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BACKGROUND: Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate different adjuvant therapies in neonatal sepsis in a network meta-analysis. METHODS: We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated adjuvant therapies in neonatal sepsis. Neonates of all gestational and postnatal ages, who were diagnosed with sepsis based on blood culture or sepsis screen were included. We searched MEDLINE, CENTRAL, EMBASE and CINAHL until 12th April 2021 and reference lists. Data extraction and risk of bias assessment were performed in duplicate. A network meta-analysis with bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. RESULTS: We included 45 studies involving 6,566 neonates. Moderate CoE showed IVIG [Relative Risk (RR); 95% Credible Interval (CrI): 1.00; (0.67–1.53)] as an adjunctive therapy probably does not reduce all-cause mortality before discharge, compared to standard care. Melatonin [0.12 (0–0.08)] and granulocyte transfusion [0.39 (0.19–0.76)] may reduce mortality before discharge, but CoE is very low. The evidence is also very uncertain regarding other adjunctive therapies to reduce mortality before discharge. Pentoxifylline may decrease the duration of hospital stay [Mean difference; 95% CrI: –7.48 days (–14.50–0.37)], but CoE is very low. CONCLUSION: Given the biological plausibility for possible efficacy of these adjuvant therapies and that the CoE from the available trials is very low to low except for IVIG, we need large adequately powered RCTs to evaluate these therapies in sepsis in neonates. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the diagnostic accuracy and utility of bedside ultrasound (US) by neonatology residents to confirm position of umbilical venous catheter (UVC), umbilical arterial catheter (UAC), and peripherally inserted central catheter (PICC). METHODS: In this prospective study, we included neonates who required UVC, UAC or PICC insertion. Two neonatology residents performed all bedside US examinations after a short period of training. Plain radiograph was taken as gold standard. Time taken for confirmation of catheter position by US and radiograph was recorded. RESULTS: We recruited 71 neonates for UVC and UAC, and 40 neonates for PICC. Sensitivity and specificity of US in identifying a malpositioned catheter was good for UVC (94% and 66.7% respectively) and UAC (86.7% and 94.5%). Agreement between radiograph and US was good for UVC [0.718 (0.512, 0.861); p < 0.001] and UAC [0.857 (0.682, 0.953); p < 0.001]. Sensitivity (47.8%) of US in identifying a malpositioned PICC was low, though specificity (82.4%) was good. Agreement between radiograph and US in identifying PICC position was poor [0.25 (–0.084, 0.545); p 0.024]. This was due to incorrect interpretation of catheter position on radiograph in some infants, which was confirmed by the radiologist. The median time taken for US was significantly less than time taken for radiograph in confirming the position of UVC (50 vs. 155 minutes; p < 0.001)), UAC (45 vs. 128 minutes; p < 0.001), and PICC (60 vs. 136 minutes; p < 0.001). CONCLUSION: US examination byneonatology residents has good diagnostic accuracy in confirming the position of UAC and UVC, and possibly PICC in neonates. The time taken to confirm catheter position by US is significantly less than radiograph. [ABSTRACT FROM AUTHOR]

BACKGROUND: Troponin-T is a commonly used cardiac biomarker, which could be useful in perinatal asphyxia. We aimed to analyze troponin-T concentrations in asphyxiated neonates and to correlate the concentrations with clinical outcomes. METHODS: Data were collected from electronic medical records of neonates diagnosed with perinatal asphyxia over a period of four years. RESULTS: There were 63 neonates with moderate to severe encephalopathy, in whom serial troponin-T concentrations had been done on days 1, 3, and 7. 53 (84%) asphyxiated infants had troponin-T concentration >100 pg/ml at 2-4 h of life. The difference in troponin-T concentrations between moderate and severe encephalopathy was not statistically significant (173 vs. 263 pg/ml, p value 0.40). The difference in the concentrations at 72 hours between cooled and non-cooled neonates was not significant (48.5 vs. 62.5 pg/ml, p value 0.22). Troponin-T concentration was significantly higher in babies with hypotensive shock and hepatic injury, but not acute kidney injury. There was no significant correlation between troponin-T and the extent of resuscitation needed. Troponin-T concentration on day 1 of lifewas significantly higher in babies who died than who survived (407 vs. 168 pg/ml, p value 0.03). ROC curve for troponin-T to predict mortality had an area under the curve (AUC) of 0.803; the best cut-off value (190 pg/ml) had 82% sensitivity and 80% specificity. CONCLUSION: There was no significant difference in troponin-T concentrations between cooled and non-cooled neonates. Troponin-T concentration had a good predictive accuracy for mortality before discharge. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency in infants is widely prevalent. Most paediatric professional associations recommend routine vitamin D prophylaxis for infants. However, the optimal dose and duration of supplementation are still debated. We aimed to compare the efficacy and safety of different vitamin D supplementation regimens in term and late preterm neonates. For this systematic review and network meta-analysis, we searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase. Randomised and quasi-randomised clinical trials that evaluated any enteral vitamin D supplementation regimen initiated within 6 weeks of life were included. Two researchers independently extracted data on study characteristics and outcomes and assessed quality of included studies. A network meta-analysis with a Bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. Primary outcomes were mean serum vitamin D concentrations and the proportion of infants with vitamin D insufficiency (VDI). We included twenty-nine trials that evaluated fourteen different regimens of vitamin D supplementation. While all dosage regimens of ≥400 IU/d increased the mean 25(OH)D levels compared with no treatment, supplementation of ≤250 IU/d and 1400 IU/week did not. The CoE varied from very low to high. Low CoE indicated that 1600 IU/d, compared with lower dosages, reduced the proportion of infants with VDI. However, our results indicated that any dosage of ≥800 IU/d increased the risk of hypervitaminosis D and hypercalcaemia. Data on major clinical outcomes were sparse. Vitamin D supplementation of 400-600 IU/d may be the most effective and safest in infants.

Context: Heel prick is one among the common painful procedures in neonates. We performed a systematic review and network meta-analysis (NMA) to compare the efficacy of different interventions for analgesia during heel prick in neonates., Evidence Acquisition: Medline, Cochrane, Embase and CINAHL databases were searched from inception until February 2023. Randomized and quasi-randomized trials that evaluated different pharmacological and non-pharmacological interventions for analgesia during heel prick for neonates were included. Data from the included trials were extracted in duplicate. A NMA with a frequentist random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. We adhered to the PRISMA-NMA guidelines., Results: One-hundred-and-three trials comparing 51 different analgesic measures were included. Among the 38 interventions, for pain "during" heel prick, non-nutritive suckling (NNS) plus sucrose [SMD -3.15 (-2.62, -3.69)], followed by breastfeeding, glucose, expressed breast milk (EBM), sucrose, NNS and touch massage, had a high certainty of evidence (CoE) to reduce pain scores when compared to no intervention. Among the 23 interventions for pain at 30 seconds after heel-prick, moderate CoE was noted for facilitated tucking plus NNS plus music, glucose, NNS plus sucrose, sucrose plus swaddling, mother holding, EBM, sucrose and NNS., Conclusions: Oral sucrose 2 minutes before combined with NNS during the procedure, was the best intervention for reducing pain during heel prick. It also effectively reduced pain scores 30 seconds and 1 minute after the procedure. Other interventions with moderate to high CoE for a significant reduction in pain during and at 30 seconds after heel prick are oral sucrose, oral glucose, EBM and NNS. All these are low-cost and feasible interventions for most of the settings.

Objective: To identify the profile of organisms causing neonatal sepsis and their antibiotic susceptibility pattern in recent years., Methods: In this prospective study, authors included neonates with blood culture proven sepsis. Antibiotic resistance patterns that were identified were extended spectrum β-lactamase, AmpC β-lactamase and possible carbapenamase producer. Xpert CARBA-R test was performed to identify genes causing carbapenem resistance., Results: There were 210 neonates with 216 episodes of blood culture proven sepsis. Klebsiella pneumoniae (n = 85) and Escherichia coli (n = 19) were the most common gram-negative organisms. Coagulase negative Staphylococcus (n = 11) and Staphylococcus aureus (n = 7) were the most common gram positive organisms. There were 17 episodes of fungal sepsis with Candida albicans (n = 6) being the most common. Sixty-five out of 216 (30%) organisms were multidrug resistant. Among the Klebsiella isolates, 32/85 (37.6%) were possible carbapenamase producers. Xpert CARBA-R performed for 13 infants showed that all were positive for New Delhi metallo-β-lactamase. Among the 19 Escherichia coli, 10/19 (37.6%) were multidrug resistant and 1/19 (5.3%) was a possible carbapenamase producer., Conclusions: The authors found a significant increase in New Delhi metallo-β-lactamase positive Klebsiella pneumoniae causing neonatal sepsis in last three years. Regular monitoring of resistance patterns and prudent use of antimicrobials are imperative in regulating the shadow pandemic of multi-drug resistant neonatal sepsis., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: There is no objective criteria to wean CPAP in preterm neonates. We aimed to assess the accuracy of 'saturation trends' to predict successful CPAP discontinuation., Methods: We included very preterm neonates who required CPAP. Index tests were 'saturation trends'. Outcome was successful CPAP discontinuation, defined as baby stable in room air for 72 h., Results: We had 120 neonates with mean±SD gestation 28.6±1.8 weeks. 96 (80%) neonates had successful discontinuation and 24 (20%) failed. Neonates with successful discontinuation had significantly greater 'saturation trends' during 24 h before discontinuing CPAP compared to those who failed [64.3 (48.1-83.7) vs. 47.3 (23.0-65.0), p = 0.001]. Saturations > 95% while on CPAP with 21% FiO2 for > 60% time had 63% sensitivity and 70% specificity to predict successful CPAP discontinuation., Conclusion: 'Saturation trends' is a readily available objective parameter that can be used to guide weaning CPAP in preterm neonates.

Background: Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive., Objectives: 1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates., Search Methods: We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials., Selection Criteria: We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone., Data Collection and Analysis: Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence., Main Results: We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials) Treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months. We report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons., Authors' Conclusions: Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The ideal threshold at which surfactant administration in preterm neonates with respiratory distress syndrome (RDS) is most beneficial is contentious. The aim of this systematic review was to determine the optimal clinical criteria to guide surfactant administration in preterm neonates with RDS., Methods: The systematic review was registered in PROSPERO (CRD42022309433). Medline, Embase, CENTRAL and CINAHL were searched from inception till 16th May 2023. Only randomized controlled trials (RCTs) were included. A Bayesian random effects network meta-analysis (NMA) evaluating 33 interventions was performed. The primary outcome was requirement of invasive mechanical ventilation (IMV) within 7 days of life., Findings: 58 RCTs were included. In preterm neonates ≤30 weeks after adjusting for the confounding factor of modality of surfactant administration, an arterial alveolar oxygen tension ratio (aAO 2 ) <0.36 (FiO 2 : 37-55%) was ranked the best threshold for decreasing the risk of IMV, very low certainty. Further, surfactant administration at an FiO 2 40-45% possibly decreased mortality compared to rescue treatment when respiratory failure was diagnosed, certainty very low. The reasonable inference that could be drawn from these findings is that surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS requiring an FiO 2 ≥ 40%. There was insufficient evidence for the comparison of FiO 2 thresholds: 30% vs. 40%. The evidence was sparse for surfactant administration guided by lung ultrasound. For the sub-group >30 weeks, nebulized surfactant administration at an FiO 2 < 30% possibly increased the risk of IMV compared to Intubate-Surfactant-Extubate at FiO 2 < 30% and 40%, and less invasive surfactant administration at FiO 2 40%, certainty very low., Interpretation: Surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS if the FiO 2 requirement is ≥40%. Future trials are required comparing lower FiO 2 thresholds of 30% vs. 40% and that guided by lung ultrasound., Funding: None., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Background: Routine monitoring of gastric residuals in preterm infants on tube feeds is a common practice in neonatal intensive care units used to guide initiation and advancement of enteral feeding. There is a paucity of consensus on whether to re-feed or discard the aspirated gastric residuals. While re-feeding gastric residuals may aid in digestion and promote gastrointestinal motility and maturation by replacing partially digested milk, gastrointestinal enzymes, hormones, and trophic substances, abnormal residuals may result in vomiting, necrotising enterocolitis, or sepsis., Objectives: To assess the efficacy and safety of re-feeding when compared to discarding gastric residuals in preterm infants.  SEARCH METHODS: Searches were conducted in February 2022 in Cochrane CENTRAL via CRS, Ovid MEDLINE and Embase, and CINAHL. We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs., Selection Criteria: We selected RCTs that compared re-feeding versus discarding gastric residuals in preterm infants., Data Collection and Analysis: Review authors assessed trial eligibility and risk of bias and extracted data, in duplicate. We analysed treatment effects in individual trials and reported the risk ratio (RR) for dichotomous data and the mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence., Main Results: We found one eligible trial that included 72 preterm infants. The trial was unmasked but was otherwise of good methodological quality. Re-feeding gastric residual may have little or no effect on time to regain birth weight (MD 0.40 days, 95% CI -2.89 to 3.69; 59 infants; low-certainty evidence), risk of necrotising enterocolitis stage ≥ 2 or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; 72 infants; low-certainty evidence), all-cause mortality before hospital discharge (RR 0.50, 95% CI 0.14 to 1.85; 72 infants; low-certainty evidence), time to establish enteral feeds ≥ 120 mL/kg/d (MD -1.30 days, 95% CI -2.93 to 0.33; 59 infants; low-certainty evidence), number of total parenteral nutrition days (MD -0.30 days, 95% CI -2.07 to 1.47; 59 infants; low-certainty evidence), and risk of extrauterine growth restriction at discharge (RR 1.29, 95% CI 0.38 to 4.34; 59 infants; low-certainty evidence). We are uncertain as to the effect of re-feeding gastric residual on number of episodes of feed interruption lasting for ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; 59 infants; very low-certainty evidence)., Authors' Conclusions: We found only limited data from one small unmasked trial on the efficacy and safety of re-feeding gastric residuals in preterm infants. Low-certainty evidence suggests re-feeding gastric residual may have little or no effect on important clinical outcomes such as necrotising enterocolitis, all-cause mortality before hospital discharge, time to establish enteral feeds, number of total parenteral nutrition days, and in-hospital weight gain. A large RCT is needed to assess the efficacy and safety of re-feeding of gastric residuals in preterm infants with adequate certainty of evidence to inform policy and practice., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Routine monitoring of gastric residual in preterm infants on gavage feeds is a common practice used to guide initiation and advancement of feeds. It is believed that an increase in or an altered gastric residual may be predictive of necrotising enterocolitis (NEC). Withholding monitoring of gastric residual may take away the early indicator and thus may increase the risk of NEC. However, routine monitoring of gastric residual as a guide, in the absence of uniform standards, may lead to unnecessary delay in initiation and advancement of feeds and hence might result in a delay in establishing full enteral feeds. This in turn may increase the duration of total parenteral nutrition (TPN) and central venous line usage, increasing the risk of associated complications. Furthermore, delays in establishing full enteral feeds increase the risk of extrauterine growth restriction and neurodevelopmental impairment., Objectives: • To assess the efficacy and safety of routine monitoring versus no monitoring of gastric residual in preterm infants • To assess the efficacy and safety of routine monitoring of gastric residual based on two different criteria for interrupting feeds or decreasing feed volume in preterm infants SEARCH METHODS: We conducted searches in Cochrane CENTRAL via CRS, Ovid MEDLINE, Embase and CINAHL in February 2022. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs), quasi- and cluster-RCTs., Selection Criteria: We selected RCTs that compared routine monitoring versus no monitoring of gastric residual and trials that used two different criteria for gastric residual to interrupt feeds in preterm infants., Data Collection and Analysis: Two authors independently assessed trial eligibility, risk of bias and extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CI). We calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH) for dichotomous outcomes with significant results. We used GRADE to assess the certainty of evidence., Main Results: We included five studies (423 infants) in this updated review. Routine monitoring versus no routine monitoring of gastric residual in preterm infants Four RCTs with 336 preterm infants met the inclusion criteria for this comparison. Three studies were performed in infants with birth weight of < 1500 g, while one study included infants with birth weight between 750 g and 2000 g. The trials were unmasked but were otherwise of good methodological quality. Routine monitoring of gastric residual:  - probably has little or no effect on the risk of NEC (RR 1.08, 95% CI 0.46 to 2.57; 334 participants, 4 studies; moderate-certainty evidence); - probably increases the time to establish full enteral feeds (MD 3.14 days, 95% CI 1.93 to 4.36; 334 participants, 4 studies; moderate-certainty evidence); - may increase the time to regain birth weight (MD 1.70 days, 95% CI 0.01 to 3.39; 80 participants, 1 study; low-certainty evidence);  - may increase the number of infants with feed interruption episodes (RR 2.21, 95% CI 1.53 to 3.20; NNTH 3, 95% CI 2 to 5; 191 participants, 3 studies; low-certainty evidence);  - probably increases the number of TPN days (MD 2.57 days, 95% CI 1.20 to 3.95; 334 participants, 4 studies; moderate-certainty evidence); - probably increases the risk of invasive infection (RR 1.50, 95% CI 1.02 to 2.19; NNTH 10, 95% CI 5 to 100; 334 participants, 4 studies; moderate-certainty evidence); - may result in little or no difference in all-cause mortality before hospital discharge (RR 2.14, 95% CI 0.77 to 5.97; 273 participants, 3 studies; low-certainty evidence). Quality and volume of gastric residual compared to quality of gastric residual alone for feed interruption in preterm infants One trial with 87 preterm infants met the inclusion criteria for this comparison. The trial included infants with 1500 g to 2000 g birth weight.  Using two different criteria of gastric residual for feed interruption: - may result in little or no difference in the incidence of NEC (RR 5.35, 95% CI 0.26 to 108.27; 87 participants; low-certainty evidence);  - may result in little or no difference in time to establish full enteral feeds (MD -0.10 days, 95% CI -0.91 to 0.71; 87 participants; low-certainty evidence); - may result in little or no difference in time to regain birth weight (MD 1.00 days, 95% CI -0.37 to 2.37; 87 participants; low-certainty evidence); - may result in little or no difference in number of TPN days (MD 0.80 days, 95% CI -0.78 to 2.38; 87 participants; low-certainty evidence); - may result in little or no difference in the risk of invasive infection (RR 5.35, 95% CI 0.26 to 108.27; 87 participants; low-certainty evidence); - may result in little or no difference in all-cause mortality before hospital discharge (RR 3.21, 95% CI 0.13 to 76.67; 87 participants; low-certainty evidence).  - we are uncertain about the effect of using two different criteria of gastric residual on the risk of feed interruption episodes (RR 3.21, 95% CI 0.13 to 76.67; 87 participants; very low-certainty evidence)., Authors' Conclusions: Moderate-certainty evidence suggests routine monitoring of gastric residual has little or no effect on the incidence of NEC. Moderate-certainty evidence suggests monitoring gastric residual probably increases the time to establish full enteral feeds, the number of TPN days and the risk of invasive infection. Low-certainty evidence suggests monitoring gastric residual may increase the time to regain birth weight and the number of feed interruption episodes, and may have little or no effect on all-cause mortality before hospital discharge. Further RCTs are warranted to assess the effect on long-term growth and neurodevelopmental outcomes., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Neonatal strokes constitute a major cause of pediatric mortality and morbidity. Neuroimaging helps in its diagnosis as well as prognostication. However, advanced imaging, including magnetic resonance imaging (MRI), carries multiple challenges. Limited data exists in the literature on imaging-based predictors of neurological outcomes in neonatal stroke in the Indian population. In this study, we reviewed our available data on neonatal stroke patients between 2015 and 2020 for clinico-radiological patterns. During this period, 17 neonatal strokes were admitted and the majority were term births with a slight male preponderance. Seizures and encephalopathy were the most common presentation. Multiple maternal risk factors such as gestational diabetes, meconium-stained liquor, APLA syndrome, fever, deranged coagulation profile, oligohydramnios, cord prolapse, and non-progressive labor were seen. Cardiac abnormalities were seen in only less than half of these patients with the most common finding being atrial septal defects (ASD). Transcranial ultrasound was performed in eight neonates and the pick-up rate of ultrasound was poor. MR imaging showed large infarcts in 11 patients. The MCA territory was most commonly involved. Interestingly, five neonates had venous thrombosis with three showing it in addition to arterial thrombosis. Associated ictal, as well as Wallerian changes, were noted in 10. Although large territorial infarcts were the most common pattern, non-contrast MR angiography did not show major vessel occlusion in these cases. Outcomes were fairly good and only three patients had a residual motor deficit at 1 year. No recurrence of stroke was seen in any of the neonates.

Multisystem inflammatory disease in neonates (MIS-N) is a disease of immune dysregulation presenting in the newborn period. Thouvgh its etiopathogenesis is proposed to be similar to multisystem inflammatory disease in Children (MIS-C), the exact pathophysiology is largely unknown as of present. The definition of MIS-N is contentious. The evidence for its incidence, the clinical features, profile of raised inflammatory markers, treatment strategies and outcomes stem from case reports, case series and cohort studies with small sample sizes. Though the incidence of MIS-N in severe acute respiratory syndrome caused by the coronavirus CoVID-2 (SARS-CoV-2) infected asymptomatic neonates is low, its incidence in symptomatic neonates is relatively higher. Further, amongst the neonates who are treated as MIS-N, the mortality rate is high. The review also evaluates the various other unresolved aspects of MIS-N from limited published literature and identifies knowledge gaps which could be areas of future research., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To determine early breastfeeding problems using LATCH tool, and analyze the impact of breastfeeding supportive measures in improving LATCH score., Methods: This prospective study included all inborn term neonates born at our center between September, 2019 and March, 2020. Breastfeeding problems were identified by LATCH score at 6-12h after birth, and were addressed by the study team providing breastfeeding support, education and training to mothers. LATCH scores were reassessed at 24-48h., Results: Among 400 mother-infant dyads, 399 (99.7%) required support to position the neonate, 190 (47.5%) had poor latch and 52 (13%) had nipple problems during initial assessment. Breastfeeding supportive measures improved the LATCH score [median (IQR) 7 (5,8) vs 8 (8,8) at 6-12 and 24-48 hours, respectively; P <0.001], and reduced the number of mothers with LATCH score <8 [288 (72%) vs 63 (15.8%); P <0.001]., Conclusion: LATCH is a comprehensive yet simple tool to identify breastfeeding problems. Given the high incidence of breastfeeding problems during early postpartum period, systematic assessment of breastfeeding related problems using LATCH tool can help timely intervention and improvement in the breastfeeding technique.

Background: There are no evidence-based recommendations for surfactant use in late preterm (LPT) and term infants with respiratory distress syndrome (RDS)., Objective: To investigate the safety and efficacy of surfactant in LPT and term infants with RDS., Methods: Systematic review, meta-analysis and evidence grading., Interventions: Surfactant therapy versus standard of care., Main Outcome Measures: Mortality and requirement for invasive mechanical ventilation (IMV)., Results: Of the 7970 titles and abstracts screened, 17 studies (16 observational studies and 1 randomised controlled trial (RCT)) were included. Of the LPT and term neonates with RDS, 46% (95% CI 40% to 51%) were treated with surfactant. We found moderate certainty of evidence (CoE) from observational studies evaluating infants supported with non-invasive respiratory support (NRS) or IMV that surfactant use may be associated with a decreased risk of mortality (OR 0.45, 95% CI 0.32 to 0.64). Very low CoE from observational trials in which surfactant was administered at FiO 2 >0.30-0.40 to infants on Continuous Positive Airway Pressure (CPAP) indicated that surfactant did not decrease the risk of IMV (OR 1.20, 95% CI 0.40 to 3.56). Very low to low CoE from the RCT and observational trials showed that surfactant use was associated with a significant decrease in risk of air leak, persistent pulmonary hypertension of the newborn (PPHN), duration of IMV, NRS and hospital stay., Conclusions: Current evidence base on surfactant therapy in LPT and term infants with RDS indicates a potentially decreased risk of mortality, air leak, PPHN and duration of respiratory support. In view of the low to very low CoE and widely varying thresholds for deciding on surfactant replacement in the included studies, further trials are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite decades of research, there is inadequate evidence on the etiological factors of brain injury in preterm infants., Objective: To study the perinatal risk factors for preterm brain injury and to assess their strength of association., Methods: In this retrospective cohort study, we included infants born at <32 weeks' gestation and had either magnetic resonance imaging (MRI) or cranial ultrasound (CUS) performed at term equivalent age. Significant brain injury was diagnosed based on Kidokoro global brain injury score was ≥4 in MRI or cystic periventricular leukomalacia in CUS., Results: Among the 698 infants, 48 had significant brain injury and 650 were taken as controls. In multiple logistic regression, intraventricular hemorrhage (IVH) grade 3-4 [adjusted odds ratio, 92.892 (19.495-442.619)], culture-positive sepsis [4.162 (1.729-10.021)], prolonged ventilation [3.688 (1.087-12.510)], and small for gestational age (SGA) [2.645 (1.181-5.924] were associated with greater risk of preterm brain injury., Conclusion: Severe IVH, culture-positive sepsis, prolonged ventilation and SGA were significant risk factors for preterm brain injury with severe IVH being the most significant contributing factor., Competing Interests: None

Importance: Bronchopulmonary dysplasia (BPD) has multifactorial etiology and long-term adverse consequences. An umbrella review enables the evaluation of multiple proposed interventions for the prevention of BPD., Objective: To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews., Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020., Study Selection: Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome., Data Extraction and Synthesis: Data extraction was performed in duplicate. Quality of systematic reviews was evaluated using Assessment of Multiple Systematic Reviews version 2, and certainty of evidence was assessed using Grading of Recommendation, Assessment, Development, and Evaluation., Main Outcomes and Measures: (1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA., Results: A total of 154 systematic reviews evaluating 251 comparisons were included, of which 110 (71.4%) were high-quality systematic reviews. High certainty of evidence from high-quality systematic reviews indicated that delivery room continuous positive airway pressure compared with intubation with or without routine surfactant (relative risk [RR], 0.80 [95% CI, 0.68-0.94]), early selective surfactant compared with delayed selective surfactant (RR, 0.83 [95% CI, 0.75-0.91]), early inhaled corticosteroids (RR, 0.86 [95% CI, 0.75-0.99]), early systemic hydrocortisone (RR, 0.90 [95% CI, 0.82-0.99]), avoiding endotracheal tube placement with delivery room continuous positive airway pressure and use of less invasive surfactant administration (RR, 0.90 [95% CI, 0.82-0.99]), and volume-targeted compared with pressure-limited ventilation (RR, 0.73 [95% CI, 0.59-0.89]) were associated with decreased risk of BPD or mortality at 36 weeks' PMA. Moderate to high certainty of evidence showed that inhaled nitric oxide, lower saturation targets (85%-89%), and vitamin A supplementation are associated with decreased risk of BPD at 36 weeks' PMA but not the competing outcome of BPD or mortality, indicating they may be associated with increased mortality., Conclusions and Relevance: A multipronged approach of delivery room continuous positive airway pressure, early selective surfactant administration with less invasive surfactant administration, early hydrocortisone prophylaxis in high-risk neonates, inhaled corticosteroids, and volume-targeted ventilation for preterm neonates requiring invasive ventilation may decrease the combined risk of BPD or mortality at 36 weeks' PMA.

Introduction: Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral palsy in preterm neonates. There is no proven therapy for PVL. This calls for appraisal of targeted therapies that have been investigated in animal models to evaluate their relevance in a clinical research context., Areas Covered: This systematic review identifies interventions that were evaluated in preclinical studies for neuroprotective efficacy against PVL. We identified 142 studies evaluating various interventions in PVL animal models (search method is detailed in section 2)., Expert Opinion: Interventions that have yielded significant results in preclinical research, and that have been evaluated in a limited number of clinical trials include stem cells, erythropoietin, and melatonin. Many other therapeutic modalities evaluated in preclinical studies have been identified, but more data on their neuroprotective potential in PVL must be garnered before they can be considered for clinical trials. Because most of the tested interventions had only a partial efficacy, a combination of interventions that could be synergistic should be investigated in future preclinical studies. Furthermore, since the nature and pattern of perinatal insults to preterm brain predisposing it to PVL are substantially variable, individualized approaches for the choice of appropriate neuroprotective interventions tailored to different subgroups of preterm neonates should be explored.

Aim: To study the impact of delivery room continuous positive airway pressure (DRCPAP) on outcomes of preterm neonates in low- and middle- income countries (LMICs) by comparing with interventions: oxygen supplementation, late DRCPAP, DRCPAP with sustained inflation, DRCPAP with surfactant and invasive mechanical ventilation (IMV)., Methods: Medline, Embase, CENTRAL, WOS and CINAHL searched. Observational studies and randomized controlled trials (RCTs) were included. Pair-wise meta-analysis and Bayesian network meta-analysis (NMA) were utilized. Primary outcome was receipt of IMV., Results: Data from 11 of the 18 included studies (4 observational studies, 7 RCTs) enrolling 4210 preterm infants was synthesized. Moderate certainty of evidence (CoE) from NMA of RCTs comparing DRCPAP with surfactant administration versus DRCPAP alone suggested no decrease in subsequent receipt of IMV [Risk ratio (RR); 95% Credible Interval (CrI): 0.73; (0.34, 1.40)]. Very low CoE from observational studies comparing use of DRCPAP versus oxygen supplementation indicated a trend towards decreased IMV [RR; 95% Confidence Interval (CI): 0.75; (0.56-1.00)]. Although moderate CoE from NMA evaluating DRCPAP versus oxygen supplementation showed a trend towards decreased receipt of surfactant, it did not reach statistical significance [RR; 95% CrI: 0.69; (0.44, 1.06)]. Moderate CoE from NMA indicated that none of the interventions, when compared with use of supplemental oxygen alone or with each other decreased mortality or bronchopulmonary dysplasia., Limitations: CoE was very low for primary outcome., Conclusions: Present evidence is not sufficient for use of DRCPAP, but also did not show harm. Since it seems unlikely that there are marked variations in patient physiology to explain the difference in efficacy between high income countries and LMICs, we suggest future research evaluating other barriers in improving the effectiveness of DRCPAP in LMICs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Background: We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity., Methods: Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines., Results: One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM >48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P < 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL., Conclusion: Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: The International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support forms the basis for guidelines developed by regional councils such as the American Heart Association (AHA) and the European Resuscitation Council (ERC). We aimed to determine if the updated guidelines are congruent, identify the source of variation, and score their quality., Methods: We compared the approach to developing recommendations, final recommendations, and cited evidence in the AHA 2020 and ERC 2021 neonatal resuscitation guidelines. Two investigators scored guideline quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool., Results: Differences in the recommendations were found between AHA 2020 and ERC 2021 neonatal resuscitation guidelines. The councils gave differing recommendations for practices that had sparse evidence and made recommendations based on expert consensus or observational studies. AGREE II assessment revealed that AHA scored better for the domain 'rigour of development', but ERC had a higher score for 'stakeholder involvement'. Both AHA and ERC scored relatively less for 'applicability'., Conclusion: AHA and ERC guidelines are predominantly based on the ILCOR CoSTR. Differences in recommendations between the two were largely related to the evidence gathering process for questions not reviewed by ILCOR, paucity of evidence for some recommendations based on existing regional practices and supported by expert opinion, and different interpretation or application of same evidence. Overall, both guidelines scored well on the AGREE II assessment, but each had domains that could be improved in future editions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: To evaluate digital tracheal intubation (DTI) when compared to laryngoscope-assisted TI; finger palpation of endotracheal tube (ETT) tip position when compared to any standard method., Design: A systematic review of Medline, Embase, CENTRAL, and CINAHL with synthesis of data using meta-analysis was performed., Main Outcome Measure: The proportion of successful TI and correct ETT tip positioning were the main outcome measures., Results: Five studies (one observational study and four RCTs) enrolling 310 neonates were included. 94% (81%-98%) of the DTI were successful on the first attempt (certainty of evidence [CoE]: low). The proportion of successful intubation on the first attempt was higher with DTI when compared to laryngoscope-assisted TI (RR 95% CI: 1.81 [1.18; 2.76]) (CoE: very low). Time to successful TI with DTI was 7.4 (95% CI: 6.3, 8.5) s (CoE: low). Time to successful TI was significantly shorter with DTI when compared to laryngoscope assisted TI (MD [95% CI]: -4.9 [-7.3, -2.4] s) (CoE: very low). There was a trend towards a higher proportion of correct ETT tip positions with finger palpation when compared to weight-based formulae alone (RR 95% CI: 1.12 [0.96; 1.31]) (CoE: very low)., Conclusions: DTI and finger palpation to ascertain ETT tip position in neonates are promising strategies. Future studies with emphasis on their learning trajectory and generalizability are needed., (© 2021 The Authors. Pediatric Pulmonology Published by Wiley Periodicals LLC.)

Importance: Prevention of hypothermia in the delivery room is a cost-effective, high-impact intervention to reduce neonatal mortality, especially in preterm neonates. Several interventions for preventing hypothermia in the delivery room exist, of which the most beneficial is currently unknown., Objective: To identify the delivery room thermal care intervention that can best reduce neonatal hypothermia and improve clinical outcomes for preterm neonates born at 36 weeks' gestation or less., Data Sources: MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL databases were searched from inception to November 5, 2020., Study Selection: Randomized and quasi-randomized clinical trials of thermal care interventions in the delivery room for preterm neonates were included. Peer-reviewed abstracts and studies published in non-English language were also included., Data Extraction and Synthesis: Data from the included trials were extracted in duplicate using a structured proforma. A network meta-analysis with bayesian random-effects model was used for data synthesis., Main Outcomes and Measures: Primary outcomes were core body temperature and incidence of moderate to severe hypothermia on admission or within the first 2 hours of life. Secondary outcomes were incidence of hyperthermia, major brain injury, and mortality before discharge. The 9 thermal interventions evaluated were (1) plastic bag or plastic wrap covering the torso and limbs with the head uncovered or covered with a cloth cap; (2) plastic cap covering the head; (3) skin-to-skin contact; (4) thermal mattress; (5) plastic bag or plastic wrap with a plastic cap; (6) plastic bag or plastic wrap along with use of a thermal mattress; (7) plastic bag or plastic wrap along with heated humidified gas for resuscitation or for initiating respiratory support in the delivery room; (8) plastic bag or plastic wrap along with an incubator for transporting from the delivery room; and (9) routine care, including drying and covering the body with warm blankets, with or without a cloth cap., Results: Of the 6154 titles and abstracts screened, 34 studies that enrolled 3688 neonates were analyzed. Compared with routine care alone, plastic bag or wrap with a thermal mattress (mean difference [MD], 0.98 °C; 95% credible interval [CrI], 0.60-1.36 °C), plastic cap (MD, 0.83 °C; 95% CrI, 0.28-1.38 °C), plastic bag or wrap with heated humidified respiratory gas (MD, 0.76 °C; 95% CrI, 0.38-1.15 °C), plastic bag or wrap with a plastic cap (MD, 0.62 °C; 95% CrI, 0.37-0.88 °C), thermal mattress (MD, 0.62 °C; 95% CrI, 0.33-0.93 °C), and plastic bag or wrap (MD, 0.56 °C; 95% CrI, 0.44-0.69 °C) were associated with greater core body temperature. Certainty of evidence was moderate for 5 interventions and low for plastic bag or wrap with a thermal mattress. When compared with routine care alone, a plastic bag or wrap with heated humidified respiratory gas was associated with less risk of major brain injury (risk ratio, 0.23; 95% CrI, 0.03-0.67; moderate certainty of evidence) and a plastic bag or wrap with a plastic cap was associated with decreased risk of mortality (risk ratio, 0.19; 95% CrI, 0.02-0.66; low certainty of evidence)., Conclusions and Relevance: Results of this study indicate that most thermal care interventions in the delivery room for preterm neonates were associated with improved core body temperature (with moderate certainty of evidence). Specifically, use of a plastic bag or wrap with a plastic cap or with heated humidified gas was associated with lower risk of major brain injury and mortality (with low to moderate certainty of evidence).

Context: Morbidity and mortality amongst extremely low birth weight (ELBW) and extremely low gestational age neonates (ELGANs) in developing nations has not been well studied., Objectives: Evaluate survival until discharge, short- and long-term morbidities of ELBW and ELGANs in LMICs., Data Sources: CENTRAL, EMBASE, MEDLINE and Web of Science., Study Selection: Prospective and retrospective observational studies were included., Data Extraction and Synthesis: Four authors extracted data independently. Random-effects meta-analysis of proportions was used to synthesize data, modified QUIPS scale to evaluate quality of studies and GRADE approach to ascertain the certainty of evidence (CoE)., Results: 192 studies enrolling 22,278 ELBW and 18,338 ELGANs were included. Survival was 34% (95% CI: 31% - 37%) (CoE-low) for ELBW and 39% (34% - 44%) (CoE-moderate) for ELGANs. For ELBW neonates, the survival for low-income (LI), lower middle-income (LMI) and upper middle income (UMI) countries was 18% (11% - 28%), 28% (21% - 35%) and 39% (36% - 42%), respectively. For ELGANs, it was 13% (8% - 20%) for LI, 28% (21% - 36%) for LMI and 48% (42% - 53%) for UMI countries. There was no difference in survival between two epochs: 2000-2009 and 2010-2020. Except for necrotising enterocolitis [ELBW and ELGANs-8% (7% - 10%)] and periventricular leukomalacia [ELBW-7% (4% - 11%); ELGANs-6% (5%-7%)], rates of all other morbidities were higher compared to developed nations. Rates of neurodevelopmental impairment was 17% (7% - 34%) in ELBW neonates and 29% (23% - 37%) in ELGANs., Limitations: CoE was very low to low for all secondary outcomes., Conclusions: Mortality and morbidity amongst ELBW and ELGANs is still a significant burden in LMICs. CoE was very low to low for all the secondary outcomes, emphasizing the need for high quality prospective cohort studies., Trial Registration: PROSPERO (CRD42020222873)., Competing Interests: The authors have declared that no competing interests exist.

Background: We present the diagnostic dilemma of a neonate with two umbilical soft tissue masses. Case report : The baby had an umbilical mass herniating through the umbilical cord, and another mass hanging from the umbilical mass by a string of tissue. Both masses were amorphous solid soft tissues and the hanging mass had hair on the surface. Clinical diagnosis was umbilical cord teratoma. However, histopathological examination of the masses showed that tissues representing various organs were arranged in cephalocaudal order as in a fetus, revealing that it was a parasitic twin. The hanging mass was probably the cephalic part and the umbilical mass was malformed torso and limbs. Conclusion : This parasitic omphalopagus heteropagus parasitic twin presented as two amorphous masses without externally identifiable anatomic structure, The parasitic twin of omphalopagus heteropagus may have unusual presentations. Histopathological examination was essential to diagnose whether it is a twin or a tumor.

Clinical profile of extreme preterm neonates and more so, of microprimies with birth weight < 800 g is not studied till now. Our article elaborates the profile of 5 microprimies with C.auris sepsis and review of literature. The mean gestational age and birth weight were 26 weeks ± 5 days and 709 ± 64 g respectively. Mortality was 80%. The organism was susceptible to micafungin, voriconazole but was resistant to fluconazole and amphotericin. Among the 5 babies, one had organ involvement in the form of cardiac vegetation. Early identification and optimal choice of drug are crucial for better survival in C.auris sepsis., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the effect of different frequencies of ventilator circuit changes in neonates and children through a systematic review and meta-analysis., Interventions: (1) "No routine change of ventilator circuit (unless visibly soiled)" versus "routine change at any fixed interval"; (2) routine change of circuit at "less frequent" versus "more frequent" intervals., Outcomes: Primary outcomes were VAP rate (number of VAP episodes per 1000 ventilator-days) and all-cause mortality before discharge., Methods: MEDLINE, CENTRAL, EMBASE, and CINAHL were systematically searched from inception till November 3, 2020. Two authors assessed trial eligibility and risk of bias, and independently extracted data. Data were synthesized using fixed effects model. GRADE was used to assess certainty of evidence (CoE)., Results: We identified six studies enrolling 768 participants evaluating circuit changes at two fixed intervals. Meta-analysis of studies on circuit changes "once in less than 7 days" versus "once weekly" showed no difference in VAP rate (risk ratio: 0.83 [0.38-1.81]; one randomized controlled trial (RCT) and 0.94 [0.49-1.81]; two before-after studies) or mortality before discharge (0.67 [0.34-1.3]; one RCT and 1.01 [0.63-1.64]; two before-after studies). CoE was very low. Less frequent circuit changes reduced health-care costs. No study evaluating "circuit changes only when visibly soiled" versus "circuit changes at a fixed interval" was identified., Conclusion: There is no evidence to suggest that ventilator circuits can be safely left unchanged until visibly soiled in neonates and children. Extending circuit changes interval to "once weekly" may not increase VAP rate (CoE-very low) and reduces healthcare costs., (© 2021 Wiley Periodicals LLC.)

We report a neonate who developed external iliac artery thrombosis after insertion of femoral venous catheter, without an apparent arterial puncture during the procedure. The baby developed acute limb ischaemia. As there was no improvement despite heparin infusion for 24 hours, thrombectomy was done. Following surgery, the limb perfusion improved gradually in 1 week. However, pulses did not reappear even after antithrombotic therapy for 3 months. There was residual Doppler abnormality in the form of severe narrowing at the origin of superficial femoral artery with reduced flow velocity in superficial femoral, popliteal and tibial arteries. The baby was kept under regular follow-up, with a plan for clinical assessment and Doppler every 6 months and to perform a vascular reconstructive surgery if he develops any clinical feature of chronic limb ischaemia. The baby is now 1 year of age. He is walking normally and there is no limb length discrepancy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None

Competing Interests: Competing interests: None declared.

Background: Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017., Objectives: To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively., Search Methods: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries., Selection Criteria: We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants., Data Collection and Analysis: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge., Main Results: We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence)., Authors' Conclusions: High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Incubators and radiant warmers are essential equipment in neonatal care, but the typical 1,500 to 35,000 USD cost per device makes it unaffordable for many units in low and middle-income countries. We aimed to determine whether stable preterm infants could maintain thermoregulation for 48 h in a low-cost incubator (LCI)., Methods: The LCI was constructed using a servo-heater costing 200 USD and cardboard infant-chamber. We conducted this open-labeled non-inferiority randomized controlled trial in a tertiary level teaching hospital in India from May 2017 to March 2018. Preterm infants on full feeds and receiving incubator or radiant warmer care were enrolled at 32 to 36 weeks post-menstrual age. We enrolled 96 infants in two strata (Strata-1< 33 weeks, Strata-2 ≥ 33 weeks at birth). Infants were randomized to LCI or standard single-wall incubator (SSI) after negative incubator cultures and monitored for 48 h in air-mode along with kangaroo mother care. The incubator temperature was adjusted manually to maintain skin and axillary temperatures between 36.5 °C and 37.5 °C. During post-infant period after 48 h, SSI and LCI worked for 5 days and incubator temperatures were measured. The primary outcome was maintenance of skin and axillary temperatures with a non-inferiority margin of 0.2 °C. Failed thermoregulation was defined as abnormal axillary temperature (< 36.5 °C or >37.5 °C) for > 30 continuous-minutes. Secondary outcomes were incidence of hypothermia and required incubator temperature. Trial registration details: Clinical Trial Registry - India (CTRI/2015/10/006316)., Findings: Prior to enrollment 79(82%) infants were in radiant warmer and 17(18%) infants were in incubator care. Median weight at enrollment in Strata-1 and Strata-2 for SSI vs. LCI was 1355(IQR 1250-1468) vs. 1415(IQR 1280-1582) and 1993(IQR 1595-2160) vs. 1995(IQR 1632-2237) grams. Mean skin temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.8 ° C  ± 0.2 vs. 36.7 ° C  ± 0.18 and 36.8 ° C  ± 0.22 vs. 36.7 ° C  ± 0.19. Mean axillary temperature in Strata-1 and Strata-2 for SSI vs. LCI was 36.9 ° C  ± 0.19 vs. 36.8 ° C  ± 0.16 and 36.8 ° C  ± 0.2 vs. 36.8 ° C  ± 0.19. Mixed-effect model done for repeated measures of skin and axillary temperatures showed the estimates were within the non-inferiority limit; -0.07 °C (95% CI -0.11 to -0.04) and -0.06 °C (95% CI -0.095 to -0.02), respectively. Failed thermoregulation did not occur in any infants. Mild hypothermia occurred in 11 of 48(23%) of SSI and 16 of 48(33%) of LCI, OR 1.28 (95%CI 0.85 to 1.91). Incubator temperature in LCI was higher by 0.7 °C (95%CI 0.52 to 0.91). In the post-infant period SSI and LCI had excellent reliability to maintain set-temperature with intra-class correlation coefficient of 0.93 (95%CI 0.92 to 0.94) and 0.96 (95%CI 0.96 to 0.97), respectively., Interpretation: Maintenance of skin and axillary temperature of stable preterm infants in LCI along with kangaroo mother care was non-inferior to SSI, but at a higher incubator temperature by 0.7 °C. No adverse events occurred and LCI had excellent reliability to maintained set-temperature., Funding: Food and Drug Administration (Award number P50FD004895)., Competing Interests: Authors AC, PA, UB, TA, GR, SMSJ, UDR, US, GT and BN report grant from Food and Drug Administration for conduct of the study. None of the authors received any personal fees or non-financial support for conduct of the study., (© 2020 The Authors.)

Objective: To assess the utility of autologous umbilical cord blood (UCB) for red cell concentrate (RCC) transfusion in preterm infants., Methods: We recruited preterm infants born at ≤30 weeks' gestation or have an estimated fetal weight <1,200 g. We intended to perform delayed cord clamping (DCC) and to collect UCB following DCC. The quality parameters used included blood culture performed once, and biochemical and haematological parameters assessed weekly., Results: Of the 46 recruited neonates, DCC could be performed for 1 minute in 11 (23.9%) and for 30-59 seconds in 10 (21.7%) infants. The success rate of UCB collection was significantly lower in infants who underwent DCC for 1 minute (27%) compared to those who underwent DCC for 30-59 seconds (70%) or immediate cord clamping (72%) (p value 0.031). Twenty-five UCBs were stored after eliminating three that had positive culture. UCB had satisfactory quality for transfusion from day 3 (when blood culture report was available) to 14 (after which pH decreased to <6.5). Thirteen infants required 27 RCC transfusions. Autologous UCB could be used for only five (18.5%) transfusions., Conclusion: The success rate of UCB collection after DCC for 1 minute is low. Autologous UCB meets less than one-fifth of transfusion requirements. Hence, autologous UCB transfusion is not a workable option in preterm infants., (© 2020 British Blood Transfusion Society.)

Neonatal encephalopathy manifests with altered sensorium, tone abnormalities, and often with abnormal movements and seizures. The causes are heterogeneous and many. We report a late preterm neonate who presented with depressed sensorium, cranial nerve abnormalities, mixed hypertonia and hypotonia, and respiratory failure. Neuroimaging and electrophysiological studies were normal. She had neutropenia and elevated lactates in blood. Her dried blood spot analysis by tandem MS/MS showed normal acylcarnitine and amino acid profile. Plasma and cerebro spinal fluid (CSF) amino acid quantification were inconclusive, CSF folate was normal. Urine organic acid analysis showed elevated lactate. Semi-quantitative analysis of urine showed borderline elevation of 3-methylglutaconic acid. Diagnosis of 3-methylglutaconic aciduria (3MGA) type VIII was suggested by whole-exome sequencing, which revealed a homozygous, likely pathogenic, missense mutation in Exon 2 of HTRA2 gene (chr2.74757898A>C). Her parents were found to be carriers of the same mutation. This underscores the importance of genetic studies in the evaluation of neonatal neuro-metabolic disorders. We report the first case of 3MGA type VIII from our region with a review of already reported 11 cases., (© 2020 Wiley Periodicals LLC.)

Background: Uncertainty exists about the optimal point at which multi-component fortifier should be added to human milk for promoting growth in preterm infants. The most common practice is to start fortification when the infant's daily enteral feed volume reaches 100 mL/kg body weight. Another approach is to commence fortification earlier, in some cases as early as the first enteral feed. Early fortification of human milk could increase nutrient intake and growth rates but may increase the risk of feed intolerance and necrotising enterocolitis (NEC)., Objectives: To assess effects on growth and safety of early fortification of human milk versus late fortification in preterm infants To assess whether effects vary based upon gestational age (≤ 27 weeks; 28 to 31 weeks; ≥ 32 weeks), birth weight (< 1000 g; 1000 to 1499 g; ≥ 1500 g), small or appropriate for gestational age, or type of fortifier (bovine milk-based human milk fortifier (HMF); human milk-based HMF; formula powder) SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8); OVID MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions (R) (1946 to 15 August 2019); MEDLINE via PubMed (1 August 2018 to 15 August 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL) (1981 to 15 August 2019). We searched clinical trials databases and reference lists of included studies., Selection Criteria: We included randomised controlled trials that compared early versus late fortification of human milk in preterm infants. We defined early fortification as fortification started at < 100 mL/kg/d enteral feed volume or < 7 days postnatal age, and late fortification as fortification started at ≥ 100 mL/kg/d feeds or ≥ 7 days postnatal age., Data Collection and Analysis: Both review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials, and we reported risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence., Main Results: We included two trials with a total of 237 infants. All participants were very low birth weight infants (birth weight < 1500 g). Early fortification was started at 20 mL/kg/d enteral feeds in one study and 40 mL/kg/d in the other study. Late fortification was started at 100 mL/kg/d feeds in both studies. One study used bovine milk-based fortifier, and the other used human milk-based fortifier. Meta-analysis showed that early fortification may have little or no effect on growth outcomes including time to regain birth weight (MD -0.06 days, 95% CI -1.32 to 1.20 days), linear growth (MD 0.10 cm/week, 95% CI -0.03 to 0.22 cm/week), or head growth (MD -0.01 cm/week, 95% CI -0.07 to 0.06 cm/week) during the initial hospitalisation period. Early fortification may have little or no effect on the risk of NEC (MD -0.01, 95% CI -0.07 to 0.06). The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). Early fortification may have little or no effect on incidence of surgical NEC, time to reach full enteral feeds, extrauterine growth restriction at discharge, proportion of infants with feed interruption episodes, duration of total parenteral nutrition (TPN), duration of central venous line usage, or incidence of invasive infection, all-cause mortality, and duration of hospital stay. The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). We did not have data for other outcomes such as subsequent weight gain after birth weight is regained, parenteral nutrition-associated liver disease, postdischarge growth, and neurodevelopmental outcomes., Authors' Conclusions: Available evidence is insufficient to support or refute early fortification of human milk in preterm infants. Further large trials would be needed to provide data of sufficient quality and precision to inform policy and practice., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)