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

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

Neurosonographic Findings in Infants with Rhesus Hemolytic Disease of Newborn: A Prospective Observational Study.

We estimated the incidence of intraventricular hemorrhage (IVH) and/or periventricular leukomalacia/echogenicity (PVL/E) in Rhesus isoimmunized infants. Seventy-one infants underwent cranial ultrasound within the first 3 days of life or discharge, whichever was earlier. Of these, 27 (38%) infants had IVH/ PVL/E. On multivariate analysis, lower gestational age (P = 0.035), small for gestational age [aOR (95% CI) 10.6 (1.9, 58.9)], and sepsis [aOR (95% CI) 4.5 (1.1, 18.4)] were independently associated with IVH/PVL.

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.

Gut microbiota of preterm infants in the neonatal intensive care unit: a study from a tertiary care center in northern India.

Introduction: Disruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life. Methods: Neonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant's life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3-V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework. Results: Fourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age <28 weeks) compared to moderate preterm infants (gestational age 29-32 weeks). Supplementation with probiotics decreased Acinetobacter and increased Bifidobacterium in the gut of preterm neonates regardless of gestational age. Conclusion: Gestational age and probiotic supplementation alter the gut microbiota of preterm infants admitted to the NICU.

Diagnostic Accuracy of Pediatrician-performed Digital Retinal Imaging with 3nethra neo for ROP Screening.

OBJECTIVES: To evaluate the accuracy of pediatrician-performed wide-field digital retinal imaging (WFDRI) for diagnosing Retinopathy of prematurity (ROP), as compared to binocular indirect ophthalmoscopy (BIO) as the reference standard. METHODS: Eligible infants undergoing ROP screening were enrolled consecutively. BIO was performed by trained ophthalmologists, followed by WFDRI (using "3nethra neo" camera) by a pediatrician. An expert pediatric ophthalmologist reviewed de-identified images for quality, presence, and severity of ROP. She was masked to the findings of BIO and the pediatrician. Diagnostic accuracy for detecting any ROP, ROP requiring treatment (Type 1), and ROP requiring referral (Type 1 or 2) were calculated for WFDRI, considering BIO as the reference standard. RESULTS: The analysis included 427 eyes. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic accuracy, and diagnostic odds ratio of WFDRI were 0.88 (95% CI: 0.81, 0.93), 0.89 (0.85, 0.92), 7.8 (5.7, 10.9), 0.14 (0.09, 0.21), 0.89 (0.85, 0.91), and 58.3 (31, 110) respectively for detection of 'any ROP'. For detecting ROP requiring treatment (Type 1), the sensitivity, specificity, NLR, and diagnostic accuracy were 0.90 (0.75, 0.97), 1.00 (0.99, 1.00), 0.11 (0.04, 0.27), and 0.99 (0.98, 1.00) respectively. For ROP requiring referral, the sensitivity, specificity, NLR, and diagnostic accuracy of pediatrician-performed WFDRI were 0.92 (0.80, 0.98), 1.00 (0.99, 1.00), 0.08 (0.03, 0.21), and 0.99 (0.98, 1.00) respectively. No serious adverse events were noted. The pediatrician and ophthalmologist had a near-perfect (k-1.00) and strong (k-0.88) agreement for ROP requiring treatment and any ROP, respectively. CONCLUSIONS: Pediatrician-performed WFDRI is feasible, safe, and has excellent diagnostic accuracy for identifying ROP requiring treatment.

Comparison of Telemedicine versus In-Person Visit for Control of Asthma in Children aged 7-17 years: A Randomized Controlled Trial.

OBJECTIVES: To compare asthma control between telemedicine and in-person visit in children aged 7 to 17 y. METHODS: A non-inferiority randomized-controlled trial was conducted at a pediatric chest clinic, involving a total of 192 patients, with 96 children in each group of telemedicine and in-person follow-up. RESULTS: There was a significant improvement in the mean asthma control test (ACT)/ Childhood asthma control test (C-ACT) scores from baseline to three months in both groups, with no significant difference in the change of means between the two groups. The mean difference in ACT/C-ACT score at three months in the telemedicine and in-person visit group was -0.35; 95% CI (-1.30 to +0.10) [p-value 0.09]. There was a significant change in the mean Pediatric Quality of Life index (PQLI) scores from 57.2 ± 10.2 to 66.82 ± 7.99 in the telemedicine group and from 56.1 ± 11.7 to 66.71 ± 4.66 in the in-person visit group, however the mean difference in PQLI score in both the groups was not significant (p = 0.91). There was no significant difference in the number of asthma exacerbations (4 vs. 1) between telemedicine and in-person visit (p = 0.10). The mean telemedicine satisfaction questionnaire score in this study was 3.8 ± 0.7, which indicates that most of the parents were satisfied with the telemedicine follow-up process. CONCLUSIONS: This study revealed that telemedicine is non-inferior to in-person visit for follow-up of children with asthma and can be used as an alternative to in-person visit for the management of asthma, especially in remote settings and pandemic situations.

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

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

Iron Overload and Anemia in Rhesus Hemolytic Disease of Newborn: A Prospective Observational Study.

This study assessed the prevalence of iron overload in infants born to Rh isoimmunized mothers. Infants born to Rh isoimmunized mothers with Indirect Coomb's Test (ICT) titers ≥1:16 were prospectively enrolled and followed until 3 mo. Hemoglobin and serum ferritin were estimated at birth and 3 mo of age. The outcomes were the incidence of iron overload (at birth and 3 mo), anemia, and the need for transfusions in the first 3 mo. Seventy-four infants were enrolled, nearly half receiving intrauterine transfusion (IUT). Sixty (82.2%) had hyperferritinemia at birth. The median (1st, 3rd quartile) ferritin levels were 456 (321, 631) µg/L. Infants who received IUTs had significantly higher serum ferritin levels at birth. Fifty-one (76.1%) infants had hyperferritinemia at 3 mo. Over three months of follow-up, 53 (71.6%) infants had anemia, of which 33 (48.5%) required packed red blood cells (PRBC) transfusion. These findings suggest that iron overload is common in these infants in the first 3 mo.

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

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

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.

Comparison of Vaginal Dinoprostone Pessary With Transcervical Balloon Catheter Plus Vaginal Misoprostol for Pre-induction Cervical Ripening: A Randomized Trial.

Aims and Objectives To compare the safety and efficacy of dinoprostone pessary with Foley plus vaginal misoprostol for cervical ripening. Materials and Methods We randomized 115 women to the pessary or Foley plus misoprostol group. Pessary was inserted for 24 hours, and in the Foley plus misoprostol group, intravaginal misoprostol 25 mcg was administered along with trans-cervical Foley insertion and repeated every six hours to a maximum dose of 100 mcg. Singleton pregnancies requiring labor induction at more than 34 weeks with a Bishop score of <6 were included. Study outcomes included induction-delivery interval (IDI), mode of delivery, change in the Bishop score, need for oxytocin augmentation, and patient discomfort as assessed by visual analog score. Results The IDI was similar between the groups (pessary vs Foley plus misoprostol; 21.27 vs 21.10 hours, p = 0.9). The mean change in the Bishop score and need for augmentation with oxytocin was significantly more in the Foley plus misoprostol group compared to pessary (2.72 vs 1.94, p = 0.001; 89.7% vs 57.9%, p = 0.0001). Pessary was better tolerated compared to Foley plus misoprostol (VAS 7.8 vs 6.68, p = 0.0001). Mode of delivery and maternal and neonatal outcomes showed no difference. Conclusion There was no significant difference between pessary and Foley plus misoprostol in the IDI and mode of delivery. Pessary was better tolerated, and augmentation with oxytocin was required less often. Foley plus misoprostol caused a faster change in the Bishop score, but oxytocin augmentation was used more often. Maternal and neonatal outcomes were similar.

Antimicrobial Resistance Patterns Among Neonates Referred to Pediatric Emergency in North India: A Prospective Cohort Study.

BACKGROUND: Sepsis is a leading cause of neonatal mortality worldwide, with a disproportionately high burden in low-income and middle-income countries. There is limited prospective data on microorganism profiles and antimicrobial resistance (AMR) in outborn newborns referred to pediatric emergency in developing countries. We aimed to assess the pathogen profile and AMR patterns in outborn neonates referred to the pediatric emergency at a tertiary care center. METHODS: In this prospective cohort study, we enrolled neonates with suspected sepsis and sent blood or cerebrospinal fluid cultures. Neonates were followed up daily until discharge or death. The isolated organisms were identified and tested for antimicrobial susceptibility. Standard definitions were used to define multidrug resistance. RESULTS: Between January 1, 2020, and December 31, 2020, 1072 outborn neonates with suspected sepsis were enrolled. The rate of proven sepsis was 223.6 (95% CI:198.7-248.4) per 1000 infants. Gram-negative sepsis was the most common (n = 107,10%), followed by gram-positive sepsis (n = 81,7.6%) and fungal sepsis (n = 67,6.3%). Coagulase-negative staphylococci (n = 69), Candida spp. (n = 68), Klebsiella spp. (n = 55), Acinetobacter spp . (n = 31) and Escherichia coli (n = 9) were the most common pathogens. Over two-thirds (68.6%) of pathogens were multidrug resistance, with an alarming prevalence in Klebsiella spp. (33/53, 62%), Acinetobacter spp. (25/30, 83%) and coagulase-negative staphylococci (54/66, 82%). In total, 124 (11.6%) neonates died in the hospital (13.3% of proven cases and 11.1% of culture-negative sepsis cases). CONCLUSIONS: High sepsis burden and alarming AMR among neonates referred to tertiary care centers warrant urgent attention toward coordinated implementation of rigorous sepsis prevention measures and antimicrobial stewardship across all healthcare levels.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Female Newborns.

OBJECTIVES: To establish gestation-wise normative data of external genitalia measurements in North Indian term and preterm female newborns. METHODS: In this cross-sectional descriptive study, institutionally-born female neonates between 28-42 wk gestation were consecutively enrolled between 24-72 h of life. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Clitoral length (CL), clitoral width (CW), ano-clitoral distance (AGDAC), ano-fourchette distance (AGDAF) and anogenital ratio (AGR)]. RESULTS: One hundred ninety-eight of 508 neonates (39%) were preterm and 310 (61%) were term. Mean (± SD) CL and CW were 4.6 ± 1.8 mm and 3.9 ± 1.6 mm, respectively. Mean (± SD) values for AGDAF, AGDAC and AGR were 9.3 ± 1.8 mm, 30.2 ± 3.9 mm, and 0.31 ± 0.05, respectively. According to these results, term female newborns with CL more than 7 mm and/or CW more than 6 mm (95th centile) warrant evaluation for clitoromegaly. An anogenital ratio greater than 0.45 should be considered as a sign of virilization in a female neonate. Gestation-wise percentile charts for CL, CW, AGDAF, AGDAC and AGR were generated. CONCLUSIONS: The percentile values defined in the study can serve as local normative data for accurate interpretation of genital measurements in North Indian female newborns and enable health care professionals for early identification of genital virilization.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Male Newborns.

OBJECTIVES: To generate gestation-wise normative data of external genitalia measurements in North Indian term and preterm male newborns. METHODS: This was a hospital-based cross-sectional observational study. Male neonates born between 28-42 wk of gestation (at 24-72 h of life) were consecutively recruited in the study. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Stretched penile length (SPL), penile width (PW), upper anogenital distance (AGDu), lower anogenital distance (AGDl) and anogenital ratio (AGR)]. RESULTS: Out of 532 newborns, 208 (39.1%) were preterm. Mean (± SD) SPL and PW were 27.9 ± 3.6 mm and 10.6 ± 1.3 mm respectively. The mean values for AGDl, AGDu and AGR were 20.13 ± 4.04 mm, 39.2 ± 5.59 mm, and 0.51 ± 0.07, respectively. SPL less than 21 mm in a term male newborn and 17.5 mm in preterm should be considered micropenis (<2.5 SD) in our population. Gestation-wise percentile charts for SPL, PW, AGDl, AGDu and AGR were generated. CONCLUSIONS: The reference values and percentile charts generated can serve as local normative data for accurate interpretation of genital measurements in North Indian newborns, assessment of ambiguous genitalia and avoiding diagnostic errors.

Care During Labour, Childbirth, and Immediate Newborn Care in India: A Review.

India is committed to achieve a single-digit neonatal mortality rate (NMR) and stillbirth rate (SBR) by 2030 through India Newborn Action Plan (INAP) 2014. However, the current rate of decline is not enough to achieve the target neonatal mortality rate. Course correction and renewed efforts are required. This review outlines the current scenario and proposed scale-up of services included during labour, childbirth, and the immediate newborn period. The article summarises the challenges and bottlenecks in achieving a reduction in neonatal mortality rate and INAP targets. India has achieved over 80% coverage of three of the four ENAP coverage targets, but antenatal care coverage is still poor. There are concerns about the quality and completeness of antenatal care visits and other program interventions. The ongoing quality assurance should be strengthened through continuous supportive supervision by involving the medical colleges in a hub and spoke model and other key stakeholders. There is a need for effective and strategic engagement of the private sector in these initiatives. The states need to systematically assess the gaps as per population requirements and find effective solutions to overcome them quickly. The state and district-wise data maps show immense variations in coverage between states and within states, mirroring the variations in NMR. This indicates the need to ensure contextual micro-plans and provides an opportunity for the districts and states to learn from each other. The recent initiatives to strengthen primary healthcare should be used as a platform for all stillbirth and neonatal mortality prevention interventions in India.

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

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

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

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

Nifty Cup Versus Katori-Spoon Feeding in Preterm Infants: A Randomized Controlled Trial.

Background: Many preterm infants cannot breastfeed directly and depend on other feeding methods. Multiple studies have compared feeding methods for such infants; however, the best method remains unknown. We compared Nifty cup with Katori-spoon feeding in preterm neonates deemed fit for oral feeding. Methods: This open-label randomized controlled trial was performed in a level III neonatal unit. Preterm (<34 weeks) neonates deemed fit to initiate oral feeding were randomly allocated to the Nifty cup and Katori-spoon groups. Patients were followed up until 40 (±2) weeks of postmenstrual age or until death, whichever occurred earlier. The primary outcome was time to achieve full oral feeding. The secondary outcomes included the time spent per feeding session, time to full direct breastfeeding, anthropometry at discharge, duration of hospitalization, and mortality. The opinions of mothers and nurses were recorded using a structured questionnaire. Results: A total of 106 participants (53 in each group) were randomized and analyzed for the primary outcome. The median (1st, 3rd quartile) time to achieve complete oral feeds was 5 (2, 11) versus 6 (4, 11) days in the Nifty cup versus Katori-spoon groups, respectively (p = 0.2). Infants in the Nifty cup group reached full breastfeeds earlier (mean difference = 12.6 days; 95% confidence interval: 4.3 to 20.8, p = 0.003) and had less vomiting (9.4% versus 26.4%, p = 0.023). Mothers and nurses felt that breast milk expression and feeding with a Nifty cup was easier. Conclusions: Compared to the Katori-spoon, feeding with a Nifty cup did not shorten the time to full oral feeds. However, it helps in attaining full breastfeeds earlier than the Katori-spoon. Trial Registration: Clinical Trials Registry-India (CTRI/2021/06/034252).