Treatment of Seizures in the Neonate: Special Report From the ILAE Task Force on Neonatal Seizures, 2022.

The International League Against Epilepsy (ILAE) task force on neonatal seizures has recently published draft guidelines and consensus-based recommendations on the treatment of neonatal seizures. This update provides a summary of the recommendations and the changes in management compared to the previous WHO ILAE guidelines, published in 2011, with emphasis on practical decision making requirements for a pediatrician.

Reliable Cerebrospinal Fluid Cytology and Immunocytochemistry Reporting over an Extended Period by the Addition of Aldehyde and Osmolyte-Based Preservative Solution.

INTRODUCTION: The cytological examination of cerebrospinal fluid (CSF) is an important investigation in the workup of various inflammatory, malignant, or traumatic disorders of the central nervous system. The cells in the CSF lyse and degenerate at a very fast rate owing to its low tonicity, buffering capacity, redox potential, and pH, making it crucial to examine it within 2 h of sampling. We have hereby designed an aliphatic aldehyde, osmolyte, metal halide, and a buffer-based solution which will preserve the cellular components of CSF for 48 h. METHODS: Thirty-nine CSF specimens were examined within 2 h of collection, and this reading was recorded as time zero reading. The CSF specimens were then divided into two tubes with (i) pre-servative:CSF ratio of 1:5; and (ii) no preservative. Total and differential leukocyte counts and immunocytochemistry were performed on the paired specimens at 24 h and 48 h and were compared with the readings at zero hours. RESULTS: The preservative-containing CSF showed significantly higher cellularity than the undiluted samples at 24 h and 48 h (p < 0.001). Median cell counts observed in the preservative-containing CSF were 5 times and 12 times higher than in the undiluted CSF. Neutrophils, lymphocytes, and RBCs showed immunopositivity for MPO, CD45, and GLUT-1 at both time intervals. CONCLUSION: Adding the prepared preservative solution to CSF in the ratio of 1:5 can optimally preserve the CSF cells for absolute and differential quantitation, morphological assessment, and immunological testing at a later date.

Online survey to assess computer vision syndrome in children due to excessive screen exposure during the COVID 19 pandemic lockdown.

Background: During the COVID-19 pandemic lockdown, the normal daily routine activities of children were restricted as a result of the need to stay indoors. Consequently, children were forced to attend online classes provided by their educational institutions at their homes. Due to the subsequent increased screen exposure, children have started complaining of blurred vision, headache, and symptoms related to computer vision syndrome (CVS), predisposing them to myopia. Objective: To determine the prevalence of CVS symptoms, such as blurring of vision, headache, and watery eyes in children, due to increased screen time during the lockdown period of the COVID-19 pandemic. Methods: This was a non-randomized, questionnaire-based study conducted at the ophthalmology department of a tertiary care pediatric hospital. The participants were parents of children aged between 6 and 16 years attending regular school. Enrolled parents were interviewed through a Google Form after completing the online consent in English. Eligible participants were recruited by a circulation of this form through multiple groups on social media, namely, WhatsApp and email. Results: A total of 145 parents participated in the study. The children were classified according to the duration of exposure to digital devices ranging from less than 2 h to less than 6 h daily. There was a significant association between the increase in the number of activities and the development of CVS symptoms in children (r = 0.15; P = 0.036). Conclusion: COVID-19 lockdown has largely affected the lifestyle of school-going children by significantly decreasing their outdoor activities and increased online exposure to screen, thus predisposing them to myopia, ocular ill health, and increased dry eye symptoms. Increased exposure to online screen was detected during this lockdown period of the COVID-19 pandemic; this strongly supports the recommendation to decrease the number of hours of online screen exposure and encourages students to regularly get engaged in outdoor activities.

Severe Multi-inflammatory Syndrome in Children Temporally Related to COVID 19-Clinical Course, Laboratory Profile and Outcomes from a North Indian PICU.

Objective: We describe the trajectory of clinical course, laboratory markers and outcomes in children with severe multi-inflammatory syndrome temporally related to COVID-19 (MIS-C) admitted to our pediatric intensive care unit (PICU). Methods: This was a prospective case series of children admitted to PICU between May 1, 2020 and January 31, 2021, fulfilling the case definition of MIS-C published by World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). We analyzed demographic, clinical, laboratory data and echocardiographic findings. We also plotted the variation in trends between survivors and nonsurvivors. Results: Of the 34 critically ill children referred to PICU with diagnosis of MIS-C only 17 fulfilled the WHO/CDC classification of MIS-C, rest were MISC mimickers albeit other tropical infections. Median age at admission was 4 years (range 1y 6 mo-8 years). Fever, rash and conjunctival redness were most prominent symptoms. Myocardial involvement was seen in 70.5% while 76.4% developed shock; Invasive mechanical ventilation was required in 64.7% cases. Inflammatory markers showed a downward trend such as-median C- reactive protein (mg/L) had a serial reduction in levels-from (median/IQR) 210 (132.60, 246.90) at admission to 52.3 (42, 120) on Day 3. Median Ferritin (ng/ml) (n = 12) was 690 (203, 1324), serum LDH (IU/L) (n = 12) was 505 (229.5, 1032) and Mean D-dimer (ng/ml) (n = 7) was 5093.85 (1991.65), suggestive of hyperinflammatory syndrome. Twelve patients received intravenous immune globulin, with adjunctive steroid therapy used in two third of the cases. Six children died, 4 of them were under-5 years of age. Tocilizumab was prescribed in two children with high vasotrope inotrope score (VIS), cardiogenic shock and oxygenation index more than 15, both survived. Conclusions: Severe MIS-C has a heterogenous presentation, local or regional outbreaks of prevalent infectious diseases often lead to confusion and overdiagnosis. Higher proportion of mortality was seen in Under -5 children with MISC. Shock-like presentation, presence of myocardial dysfunction or nonsurvivor status is associated with higher trend of inflammatory markers and more profound multi-organ dysfunction. If disease progresses rapidly despite first line therapy (IvIg and steroids), use of Tocilizumab should be considered-as a rescue therapy under resource limitations in the absence of extracorporeal support.

Effect of Kangaroo Mother Care on Duration of Phototherapy on Neonatal Jaundice: A Randomized Controlled Trial.

Neonatal hyperbilirubinemia (NNH) is a common morbidity in the neonatal period, especially in the preterm and low-birth-weight babies. Low-birth-weight babies receiving phototherapy do not receive kangaroo mother care (KMC), which may hamper their weight gain and establishment of breast-feeding. The authors investigated the effect of KMC on duration of phototherapy in neonates admitted to a level III nursery with neonatal hyperbilirubinemia. Fifty neonates with gestational age of 30 to 40 wk, birth weight 1001-1999 g, and requiring phototherapy were randomized. Control group received phototherapy in a conventional manner. The intervention group received KMC for 1 h every 8 hourly. The mean (± SD) of total duration of phototherapy required in control group and in KMC group was 39.12 ± 15.3 and 19.44 ± 6.54 h, respectively and this difference was statistically significant.

Early Total Versus Gradually Advanced Enteral Nutrition in Stable Very-Low-Birth-Weight Preterm Neonates: A Randomized, Controlled Trial.

OBJECTIVE: To assess whether early total enteral nutrition (80 mL/kg/d) started on day 1 of life in hemodynamically stable preterm very-low-birth-weight (VLBW) neonates with the rapid advancement of feeds (20 mL/kg/d) help in the earlier achievement of full feeds (180 mL/kg/d). METHODS: Early total enteral nutrition (intervention) group feeding was started with 80 mL/kg/d on the first day in all hemodynamically stable neonates admitted with birth weight of 1000-1499 grams, born at 29-33 wk of gestation as determined by first-trimester ultrasonography (USG) or expanded New Ballard Score (NBS) and was advanced by 20 mL/kg/d until maximum feeds of 180 mL/kg/d were achieved; while in control group feeding was started with 30 mL/kg/d on the first day and was advanced by 20 mL/kg/d until maximum feeds were achieved. Primary outcome measure was time taken to achieve full feeds; secondary outcomes were duration of hospital stay, necrotizing enterocolitis (NEC), time to regain birth weight, duration of antibiotics, and death. RESULTS: Sixty VLBW neonates (1000-1499 g) with comparable baseline demographics were randomized within 24 h of admission to two groups. Early total enteral nutrition intervention group (group I, n = 31) achieved the target of full enteral nutrition at median 6 d; IQR: 0 to 7.8 d, a significantly shorter time compared to the controls (n = 29) (median 10 d; IQR: 9 to 11.0 d; p = < 0.05). CONCLUSION: Early total enteral nutrition started from the first day of life results in significantly less time to achieve full feeds in hemodynamically stable preterm and VLBW infants.

Varied Clinical Presentation and Management of Paediatric Vallecular Cyst.

The current article aims to highlight the varied presentation and management of vallecular cysts. We report three children, aged four years, 11 months and three days, diagnosed with vallecular cyst presenting to the Chacha Nehru Bal Chikitsalaya hospital, New Delhi, India in 2018 and 2019. They were reviewed retrospectively for clinical presentation, diagnostic tools and treatment options. All three cases had respiratory and feeding difficulties. The diagnosis in all of the three cases was made with laryngoscopy (flexible/direct) and imaging. All three patients were treated with the transoral approach aimed at the excision of the cyst using cold instruments. The postoperative period was uneventful. No recurrences were observed during the long-term follow-up. Vallecular cysts should be considered as one of the differentials in children with respiratory distress and dysphagia despite being a rare anomaly. A direct transoral approach is recommended for the excision of the vallecular cyst as it is a safe and reliable method with no recurrences to date.

Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial.

BACKGROUND: Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. METHODS: This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. DISCUSSION: This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Evaluation of Risk Factors Affecting Outcome in Outborn Surgical Neonates.

BACKGROUND: Mortality in surgical neonates contributes to neonatal mortality rates. The study was conceptualized to study clinical and nonclinical factors affecting mortality in surgical neonates so that timely intervention could result in improved survival of the neonates. MATERIALS AND METHODS: The study was initiated after approval from the institutional ethics committee and included 120 surgical neonates over a period of 18 months after obtaining consent from the parents/caregivers. Predesigned pro forma was used to record the details of antenatal care received, place of birth, travel history, maternal education and gestational age, and clinical condition at the time of admission. Values of biochemical tests such as serum electrolytes, serum creatinine, and arterial blood gasses were recorded. The need of inotrope support, blood or blood product transfusion, and postoperative ventilator support and intensive care unit (ICU) care was recorded. The results of the two groups, i.e., survivals and mortality, were compared. Outcome was recorded as mortality at 30 days or earlier. RESULTS: Irrespective of the surgical condition, the survival rate was significantly better in those babies who weighed more than 2.5 kg at the time of admission, had capillary refill time of <3 s, had serum ionized calcium levels more than 1 mmol/L, and did not require inotropes, blood or blood product transfusion, and postoperative ICU care and ventilator support. The place of birth, educational status of the mother, gestational age, and distance traveled for care had no statistically significant effect on survival. CONCLUSION: There is a statistically significant correlation between the survival of the babies who weighed more than 2.5 kg and are more physiologically preserved at the time of admission. Mortality rates can be decreased by timely interventions to reduce the need of inotropes, blood or blood products, and ICU care and ventilator support during their postoperative recovery.

ROP examination of premature babies at an eye hospital referred from urban and semi-urban NICUs.

INTRODUCTION: Retinopathy of prematurity (ROP) is seen in low gestational age (GA) and birth weight (BW) babies leading to retinal vascular damage. Screening of preterm would help in early identification of this, sight-threatening disease. Multiple factors play an important role in planning screening strategies for these preterm. The objective of this study was done to find the differences and the reasons affecting the proportion of ROP distribution between urban and semi-urban regions in North India. MATERIALS AND METHODS: In this retrospective, comparative study, all babies referred for ROP examination by paediatricians or other general ophthalmologists between 2013 to 2016 were included in the study. Demographic, clinical and treatment related findings were recorded. RESULTS: Five hundred and fifty eight babies (467: urban and 91: semi urban) were examined for ROP. The mean BW in urban and semi-urban settings was 1348.6 ± 395.21 gm and 1703.77 ± 401.76 gm respectively. The mean GA was 30.99 ± 2.93 weeks and 30.73 ± 2.08 weeks in the urban and semi-urban cohorts respectively. The average time for first ophthalmic examination following birth was 23.82 ± 13.69 (range: 3-77) days in urban and 101.16 ± 238.26 (range: 13- 330) days in semi-urban settings. 94% of the babies completed all screening examination visits. Any ROP was identified in 12% and 33.0% of urban and semi-urban cohorts respectively; Type 1 was detected in 7.5% of urban babies and 24% of semi-urban babies. CONCLUSION: Proportion of ROP in the urban region was 3 times lesser than the semiurban region. Differences in proportion of babies developing any ROP and Type 1 ROP between semi-urban and urban groups is likely due to selection bias, as a high proportion of semi-urban babies did not attend for examination or failed to complete all the examinations necessary. This was particularly true for females. More needs to be done to increase access to regular, systematic screening of preterm babies within neonatal units.

Providing Expressed Breast Milk to Preterm Neonates Admitted in an Extramural Neonatal Intensive Care Unit: Where do we stand?

Provision of expressed breast milk (EBM) to premature neonates poses a great challenge in extramural Neonatal Intensive Care Units (NICUs). We conducted a questionnaire-based survey to identify the various challenges faced by the parents to provide EBM to their hospitalized premature infant. 40 preterm neonates (<34 wk gestation and <1500 g weight) planned to be started on EBM were included in the study. The median (range) duration after which EBM was received in NICU after the time it was asked for was 34.5 (13 to 40) hours, and it was received in a clean, sterile and covered container in only 8 (20%) cases. There were multiple hurdles in ensuring early availability of EBM in optimal condition. Sensitization and motivation of families regarding the importance of ensuring early administration of EBM to their prematurely delivered neonate may lead to substantial improvement in outcome of these neonates.

Goat lung surfactant for treatment of respiratory distress syndrome among preterm neonates: a multi-site randomized non-inferiority trial.

OBJECTIVE: To investigate the safety and efficacy of goat lung surfactant extract (GLSE) compared with bovine surfactant extract (beractant; Survanta®, AbbVie, USA) for the treatment of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: We conducted a double-blind, non-inferiority, randomized trial in seven Indian centers between June 22, 2016 and January 11, 2018. Preterm neonates of 26 to 32 weeks gestation with clinical diagnosis of RDS were randomized to receive either GLSE or beractant. Repeat dose, if required, was open-label beractant in both the groups. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (PMA). Interim analyses were done by an independent data and safety monitoring board (DSMB). RESULT: After the first interim analyses on 5% enrolment, the "need for repeat dose(s) of surfactant" was added as an additional primary outcome and enrolment restricted to intramural births at five of the seven participating centers. Following second interim analysis after 98 (10% of 900 planned) neonates were enroled, DSMB recommended closure of study in view of inferior efficacy of GLSE in comparison to beractant. There was no significant difference in the primary outcome of death or BPD between GLSE group (n = 52) and beractant group (n = 46) (50.0 vs. 39.1%; OR 1.5; 95% CI 0.7-3.5; p = 0.28). The need for repeat dose of surfactant was significantly higher in GLSE group (65.4 vs. 17.4%; OR 9.0; 95% CI 3.5-23.3; p < 0.001). CONCLUSIONS: Goat lung surfactant was less efficacious than beractant (Survanta®) for treatment of RDS in preterm infants. Reasons to ascertain inferior efficacy of goat lung surfactant requires investigation and possible mitigating strategies in order to develop a low-cost and effective surfactant.

Association of vitamin D deficiency with an increased risk of late-onset neonatal sepsis.

BACKGROUND: Vitamin D deficiency in mothers and neonates is being recognised increasingly as a leading cause of many adverse health effects in the newborn infant, including sepsis. METHODS: A prospective observational study was conducted at a tertiary care Paediatric teaching hospital in northern India to assess vitamin D deficiency as a possible risk factor for late-onset sepsis (LOS) in term and late preterm neonates and also to examine the correlation between maternal and infant vitamin D levels during the neonatal period. Late-onset sepsis (LOS) was defined as the development of signs and symptoms of severe sepsis after 72 h of life and a positive sepsis screen. All term and late preterm neonates admitted with LOS between September 2015 and February 2016 who had not been previously admitted for >48 h and had not been prescribed antibiotics or vitamin D were included in the study. Matched controls were recruited from otherwise healthy neonates admitted with physiological hyperbilirubinaemia. Serum 25(OH) vitamin D was assessed in neonates in both groups and their mothers. RESULTS: A total of 421 neonates were admitted to the neonatal intensive care unit during the study period, 120 of whom satisfied the inclusion criteria, and 60 were recruited as cases. Sixty neonates were recruited as controls who were similar in gender, gestational age, age at admission and anthropometry. The study group had significantly lower mean (SD) vitamin D levels [15.37 ng/ml (10.0)] than the control group [21.37 ng/ml (9.53)] (p = 0.001). The odds ratio was 1.7 (95% CI 0.52-5.51) for LOS in vitamin D-deficient neonates. Mothers of septic neonates also had significantly lower mean (SD) vitamin D levels [17.87 (11.89)] than the mothers of non-septic neonates [23.65 ng/ml (9.55)] (p = 0.004). Maternal vitamin D levels strongly correlated to neonatal vitamin D levels in both groups. CONCLUSION: Neonates with vitamin D deficiency are at greater risk of LOS than those with sufficient vitamin D levels.

Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India.

BACKGROUND: There is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them. METHODS: In this prospective observational cohort study (2011-2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant. RESULTS: Of the total of 2588 neonates enrolled, culture positive sepsis and total sepsis-i.e. culture positive and/or culture negative sepsis-was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens-Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)-showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks' gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth. CONCLUSIONS: In this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.

This hospital-record review describes the clinical profile of hypernatremic dehydration in neonates. 49 neonates (3.4% of the total admitted newborns) developed hypernatremic dehydration between January 2014 and August 2015. The major presenting complaints were fever (34.6%), poor feeding (42.8%), loose stools (40.8%) and lethargy (26.5%). The mean (SD) time needed for correction of hypernatremia was 38.6 (15.1) hours. Exclusively breastfed neonates had lesser complication rates of hypernatremic dehydration.