Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial.

Importance: Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. Objective: To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. Design, Setting, and Participants: This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Interventions: Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Results: Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. Conclusions and Relevance: In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. Trial Registration: ClinicalTrials.gov Identifier: NCT03409770.

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.

Hemodynamic effects of noradrenaline in neonatal septic shock: a prospective cohort study.

BACKGROUND: The incidence of neonatal septic shock in low-income countries is 26.8% with a mortality rate of 35.4%. The evidence of the hemodynamic effects of noradrenaline in neonates remains sparse. This study was carried out to evaluate the effects of noradrenaline in neonates with septic shock. METHODS: This was a single-center prospective cohort study in a tertiary care hospital's level III neonatal intensive care unit. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. RESULTS: A total of 21 babies were analyzed. The cohort comprised 17 preterm neonates. The mean age of presentation with septic shock was 74.3 h. Resolution of shock at one hour after starting noradrenaline was achieved in 76.2% of cases. The median duration of hospital stay was 14 days. The mean blood pressure improved after the initiation of noradrenaline from 30.6 mm of Hg [standard deviation (SD) 6.1] to 37.8 mm of Hg (SD 8.22, p < 0.001). Fractional shortening improved after noradrenaline initiation from 29% (SD 13.5) to 45.1% (SD 21.1, p < 0.001). The mortality rate was 28.6% in our study. CONCLUSION: Noradrenaline is a potential drug for use in neonatal septic shock, with improvement in mean blood pressure and fractional shortening; however, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Neonatal sepsis is one of the leading causes of neonatal mortality. In neonates with septic shock, mortality is high at 35.4% in low- and middle-income countries. The evidence of the hemodynamic effects of noradrenaline in neonates is still sparse, so we carried out a study in our tertiary care neonatal intensive care unit to evaluate the effects of noradrenaline in neonates with septic shock. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. A total of 21 babies were analyzed. We found that there was a statistically significant improvement in the mean blood pressure and fractional shortening after noradrenaline initiation. The mortality rate was 28.6% in our study. We conclude that noradrenaline is a relatively safe and effective drug for the treatment of neonatal septic shock. However, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Duration of birth depression and neurodevelopmental outcomes after whole-body hypothermia for hypoxic ischemic encephalopathy in India, Sri Lanka and Bangladesh - an exploratory analysis of the HELIX trial.

Background: Effect of duration of birth depression on neurodevelopmental outcomes in low- and middle-income countries (LMICs) is not known. We examined the association of birth depression with brain injury, neurodevelopmental outcomes, and hypothermia after hypoxic ischemic encephalopathy (HIE) in south Asia. Methods: We compared cerebral magnetic resonance (MR) at 2 weeks, and adverse outcomes (death or moderate or severe disability) at 18 months in 408 babies with moderate or severe HIE who had long birth depression (positive pressure ventilation (PPV) >10 min or Apgar score<6 at 10 min or cord pH < 7.0) and short birth depression (PPV for 5-10 min or Apgar score<6 at 5 min, but ≥6 at 10 min). Findings: Long depression group (n = 201) had more severe HIE (32.8% versus 6.8%), mortality (47.5% versus 26.4%), death or disability at 18 months (62.2% versus 35.4%) (all p < 0.001), MR injury (Odds ratio; 95% CI) to basal ganglia (2.4 (1.3, 4.1); p = 0.003), posterior limb of internal capsule (2.3 (1.3, 4.3); p < 0.001) and white matter (1.7 (1.1, 2.7); p = 0.021), and lower thalamic N-acetylaspartate levels (7.69 ± 1.84 versus 8.29 ± 1.60); p = 0.031) than short depression group (n = 207). Three babies had no heartbeat at 5 min, of which 1 died and 2 survived with severe disability. No significant interaction between the duration of birth depression and whole-body hypothermia was seen for any of the MR biomarker or clinical outcomes. Interpretation: Long birth depression was associated with more brain injury and adverse outcomes than short depression. Effect of hypothermia was not modified by duration of birth depression. Funding: National Institute for Health Research.

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Background: Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. Objectives: The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. Methodology: A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. Results: The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). Conclusion: The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Point-of-care Ultrasound to Diagnose and Monitor the Course of Necrotizing Enterocolitis.

Context: Neonatal gut ultrasound (US) is an emerging clinical tool for quick diagnosis and prognosis in various abdominal pathologies. In this review, we summarize normal gut US findings and concentrate on the specifications of diagnosing necrotizing enterocolitis. Evidence: A comprehensive literature search was conducted across numerous sources with relevant keywords along with the specified age group of 0-28 days of life. Findings: This review describes the normal gut US picture with the basic technicalities needed to master the art of point-of-care (POC) abdominal US. This modality is gaining importance due to its accuracy, applicability, safety, and affordability. Key findings include altered bowel perfusion, decreased peristalsis, and bowel wall thickening with better precision compared to abdominal X-ray (AXR). Many meta-analyses and narrative reviews have already demonstrated their usefulness. The high specificity and positive predictive value could make this tool a guide for early identification and prompt surgical intervention in the dreaded diagnosis of necrotizing enterocolitis. Conclusion: Emerging evidence and expertise in the field of abdominal US will make it a valuable tool for early diagnosis and prognosis of necrotizing enterocolitis.

Randomised controlled trial to compare the effect of PIOMI (structured) and routine oromotor (unstructured) stimulation in improving readiness for oral feeding in preterm neonates.

Background: Oral motor stimulation interventions improve oral feeding readiness and earlier full oral feeding in preterm neonates. However, using a structured method may improve the transition time to full oral feeds and feeding efficiency with respect to weight gain and exclusive breastfeeding when compared to an unstructured intervention. Objective: To compare the effect of Premature Infant Oral Motor Intervention (PIOMI) and routine oromotor stimulation (OMS) on oral feeding readiness. Methods: Randomised controlled trial conducted in a neonatal intensive care unit between June-December 2022. Preterm neonates, 29+0-33+6 weeks corrected gestational age, were studied. The intervention group received PIOMI and the control group received OMS. Primary outcome: time to oral feeding readiness by Premature Oral Feeding Readiness Assessment Scale (POFRAS) score ≥30. Secondary outcomes: time to full oral feeds, duration of hospitalisation, weight gain, and exclusive breastfeeding rates. Results: A total of 84 neonates were included and were randomised 42 each in PIOMI and OMS groups. The mean chronological age and time to oral feeding readiness were lower by 4.6 and 2.7 days, respectively, for PIOMI. The transition time to full oral feeds was 2 days lower for PIOMI and the duration of hospitalisation was 8 days lower. The average weight gain was 4.9 g/kg/day more and the exclusive breastfeeding rates at 1 month and 3 months post-discharge were higher by 24.5% and 27%, respectively, for the PIOMI group. The subgroup analysis of study outcomes based on sex and weight for gestational age showed significant weight gain on oral feeds in neonates receiving PIOMI. Similarly, the subgroup analysis based on gestational age favoured the PIOMI group with significantly earlier transition time and weight gain on oral feeds for the neonates >28 weeks of gestational age. The odds of achieving oral feeding readiness by 30 days [OR 1.558 (0.548-4.426)], full oral feeds by 45 days [OR 1.275 (0.449-3.620)], and exclusive breastfeeding at 1 month [OR 6.364 (1.262-32.079)] and 3 months [3.889 (1.186-12.749)] after discharge were higher with PIOMI. Conclusion: PIOMI is a more effective oromotor stimulation method for earlier and improved oral feeding in preterm neonates. Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=70054&EncHid=34792.72281&modid=1&compid=19','70054det', identifier, CTRI/2022/06/043048.

Whole-Body Hypothermia, Cerebral Magnetic Resonance Biomarkers, and Outcomes in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy Born at Tertiary Care Centers vs Other Facilities: A Nested Study Within a Randomized Clinical Trial.

Importance: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown. Objective: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn). Design, Setting, and Participants: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks' gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020. Exposure: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months. Results: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). Conclusions and Relevance: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs. Trial Registration: ClinicalTrials.gov Identifier: NCT02387385.

Management of neonatal pulmonary hypertension-a survey of neonatal intensive care units in India.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). METHODS: A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. RESULTS: There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1-3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. CONCLUSION: We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

A detailed echocardiographic evaluation of ventricular functions in stable full term small for gestational age babies.

PURPOSE: SGA infants with fetal growth restriction have reduced ability to adapt themselves to the postnatal life because of certain epigenetic changes in cardiac function. The aim of the present study is to assess and compare the cardiac functions of fetal growth restricted SGA newborns to the term stable AGA newborns, and evaluate any differences in the cardiac functions during the postnatal transitional circulation. METHOD: This observational study was conducted at a multispecialty tertiary care hospital in Western India from June to November 2021. The newborns were evaluated using bedside echocardiography at 24-48 h and repeat screening after 48 h. The echocardiographic assessment of the systolic function was done using EF, FS, FAC and TAPSE; diastolic function using E/A wave ratio and global functioning using LV MPI. RESULT: Twnety-four babies were included in cases and 30 in the control arm of the study. Maternal and newborn characteristics were comparable between the two groups. FS, EF for left ventricle and TAPSE, FAC for right ventricular systolic function were significantly lower in SGA group (p = 0.02, 0.02, 0.00 and 0.01; respectively). The current study revealed a lower tricuspid E/A ratio and higher mitral E/A ratio with a significant difference beyond 48 h in the first week of life (p value 0.00). Left ventricular MPI was significantly higher in SGA infants compared to AGA infants during two subsequent readings in immediate newborn period with p values 0.01 and 0.02 respectively. The subgroup analysis revealed that fetal growth-restricted neonates with absent end-diastolic flow had a greater impact on ventricular functions. CONCLUSION: Present study showed a significant systolic and diastolic dysfunction during initial newborn period in growth restricted SGA infants.

Oral versus intravenous sildenafil for pulmonary hypertension in neonates: a randomized trial.

BACKGROUND: Sildenafil is the drug of choice for neonatal pulmonary hypertension in developing countries where inhaled nitric oxide is not available. Available as oral and intravenous preparation - no study has been done in the past to compare the two forms. Each has its own benefits - but requires comparison in terms of efficacy and safety. This study was done to compare the efficacy of oral versus intravenous (IV) sildenafil in infants with mild to moderate pulmonary hypertension. METHODS: An open labelled randomized trial was conducted in a neonatal intensive care unit of urban tertiary hospital in western India between February 2019 to December 2020. Infants born after 34 weeks of gestation with Pulmonary arterial pressure (PAP) > 25 mm Hg measured by echocardiography, within 72 h of birth, were enrolled for the study. Participants were randomly assigned to receive sildenafil either orally or by intravenous route. Primary outcome was the time taken for PAP to decrease below 25 mm Hg. Secondary outcomes were time taken for oxygenation index to decrease by 25%, duration of invasive and non-invasive mechanical ventilation, nasal oxygen, hospital stay, time to achieve full feeds, mortality, and side effects. RESULTS: Forty patients were enrolled. The baseline characteristics of neonates in both groups were similar except for APGAR scores at 1 min and 5 min, with oral group having lower score [MEDIAN (IQR) 5.00 (4.00- 7.00) and 7.00 (6.00- 8.00)] compared to IV group [MEDIAN (IQR) 7.00 (6.00-8.00) and 9.00 (8.00-9.00)] respectively. Time taken for PAP to decrease below 25 mm was not statistically different between the oral and intravenous groups. Systemic hypotension occurred in 4 neonates of the intravenous group but none in the oral group. CONCLUSION: Oral and intravenous sildenafil had equal efficacy at reducing PAP in neonatal pulmonary hypertension, albeit intravenous sildenafil use was associated with a greater complication rate. TRIAL REGISTRATION: Trial was registered in the clinical trials registry of India [ CTRI/2019/04/018781 ][25/04/2019].

Sirolimus used for treatment of retroperitoneal arteriovenous malformation in a premature neonate.

We describe a case of a premature infant with antenatally detected retroperitoneal arteriovenous malformation (AVM) with extensive intraspinal extension. Treatment of the malformation with embolectomy and sclerotherapy was not feasible in view of intraspinal extensions and small size of vessels of the lesion. During a trial of propranolol over 20 days, the lesion progressed in size, roughly doubling in volume and was accompanied with deranged coagulation parameters. Treatment was therefore switched to oral prednisolone and sirolimus. The steroid was stopped after 6 weeks and sirolimus was continued with serum drug level monitoring and serial imaging of the malformation. After 4 months of sirolimus, the AVM remained at the same size as at the start of treatment, thus we propose that the drug may have arrested the growth of the lesion. This case highlights the use of sirolimus in management of AVMs in infants.

Unusual case of immune haemolytic disease causing severe neonatal cholestasis in a newborn.

Neonatal hyperbilirubinaemia is a very common entity witnessed in most of the newborns. Rarely are there events where the bilirubin levels reach extreme values mandating invasive therapy. Unconjugated hyperbilirubinaemia when solely present is easy to manage and diagnose the common aetiological factors associated with it. The issue arises when we come across a mixed picture of conjugated with unconjugated hyperbilirubinaemia and puts us in a dilemma as to what are we treating. Our case highlights a similar picture where we witnessed the highest documented levels of total bilirubin but to our surprise the major component of which was direct bilirubin. This report takes us through the differentials which were ruled out and our management strategies for solving this rare mystery.

Shock and dyselectrolytemia in a neonate with late-onset COVID-19 infection.

Most reports of COVID-19 in neonates suggest that they are infected postnatally and present with gastrointestinal or respiratory symptoms. We describe a neonate who had community-acquired COVID-19, and presented with late-onset sepsis and developed dyselectrolytemia. The 26-day-old male baby had fever, feed refusal and shock. Rapid antigen test for SARS-CoV-2 by nasopharyngeal swab was positive and levels of circulating inflammatory markers were high. The baby was supported with antibiotics, and inotropic and vasopressor drugs. He had seizures and bradycardia due to dyselectrolytemia on day 2 of admission. On day 3, he had respiratory distress, with non-specific chest radiographic findings, and was managed with non-invasive support for 24 hours. The baby was discharged after 8 days. On serial follow-up, he was breastfeeding well and gaining weight appropriately with no morbidity. Our report highlights a unique presentation of COVID-19, with late-onset infection and shock-like features along with dyselectrolytemia and seizures.

Improving donor human milk collection in a hospital without a human milk bank: a quality improvement initiative at an urban tertiary-care teaching hospital.

Feed intolerance and necrotising enterocolitis (NEC) are challenges while treating sick neonates. These can be reduced by giving human milk, but adequate availability of mother's own milk or pasteurised donor human milk (PDHM) is a challenge in neonatal setups, like ours, without an attached human milk bank. Hence, this quality improvement initiative was taken to improve donor human milk collection in our urban tertiary-care teaching hospital, to at least 500 mL per week in 4 weeks. After analysing the problem, our quality improvement team identified a shortage of human milk donation that was due to low awareness among the stakeholders and lack of a system to collect and store human milk and transport it to a milk bank. The team first established a system of supplies needed for milk collection, storage and transportation. It then tested change idea of information, education and counselling to increase milk donation. The team carried out a few plan-do-study-act cycles (individual and group counsellings, and usage of videos and information leaflets) to test the change ideas and adapted a few and abandoned some. During this journey, the milk collection increased to above the target amount. Various challenges were addressed, and there was a need for constant motivation of the stakeholders, especially the mothers, and now there is sustained milk donation in the setup. This is incorporated in the standard operating procedure and as a quality indicator of the unit for sustaining the changes in the unit. Our initiative can be replicated in other setups for increasing collection of donor human milk. Greater PDHM availability for sick neonates will, in effect, reduce NEC and feeding intolerance rates, leading to reduced hospital stay, morbidity, mortality and economic burden.

Neonatal Schwartz-Jampel syndrome type II: a rare case of peripheral origin of neonatal hypertonia.

Neonatal Schwartz-Jampel syndrome type II is a rare and severe form of genetic disorder. Different from the classical appearance in infancy, neonatal presentation involves respiratory and feeding difficulties, along with characteristic pursed appearance of the mouth, myotonia, skeletal dysplasia and severe fatal hyperthermia. The clinical spectrum of this syndrome is so wide that it easily baffles with more common differentials. In this case report, a neonate born to third-degree consanguineous marriage with previous two abortions presented with respiratory difficulty, severe hyperthermia and feeding difficulty, which were daunting challenges to manage due to being refractory to standard line of management. Severe myotonia and gross dysmorphism were challenging dots to connect. Targeted exome sequencing was a ray of hope, which revealed homozygous mutation in the leukaemia inhibitory factor receptor gene on chromosome 5p13, confirming the genetic diagnosis for a fairly common spectrum of symptoms. The neonate later developed pneumoperitoneum and succumbed to underlying severe neonatal illness.

Focal congenital hyperinsulinism resulting from biallelic loss of function of KCNJ11 gene.

Congenital hyperinsulinism (CHI) characterised by inappropriate secretion of insulin despite low blood glucose can result in irreversible brain damage if not promptly treated. The most common genetic cause of hyperinsulinism is the pathogenic variants in ABCC8 and KCNJ11, causing dysregulated insulin secretion. Rapid testing is crucial for all patients because finding a mutation significantly impacts this condition's clinical management. We report a rare case of focal CHI after a homozygous KCNJ11 mutation who underwent a selective lesionectomy and required octreotide for euglycaemia.