfunction (BBD) and those with high-grade VUR. In children with VUR, prophylaxis should be stopped if the child is toilet trained, free of BBD, and has not had a UTI in the last 1 year. Surgical intervention in high-grade VUR can be considered for parental preference over antibiotic prophylaxis or in children developing recurrent breakthrough febrile UTIs on antibiotic prophylaxis.

Cost analysis of telemedicine use in paediatric nephrology-the LMIC perspective.

BACKGROUND: The overall cost of managing chronic diseases is a significant barrier to accessing complete and timely healthcare, especially in rural and geographically isolated areas. This cost disparity becomes more pronounced in the case of children and more so in under-resourced regions of the world. In the era of COVID-19, as the need for physical distancing increased, there was a transition in approach to healthcare provision to telemedicine consultations. This study evaluates the cost saving using teleconsultations in a paediatric nephrology clinic. METHODS: This prospective cohort study was conducted at AIIMS Jodhpur, a tertiary care centre in western Rajasthan from March 2021 to October 2022. All consecutive paediatric (29 days-18 years) patients attending telemedicine services for kidney-related illness were enrolled. Basic demographic details were collected. Cost analysis was done after 6 months, regarding perceived cost savings for the patient and family by using telehealth for follow-up during 6 months starting from enrolment. RESULTS: A total of 112 patients were enrolled; 266 teleconsultations attended; 109 patients who could be followed up saved INR 457,900 during 6 months of follow-up. The average cost saving was INR - 1577/patient/visit. Patients saved 4.99% of the family income (median 2.16% (IQR 0.66-5.5)). The highest expenditure per visit was incurred for food and transport. The median distance from the residence to the clinic was 122.5 km (IQR 30-250). Over the 6-month study period, patients saved a travel distance of 83,274 km (743 km/patient). CONCLUSIONS: The use of telemedicine as a follow-up method helps save significant costs and distances travelled by patients. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Periodic Rotation versus Continuous Application of Same Nasal Interface for Non-invasive Respiratory Support in Preterm Neonates: A Systematic Review and Meta-analysis.

OBJECTIVES: To review whether the periodic rotation of nasal mask with binasal prongs is superior to continuous application of either of the interfaces in preterm infants on non-invasive positive pressure respiratory support. METHOD: The authors searched Medline, CINAHL, Embase, Web of Science, and CENTRAL for randomized controlled trials (RCTs) comparing periodic rotation of the two interfaces (mask or prongs) against the continuous application of either, in preterm infants on nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV). They performed a random-effects meta-analysis using RevMan 5.4. The primary outcome was the incidence of moderate to severe nasal injury. Other outcomes included any nasal injury, need for invasive ventilation, duration of respiratory support, hospital stay, and mortality. RESULTS: Four RCTs (520 participants) were included. There was no difference in the incidence of moderate to severe nasal injury between periodic rotation vs. continuous nasal mask (3 RCTs, 293 participants; RR: 1.75, 95% CI: 0.73-4.19), or periodic rotation vs. continuous binasal prongs (3 RCTs, 296 participants; RR: 0.40, 95% CI: 0.14-1.11). Periodic rotation lowered the incidence of any grade nasal injury compared to continuous binasal prongs (RR: 0.61, 95% CI: 0.49-0.75) but not compared to continuous nasal mask (RR: 1.38, 95% CI: 0.92-2.06). Periodic rotation was associated with longer non-invasive respiratory support (compared to prongs) and prolonged hospital stay (compared to masks). There were no significant differences in other clinical outcomes. CONCLUSIONS: Among preterm infants receiving non-invasive respiratory support, periodically rotating a nasal mask with short binasal prongs may not be superior to the continuous application of nasal masks.

Blueprint designing and validation for competency-based curriculum for theory assessment in community medicine.

Background: Blueprint provides a base for assessment by assigning proportionate weightage to various content areas and helps the paper setter to construct a uniform and valid assessment. This study aimed to design and validate a blueprint for theory in Community Medicine as per the new curriculum for Medical Undergraduates in India. Methods: Blueprint in community medicine was designed by assigning impact score (I) and frequency score (F) for the competencies. Blueprint was validated using the Content Validity Index (CVI), and inter-rater agreement for subject experts using Fleiss' kappa statistics was calculated. Feedback from faculty and students was obtained afterward to assess the postimplementation response. Results: Blueprint was designed by an expert group where impact score and frequency score were assigned to 146 competencies in the theory of Community Medicine. In Delphi survey I, 63.2% of subject experts responded, while in Delphi survey II, a response rate of 58.3% was achieved. Value of the Fleiss' Kappa test for an inter-rater agreement was 0.68, i.e. "substantial agreement," while CVI among the raters came out to be 0.86, i.e. overall valid assessment. Feedback of faculty (n = 11) suggested that the blueprint was helpful and standardized the paper setting, whereas feedback from students (n = 138) depicted that it helped in preparing for exams, and they would recommend it to other students. Conclusion: Validated blueprint by consensus of subject experts has impact score and frequency score along with topic-wise distribution of marks for the convenience of faculty and its utility is well proven among learners too.

Use of exemplars-based feedforward to improve the performance of medical students in constructed response assessment.

Background: Exemplars are the graded responses to theory questions from previous examinations and are considered as means to guide students about what is valued by assessors; hence giving feed forward to students before the exam and developing self-regulated learning among students. The present study was undertaken to compare the effect on performance of students between intervention (didactic lecture and exemplar) and control group (didactic lecture). Methods: This study was an interventional study conducted among 256 students of a medical college in Rajasthan, India. Participants were randomized to either the control group A or to the interventional group B. Outcomes included a post intervention test evaluating the knowledge gained after the session and students 'attitudes about the same. A focus group discussion was conducted investigating the perceptions. The feedback from faculty was also taken. Results: The mean post test score of intervention group was found to be 6.1 ± 1.74 and of the control group was 5.5 ± 1.6; significantly higher with p-value of 0.03. Out of 128 participants in group B, majority (n = 94,73%) believed that exemplars improve learning and created their interest in topic (n = 78, 60.9%). Most of students (66%) were of the opinion that exemplars should be regularly used with didactic lectures. Key themes identified from focus group were: advantages of the exemplars-based feedforward, challenges in implementation and ways to improve the method. Conclusion: Exemplars improved the performance of students. The faculty members and students agreed that they are an effective tool to enhance learning.

Levetiracetam versus Phenobarbitone for Management of Neonatal Seizures: A Systematic Review and Meta-analysis.

OBJECTIVES: To review whether levetiracetam is non-inferior to phenobarbitone as the first-choice antiseizure medication (ASM). METHODS: The authors searched Medline, Embase, Web of Science, Scopus, and Cochrane Library for randomized controlled trials (RCTs) published until May 31, 2023. RCTs comparing the efficacy and safety of levetiracetam and phenobarbitone as first-line ASM in neonatal seizures were included. Random effects meta-analysis was performed, and the Risk of Bias version 2 tool was used for quality assessment. RESULTS: Eleven RCTs enrolling 821 neonates [mostly term, with hypoxic-ischemic encephalopathy (HIE)] were included. There was no significant difference in seizure control between levetiracetam and phenobarbitone (10 RCTs, 786 participants; relative risk RR: 1.11; 95% CI: 0.79, 1.54; I2- 88%). Neonates in the levetiracetam group had a significantly lower incidence of hypotension (RR: 0.28; 95% CI: 0.09, 0.86), respiratory depression (RR: 0.36, 95% CI: 0.19, 0.66), and depressed sensorium (RR: 0.52, 95% CI: 0.27, 1.00). Three studies compared neurodevelopmental outcomes; however two of them were cross-over trials where infants received both drugs. Only one RCT enrolled pure cohorts and showed better neurodevelopment in the levetiracetam group at one month of age. CONCLUSIONS: With the limitation of very-low certainty evidence, the results of this systematic review suggest that levetiracetam may be non-inferior to phenobarbitone for managing neonatal seizures. Considering a better safety profile and marginally better neurodevelopment in the short term, levetiracetam may be considered an initial choice for managing neonatal seizures. REGISTRATION NUMBER: PROSPERO (CRD42023438018).

Spectrum and Trends of Intestinal Parasitic Infections at a Tertiary Care Hospital during Pandemic Times: A Laboratory-Based Retrospective Study.

Introduction Intestinal parasitic infections continue to loom in developing countries with low sanitation and socioeconomic conditions. Pandemic times are especially important to study the prevalence of these pathogens since the focus of all healthcare services was coronavirus disease 2019 (COVID-19). This study aimed to evaluate the prevalence and time-trend of intestinal parasitic infections in the capital region of India during the pandemic times. Methods In this cross-sectional study, a retrospective review based on data from the past 2 years in the post-COVID-19 pandemic was used. Descriptive and time-trend analyses were applied to the data. Time series analysis was analyzed using the best fit autoregressive integrated moving average (ARIMA) model to look for seasonality in trends and forecasting. Results A total of 7267 patients' stool samples over a 2-year pandemic period were included in the study. Intestinal parasites were detected in 11.18% (813/7276) patients. Giardia lamblia (2.28%) and Blastocystis hominis (3.78%) were the predominant ones. Time-trend analysis from 2020 to 2021 using ARIMA model predicted an increasing trend with waning of pandemic. The most prevalent infection was found in the monsoon and autumn months. Conclusion Rates of infection with Giardia lamblia and Blastocystis hominis have increased in comparison to other protozoan infections like Entamoeba histolytica when compared with prepandemic hospital-based studies. With fading of the pandemic, further increasing trends are predicted.

Mortality in Two Waves of COVID-19: A Comparative Analysis of a Tertiary Care Hospital in India.

Background COVID-19 has spread as two distinct surges of cases in many countries. Several countries have reported differences in disease severity and mortality in the two waves. Objective Compare the in-hospital mortality in the two COVID-19 waves at a tertiary care hospital in India. Methods We conducted a retrospective data collection. Distinct periods of surges in cases and admissions were defined as the first wave spanning from March 2020 to December 2020 and the second wave from April 2021 to June 21, 2021. The primary outcome of this study was to compare mortality rates in terms of total hospital mortality rate (TMR) and case fatality rate (CFR). Results Mortality rates of wave 2 were approximately 10 times that of wave 1 (TMR of 20.3% in wave 2 versus 2.4% in wave 1 and CFR of 1.5% versus 17.7% in wave 1 and 2, respectively). Mortalities in wave 2 had a larger proportion of severe disease at presentation, faster progression of symptoms to death, and more patients without any chronic comorbid condition dying due to the direct effect of COVID-19 acute respiratory distress syndrome (ARDS). Conclusion Our data matches the worldwide reported pooled hospital mortality figures and shows the comparative difference in disease severity between the two waves.

To feed or not to feed during therapeutic hypothermia in asphyxiated neonates: a systematic review and meta-analysis.

The practice of withholding feed during therapeutic hypothermia (TH) in neonates with hypoxemic ischemic encephalopathy (HIE) is based on conventions rather than evidence. Recent studies suggest that enteral feeding might be safe during TH. We systematically compared the benefits and harms of enteral feeding in infants undergoing TH for HIE. We searched electronic databases and trial registries (MEDLINE, CINAHL, Embase, Web of Science, and CENTRAL) until December 15, 2022, for studies comparing enteral feeding and non-feeding strategies. We performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II/III necrotizing enterocolitis (NEC). Other outcomes included the incidence of any stage NEC, mortality, sepsis, feed intolerance, time to full enteral feeds, and hospital stay. Six studies ((two randomized controlled trials (RCTs) and four nonrandomized studies of intervention (NRSIs)) enrolling 3693 participants were included. The overall incidence of stage II/III NEC was very low (0.6%). There was no significant difference in the incidence of stage II/III NEC in RCTs (2 trials, 192 participants; RR, 1.20; 95% CI: 0.53 to 2.71, I2, 0%) and NRSIs (3 studies, no events in either group). In the NRSIs, infants in the enteral feeding group had significantly lower sepsis rates (four studies, 3500 participants, RR, 0.59; 95% CI: 0.51 to 0.67, I2-0%) and lower all-cause mortality (three studies, 3465 participants, RR: 0.43; 95% CI: 0.33 to 0.57, I2-0%) than the infants in the "no feeding" group. However, no significant difference in mortality was observed in RCTs (RR: 0.70; 95% CI: 0.28 to 1.74, I2-0%). Infants in the enteral feeding group achieved full enteral feeding earlier, had higher breastfeeding rates at discharge, received parenteral nutrition for a shorter duration, and had shorter hospital stays than the control group.  Conclusion: In late preterm and term infants with HIE, enteral feeding appears safe and feasible during the cooling phase of TH. However, there is insufficient evidence to guide the timing of initiation, volume, and feed advancement. What is Known: • Many neonatal units withhold enteral feeding during therapeutic hypothermia, fearing an increased risk of complications (feed intolerance and necrotizing enterocolitis). • The overall risk of necrotizing enterocolitis in late-preterm and term infants is extremely low (< 1%). What is New: • Enteral feeding during therapeutic hypothermia is safe and does not increase the risk of necrotizing enterocolitis, hypoglycemia, or feed intolerance. It may reduce the incidence of sepsis and all-cause mortality until discharge.

Biomarkers for prediction of acute kidney injury in pediatric patients: a systematic review and meta-analysis of diagnostic test accuracy studies.

BACKGROUND: Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury further. Novel biomarkers may aid in the early detection of AKI. The utility of these biomarkers across various clinical settings in children has not been evaluated systematically. OBJECTIVE: To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients. DATA SOURCES: We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022. STUDY ELIGIBILITY CRITERIA: Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included. PARTICIPANTS AND INTERVENTIONS: Participants in the study included children (aged less than 18 years) at risk of AKI. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the QUADAS-2 tool for the quality assessment of the included studies. The area under the receiver operating characteristics (AUROC) was meta-analyzed using the random-effect inverse-variance method. Pooled sensitivity and specificity were generated using the hierarchical summary receiver operating characteristic (HSROC) model. RESULTS: We included 92 studies evaluating 13,097 participants. Urinary NGAL and serum cystatin C were the two most studied biomarkers, with summary AUROC of 0.82 (0.77-0.86) and 0.80 (0.76-0.85), respectively. Among others, urine TIMP-2*IGFBP7, L-FABP, and IL-18 showed fair to good predicting ability for AKI. We observed good diagnostic performance for predicting severe AKI by urine L-FABP, NGAL, and serum cystatin C. LIMITATIONS: Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Urine NGAL, L-FABP, TIMP-2*IGFBP7, and cystatin C showed satisfactory diagnostic accuracy in the early prediction of AKI. To further improve the performance of biomarkers, they need to be integrated with other risk stratification models. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021222698). A higher resolution version of the Graphical abstract is available as "Supplementary information".