Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Surfactant administration in preterm babies (28-36 weeks) with respiratory distress syndrome: LISA versus InSurE, an open-label randomized controlled trial.

INTRODUCTION: INtubate-SURfactant-Extubate (InSurE) approach is traditional method of surfactant delivery in preterm neonates with respiratory distress syndrome (RDS). Newer, less invasive surfactant administration (LISA) techniques lessen the need for mechanical ventilation and its adverse consequences. Evidence on the favorable effects of LISA can't be extrapolated from developed to developing countries. Aim of study is to compare the effectiveness of InSurE and LISA. OBJECTIVES: Primary outcome was to find need of intubation and mechanical ventilation within 72 h of birth. Neonates were followed until discharge/death for adverse events and complications. MATERIALS AND METHODS: Open-label randomized controlled trial (RCT) was conducted at tertiary neonatal intensive care unit. Preterm neonates with diagnosis of RDS were randomized in two groups (InSurE or LISA) to receive surfactant soon after birth. Nasal intermittent positive pressure ventilation (NIPPV) was used as primary mode of respiratory support. RESULTS: A total of 150 neonates were analyzed (75 in each group). Insignificant statistical difference was seen in the need for intubation and mechanical ventilation within 72 h of birth between the two groups (InSurE, 30 [40%] and LISA, 30 [40%], relative risk 1.0, 95% confidence interval 0.68-1.48). Twelve percent (n = 9, LISA group) and 14.6% (n = 11 InSurE group) had adverse events during the procedure. Also, we observed insignificant statistical difference in the rates of major complications or duration of respiratory support, hospital stay, and mortality. CONCLUSION: LISA and InSurE are equally effectiSpontaneously breathing pretermve for surfactant administration in the treatment of RDS, when NIPPV is the primary mode of respiratory support. More RCTs are required to compare the efficacy and long-term outcomes of LISA with InSurE.

Outcomes in neonates born to mothers with COVID-19 during the second wave in India.

COVID-19 pandemic has affected all age groups globally including pregnant women and their neonates. The aim of the study was to understand outcomes in neonates of mothers with COVID-19 during the first and second waves of COVID-19 pandemic. A retrospective analysis of 2524 neonates born to SARS-CoV-2-infected mothers was conducted during the first wave (n = 1782) and second wave (n = 742) of the COVID-19 pandemic at five study sites of the PregCovid registry in Maharashtra, India. A significant difference was noted in preterm birth, which was higher in the second wave (15.0%, 111/742) compared to the first wave (7.8%, 139/1782) (P < 0.001). The proportion of neonates requiring NICU admission was significantly higher in the second wave (19.0%, 141/742) as compared to that in the first wave (14.8%, 264/1782) (P < 0.05). On comparing regional differences, significantly higher neonatal complications were reported from Mumbai metropolitan region (P < 0.05). During the second wave of COVID-19, birth asphyxia and prematurity were 3.8- and 2.1-fold higher respectively (P < 0.001). Neonatal resuscitation at birth was significantly higher in second wave (3.4%, 25/742 vs 1.8%, 32/1782) (P < 0.05). The prevalence of SARS-CoV-2 infection in neonates was comparable (4.2% vs 4.6%) with no significant difference between the two waves. CONCLUSION: Higher incidence of adverse outcomes in neonates born to SARS-CoV-2-infected mothers in the second wave of COVID-19 as compared to the first wave. TRIAL REGISTRATION: PregCovid study is registered with the Clinical Trial Registry of India (CTRI/2020/05/025423, Registered on 28/05/2020). WHAT IS KNOWN: • The second wave of COVID-19 was more lethal to pregnant women than the first wave. Newborns are at risk of developing complications. WHAT IS NEW: • Birth asphyxia, prematurity, and neonatal resuscitation at birth were significantly higher in the second wave as compared to those in the first wave of the COVID-19 pandemic in India.

Levetiracetam or Phenobarbitone as a First-Line Anticonvulsant in Asphyxiated Term Newborns? An Open-Label, Single-Center, Randomized, Controlled, Pragmatic Trial.

BACKGROUND AND OBJECTIVE: Neonatal seizures are one of the most challenging problems for experts across the globe. Although there is no consensus on the "ideal" treatment of neonatal seizures, phenobarbitone has been the drug of choice for decades. Unfortunately, although extensively studied in adults and children, levetiracetam lacks rigorous evaluation in the neonatal population, despite its frequent use as an off-label drug. The objective of this open-label, randomized, active-control, single-center, pragmatic trial was to compare the effectiveness of levetiracetam with phenobarbitone for term asphyxiated infants as a first-line drug. METHODS: The participants included in this study were inborn term asphyxiated infants with seizures in the first 48 hours of life. Infants satisfying the inclusion criteria were randomized to receive levetiracetam (20 mg/kg) or phenobarbitone (20 mg/kg). Clinical seizure control was noted. Infants who failed to respond to the primary drug were given the other group drug. RESULTS: Of 103 eligible infants, 82 were randomly assigned (44 levetiracetam group, 38 phenobarbitone group). Clinical seizure control with the primary drug and maintenance of the same for 24 hours was observed in 29 infants (65.9%) in the levetiracetam group and 13 infants (34.2%) in the phenobarbitone group (P < .05, relative risk 0.52, 95% confidence interval 0.32-0.84). Of the infants in the phenobarbitone group who did not respond to the primary drug, 57.8% were controlled after adding levetiracetam. CONCLUSION: Levetiracetam can be used with effectiveness as a first- and second-line drug in asphyxiated term infants. A more extensive study on pharmacokinetics and optimal regimen is required.

Quality improvement in Kangaroo Mother Care: learning from a teaching hospital.

BACKGROUND: Kangaroo Mother Care (KMC) is a low-resource, evidence-based, high-impact intervention for low-birth weight (LBW) care. Quality improvement in KMC requires meso-level, macro-level and micro-level interventions. Our institution, a public teaching hospital, hosts a level-II/III neonatal intensive care unit (NICU). The average demand for beds typically exceeds available capacity, with 60% occupancy attributed to LBW patients. There was low uptake of KMC practice at our unit. AIM STATEMENT: In the initial phase, we aimed to improve the coverage of KMC in admitted eligible neonates from a baseline of 20%-80% within 15 days. After a period of complacency, we revised the aim statement with a target of improving the percentage of babies receiving 6-hour KMC from 30% to 80% in 12 weeks. METHODS: We report this quasi-experimental time-series study. With the Point of Care Quality Improvement methodology, we performed Plan-Do-Study-Act (PDSA) cycles to improve KMC practice. We involved all the healthcare workers, mothers and caregivers to customise various KMC tools (KMC book format, KMC bag, mother's gown) and minimise interruptions. Feedback from all levels guided our PDSA cycles. RESULTS: The percentage of babies receiving at least 1-hour KMC increased from 20% to 100% within 15 days of August 2017. In the improvement phase, baseline 6-hour KMC coverage of 30% increased to 80% within 12 weeks (October-December 2017). It sustained for more than 2 years (January 2018 till February-2020) at 76.5%±2.49%. CONCLUSIONS: Quality improvement methods helped increase the coverage and percentage of babies receiving 6-hour KMC per day in our NICU. The duration specified KMC coverage should be adopted as the quality indicator of KMC. The training of healthcare workers and KMC provider should include hands-on sessions involving the mother and the baby. Maintaining data and providing suitable KMC tools are necessary elements for improving KMC. Minimising interruption is possible with family support and appropriate scheduling of activities. Having a designated KMC block helps in peer motivation.

Analgesic effect of oral glucose in preterm infants during venipuncture--a double-blind, randomized, controlled trial.

The aim of the present study was to evaluate the effect of different concentrations of glucose on measures of neonatal pain during venipuncture. A randomized, double-blind, placebo controlled trial was carried out at the neonatal intensive care unit at the King Edward Memorial Hospital. Sixty healthy preterm infants of gestation age 28-37 weeks and postnatal age 2-28 days were randomized to receive 2 ml of one of three solutions (sterile water, 10 per cent wt/vol. glucose and 25 per cent wt/vol. glucose) in the mouth 2 min before venipuncture. There was a significant reduction in duration of first cry in the babies given 25 per cent glucose compared with controls and those given 10 per cent glucose. There was no significant effect on heart rate, respiratory rate or oxygen saturation. It is concluded that concentrated glucose solution seems to reduce pain and may be a useful and safe analgesic for minor procedures in neonates.