Changing Patterns of Organisms Causing Neonatal Sepsis and Their Antimicrobial Sensitivity Profile in a Tertiary Center - A Prospective Study.

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 ß-lactamase, AmpC ß-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-ß-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-ß-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.

Anti-seizure medications for neonates with seizures.

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.

Clinical decision thresholds for surfactant administration in preterm infants: a systematic review and network meta-analysis.

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 (aAO2) <0.36 (FiO2: 37-55%) was ranked the best threshold for decreasing the risk of IMV, very low certainty. Further, surfactant administration at an FiO2 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 FiO2 ≥ 40%. There was insufficient evidence for the comparison of FiO2 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 FiO2 < 30% possibly increased the risk of IMV compared to Intubate-Surfactant-Extubate at FiO2 < 30% and 40%, and less invasive surfactant administration at FiO2 40%, certainty very low. Interpretation: Surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS if the FiO2 requirement is ≥40%. Future trials are required comparing lower FiO2 thresholds of 30% vs. 40% and that guided by lung ultrasound. Funding: None.

Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants.

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.

Re-feeding versus discarding gastric residuals to improve growth in preterm infants.

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.

Multisystem inflammatory disease in neonates (MIS-N) due to maternal COVID-19.

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.

Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS: Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS: Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS: In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.

LATCH Score for Identification and Correction of Breastfeeding Problems - A Prospective Observational Study.

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.

Role of advanced (magnetic resonance) neuroimaging and clinical outcomes in neonatal strokes: Experience from tertiary care center.

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.

Determination of Predictors of Brain Injury in Very Preterm Infants - A Retrospective Cohort Study.

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.

Dextrose Gel for Neonates at Risk With Asymptomatic Hypoglycemia: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Hypoglycemia occurs in 5% to 15% of neonates in the first few days. A significant proportion requires admission for intravenous fluids. Dextrose gel may reduce admissions and mother-infant separation. We aimed to study the utility of dextrose gel in reducing the need for intravenous fluids. METHODS: This stratified randomized control trial included at-risk infants with asymptomatic hypoglycemia. Study populations were stratified into 3 categories: small for gestational age (SGA) and intrauterine growth-restriction (IUGR), infants of diabetic mothers (IDM) and large for gestational age (LGA), and late preterm (LPT) neonates. Intervention group received dextrose gel followed by breastfeeding, and the control group (CG) received only breastfeeding. RESULTS: Among 629 at-risk infants, 291 (46%) developed asymptomatic hypoglycemia; 147 (50.4%) in the dextrose gel group (DGG) and 144 (49.6%) in CG. There were 97, 98, and 96 infants in SGA/IUGR, IDM/LGA, and LPT categories, respectively. Treatment failure in the DGG was 17 (11.5%) compared to 58 (40.2%) in CG, with a risk ratio of 0.28 (95% confidence interval [CI]: 0.17-0.46; P < .001). Treatment failure was significantly less in DGG in all 3 categories: SGA/IUGR, IDM/LGA, and LPT with a risk ratio of 0.29 (95% CI:0.13-0.67), 0.31 (95% CI:0.14-0.66) and 0.24 (95% CI:0.09-0.66), respectively. CONCLUSIONS: Dextrose gel reduces the need for intravenous fluids in at-risk neonates with asymptomatic hypoglycemia in the first 48 hours of life.

Emerging neuroprotective interventions in periventricular leukomalacia - A systematic review of preclinical studies.

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.

Interventions to Prevent Bronchopulmonary Dysplasia in Preterm Neonates: An Umbrella Review of Systematic Reviews and Meta-analyses.

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.

Surfactant therapy in late preterm and term neonates with respiratory distress syndrome: a systematic review and meta-analysis.

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 FiO2 >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.

Delivery room CPAP in improving outcomes of preterm neonates in low-and middle-income countries: A systematic review and network meta-analysis.

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.