A meta-analysis and mapping of global mpox infection among children and adolescents.

Monkeypox (mpox) is a significant health concern affecting children and adolescents globally. This systematic review and meta-analysis aims to synthesise the available evidence on the proportion of children and adolescents affected by the mpox virus. A comprehensive search was conducted in seven electronic databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, EBSCOHost, and Cochrane) to identify the original reports on mpox cases in children and adolescents till 15 January 2023. Descriptive reports on probable or laboratory-confirmed mpox in children and adolescents (0-17 years old) were considered eligible. Studies not providing separate data for the above age group and case-control studies were excluded. The primary outcome was pooled proportion of mpox cases among children and adolescents. Proportion meta-analysis and heterogeneity between studies were determined using a restricted maximum likelihood estimator, and a random-effects model was fitted to the data. Sensitivity analysis and subgroup analysis were also conducted. A drapery plot was also provided as a complementary figure to the forest plot. The protocol was prospectively registered with PROSPERO (CRD42023392475). A total of 440 studies were identified, of which 37 were included in the review and 25 in the meta-analysis (62,701 participants with 3306 children and adolescents). The pooled proportion of children and adolescents was 0.46 (95% CI: 0.30-0.63, I2 :100%). The proportion of children and adolescents was significantly lower (p < 0.001) in the ongoing pandemic 0.04 (95% CI: 0.00-0.32) than before 2022 0.62 (95% CI: 0.49-0.74). The meta-regression showed that the higher the study's sample size, the lower the proportion of children among the mpox cases. Both overall and subgroup heterogeneity were high. Adolescents and children below 5 years are commonly affected by the ongoing pandemic. In conclusion, the high proportion of children affected by the mpox virus highlights the need for increased research and targeted interventions to prevent and control the spread of the virus in this population.

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.

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".

Incidence, predictors, and short-term outcomes of acute kidney injury in children with diabetic ketoacidosis: a systematic review.

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). A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Diagnostic accuracy of renal angina index alone or in combination with biomarkers for predicting acute kidney injury in children.

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.

Three-hourly versus two-hourly feeding interval in stable preterm infants: an updated systematic review and meta-analysis of randomized controlled trials.

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.

RAM cannula versus short binasal prongs for nasal continuous positive airway pressure delivery in preterm infants: a randomized, noninferiority trial from low-middle-income country.

To determine if RAM cannula is non-inferior to short binasal prongs (SBP) in providing nasal continuous positive airway pressure (CPAP) in preterm infants with respiratory distress syndrome (RDS). In this randomized, open-label, noninferiority trial from a low-middle-income country, we enrolled 254 preterm infants (28-34 weeks gestational age) with RDS who needed CPAP as primary respiratory support. The eligible infants were randomized to either RAM cannula or SBP interface groups. The primary outcome was CPAP failure (defined as the need for intubation or non-invasive positive pressure ventilation) within 72 h of randomization. The noninferiority margin was defined as a 10% or less absolute difference in CPAP failure rates. The secondary outcomes included nasal trauma and adverse events. We analyzed by per-protocol (primary) and intention to treat. CPAP failure has been seen in 25 infants (19.7%) in the RAM cannula group versus 22 (17.3%) in the SBP group (RD -2.36%; 95% CI -11.9 to 7.2 [beyond inferiority margin]; p = 0.6). Moderate and severe nasal trauma was less in RAM cannula (2.4 vs. 8.7%; RR 0.27; 95% CI 0.08-0.95; p 0.028). Duration of CPAP was also significantly shorter in the RAM cannula group (MD -12.4 h; 95% CI -20.34 to -4.46, p 0.017). There were no differences in other adverse events. CONCLUSIONS: RAM cannula was not non-inferior to SBP in providing CPAP to preterm infants with respiratory distress syndrome. TRIAL REGISTRATION: Registered at Clinical Trial Registry of India (CTRI/2020/03/024097). WHAT IS KNOWN: • RAM cannula is used for providing supplemental oxygen therapy. There is conflicting evidence on its efficacy in delivering CPAP support in preterm infants. WHAT IS NEW: • RAM cannula was not non-inferior to SBP in providing CPAP to preterm infants with respiratory distress syndrome. • RAM cannula causes less nasal trauma than short binasal prongs.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

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.

Portal vein thrombosis, livedo reticularis, polymicrobial sepsis and high antiphospholipid antibody titers in a newborn: A clinicopathological conference of antiphospholipid-associated neonatal syndrome.

Neonatal Antiphospholipid syndrome (APS) is a rare disease related to transplacental passage of antiphospholipid (aPL) antibodies from the mother or de novo production of aPL in a newborn. Neonatal aPL antibodies have rarely been associated with thrombosis. We describe a 5-week-old infant who developed fever, portal vein thrombosis and livedo reticularis like skin rash. Evaluation for thrombosis revealed high titers of antiphospholipid (aPL) antibodies (dual positive) in the child without any evidence of aPL antibodies in the mother, suggesting a de novo production in the child. Autopsy findings revealed umbilical vein sepsis with thrombosis of portal vein secondary to gram positive cocci which led to multiple liver and lung abscesses. Additionally, the baby had disseminated Cytomegalovirus (CMV) disease (acquired postnatally) involving walls of umbilical and portal vein, liver, lungs, adrenals, pancreas, thymus, and kidneys. Our case highlights the need for testing of aPL in every neonate with arterial or venous thrombosis even when the mother may have no features suggestive of an autoimmune disease.

Non-antibiotic interventions for prevention of urinary tract infections in children: a systematic review and meta-analysis of randomized controlled trials.

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.

Routine prefeed gastric aspiration in preterm infants: a systematic review and meta-analysis.

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.

Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prevalence & spectrum of congenital anomalies at a tertiary care centre in north India over 20 years (1998-2017).

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.

Efficacy and Safety of Phenobarbitone as First-Line Treatment for Neonatal Seizure: A Systematic Review and Meta-Analysis.

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.

Radiological Findings of COVID-19 in Children: A Systematic Review and Meta-Analysis.

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.

Clinical Features and Outcome of SARS-CoV-2 Infection in Neonates: A Systematic Review.

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.

Microorganisms Profile and Antimicrobial Resistance Pattern in Outborn Neonates in Northern India: A Hospital-Based Observational Study.

BACKGROUND: Neonates born somewhere else (outborn) and treated in a referral centre have different microbiological profile. We report the microorganism's profile and antimicrobial resistance (AMR) in blood culture proven sepsis in outborn neonates. METHODS: Culture positive neonatal sepsis from a neonatal unit of a referral institute catering to outborn neonates was studied over an 18 months duration. Data from the hospital information system were used to analyse the culture positivity rates, the spectrum of the microorganisms isolated and AMR pattern. RESULTS: Out of 5258 admitted neonates, 3687 blood samples were sent for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Gram-positive cocci (GPC) were the most common [240 (45%)] followed by gram-negative bacilli (GNB) [233 (43.4%)] and fungi [64 (11.9%)]. Coagulase negative staphylococcus (CONS) contributed to two-thirds of GPC followed by Klebsiella [93 (17.3%)] and Acinetobacter species [52 (9.7%)]. In 403 (75%) neonates, organisms grew in the samples sent at or within 24 h of admission. The case fatality rate was significantly higher in those with culture positive sepsis. The resistance to meropenem and imipenem was documented in 57.1% and 49.7%, respectively and 48% of the GNB was multidrug resistant. CONCLUSIONS: CONS followed by Klebsiella species were the most common organisms isolated. Three-fourths of the neonates had organisms grown at or within 24 h from admission. More than half of the GNB were multidrug resistant. The case fatality rate was significantly higher in those with culture positive sepsis.

Sepsis is the third most common cause of neonatal mortality globally. Outborn neonates differ in their microorganisms' profile and antimicrobial resistance (AMR) pattern in comparison to inborn neonates. In this study, we report the microorganisms profile and their AMR pattern in blood culture proven sepsis in a large cohort of outborn (extramural) neonates admitted to the index institute. We have also presented the state-wise profile and have compared their AMR pattern. Out of the 5258 admitted neonates, 3687 blood samples were sent for culture for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Coagulase-negative staphylococcus (CONS) followed by Klebsiella species were the most common organisms isolated from this large cohort of outborn neonates. More than 75% of the neonates grew the organisms within 24 h from admission indicating that many of them harboured the organisms at admission. Case fatality rate was significantly higher in those neonates with culture positive sepsis in comparison to culture negative sepsis. Close to 50% of the gram-negative bacilli isolates were multidrug resistant and half of them were extensively drug resistant. A significant between-state difference in organism profile and their AMR patterns were observed.

Oral Paracetamol vs Oral Ibuprofen in Patent Ductus Arteriosus: A Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: To test the hypothesis that oral paracetamol is non-inferior to oral ibuprofen in closing hemodynamically significant patent ductus arteriosus (hsPDA) with an a priori noninferiority (NI) margin of 15%. STUDY DESIGN: Multicenter, randomized, controlled, NI trial conducted in level III neonatal intensive care units. Consecutively inborn preterm neonates of <32 weeks of gestation with hsPDA were included. Those with structural heart disease, major malformations, and contraindications for enteral feeding or for administration of study drugs were excluded. Interventions included oral paracetamol in the experimental arm and oral ibuprofen in the active control arm. The primary outcome was closure of hsPDA by 24 hours from the last dose of the study drug. Secondary outcome measures included closure of hsPDA by 24 hours after the first course of the study drug, rate of reopening after the first course, and adverse events associated with the study drug. RESULTS: Out of 1250 neonates screened, 161 were randomized. Oral paracetamol was noninferior to oral ibuprofen in closure of hsPDA by both per protocol analysis (62 [95.4%] vs 63 [94%]; relative risk [RR], 1.01 [95% CI, 0.94-1.1]; risk difference [RD], 1.4 [95% CI, -6 to 9]; P = .37) and intention-to-treat analysis (63 [89%] vs 65 [89%]; RR, 0.99 [95% CI, 0.89-1.12]; RD, -0.3 [95% CI, -11 to 10]; P = .47). All adverse events were comparable in the 2 study arms. CONCLUSIONS: Oral paracetamol is noninferior to oral ibuprofen for the closure of hsPDA in preterm neonates of <32 weeks of gestation. No difference was observed in the adverse events studied.

Intramuscular Followed by Oral Vitamin A Supplementation in Neonates with Birth Weight from 750 to 1250 g: A Randomized Controlled Trial.

Multiple intramuscular (IM) injections of vitamin A have been shown to decrease bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. However, this regime is neither practical nor popular. Oral vitamin A has failed to achieve adequate plasma levels. We aimed to investigate if a schedule of initial IM followed by oral supplementation can reduce vitamin A deficiency. This was a blinded, randomized controlled trial, conducted in a level III neonatal unit. Neonates with birth weight from 750 to 1250 g, were enrolled at the age of 24-96 h of life. They were randomly allocated to vitamin A supplementation (VAS) (n = 61) or placebo group (n = 59). VAS group received vitamin A 5000 IU IM on alternate days till establishment of adequate enteral feeds, followed by oral 10,000 IU daily for 28 days. The primary outcome was incidence of vitamin A deficiency (plasma retinol < 200 µg/L) on day 28. A total of 120 neonates with mean (SD) gestation age and birth weight of 31 (2.4) weeks and 1065 (141) g, respectively were enrolled. More than 90% of cases were vitamin A deficient at the baseline. The proportion of vitamin A deficient infants on day 28 of study was significantly lower in VAS group compared to placebo group (4% vs. 61%, p < 0.001). The median (1st-3rd quartile) plasma retinol levels (µg/L) were significantly higher in VAS group compared to placebo [489 (295,627) vs. 184 (156,240), p < 0.001]. We conclude that the IM followed by oral VAS significantly reduced the incidence of vitamin A deficiency in VLBW infants.