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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 metaanalysis 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. [ABSTRACT FROM AUTHOR]

Context Many preterm neonates often cannot be fed enterally and hence do not receive the benefits of colostrum. Oropharyngeal application of colostrum is a novel way of harnessing the immunological benefits of colostrum. Randomized controlled trials (RCTs) investigating the efficacy of this approach have shown variable results. Objective The aim of this systematic review was to synthesize available data on the effect of oropharyngeal application of colostrum or mother's own milk (CMOM) in preterm infants. Data Sources Six electronic databases (MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library) were searched until January 13, 2022. Only RCTs comparing oral application of CMOM with placebo/routine care in preterm infants were eligible. Studies enrolling term neonates or administering enteral feeds were excluded. Data Extraction Two investigators independently extracted data using a structured proforma. Data Analysis The Cochrane Risk of Bias 2 tool was used to assess bias. Random-effects meta-analysis was undertaken using RevMan 5.4 software. From 2787 records identified, 17 RCTs enrolling 4106 preterm infants were included. There was no significant difference between groups in incidence of necrotizing enterocolitis (NEC) stage 2 or higher (RR = 0.65; 95%CI, 0.36–1.20; 1089 participants in 12 trials). Application of CMOM significantly reduced the incidence of sepsis (RR = 0.72; 95%CI, 0.56–0.92; 1511 participants in 15 studies) and any stage of NEC (RR = 0.58; 95%CI, 0.37–0.92; 1616 participants in 16 trials). The CMOM group achieved full enteral feeds 1.75 days sooner (95%CI, 0.3–3.2 days; 1580 participants in 14 studies) and had higher weight at discharge (MD = 43.9 g; 95%CI, 3–85 g; 569 participants in 3 studies). There were no statistically significant differences in other outcomes. Conclusions Evidence with low to very low certainty suggests CMOM has a beneficial effect on NEC (any stage), sepsis, and time to full enteral feeds. Given its low cost and minimal risk of harm, routine CMOM use may be considered in preterm neonates. Prospero Registration Number CRD42021262763 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To synthesize the current evidence for the presence of SARS-CoV-2 RNA in the human milk of mothers with confirmed COVID-19 and its potential role in neonatal SARS-CoV-2 infection. Materials and methods: Using terms related to novel coronavirus 2019 and human milk, a systematic search was performed in three electronic databases (PubMed, EMBASE, and Web of Science) for studies published between December 2019 and 15 October 2020. Published peer-reviewed studies reporting the results of RT-PCR for SARS-CoV-2 RNA in human milk in mothers with confirmed COVID-19 were included. Proportion meta-analysis of case series and prospective cohort studies was performed using STATA version 14.2 (StataCorp, College Station, TX) and pooled estimate (with 95% confidence interval) of overall incidence of SARS-CoV-2 transmission was calculated. Results: We identified 936 records, of which 34 studies (24 case-reports, 10 cohort studies) were eligible for this systematic review. A total of 116 confirmed COVID-19 lactating women (88 in cohort and 28 in case-reports) underwent RT-PCR testing in human milk, and 10 (six in case reports) were detected to have SARS-CoV-2 RNA. The overall pooled proportion (from cohort studies) for SARS-CoV-2 RNA detection in human milk was 2.16% (95% CI: 0.0–8.81%, I²: 0%). Four studies (six patients) also reported the presence of SARS-CoV-2 specific antibodies (along with RT-PCR) in human milk. Conclusions: The limited low-quality evidence suggests that SARS-CoV-2 RNA is detected in human milk in an extremely low proportion, however, based on current evidence no conclusion can be drawn about its infectivity and impact on the infants. In concordance with World Health Organization recommendations, exclusive breastfeeding should be considered in all cases unless any other contraindication exists. [ABSTRACT FROM AUTHOR]

Early recognition of patients at risk for severe acute kidney injury (AKI) by renal angina index (RAI) may help in the early institution of preventive measures. Objective was to evaluate performance of RAI alone or in combination with biomarkers in predicting severe AKI (KDIGO stage 2 and 3 or equivalent) and receipt of kidney replacement therapy (KRT) in critically ill children. We searched PubMed, EMBASE, Web of Sciences, and CENTRAL for studies published till May 2021. Search terms included acute kidney injury, pediatrics, adolescent, renal angina index, and biomarker. Proceedings of relevant conferences and references of included studies were also scrutinized. Two reviewers independently assessed the study eligibility. Cohort and cross-sectional studies evaluating the diagnostic performance of RAI in predicting AKI or receipt of KRT in children were included. Eligible participants were the children less than 18 years with RAI assessment on day 0 ofadmission. We followed PRISMA-DTA guidelines and used the QUADAS-2 tool for quality assessment. A bivariate model for meta-analysis was used to calculate the summary estimates of diagnostic parameters. Major outcomes were the diagnostic accuracy of RAI (≥ 8) alone or with biomarkers in predicting severe AKI and KRT receipt. Diagnostic accuracy was reported using summary sensitivity, specificity, and area under the curve (AUC). Overall, 22 studies (24 reports, 14,001 participants) were included. RAI ≥ 8 on day 0 has summary sensitivity, specificity, and AUC of 0.86 (95% CI, 0.77–0.92), 0.77 (0.68–0.83), and 0.88 (0.85–0.91) respectively for prediction of severe AKI on day 3. In comparison, a combination of RAI and urinary neutrophil gelatinase-associated lipocalin (NGAL) showed summary sensitivity, specificity, and AUC of 0.76 (0.62–0.85), 0.89 (0.74–0.96), and 0.87 (0.84–0.90) respectively for predicting severe AKI. The sensitivity, specificity, and AUC of RAI for predicting receipt of KRT were 0.82 (0.71–0.90), 0.74 (0.66–0.81), and 0.85 (0.81–0.88) respectively. In meta-regression, only the study setting (sepsis vs. heterogenous) was associated with heterogeneity. We observed substantial heterogeneity among eligible studies. Five studies had concerns in patient selection, and seven studies also had applicability concerns in patient selection for this review. Moderate certainty evidence showed that RAI ≥ 8 has good predicting ability in recognizing children at risk of severe AKI and receipt of KRT. The combination of urinary NGAL and RAI further improves the predicting ability (low-certainty evidence). Further studies are required on the context-driven assessment of novel biomarkers in the early prediction of AKI in RAI-positive children. Systematic review registration number: CRD4202122268. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Evidence from randomized controlled trials (RCTs) suggests that three-hourly feeding is safe and might help achieve full feeds earlier in preterm infants. We systematically compared the benefits and harms of three-hourly and two-hourly feeding schedules in preterm infants. We searched electronic databases (MEDLINE, CINAHL, Embase, Web of Science, and Scopus) and trial registries until November 16, 2021, for RCTs comparing the two feeding schedules. We did a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II or III necrotizing enterocolitis (NEC). Other outcomes were the incidence of any stage NEC, mortality, time to full enteral feeds, and hospital stay. Six trials (872 participants) are included. There was no significant difference in the incidence of stage II/III NEC (3 trials; 530 participants; RR 1.39; 95% CI: 0.53, 3.65; I2 − 0%, low certainty), and any stage NEC (5 studies; 767 participants; RR 0.98; 95% CI: 0.53, 1.82; I2 -0%, very low certainty) between three and two-hourly feeding groups. There was no difference in achieving full feeds (5 trials; 755 participants; MD: − 0.0 days; 95% CI: − 0.32, 0.31, low certainty) or other outcomes. On subgroup analysis, neonates with birthweight < 1000 g and in the three-hourly feeding regime achieved full enteral feeds slower than those in the two-hourly feeding group (1 trial; 84 participants; MD: 2.9 days, 95% CI: 1.16, 4.64, low certainty). Conclusion: In stable preterm infants (1000–1500 g), three-hourly feeding can be followed safely. In infants < 1000 g, there is insufficient evidence to advise on an optimal feeding interval, although a 2-h interval might be preferable. Prospero Registration Number: CRD42021246568. What is Known: • Most of the units follow two-hourly feeding schedules without any evidence. • Recent trials suggest that the three hourly feeding schedules can be safely followed in stable preterm infants. What is New: • Low certainty evidence suggests that three-hourly feeding is safe in stable preterm infants (1000-1500 grams). • In infants with birthweight <1000 grams, two-hourly feeding may be considered as it was associated with a shorter time to full feeds in subgroup analysis. [ABSTRACT FROM AUTHOR]

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness. [ABSTRACT FROM AUTHOR]

Background & objectives: Congenital anomalies lead to significant morbidity and mortality. Systematically published data on the prevalence and spectrum of congenital anomalies from India are scarce. This study was aimed to ascertain the prevalence, spectrum, trend, and outcome of congenital anomalies at a tertiary care centre in north India over two decades. Methods: Electronic records of all live births from January 1998 to December 2017 were retrieved, and the neonates with congenital anomaly were included in this retrospective analysis. International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) was used for uniformity and international comparison. The further sub-categorization was done as per the WHO birth defects surveillance manual. The prevalence of individual as well as overall congenital anomalies was calculated. Run charts were used to analyze the trends. Results: In the two decades studied (1998-2017), there were 86850 live births, of which 1578 [1.82%, 95% confidence interval (CI): 1.73-1.91%] neonates had a major congenital anomaly. The overall prevalence of anomalies was 182 (95% CI: 173-191) per 10,000 live births. Malformation of the circulatory system was the most common (28.0%) followed by musculoskeletal (18.6%) and urinary system (14.3%). Congenital anomaly-related death rate was 6.78 per 1000 live births. No significant trend was observed in the annual prevalence, individual malformations or contribution of congenital anomalies to overall mortality over the two decades. Interpretation & conclusions: Our results showed a high prevalence of congenital anomalies which could be responsible for significant mortality, warranting the need for a national surveillance programme and birth defect services. It is important to have a national database to know the overall burden and spectrum of congenital anomalies in the country. [ABSTRACT FROM AUTHOR]

Despite lack of evidence, the practice of routine prefeed gastric residue aspiration before the next feed is common. Recent studies suggest that this practice might be even harmful. Therefore, we aimed to evaluate the effect of avoiding routine prefeed gastric residue aspiration as compared to routine aspiration, on various clinical outcomes in preterm infants. We searched five different electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library) until March 8, 2021. Only randomized controlled trials comparing the practice of routine prefeed gastric aspiration with no routine aspiration in preterm infants were considered eligible. The random-effects meta-analysis was done using RevMan 5.3 software. Of the 894 unique records identified by our search, we included 6 studies (451 participants) in the review. There was no significant difference in the incidence of necrotizing enterocolitis (RR 0.80; 95% CI 0.31 to 2.08; 421 participants in 5 trials). Avoiding routine prefeed aspiration was associated with achieving full enteral feeds earlier (MD − 3.19 days, 95% CI − 4.22 to − 2.16), shorter duration of hospitalization (MD − 5.32 days; 95% CI − 10.25 to − 0.38), and lower incidence of late-onset sepsis (RR 0.77; 95% CI 0.60 to 0.99). Time to regain birth weight, days of total parenteral nutrition or central venous line usage, culture-positive sepsis, and all-cause mortality did not differ between the two groups. Conclusion: In the absence of other signs of feed intolerance, routine prefeed gastric residue aspiration should be avoided in preterm infants. Prospero registration number: CRD42020197657 What is Known: • Though, routine prefeed aspiration before next feed is a common practice in preterm gavage-fed infants. • Recent study suggests that the omission of routine gastric residual evaluation led to improved weight gain and earlier hospital discharge. What is New: • Low- to moderate-quality evidence suggest that avoiding routine prefeed gastric residue monitoring helps in the reduction of late-onset sepsis, achieving full enteral feeds earlier, and earlier discharge from the hospital. • Abandoning the practice of routine prefeed aspiration in absence of other signs of feed intolerance in preterm low birthweight neonates is safe. [ABSTRACT FROM AUTHOR]

Background: The majority of the children with SARS-CoV-2 infection present with respiratory symptoms, hence various chest imaging modalities have been used in the management. Knowledge about the radiological findings of coronavirus disease (COVID-19) in children is limited. Hence, we systematically synthesized the available data that will help in better management of COVID-19 in children.Methods: Four different electronic databases (MEDLINE, EMBASE, Web of Science and CENTRAL) were searched for articles reporting radiological findings in children with COVID-19. Studies reporting thoracic radiological findings of COVID-19 in patients aged <19 years were included. A random-effect meta-analysis (wherever feasible) was performed to provide pooled estimates of various findings.Results: A total of 1984 records were screened of which forty-six studies (923 patients) fulfilled the eligibility criteria and were included in this systematic review. A chest computed tomography (CT) scan was the most frequently used imaging modality. While one-third of the patients had normal scans, a significant proportion (19%) of clinically asymptomatic children had radiological abnormalities too. Unilateral lung involvement (55%) was frequent when compared with bilateral and ground-glass opacities were the most frequent (40%) definitive radiological findings. Other common radiological findings were non-specific patchy shadows (44%), consolidation (23%), halo sign (26%), pulmonary nodules and prominent bronchovascular marking. Interstitial infiltration being the most frequent lung ultrasound finding.Conclusion: CT scan is the most frequently used imaging modality for COVID-19 in children and can detect pneumonia before the appearance of clinical symptoms. Undefined patchy shadows, grand-glass opacities and consolidation are commonly observed imaging findings in COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to systematically synthesize the currently available literature on various modes of transmission (congenital, intrapartum, and postpartum), clinical features and outcomes of SARS-CoV-2 infection in neonates.Methods: We conducted a comprehensive literature search using PubMed, EMBASE, and Web of Science until 9 June 2020. A combination of keywords and MeSH terms, such as COVID-19, coronavirus, SARS-CoV-2, 2019-nCoV, severe acute respiratory syndrome coronavirus 2, neonates, newborn, infant, pregnancy, obstetrics, vertical transmission, maternal-foetal transmission and intrauterine transmission, were used in the search strategy. We included studies reporting neonatal outcomes of SARS-CoV-2 proven pregnancies or neonatal cases diagnosed with SARS-CoV-2 infection.Results: Eighty-six publications (45 case series and 41 case reports) were included in this review. Forty-five case series reported 1992 pregnant women, of which 1125 (56.5%) gave birth to 1141 neonates. A total of 281 (25%) neonates were preterm, and caesarean section (66%) was the preferred mode of delivery. Forty-one case reports describe 43 mother-baby dyads of which 16 were preterm, 9 were low birth weight and 27 were born by caesarean section. Overall, 58 neonates were reported with SARS-CoV-2 infection (4 had a congenital infection), of which 29 (50%) were symptomatic (23 required ICU) with respiratory symptoms being the predominant manifestation (70%). No mortality was reported in SARS-CoV-2-positive neonates.Conclusion: The limited low-quality evidence suggests that the risk of SARS-CoV-2 infections in neonates is extremely low. Unlike children, most COVID-positive neonates were symptomatic and required intensive care. Postpartum acquisition was the commonest mode of infection in neonates, although a few cases of congenital infection have also been reported. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection. We searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model. Pooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00–1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31–1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55–4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58–1.88). HCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background and Objective: Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically synthesize the data on the efficacy and safety of phenobarbitone as a first-line agent and compare it against other anti-epileptic drugs (AEDs) in neonates.Methods: Using keywords related to the study population (neonatal seizure) and intervention (phenobarbitone), we searched CENTRAL, Embase, PubMed and Web of Science until 15 December 2020. Randomized controlled trials (RCTs) comparing phenobarbitone with any other AED as first-line therapy for seizure control in the neonates were considered eligible. The random-effect meta-analysis was done using RevMan 5.3 software.Results: We screened through 443 records and identified nine eligible studies (719 participants). Five RCTs comparing phenobarbitone with levetiracetam did not find any difference in seizure control with the first dose [risk ratio (RR) 1.43, 95% CI 0.79-2.57] or adverse effects (RR 4.66; 95% CI 0.33-65.83). Two trials comparing phenobarbitone and phenytoin also did not find any difference in seizure control with the first dose (RR 2.09; 95% CI 0.31-14.03) and other outcomes. Only one RCT compared phenobarbitone and lorazepam and found lorazepam to be more efficacious in seizure control with the first dose (RR 0.71; 95% CI 0.53-0.94). Three trials compared neurodevelopmental outcomes, in which levetiracetam was better in two, whereas one did not find any difference.Conclusion: Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam. The data over the long-term neurodevelopmental outcome are lacking. The existing evidence is insufficient to recommend other drugs over phenobarbitone. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Thrombocytopenia is associated with late closure of patent ductus arteriosus (PDA). There are few studies evaluating platelet transfusions to treat PDA. We compared liberal platelet-transfusion criteria (to maintain a platelet count >100 000 per µL) versus standard criteria achieve earlier PDA closure among thrombocytopenic preterm neonates (<35 weeks' gestation) with hemodynamically significant PDA (hs-PDA) presenting within the first 2 weeks of life. METHODS: Thrombocytopenic (<100 000 per µL) preterm neonates with hs-PDA were enrolled and randomly allocated to the liberal and standard transfusion groups: 22 in each arm. They underwent echocardiography daily until closure of PDA, completion of 120 hours follow-up, or death. All subjects received standard cotreatment with nonsteroidal antiinflammatory drugs. Primary outcome of time to PDA closure was compared by survival analysis. Multivariate Cox proportional hazard regression was performed with randomization group, baseline platelet count, gestational age, and age at enrollment as predictor variables. RESULTS: Median time to PDA closure was 72 (95% confidence interval [CI] 55.9-88.1) versus 72 (95% CI 45.5-98.4) hours in the liberal versus restrictive transfusion groups, respectively (unadjusted hazard ratio 0.88 [95% CI 0.4-1.9]; P = .697). Despite adjusting for potential confounders, there was no significant difference in time to PDA closure. In the liberal transfusion group, 41% of infants had any grade of intraventricular hemorrhage compared with 4.5% in the restrictive group (P = .009). CONCLUSIONS: Attempting to maintain a platelet count >100 000 per µL by liberally transfusing platelets in preterm thrombocytopenic neonates with hs-PDA does not hasten PDA closure. [ABSTRACT FROM AUTHOR]

Background: Exchange transfusion (ET) for hyperbilirubinemia is associated with many complications. The complications are underreported as most of the published studies are retrospective, used varying definitions of adverse events (AEs) and variable follow-up periods. Aim: We evaluated the incidence of clinical, biochemical, hematological, and radiological AEs, including serious AEs, within 2 weeks of ET for hyperbilirubinemia in neonates, using standard definitions. Materials and Methods: This prospective observational study was conducted in level III newborn unit of north India from February 2008 to February 2009. We enrolled consecutive inborn and outborn neonates admitted with hyperbilirubinemia and required ET. Babies requiring partial exchange for anemia/polycythemia or ET for indications other than hyperbilirubinemia were excluded. They were prospectively monitored for clinical, biochemical, hematological, and radiological AEs up to 2 weeks following the procedure. We calculated the incidence/AE rate (AER) as the rate of events per 100 ET and compared them among various groups using the Chi-square test. The SPSS v20 was used for the analysis, and value of P < 0.05 was considered as statistically significant. Results: A total of 202 neonates were screened and 141 neonates (182 ET) were enrolled. The overall AER was 112/100 ETs. The most common AE was biochemical (45.6/100 ET), followed by hematological (44.5/100 ETs), clinical (15.9/100 ETs), and radiological (8.9/100 ETs). Severe AER was 12.6/100 ETs. The AER was significantly more in lower gestation and birth weight groups. Conclusion: ET is a high-risk procedure and should be performed only when the benefit of the procedure offsets the risks. [ABSTRACT FROM AUTHOR]

Since May 2022, there have been more than 85,000 cases of Mpox worldwide, of which approximately 0.1% are in the paediatric age group (<18 years) [[1]]. Both parents had Mpox infection and were in close contact with the infant, and the transmission route was most probably perinatally acquired from caregivers (although vertical transmission cannot be ruled out as the placenta was not examined). [Extracted from the article]

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). [ABSTRACT FROM AUTHOR]

Background: One-third of children with type 1 diabetes mellitus manifest with diabetic ketoacidosis (DKA). Most children presenting with DKA are in a volume-depleted state, leading to acute kidney injury (AKI). Besides volume depletion, hyperglycemia can induce tubular injury and kidney inflammation. Therefore, a thorough knowledge of incidence of AKI, risk factors, and outcomes in pediatric DKA is desirable to improve its management and outcomes. Objective: To synthesize currently available evidence on the incidence, risk factors, and outcomes of AKI in children with DKA. Data sources: We searched three electronic databases (EMBASE, PubMed, and Web of Science) from inception to September 2022 for original studies reporting AKI in children with DKA. Search strategies for the individual databases were drafted using free text words and MeSH incorporating "acute kidney injury" and "diabetic ketoacidosis." Study eligibility criteria: Cohort and cross-sectional studies reporting AKI in children with type 1 DM and DKA were included. Participants and interventions: Children (aged less than 18 years) with type 1 DM and DKA. Study appraisal and synthesis methods: The critical appraisal tool of NHLBI for cohort studies was used to assess the quality of the studies. We estimated the pooled incidence of AKI with 95% CI in children with DKA using a random effects model. The primary outcome was the pooled incidence of AKI during the DKA episodes. Results: Twenty-one studies assessing 4087 children (4500 DKA episodes) reported AKI during DKA episodes. The pooled incidence of any stage of AKI during the DKA episode was 47% (95% CI: 40 to 55). Severe AKI was observed in 28% (21 to 35) of DKA episodes; however, only 4% (1 to 11%) of children with AKI received dialysis. Low serum bicarbonate, low corrected sodium, higher blood sugar, and high blood urea nitrogen at presentation have been reported to be associated with the development of AKI. Conclusion: AKI developed in almost half of the DKA episodes, and every fourth DKA episode was associated with severe AKI. The recovery rate from DKA-associated AKI appears to be high; however, further studies are needed to assess the exact impact of AKI on long-term outcomes. Registration: PROSPERO (CRD42022303200). [ABSTRACT FROM AUTHOR]

Dear Editor, We read the recent systematic review by Gu et al. [[1]] on the efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia. The forest plot for meta-analysis of exchange transfusion shows that in the Saeidi et al. study [[5]] there was one event in the fluid supplementation group and six events in the control group. Moreover, when there is no difference in the duration of phototherapy and the need for exchange transfusion, this therapy cannot be recommended. [Extracted from the article]

Background: Preterm neonates are not able to breastfeed due to immature sucking swallow reflexes and are kept on an alternative method of feeding until they are able to do so. The time to reach full oral feeds and breastfeed, the duration of feeding, and spillage are important parameters that need to be observed so that a baseline value can be provided, which can help healthcare professionals see the progression and appropriateness of feeding preterm neonates. Objective: To assess the duration of feeding, spillage, weight changes, days to reach full oral feeds, full breastfeed, and length of hospitalization among preterm neonates. Material and Methods: A descriptive study was carried out on 106 preterm neonates in the step-down unit of the NICU, PGIMER, Chandigarh. The variables under study were duration of feeding, spillage, weight changes, days to reach full oral feeds, days to reach full breastfeed, and length of hospitalization. The tools for data collection used were a socio-demographic profile along with a clinical profile of neonates, a neonatal assessment, and an observation sheet to record spillage and duration of feeding. The methods of data collection used were observation and biophysiological methods. Weight was assessed by the infant weighing scale present in the unit (in grams) and to measure spillage, a bib was used, and its pre- and post-feeding weight was measured on a diaper weighing machine. The values are expressed in grams. The data were collected from July 2021 to November 2021. The data are analyzed using the SPSS version 23.0. Results: The results showed that neonates took an average of mean ± SD (range) 15.0 ± 3.12 (10−26) min to complete one feeding session, and spillage was around 1.37± 0.3 (0.8−2.3) g. The transition time to full oral feeds was 8.01 ± 7.21 (1–44) days, and the average time to reach full breastfeed was 26.7 ± 12.1 (5−56) days. Conclusion: The present study has provided valuable data on duration of feeding and spillage that serves as a guide for the amount of milk that can be added to the prescribed feed. The information is also helpful in educating the parents to be patient while feeding the baby and wait for at least 3 weeks to 2 months to reach full breastfeed. Gestational age at birth and birth weight affect (negative correlation) the time to reach full oral feeds, breastfeed, and length of hospital stays (p <.05). [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: There is limited literature on the incidence of acute kidney injury (AKI) and associated mortality in hospitalized children. To systematically assess the worldwide incidence of AKI in hospitalized children to inform policymakers regarding appropriate health resource allocation. METHODS: Three different databases were searched (PubMed, Embase, Web of Sciences) from March 2012 to January 2022 without language or geographical restrictions. We included cohort and cross-sectional studies that reported AKI incidence in hospitalized children. Eligible studies had at least 100 participants and used the standard Kidney Disease Improving Global Outcomes criteria to define AKI. Two authors extracted data on the study and patients' characteristics and outcomes (incidence and AKI-associated mortality) and performed the risk of bias assessment. We used a random-effects meta-analysis to generate pooled estimates. RESULTS: We included 94 studies (202 694 participants) from 26 countries. The incidence of any AKI was 26% (95% confidence interval: 22-29), and that of moderate-severe AKI was 14% (11-16). The incidence of AKI was similar in high-income 27% (23-32), low-middle-income 25% (13-38), and low-income 24% (12-39) countries. Overall, AKI-associated mortality was observed in 11% (9-13) of the pediatric population. AKI-associated mortality rate was highest at 18% (11-25) and 22% (9-38) in low-income and low-middle-income countries, respectively. CONCLUSIONS: AKI was observed in one-quarter of the hospitalized children and is associated with increased mortality risk. Low-income and low-middle-income countries had observed higher mortality rates compared with high-income countries despite a similar AKI burden. [ABSTRACT FROM AUTHOR]

Dear Sir, The trial by Balachander et al. [[1]] showed that ibuprofen and paracetamol (PCM) are equally efficacious for ductal closure in preterm infants. In the current era, there is a lot of controversy over the treatment of patent ductus arteriosus (PDA) and many of the centers prefer "not to treat" patent ductus arteriosus (PDA) in babies' > 32 weeks/1500 g [[3]]. Low platelet count is an independent predictor of delayed closure and treatment failure in PDA [[8]]. [Extracted from the article]

In spite of intensive research on the association between type 1 diabetes mellitus (T1DM) and neonatal hyperbili-rubinaemia, the mystery remains unsolved. A recently article by Liao et al. in Paediatrics and International Child Health estimated that neonates with hyperbilirubinaemia might have a 66% higher risk of developing T1DM in childhood [[1]]. Surprisingly, physiological hyperbilirubinaemia (which should be protective) appears to be a risk factor for T1DM but not pathological hyperbilirubinaemia (requiring phototherapy), which is not biologically plausible. [Extracted from the article]

In this correspondence, we raised our concerns about the methodological issues in the recent network meta-analysis by Yang et al. These issues require close attention because such meta-analysis forms the basis of major guidelines and helps clinicians make informed decisions. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To synthesize the evidence on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adolescents with overweight or obesity.For this systematic review and network meta‐analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta‐analysis to compare GLP‐1RAs and placebo, followed by a drug‐wise network meta‐analysis (NMA) to compare GLP‐1RAs against each other.We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP‐1RAs reduced weight (mean difference −4.21 kg, 95% confidence interval [CI] −7.08 to −1.35) and body mass index (BMI; mean difference −2.11 kg/m2, 95% CI −3.60 to −0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide.The evidence suggests that GLP‐1RAs reduce most weight‐related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head‐to‐head comparisons, pragmatic design, adiposity‐related outcomes, and economic evaluation can further guide the use and choice of GLP‐1RAs. [ABSTRACT FROM AUTHOR]

To the Editor, The trial by Cavallin et al. [[1]] showed that along with others, home delivery is an independent risk factor for the need of exchange transfusion in neonates. The authors mentioned various causes of death like kernicterus (28 cases), encephalopathy (eight cases), hyperbilirubinemia (seven cases), etc. Similarly, encephalopathy stands for bilirubin encephalopathy or its encephalopathy of another etiology, is not clear. [Extracted from the article]

The article by Bhasin et al. [[1]] compared various clinical, biochemical and echocardiographic markers of myocardial dysfunction in neonates with and without perinatal asphyxia. Despite the title (Myocardial dysfunction as a predictor of the severity and mortality of hypoxic-ischaemic encephalopathy in severe perinatal asphyxia: a case-control study), the results do not fully support it. The optimal way to present such conclusions in a case-control study is by calculating odds ratios and risk ratios. [Extracted from the article]

We read the article by Khuwuthyakorn et al. [[1]] which compared the efficacy of oral ibuprofen and oral indomethacin in very low-birthweight (VLBW) infants. Recent evidence shows that paracetamol is as effective as other therapies and remains a good alternative therapeutic agent when ibuprofen and indomethacin are contraindicated. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. [Extracted from the article]

We read with interest the article by Prashantha et al. regarding the safety of low-cost devices for therapeutic hypothermia (TH) in low- and middle-income countries (LMIC) such as India [[1]] and wish to make certain points. For it to be standard care in India, its long-term efficacy needs to be proved in large multi-centre randomised controlled trials (RCT) following standard study protocols. [Extracted from the article]

Cytomegalovirus (CMV) infection has been involved in vascular disease in immunodeficient adults. Here we report a 6-month-old boy with cytomegalovirus infection who developed medium vessel vasculitis along with coronary aneurysms. [ABSTRACT FROM AUTHOR]

A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56–1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28–0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29–0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56–1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21–0.69). Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions. What is Known: • Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance. • Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults. What is New: • Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract. • Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection has been involved in vascular disease in immunodeficient adults. Here we report a 6-month-old boy with cytomegalovirus infection who developed medium vessel vasculitis along with coronary aneurysms. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 12 year old boy, suffering from acute lymphoid leukemia (ALL) on Berlin-Frankfurt-Muenster (BFM) high-risk protocol and had fever up to 101-102 degree Fahrenheit along with neutropenia. Chest x-ray and contrast-enhanced computerized tomography (CECT) chest showed fungal infection in right upper zone. Ultrasound abdomen was done which showed a fungal ball in left kidney. Treating the ALL with chemotherapy.

The article presents the case of a two-month-old boy with congenital hydrocephalus and expert opinion on the condition. Other topics mentioned include the condition of the infant upon birth, results of clinical examination, possibility of atresia of foramina of Magendie and Luschka as a rare cause of obstructive hydrocephalus, and classical treatment.