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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.

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.

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.

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...

We here report an unusual case of a term neonate who presented with myoclonic seizures and lactic acidemia at 30 hours of life, who was later on diagnosed as a case of pyridoxine dependant epilepsy. Pyridoxine dependant epilepsy is one of the rare but easily treatable causes of refractory neonatal seizures. Failure to diagnose and treat this condition early would result in devastating neurodevelopmental outcomes for the surviving newborn.

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.