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.

Congenital Chylothorax: Conservative Management Counts.

Nonimmune hydrops is a common cause of hydrops fetalis. Here, we report a rare case of congenital chylothorax which presented with nonimmune hydrops and was effectively managed by conservative measures.

Diagnostic Utility of Cerebrospinal Fluid Procalcitonin in Neonatal Meningitis.

We aimed to study the diagnostic utility of cerebrospinal fluid (CSF) procalcitonin (PCT) in neonates with meningitis. All the neonates with sepsis who qualified for lumbar puncture were prospectively evaluated. The neonates were classified into Meningitis and No meningitis group based on predefined criteria. CSF PCT was estimated in these neonates along with cytological and biochemical parameters. A total of 113 neonates were included in the study with 29 in the meningitis group and 84 in the no meningitis group. The median PCT levels were higher in babies with meningitis as compared to those without meningitis [0.194 (0.034-0.534) in meningitis group vs. 0.012 (0.012-0.012) ng/ml in no meningitis group, p < 0.001]. The area under curve for CSF PCT was 0.867 (0.77-0.95) and at a cut-off level of 0.120 ng/ml CSF PCT had a sensitivity of 83%, specificity of 84% and positive and negative predictive likelihood ratios of 5.35 and 0.20, respectively for the diagnosis of meningitis. CSF PCT has a good diagnostic accuracy similar to other parameters in the diagnosis of neonatal meningitis and can be considered as an additional diagnostic marker particularly when CSF culture is negative and cytochemical analysis is inconclusive.

Ten Versus 14 Days of Antibiotic Therapy in Culture-Proven Neonatal Sepsis: A Randomized, Controlled Trial.

OBJECTIVES: To compare the efficacy of 10 d versus 14 d of antibiotic therapy in neonates with culture-positive sepsis. METHODS: Neonates with culture-positive sepsis were randomized to either 10-d or 14-d antibiotic therapy. These neonates were followed up to 28 d after discharge for treatment failure. Primary outcome of the study was treatment failure which was defined as readmission to the NICU within 4 wk of discharge with blood culture growing same organism with similar antibiogram or any readmission with signs of sepsis with negative blood culture. RESULTS: A total of 70 neonates were randomized to receive either 10 d (n = 35) or 14 d (n = 35) of antibiotic therapy. Gram-negative infections were encountered in majority of the neonates. Treatment failure occurred in 1 neonate in 10-d group and none in 14-d group. The duration of hospital stay was significantly less in 10-d group as compared to 14-d group (16 d vs. 23 d, p  <  0.01). CONCLUSIONS: Ten days of antibiotics in neonates with culture-positive sepsis, who have achieved clinical and microbiologic remission at day 7, is noninferior to 14 d of therapy. Larger adequately powered trials will address this issue with certainty.

Reference Ranges of Different Lymphocyte Subsets in Indian Children: A Multi-Centric Study.

OBJECTIVE: To determine the reference ranges of various lymphocyte subsets in healthy Indian children. DESIGN: Descriptive cross-sectional study. SETTING: Four centers in India representing four geographical regions. PARTICIPANTS: 1104 children from neonatal age to 18 years of age. MEASUREMENT: One time measurement of absolute count and percentages of different lymphocyte subsets i.e. T lymphocytes (CD3+T, CD4+T, CD8+T cells), B lymphocytes (CD19+B cells) and Natural Killer lymphocytes (CD15/16+NK cells) in whole blood using multicolor flow cytometry. RESULTS: The absolute cell counts of various lymphocytes were found to increase from newborn to 10 months of age, followed by gradual decline until 18 years; however, the proportion of immune cells remained largely similar. Gender did not have a significant impact on the reference ranges, whereas counts were found to vary as per the geographical locations. CONCLUSIONS: These reference ranges will be useful to monitor and predict the immune status in pediatric population. The variation in region wise ranges could be confirmed by testing more number of samples in the specific age groups.

Levetiracetam versus Phenobarbitone in Neonatal Seizures - A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of neonatal seizures. DESIGN: Open labelled, Randomized controlled trial. SETTING: Level III Neonatal Intensive Care Unit (NICU). PARTICIPANTS: 100 neonates (0-28 days) with clinical seizures. INTERVENTION: If seizures persisted even after correction of hypoglycemia and hypocalcemia, participants were randomized to receive either Levetiracetam (20 mg/kg) or Phenobarbitone (20 mg/kg) intravenously. The dose of same drug was repeated if seizures persisted (20 mg/kg of Levetiracetam or 10 mg/kg of Phenobarbitone) and changeover to other drug occurred if the seizures persisted even after second dose of same drug. MAIN OUTCOME MEASURES: Cessation of seizures with one or two doses of the first drug, and remaining seizure-free for the next 24 hours. RESULTS: Seizures stoped in 43 (86%) and 31 (62%) neonates in Levetiracetam and Phenobarbitone group, respectively (RR 0.37; 95%CI 0.17, 0.80, P<0.01). 10 neonates had adverse reactions in the phenobarbitone group (hypotension in 5, bradycardia in 3 and requirement of mechanical ventilation in 2 neonates) while none had any adverse reaction in Levetiracatam group. CONCLUSIONS: Levetiracetam achieves better control than Phenobarbitone for neonatal seizures when used as first-line antiepileptic drug, and is not associated with adverse drug reactions.

Congenital amastia.

A 3-d-old female baby presented with bilateral congenital absence of breast tissue, areolae and nipples. No other anomalies were noted. There was also a history of absence of nipples, areolae and breast tissue in the mother and two other family members of maternal side. Investigations done during the hospital stay including ultrasound of the chest wall, abdomen and head were all normal. Congenital isolated bilateral amastia was diagnosed after complete investigations.