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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 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 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

Aim: The 2015 recommendation of the International Liaison Committee on Resuscitation of no routine tracheal suctioning in non-vigorous neonates born through meconium-stained amniotic fluid (MSAF) was based on very low certainty of evidence (CoE) necessitating ongoing monitoring. The aim of this systematic review was to perform a meta-analysis of observational studies comparing the effect of implementing immediate resuscitation without routine tracheal suctioning versus with routine suctioning in neonates born through MSAF. Methods: MEDLINE, Embase, CENTRAL, and Web of Science were searched. Observational studies with a before-and-after design were included. Two authors extracted data independently. CoE based on GRADE recommendations was performed. Results: 13 studies were included. Clinical benefit or harm could not be excluded for the composite primary outcome of mortality or requirement of extracorporeal membranous oxygenation (ECMO) (relative risk, 95% confidence interval: 0.74 [0.47–1.17]), and mortality (0.68 [0.42–1.11]). “Routine tracheal suctioning” epoch had possibly lesser risk of meconium aspiration syndrome (MAS) when compared to “no routine tracheal suctioning” epoch (0.68 [0.47–0.99]). “Routine tracheal suctioning” epoch also possibly had a lower risk of hospital admission for respiratory symptoms, requirement of non-invasive respiratory support, invasive mechanical ventilation, surfactant treatment, air leak, and low-flow oxygen therapy. Clinical benefit or harm could not be excluded for the outcome of mortality or ECMO among those diagnosed with MAS (1.09 [0.86–1.39]), but “routine tracheal suctioning” was possibly associated with lower risk of respiratory morbidities among those diagnosed with MAS. The CoE was very low for most of the outcomes evaluated. Conclusions: Due to the very low CoE for the outcomes evaluated, no definitive conclusions can be drawn warranting the need for additional studies.

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.

Background: Sedation to preterm neonates receiving less invasive surfactant administration (LISA) for respiratory distress syndrome is controversial. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies (OS) to evaluate the effect of sedative drugs for LISA on respiratory outcomes and adverse effects. Results: One RCT (78 neonates) and two OS (519 neonates) were analyzed in pairwise meta-analysis and 30 studies (2164 neonates) in proportion-based meta-analysis. Sedative drugs might not affect the duration of the procedure [RCT: mean difference (MD) (95% CI); −11 (−90; 67) s; OS: MD 95% CI: −60 (−178; 58) s; low certainty of evidence (CoE)]. Evidence for success at the first attempt and rescue intubation was uncertain (very low CoE). The risk of nasal intermittent positive pressure ventilation [RCT: 1.97 (1.38–2.81); OS: RR, 95% CI: 2.96 (1.46; 6.00), low CoE], desaturation [RCT: RR, 95% CI: 1.30 (1.03; 1.65), low CoE], and apnea [OS: RR, 95% CI: 3.13 (1.35; 7.24), very low CoE] might be increased with sedation. Bradycardia, hypotension, and mechanical ventilation were comparable between groups (low CoE). Conclusions: Use of sedative drugs for LISA temporarily affects the newborn’s breathing. Further trials are warranted to explore the use of sedation for LISA. Impact: The effect of sedative drugs (analgesics, sedatives, anesthetics) compared to the effect of no-sedation for LISA in preterm infants with RDS is underexplored.This systematic review and meta-analysis assesses the impact of sedative drugs compared to no-sedation for LISA on short-term pulmonary outcomes and potential adverse events.Sedative drugs for LISA temporarily affect the newborn’s breathing (desaturation, apnea) and increase the need for nasal intermittent positive pressure ventilation. For most outcomes, certainty of evidence is low/very low.

Objective The International Liaison Committee on Resuscitation (ILCOR) 2015 gave a weak recommendation based on low certainty of evidence against routine endotracheal (ET) suctioning in non-vigorous (NV) neonates born through meconium-stained amniotic fluid (MSAF) and suggested for immediate resuscitation without direct laryngoscopy. A need for ongoing surveillance post policy change has been stressed upon. This study compared the outcomes of NV MSAF neonates before and after implementation of the ILCOR 2015 recommendation. Study Design This was a prospective cohort study of term NV MSAF neonates who underwent immediate resuscitation without ET suctioning (no ET group, July 2018 to June 2019, n = 276) compared with historical control who underwent routine ET suction (ET group, July 2015 to June 2016, n = 271). Results Baseline characteristics revealed statistically significant higher proportion of male gender and small for gestational age neonates in the prospective cohort. There was no significant difference in the incidence of primary outcome of meconium aspiration syndrome (MAS) between the groups (no ET group: 27.2% vs ET group: 25.1%; p = 0.57). NV MSAF neonates with hypoxic ischemic encephalopathy (HIE) was significantly lesser in the prospective cohort (no ET group: 19.2% vs ET group: 27.3%; p = 0.03). Incidence of air leaks and need for any respiratory support significantly increased after policy change. In NV MSAF neonates with MAS, need for mechanical ventilation (MV) (no ET group: 24% vs ET group: 39.7%; p = 0.04) and mortality (no ET group: 18.7% vs ET group: 33.8%; p = 0.04) were significantly lesser. Conclusion Current study from a developing country indicates that immediate resuscitation and no routine ET suctioning of NV MSAF may not be associated with increased risk of MAS and may be associated with decreased risk of HIE. Increased requirement of any respiratory support and air leak post policy change needs further deliberation. Decreased risk of MV and mortality among those with MAS was observed. Key Points

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.To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews.MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020.Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome.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.(1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA.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.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.

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. 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). 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.

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).

BackgroundWe investigated the impact of policy change in delivery room resuscitation from routine endotracheal (ET) suctioning of non-vigorous neonates born through meconium-stained amniotic fluid (MSAF) to immediate non-invasive respiratory support.DesignSingle-centre cohort study. Prospective group (October 2016–September 2017)—non-vigorous neonates born through MSAF managed according to the current (2015) guidance of commencing respiratory support without prior suctioning. Retrospective group (August 2015–July 2016)—non-vigorous neonates born through MSAF who underwent routine ET suctioning.Results1138 neonates born through MSAF were analysed. No differences in the incidence of meconium aspiration syndrome (MAS), requirement of mechanical ventilation, inhaled nitric oxide or surfactant therapy were found between groups. Less neonatal intensive care unit (NICU) admissions were necessary in the prospective cohort compared with the retrospective group (19.1% vs 55.6%, respectively; pConclusionThe policy change towards not routinely suctioning non-vigorous neonates born through MSAF at birth was not associated with an increase in the local incidence of MAS and was associated with fewer NICU admissions.

A singleton term male neonate is born of a nonconsanguineous marriage with no significant antenatal history and a birthweight of 2,600 g via cesarean section. He does not cry immediately after birth and is resuscitated with positive pressure ventilation for 2 minutes. The Apgar scores are 3 at 1 minute and 7 at 5 and 10 minutes. The extramurally delivered newborn is brought to the NICU for postresuscitation care. On initial examination, the neonate is encephalopathic with altered sensorium, hypotonia, and poor respiratory efforts. The heart rate is 110 beats/min with good volume pulses and a capillary refilling time of less than 3 seconds. Features of multiple right-sided lower motor neuron type of cranial nerve palsies (cranial nerves V, VII, IX, X) are seen on clinical examination. These include deviation of the angle of mouth to the left side, obliteration of nasolabial fold and failure to close the eyelid on the right side, abnormal gag reflex, and pooling of secretions. In view of poor breathing efforts, the newborn undergoes intubation and is started on conventional mechanical ventilation. Cord arterial blood gas reveals a pH of 7.25 and a base deficit of −5 mmol/L, which is normal. Routine supplementation with intravenous vitamin K is given. A provisional diagnosis of perinatal asphyxia with hypoxic-ischemic encephalopathy (HIE) with brainstem involvement is made. ### Day 1 to Day 10 The respiratory …

The diagnosis of a right atrial mass in a neonate should be treated as an emergency. There are three major differential diagnoses for a right atrial mass-thrombus, infectious vegetation, and myxoma. Embolization of the mass can result in life-threatening complications and hence timely diagnosis and treatment is vital. This case series describes the clinical course, management, and outcome of four neonates who presented with a right atrial mass.

BackgroundThere are no evidence-based recommendations for surfactant use in late preterm (LPT) and term infants with respiratory distress syndrome (RDS).ObjectiveTo investigate the safety and efficacy of surfactant in LPT and term infants with RDS.MethodsSystematic review, meta-analysis and evidence grading.InterventionsSurfactant therapy versus standard of care.Main outcome measuresMortality and requirement for invasive mechanical ventilation (IMV).ResultsOf 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.ConclusionsCurrent 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.

BACKGROUND: Wide variation in the care practices and survival rates of neonates born at peri-viable gestational ages of 22+0 – 24+6 weeks. This study elucidates the postnatal risk factors for morbidity/mortality, contrasts the care practices and short-term outcomes of this vulnerable group of preterm neonates from a single center with others. METHODS: Retrospective study of neonates born at 22+0 –24+6 weeks in a level 3 neonatal intensive care unit in UK, over a period of 4 years (2016–2019). RESULTS:94 neonates given active care were studied. Survival until discharge was 51.1%(22–23 wks –44%, 24 wks –59.1%) and survival with no major brain injury (MBI) [grade III/IV IVH, cystic periventricular leukomalacia] was 38.3%(22–23 wks –32%, 24 wks –45.4%). Of those who survived until discharge, 75%had no MBI (22–23 wks –72.7%, 24 wks –76.9%). Neonates requiring significant respiratory support within first 72 hours as well as needing rescue high frequency ventilation had significantly high risk of mortality or MBI [aOR –7.17 (2.24–25.79), p = 0.00; 4.76 (1.43–20.00), p = 0.01]. CONCLUSIONS: Survival rate differed from other centres. MBI was low amongst survivors. Severe respiratory disease in the initial days was associated with a higher risk of death or MBI.

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.

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.

Introduction: Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered. Methods: Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (7 days); advancement day: early (7 days); increment volume: small volume (SV) (Results: A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE–very low). Conclusions: Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted.

We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.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.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, PPROM48 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.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.

AIM To assess the effectiveness and safety of levetiracetam when used as first-line treatment of neonatal seizures. METHOD Four electronic databases, Medline, Embase, Web of Science, and ClinicalTrials.gov were systematically searched from inception until 20th November 2020. Randomized controlled trials (RCTs) and observational studies that included neonates born preterm and term were eligible for inclusion. The primary outcome measure was levetiracetam effectiveness, defined as seizure cessation within 24 hours of starting treatment. Secondary outcomes included short-term adverse events, mortality before discharge, and long-term neurodevelopmental outcomes. RESULTS Fourteen studies assessing 1188 neonates were included: four RCTs, three observational trials with phenobarbital as the control arm, and seven observational studies of levetiracetam with no control arm. Pooled efficacy of levetiracetam from observational studies was 45% (95% confidence interval [CI] 34-57%) (GRADE - very low). Meta-analysis of RCTs evaluating levetiracetam versus phenobarbital showed that both were equally effective (risk ratio [95% CI] 0.6 [0.30-1.20]) (GRADE - very low). Levetiracetam resulted in a lower risk of short-term adverse events compared to phenobarbital (risk ratio [95% CI] 0.24 [0.06-0.92]) (GRADE - moderate). INTERPRETATION Very low certainty of evidence suggests levetiracetam might not be more effective than phenobarbital. Moderate certainty of evidence indicates levetiracetam is associated with a lower risk of adverse events. Future trials on neonatal antiseizure medication therapy should include continuous electroencephalogram (EEG) monitoring as standard of care and enrol a homogenous population with similar seizure aetiology. What this paper adds Levetiracetam is effective in 45% of neonatal seizures. Levetiracetam might not be more effective than phenobarbital. Levetiracetam is likely to be safer than phenobarbital. Evidence available is limited and of very low certainty.

Background Seizures are the most significant neonatal emergency, with implications on neurodevelopment and mortality. Evidence for the best management of them still remains limited. Phenobarbital is currently the most used drug for neonatal seizure management. The use of Levetiracetam as an alternative is increasing. It is hypothesised to have a better safety profile. Objectives Assess the effectiveness and safety of levetiracetam when used as the first line treatment of neonatal seizures. Methods Three electronic databases; MEDLINE, EMBASE, and Web of Science were systematically searched from inception until 20th November 2020. Randomized controlled trials (RCTs) and observational studies that included term and preterm neonates were eligible for inclusion. The primary outcome measure was effectiveness of levetiracetam, defined as seizure cessation within 24 hours of starting treatment. Secondary outcomes included short-term adverse events, mortality before discharge and long-term neurodevelopmental outcomes. Results 14 studies assessing 1,188 neonates were included. Four were RCTs, three observational trials with phenobarbital as the control arm and seven observational studies of levetiracetam with no control arm. Pooled efficacy of levetiracetam from observational studies was 45% (95% CI- 34%-57%). Meta-analysis of RCTs evaluating levetiracetam versus phenobarbital showed that both were equally effective [RR (95% CI) - 0.6 (0.3–1.20)] (GRADE – Very low). Levetiracetam resulted in a lower risk of short-term adverse events compared to phenobarbital [RR (95% CI) - 0.24 (0.06–0.92)] (GRADE – Moderate). Conclusions Very low-quality evidence suggests that levetiracetam might not be more effective than phenobarbital. Moderate quality evidence indicates levetiracetam is associated with a lower risk of adverse events.

Objectives To compare the efficacy of different noninvasive respiratory support (NRS) modes for primary respiratory support of preterm infants with respiratory distress syndrome (RDS). Design Systematic review and network meta‐analysis using the Bayesian random‐effects approach. MEDLINE, EMBASE, and CENTRAL were searched. Interventions High flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), bilevel CPAP (BiPAP), noninvasive positive pressure ventilation (NIPPV). Main Outcome Measures Requirement of invasive mechanical ventilation (MV), any treatment failure. Results A total of 35 studies including 4078 neonates were included. NIPPV was more effective in decreasing the requirement of MV than CPAP (risk ratios [95% credible interval]: 0.60 [0.44, 0.77]) and HFNC [0.66 (0.43, 0.97)]. Surface under the cumulative ranking curve (SUCRA) for NIPPV, BiPAP, HFNC, and CPAP were 0.95, 0.59, 0.32, and 0.13. For the outcome of treatment failure, both NIPPV and BiPAP were more efficacious compared to CPAP and HFNC (0.56 [0.44, 0.71] {NIPPV vs CPAP}, 0.69 [0.51, 0.93] {BiPAP vs CPAP}, 0.42 [0.30, 0.63] {NIPPV vs HFNC}, 0.53 [0.35, 0.81] {BiPAP vs HFNC}). The SUCRA for NIPPV, BiPAP, CPAP, and HFNC were 0.96, 0.70, 0.32, and 0.01. NIPPV was associated with a reduced risk of air leak compared to BiPAP and CPAP (0.36 [0.16, 0.73]; 0.54 [0.30, 0.87], respectively). NIPPV resulted in lesser incidence of bronchopulmonary dysplasia or mortality when compared to CPAP (0.74 [0.52, 0.98]). Nasal injury was lesser with HFNC compared to CPAP (0.15 [0.01, 0.60]). Conclusions Most effective primary mode of NRS in preterm neonates with RDS was NIPPV.

BACKGROUND Multiple noninvasive respiratory support (NRS) modalities are used for postextubation support in preterm neonates. Seven NRS modalities were compared-constant flow continuous positive airway pressure (CPAP) (CF-CPAP) (bubble CPAP; ventilator CPAP), variable flow CPAP (VF-CPAP), high flow nasal cannula (HFNC), synchronized noninvasive positive pressure ventilation (S-NIPPV), nonsynchronized NIPPV (NS-NIPPV), bilevel CPAP (BiPAP), noninvasive high-frequency oscillation ventilation (nHFOV). DESIGN Systematic review and network meta-analysis (NMA) using the Bayesian random-effects approach. MEDLINE, EMBASE, CENTRAL, WHO-ICTRP were searched. MAIN OUTCOME MEASURE Requirement of invasive mechanical ventilation within 7 days of extubation. RESULTS A total of 33 studies with 4080 preterm neonates were included. S-NIPPV, NS-NIPPV, nHFOV, and VF-CPAP were more efficacious in preventing reintubation than CF-CPAP (risk ratio [RR] [95% credible intervals {CrI}]: 0.22 [0.12, 0.35]; 0.44 [0.27, 0.67]; 0.42 [0.18, 0.81]; 0.73 [0.52, 0.99]). Surface under the cumulative ranking curve (SUCRA) value ranked S-NIPPV to be the best postextubation intervention (SUCRA: 0.98). S-NIPPV was more effective than NS-NIPPV, BiPAP, VF-CPAP, and HFNC (RR [95% CrI]: 0.52 [0.24, 0.97]; 0.32 [0.14, 0.64]; 0.30 [0.16, 0.50]; 0.24 [0.12, 0.41]). NS-NIPPV resulted in lesser reintubation compared to VF-CPAP and HFNC (RR [95% CrI]: 0.61 [0.36, 0.97]; 0.49 [0.27, 0.80]). BiPAP, VF-CPAP, and HFNC had comparable efficacies. The overall quality of evidence was very low to moderate. CONCLUSION Results of this NMA indicate that S-NIPPV might be the most effective and CF-CPAP the least effective NRS modality for preventing extubation failure.

A 33-week-gestation female neonate with a birthweight of 1,920 g is born via vaginal delivery to a primigravida woman who is blood group A positive. She is referred to the NICU 1 hour after birth as a case of antenatally diagnosed hydrops fetalis. ### Admission to 44 Hours After Birth The newborn has stable vital signs with no respiratory distress or circulatory insufficiency. She is pale, with a distended abdomen, and tense on palpation. Ultrasonography reveals significant ascites with no pleural or pericardial effusion. A complete blood cell (CBC) count reveals anemia with a hematocrit of 30%. The total leukocyte count, absolute neutrophil count, and platelet count are within normal reference ranges for gestational age. Direct Coombs test (DCT) result is negative. A provisional diagnosis of hydrops fetalis with anemia is rendered, and congenital parvovirus infection is considered as a strong possibility. ### 44 to 96 Hours After Birth The neonate develops indirect hyperbilirubinemia with a total serum bilirubin value of 15 mg/dL (256.5 μmol/L) with a further drop in hematocrit to 26%. The CBC count reveals new-onset thrombocytopenia, with a platelet count of 50×103/μL (50×109/L), leukopenia with a total leukocyte count of 3,600/μL (3.6×109/L), and neutropenia with an absolute neutrophil count of 800/μL (0.80×109/L). The peripheral smear shows red blood cells (RBCs) with 12% reticulocytes, fragmented cells, spherocytes, target cells, and anisopoikilocytosis. Both white blood cells and platelets are also reduced in the peripheral smear. Results of both the DCT and the indirect Coombs test are negative. The neonate is treated with phototherapy, …

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).

Background: Donor human milk plays a vital part in the care of sick neonates. There is paucity of literature on the profile of human milk donors of low- and middle-income countries (LMICs). Materia...

A 7-day-old neonate presents to our NICU with multiple jerky movements of both upper and lower limbs and floppiness. He is the product of a third-degree consanguineous marriage and is born in a peripheral institution. He has a sister who is 6 years old and is healthy. ### Birth to 7 Days after Birth The neonate is born vaginally and requires bag and mask ventilation for 5 minutes. He is transferred to a level II NICU, where he stays for 5 days. He exhibits features of encephalopathy and also has a multifocal clonic seizure 2 hours after birth; he receives a single loading dose of phenobarbital. He is diagnosed as having hypoxic-ischemic encephalopathy (HIE) grade 2. Subsequently, his sensorium improves and he is discharged while breastfeeding exclusively. Since day 6, he has been having multiple episodes of multifocal clonic seizures and is brought to our NICU on day 7. ### Day 7 to Day 23 A strong suspicion of neurometabolic disorder arises in view of consanguinity and refractory seizures. He is nil per os. He requires full loading doses of antiepileptic drugs (AEDs) phenytoin and phenobarbital, after which his seizures stop. Testing for blood glucose, arterial lactate, pH, serum ammonia, urine ketones, and urine-reducing substances and tandem mass spectroscopy …

Sir,The original research titled “A randomized controlled trial comparing the effect of fortification of human milk with an infant formula powder versus unfortified human milk on the growth of pret...

Importance The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck. Objective To evaluate 14 corticosteroid regimens used to prevent BPD: moderately early-initiated, low cumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone (MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, low cumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD). Data Sources PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization’s International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020. Study Selection In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included. Data Extraction and Synthesis Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model. Main Outcomes and Measures Primary combined outcome was BPD, defined as oxygen requirement at 36 weeks’ postmenstrual age (PMA), or mortality at 36 weeks’ PMA. The secondary outcomes included 15 safety outcomes. Results A total of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimens were associated with a decreased risk of BPD or mortality, including EHC (risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT (RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX (RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX (RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); and MoMdDX (RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed that MoMdDX (SUCRA, 0.91), MoHdDX (SUCRA, 0.86), and LaHdDX (SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX (RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX (RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX (RR, 4.96; 95% CrI, 1.14-14.75); and MoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHC was associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDX showed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.10-30.91). MoHdDX had a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11). Conclusions and Relevance This study suggested that MoMdDX may be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.

A late preterm male infant of 36 weeks gestation and a birth weight of 2100 g was admitted on day 35 of life with complaints of respiratory distress and lethargy. He was diagnosed as a case of sepsis screen positive culture negative sepsis and was managed with respiratory support and intravenous antibiotics for 10 days. The infant improved clinically and was on spoon feeds by day 14 of admission. On day 14 of admission, he developed new-onset respiratory distress and was diagnosed as a case of nosocomial pneumonia based on chest radiography findings. The blood culture grew a rare organismCedecea lapageiand a diagnosis of sepsis was also made. The antibiotics were tailored as per the blood culture sensitivity pattern and the infant had clinical improvement in the next 72 hours.

A preterm 32-week neonate presented on the 14th day of life with respiratory distress and cyanosis. The respiratory distress worsened progressively, which was managed with continuous positive airway pressure support. The neonate had blood-tinged oral secretions on the 39th day of life, for which bronchoscopy was performed, whose findings were suggestive of pulmonary hemosiderosis. Lung biopsy confirmed the diagnosis of pulmonary interstitial glycogenosis with pulmonary arterial hypertension. The neonate was treated successfully with systemic corticosteroids and discharged home at 3 months of age.