Providing Positive End-Expiratory Pressure during Neonatal Resuscitation: A Meta-analysis.

Our objective was to conduct a systematic review and meta-analysis evaluating the effects of administering positive end-expiratory pressure (PEEP) during neonatal resuscitation at birth. Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases were systematically searched from inception to 15 December 2020. Randomized controlled trials and cohort studies were held eligible. Studies were included if they compared the administration of PEEP using either a T-piece resuscitator or a self-inflating bag with a PEEP valve versus resuscitation via a self-inflating bag without a PEEP valve. Data were extracted by two reviewers independently. The credibility of evidence was appraised with the Grading of Recommendations, Assessment, Development, and Evaluations approach. Random-effects models were fitted to provide pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs). Overall, 10 studies were included, comprising 4,268 neonates. This included five randomized controlled trials, one quasi-randomized trial, and four cohort studies. The administration of PEEP was associated with significantly lower rates of mortality till discharge (odds ratio [OR]: 0.60, 95% CI: 0.49-0.74, moderate quality of evidence). The association was significant in preterm (OR: 0.57, 95% CI: 0.46-0.69) but not in term (OR: 1.03, 95% CI: 0.52-2.02) neonates. Low-to-moderate quality evidence suggests that providing PEEP during neonatal resuscitation is associated with lower rates of mortality in preterm neonates. Evidence regarding term neonates is limited and inconclusive. Future research is needed to determine the optimal device and shed more light on the long-term effects of PEEP administration during neonatal resuscitation. This study is registered with PROSPERO with registration number: CRD42020219956. KEY POINTS: · PEEP administration during neonatal resuscitation in the delivery room reduces mortality in preterm.. · Evidence regarding term neonates is limited and inconclusive.. · Future research is needed to determine the optimal device..

Surfactant delivery via thin catheter in preterm infants: A systematic review and meta-analysis.

OBJECTIVE: Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants <29 weeks' gestation and the neurodevelopmental outcomes remain unclear. Thus, our objective was to systematically review and meta-analyze the efficacy and safety of STC compared to intubation for surfactant or nasal continuous positive airway pressure (nCPAP) in preterm infants with RDS. METHODS: Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE. RESULTS: Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate). CONCLUSIONS: Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation.

COVID-19 Disease in Under-5 Children: Current Status and Strategies for Prevention including Vaccination.

Since the coronavirus disease (COVID-19) pandemic hit the globe in early 2020, we have steadily gained insight into its pathogenesis; thereby improving surveillance and preventive measures. In contrast to other respiratory viruses, neonates and young children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have a milder clinical presentation, with only a small proportion needing hospitalization and intensive care support. With the emergence of novel variants and improved testing services, there has been a higher incidence of COVID-19 disease reported among children and neonates. Despite this, the proportion of young children with severe disease has not increased. Key mechanisms that protect young children from severe COVID-19 disease include the placental barrier, differential expression of angiotensin-converting enzyme 2 (ACE-2) receptors, immature immune response, and passive transfer of antibodies via placenta and human milk. Implementing mass vaccination programs has been a major milestone in reducing the global disease burden. However, considering the lower risk of severe COVID-19 illness in young children and the limited evidence about long-term vaccine safety, the risk-benefit balance in children under five years of age is more complex. In this review, we do not support or undermine vaccination of young children but outline current evidence and guidelines, and highlight controversies, knowledge gaps, and ethical issues related to COVID-19 vaccination in young children. Regulatory bodies should consider the individual and community benefits of vaccinating younger children in their local epidemiological setting while planning regional immunization policies.

Therapeutic Hypothermia for Neonatal Encephalopathy in Low- and Middle-Income Countries: A Meta-Analysis.

BACKGROUND: Perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) represent substantial sources of neonatal morbidity and mortality in low- and middle-income countries (LMICs), leading to high rates of adverse long-term neurological outcomes. METHODS: A systematic review with meta-analysis of randomized controlled trials in LMICs was conducted. PubMed, Scopus, Web of Science, CENTRAL, ClinicalTrials.gov, and Google Scholar were searched from inception to August 20, 2021. The population of the study consisted of neonates with gestational age ≥34 weeks and HIE. The main endpoints were overall mortality and the composite outcome of death or severe disability. The certainty of evidence was evaluated with the GRADE approach. RESULTS: Ten studies were included comprising 1,293 neonates. Some concerns of bias were raised due to the nonblinded nature of the intervention. The risk of death was similar between the two groups (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.52-1.18). No significant differences were observed in the composite outcome of death or severe disability between the two groups (RR: 0.78, 95% CI: 0.56-1.10, very low quality of evidence). Furthermore, no significant differences were observed in the endpoints of sepsis, shock, acute kidney injury, major arrhythmia, and length of hospital stay. Therapeutic hypothermia was associated with significantly higher risk of thrombocytopenia (RR: 2.13, 95% CI: 1.34-3.38) and clinically significant hemorrhage (RR: 1.57, 95% CI: 1.25-1.97). CONCLUSION: Therapeutic hypothermia probably results in little to no difference in clinical outcomes among neonates with HIE in LMICs. Further large-scale research targeting proper patient selection is needed to elucidate the utility of therapeutic hypothermia in resource-limited settings. PROTOCOL REGISTRATION: The protocol of the study has been prospectively registered by Prospero, CRD42021272284.

A systematic review of surfactant delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization: Methods, limitations, and outcomes.

Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization. These less invasive techniques are promising and have several advantages over INSURE (Intubation-Surfactant-Extubation) and thin catheter techniques. The objective of this review is to discuss the requisites, techniques, short-term outcomes, and adverse events associated with these methods.

Role of DVET in severe neonatal sepsis in an era of high antibiotic resistance: a retrospective observational study.

AIM: Sepsis is a significant cause of mortality and morbidity in the NICU despite the potent armamentarium of antibiotics. Recently, there has been a considerable increase in antimicrobial resistance even to high-end 3rd line antibiotics. Thus, there is a need to look into adjunctive therapies. This study aims to study the role of double volume exchange transfusion (DVET) in reducing mortality due to severe sepsis. METHODS: All neonates with severe sepsis admitted in NICU from January 2017 to September 2019 were included in the study. Seven neonates who met inclusion criteria and received DVET were compared to 21 gestation and severity matched controls, who received standard therapy (ST) alone. The primary outcome studied was mortality before discharge in both the groups. Other results analyzed were the incidence of persistent thrombocytopenia and refractory shock. RESULTS: There was a significant reduction in mortality in the intervention group (57% vs. 71% (p = .004). There was also a significant reduction both in the incidence of refractory shock (71% vs. 75%; p = .01) and persistent thrombocytopenia (86% vs. 65%; p = .03) in the DVET group. No significant adverse effects occurred following DVET. CONCLUSIONS: In neonates with severe sepsis, DVET may be a useful adjunct therapy. It may reduce mortality and decreased the incidence of refractory shock and thrombocytopenia. DVET is a safe procedure in severely sick and septic neonates.

Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia.

To evaluate the role of urinary beta-2 microglobulin (B2mG) as an early predictive biomarker of acute kidney injury (AKI) in neonates with perinatal asphyxia. In this prospective cohort study, 80 term infants with perinatal asphyxia were included. The neonates were divided into AKI and no-AKI groups. Urinary B2mG levels were measured at 24 h of life. The diagnostic efficacy of the biomarker was determined using receiver operating characteristic (ROC) curves. Compared to infants without AKI, infants with AKI had higher levels of urinary B2mG (mean 6.8 versus 2.6 mg/L, p < 0.001). Area under the receiver operating characteristic curve (ROC curve) was 0.944. The balanced sensitivity/specificity trade-off was found at a cut-off value of 3.8 mg/L (81% sensitive and 81.6% specific).Conclusion Urinary B2mG can be useful to predict AKI early in term neonates with perinatal asphyxia. What is Known: • AKI is seen in 20-40% of neonates with asphyxia. • AKI affects the treatment plan and the prognosis of such neonates. What is New: • Urinary biomarkers are the easiest way to diagnose AKI in asphyxiated neonates. • Beta 2 microglobulin is the cheapest and readily available one such urinary biomarker with good sensitivity and specificity.

Surfactant delivery via thin catheters: Methods, limitations, and outcomes.

Various less invasive surfactant administration strategies like surfactant replacement therapy via thin catheters, laryngeal mask airway, pharyngeal instillation, and nebulized surfactant are increasingly being practiced to avoid the harmful effects of endotracheal intubation and ventilation. Numerous studies have been done to study surfactant replacement via thin catheters whereas little data is available for other methods. However, there are variations in premedication policies, type of respiratory support used in these studies. Surfactant delivery using thin catheters has been reported to be associated with decrease in the need for mechanical ventilation (MV), duration of MV, bronchopulmonary dysplasia and neonatal mortality. With the current evidence, among all the available surfactant delivery methods, the one using thin catheters appears to be the most feasible and beneficial to improve clinical neonatal outcomes.

Is application of salt for 3 days locally is sufficient to treat umbilical granuloma?

BACKGROUND: The falling of Umbilical stump occurs by 7-15 days of age. The healing of umbilical stump may be complicated by Umbilical Granuloma. It is often treated by chemical cauterisation which require repeated applications and may lead to local or systemic complications. Common salt by way of its dessicative property may help in treatment of Umbilical Granuloma. OBJECTIVE: The objective of the study is to assess the role of common salt application in umbilical granuloma. MATERIALS AND METHODS: This is retrospective study over 3 years from a pediatric surgery unit in Northern India. The study subjects were infants less than 10 weeks of age who presented with umbilical granuloma. The method of salt application was 1 pinch of common salt for 1 hour twice a day for 3 consecutive days. The babies were assessed at day 5th for resolution. The success was defined as thrice resolution after 3 cycles. The baseline demographic details were taken and the association of success of treatment was analyzed. RESULTS: A total of 36 infants were given treatment in form of common salt application for treatment of umbilical granuloma. The success of around 96% and the cases which presented early responded well. Most of the cases resolved after 3 cycles of treatment. CONCLUSION: The common salt application is effective in treatment of granuloma without any side effects.

Neonate with chikungunya.

Chikungunya although rare should be considered in any neonate presenting with fever and facial hyperpigmentation or encephalopathy especially in endemic areas.

Congenital dengue in neonate.

Congenital dengue should be considered as a cause of fever and rash in a neonate born to a mother especially in endemic areas.

Comparative efficacy of methods for surfactant administration: a network meta-analysis.

OBJECTIVES: To compare surfactant administration via thin catheters, laryngeal mask, nebulisation, pharyngeal instillation, intubation and surfactant administration followed by immediate extubation (InSurE) and no surfactant administration. DESIGN: Network meta-analysis. SETTING: Medline, Scopus, CENTRAL, Web of Science, Google-scholar and Clinicaltrials.gov databases were systematically searched from inception to 15 February 2020. PATIENTS: Preterm neonates with respiratory distress syndrome. INTERVENTIONS: Less invasive surfactant administration. MAIN OUTCOME MEASURES: The primary outcomes were mortality, mechanical ventilation and bronchopulmonary dysplasia. RESULTS: Overall, 16 randomised controlled trials (RCTs) and 20 observational studies were included (N=13 234). For the InSurE group, the median risk of mortality, mechanical ventilation and bronchopulmonary dysplasia were 7.8%, 42.1% and 10%, respectively. Compared with InSurE, administration via thin catheter was associated with significantly lower rates of mortality (OR: 0.64, 95% CI: 0.54 to 0.76), mechanical ventilation (OR: 0.43, 95% CI: 0.29 to 0.63), bronchopulmonary dysplasia (OR: 0.57, 95% CI: 0.44 to 0.73), periventricular leukomalacia (OR: 0.66, 95% CI: 0.53 to 0.82) with moderate quality of evidence and necrotising enterocolitis (OR: 0.67, 95% CI: 0.41 to 0.9, low quality of evidence). No significant differences were observed by comparing InSurE with administration via laryngeal mask, nebulisation or pharyngeal instillation. In RCTs, thin catheter administration lowered the rates of mechanical ventilation (OR: 0.39, 95% CI: 0.26 to 0.60) but not the incidence of the remaining outcomes. CONCLUSION: Among preterm infants, surfactant administration via thin catheters was associated with lower likelihood of mortality, need for mechanical ventilation and bronchopulmonary dysplasia compared with InSurE. Further research is needed to reach firm conclusions about the efficacy of alternative minimally invasive techniques of surfactant administration.

Effectiveness of theophylline administration in neonates with perinatal asphyxia: a meta-analysis.

AIM: To evaluate the effects of prophylactic theophylline in renal function and survival rates of asphyxiated newborns. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar databases were systematically searched. All randomized controlled trials evaluating the efficacy of theophylline in the prevention of perinatal asphyxia were selected. RESULTS: A total of seven studies were included with a total of 458 asphyxiated neonates. Incidence of acute kidney injury was significantly lower in neonates receiving theophylline (OR: 0.24, 95% CI: [0.16, 0.36]), while mortality rates were similar between the two groups (OR: 0.86, 95% CI: [0.46, 1.62]). Theophylline administration was associated with significantly decreased serum creatinine levels (MD: -0.57 mg/dl, 95% CI: [-0.68, -0.46]) and elevated glomerular filtration rate (MD: 13.79 ml/min/1.73 m2, 95% CI: [11.91, 15.68]) in the third day of life. Theophylline also lead to lower ß2-microglobulin levels, higher urine output and negative fluid balance. CONCLUSIONS: The present findings suggest the effectiveness of theophylline in ameliorating renal function of asphyxiated neonates. Future large-scale trials should assess potential long-term adverse outcomes in clinical practice.KeynotesAsphyxia is a major cause of acute kidney injury in neonatesAcute kidney injury is associated with adverse clinical outcomes in asphyxiated neonates.Theophylline administration leads to significantly lower incidence of acute kidney injury in asphyxiated neonates.

Maternal and perinatal outcomes in pregnant women infected by SARS-CoV-2: A meta-analysis.

Evidence concerning coronavirus disease-19 (covid-19) in pregnancy is still scarce and scattered. This meta-analysis aims to evaluate maternal and neonatal outcomes in covid-19 pregnancies and identify factors associated with perinatal viral transmission. Medline, Scopus, CENTRAL, Web of Science and Google Scholar databases were systematically searched to 3 June 2020. Overall, 16 observational studies and 44 case reports/series were included. Fever was the most frequent maternal symptom, followed by cough and shortness of breath, while about 15 % of infected were asymptomatic. Severe disease was estimated to occur in 11 % of women in case reports/series and in 7 % (95 % CI: 4 %-10 %) in observational studies. Two maternal deaths were reported. The rate of neonatal transmission did not differ between women with and without severe disease (OR: 1.94, 95 % CI: 0.50-7.60). Preterm birth occurred in 29.7 % and 16 % (95 % CI: 11 %-21 %) in data obtained from case series and observational studies, respectively. Stillbirth occurred in 3 cases and 2 neonatal deaths were observed. Vertical transmission was suspected in 4 cases. Fever was the most common neonatal symptom (40 %), followed by shortness of breath (28 %) and vomiting (24 %), while 20 % of neonates were totally asymptomatic. In conclusion, the maternal and neonatal clinical course the infection is typically mild, presenting low mortality rates. The risk of vertical transmission is suggested to be low and may not be affected by the severity of maternal disease. Further large-scale studies are needed to clarify the risk factors associated with viral transmission and severe infection in the neonatal population.

Perinatal COVID-19: review of current evidence and practical approach towards prevention and management.

The clinical spectrum of the perinatal COVID-19 and prospective data on neonatal outcomes remains largely unexplored. Most of the existing literature is in the form of case series or single-centre experience. In this review, we aim to summarize available literature on the clinical spectrum of COVID-19 in neonates and mothers and suggest a practical approach towards management of clinical scenarios. This review explores the clinical characteristics and outcomes of COVID-19 in neonates born to mothers who were detected with the virus during the pregnancy. We conducted a comprehensive search of PubMed, Google Scholar and Cochrane Database of Systematic Review between November 2019 and June 2020 and screened articles related to perinatal COVID-19. This review included 786 mothers, among which 64% (504) were delivered by caesarian section. There were 3 still births and 107 (14%) were delivered preterm. Out of 793 neonates born, 629 neonates (79%) were tested after birth. The commonest symptom in neonates was respiratory distress. Respiratory support was needed in 60 neonates (7.6%), with 14 babies needing mechanical ventilation (1.8%), 25 needing non-invasive ventilation and 21 needing nasal oxygen. Only 35 of the 629 tested neonates (5.5%) were positive for COVID-19. Of the 35 positive neonates, 14 (40%) were symptomatic. The COVID-19 seems to have favourable neonatal outcomes. Majority of neonates are asymptomatic. Respiratory distress is the most common manifestation. What is known: •COVID-19 affects all ages. •Neonatal disease is usually mild. What is new: •Vertical transmission is a possible route of infection in neonates. •Breast milk and skin-to-skin contact are safe in COVID-19-infected mothers if performed with appropriate use of precautions such as hand and breast hygiene and masking.

Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach.

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

Systematic review found that using thin catheters to deliver surfactant to preterm neonates was associated with reduced bronchopulmonary dysplasia and mechanical ventilation.

AIM: Surfactant delivery is a cornerstone for managing respiratory distress in preterm neonates, but data on the best surfactant delivery methods have been conflicting. METHODS: A systematic literature review using the PubMed, Embase, Cochrane Library and Web of Science databases identified papers published up to November 5, 2019. Additional studies were identified from trial registries, conference proceedings and the reference lists of the selected papers. RESULTS: We identified 15 studies covering 4926 preterm infants. The randomised controlled trials (RCTs) and observational studies both showed significant reductions in early intubation rates with use of thin catheters. The relative risk (RR) was 0.63 and the 95% confidence interval (95% CI) was 0.55-0.72 (P < .01), with an odds ratio (OR) of 0.40 and 95% CI of 0.35-0.45 (P < .0001). The collective results from the RCTs revealed a significant decrease in bronchopulmonary dysplasia (BPD) rates in the thin catheter group (RR, 0.47; 95% CI 0.33-0.66; P < .01). These findings were consistent with the observational studies (OR 0.47; 95% CI 0.43-0.52; P < .01). CONCLUSION: Using thin catheters to deliver surfactant in comparison with intubate-surfactant-extubate (INSURE) to newborn preterm infants with respiratory distress was associated with a reduced incidence of BPD and less need for mechanical ventilation.