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.

Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy.

Importance: Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden. Objective: To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia. Design, Setting, and Participants: This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023. Exposure: Whole-blood RNA that underwent next-generation sequencing. Main Outcome and Measures: The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort. Results: The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14). Conclusions and Relevance: This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

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.

Comparison of Two Pumping Strategies to Improve Exclusive Breastfeeding at Discharge in Mothers of VLBW Infants with Low Milk Output - A Pilot Randomized Controlled Trial.

OBJECTIVES: To compare the effect of two strategies of breast pumping -power pumping (PP) vs. routine pumping (RP) over one week in mothers of very low birth weight (VLBW) infants with low milk output to improve breastfeeding rates at discharge. METHODS: Mothers with low milk output, defined as inability to express sufficient breastmilk to meet the feeding requirements of their infant on or after post-natal day 14, were randomized to receive power pumping vs. routine pumping - once daily for 7 d coupled with routine lactation support and hand expression 3 hourly in both groups. The primary outcome was exclusive breastfeeding at discharge. RESULTS: There was no difference in the two pumping strategies with respect to exclusive breastfeeding rates [61.1% in PP vs. 50% in RP group; (p = 0.477, RR 1.2; 95% CI 0.76 to 2.17)]. Median milk volume pumped in the individual power pumping session on 7th day of intervention was significantly higher than that in the individual routine pumping session on the 7th day (50 mL vs. 27 mL, p = 0.014). The cumulative median milk volume expressed per individual pumping session over the 7 sessions of power pumping was also higher than that with routine pumping (305 mL vs. 213 mL, p = 0.054). CONCLUSIONS: In this pilot trial, expressed milk volume was significantly higher after each individual power pumping session compared to routine pumping. However, the exclusive breastfeeding rates at discharge were similar in the two groups.

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.

Pain and Physiological Stress During Minimally Invasive Surfactant Therapy (MIST) in Very Preterm Infants.

OBJECTIVE: To evaluate the pain or physiological stress caused during minimally invasive surfactant therapy (MIST) to very preterm neonates. METHODS: In this prospective observational study conducted in a tertiary NICU, very preterm neonates were assessed for pain using Premature Infant Pain Profile-Revised (PIPP-R) score before, during and after MIST. Changes in the heart rate and oxygen saturation were also recorded during the procedure. RESULTS: 23 neonates who received MIST were assessed for pain using PIPP-R. Mean (SD) PIPP-R score during MIST was 3.87(1.3), before; 12.83 (1.9), during; and 6.26 (1.0), after the procedure, respectively (all P<0.001). Heart rate and oxygen saturation were also significantly reduced during MIST (P<0.001). CONCLUSION: The high PIPP-R scores during surfactant administration suggest that MIST can cause moderate to severe pain/discomfort and significant physiological stress in very preterm infants.

The dilemma of feeding during the treatment of patent ductus arteriosus with oral ibuprofen in preterm infants ≤30 weeks of gestation-a randomized controlled trial.

OBJECTIVES: To evaluate the effect of minimal enteral feeding (MEN) versus withholding feeding on time to reach full feeds during treatment of hs-PDA with oral ibuprofen in infants ≤30 weeks. STUDY DESIGN: We performed a single-center, randomized control trial of 126 premature infants born ≤30 weeks gestation, <7 days of age with hs-PDA comparing continuation of MEN (n = 64) vs no feeding (n = 62) during treatment. The primary outcome was time to reach a feed volume of 150 ml/kg/day. Secondary outcomes included were episodes of feed intolerance, GI bleed, NEC and other comorbidities. RESULTS: There was no difference in the time to reach full feeds - median age of 16 days in both groups (p = 0.573). Incidence of feed intolerance, NEC and other secondary outcomes were also similar in both groups. CONCLUSIONS: Continuing MEN during treatment of hs-PDA with oral ibuprofen does not decrease time to reach full enteral feeds in very preterm infants.

Ultrasound-Guided Umbilical Venous Catheter Insertion to Reduce Rate of Catheter Tip Malposition in Neonates: A Randomized, Controlled Trial.

OBJECTIVE: To investigate whether ultrasound-guided umbilical venous catheter (UVC) insertion (US group) reduced the rate of malpositioning of the catheter tip compared to the standard method of insertion (SD group). METHODS: In this open-label, randomized, controlled trial, neonates admitted to NICU within the first week of life were randomly assigned to the US group (n = 26) or SD group (n = 27). Neonates with major congenital anomalies of the thorax and abdomen were excluded. The primary outcome was the rate of malpositioning of the catheter tip. RESULTS: The rate of malpositioning of the catheter tip was observed in a significantly lower number of neonates in the US group as compared to the SD group (11/26, 42.3% vs. 20/27, 74%; RR = 0.57, 95% CI: 0.34 to 0.94, p = 0.019). As more of the UVCs were positioned optimally in the first attempt in the US group than SD group, the need for repeated attempts at catheter repositioning was reduced, resulting in reduced procedure time (minutes) [mean (SD), 23.96 (6.42) vs. 30 (1.83); mean difference 6.04 (95% CI: 3.46 to 8.62), p = 0.005]. This also led to a reduction in the additional X-ray exposure in the US group (n = 11) compared to the SD group (n = 20) [95% CI: 3.12 to 44.26; p = 0.020]. CONCLUSION: Ultrasound-guided UVC insertion significantly reduced the rate of catheter tip malposition. It also reduced the number of attempts at catheter manipulation, procedure time, and X-ray exposures. With adequate training, it could be incorporated into routine bedside practice during UVC insertion for optimum placement. TRIAL REGISTRATION: Clinical Trial Registry of India ( www.ctri.nic.in ) CTRI/2021/03/031894.

Impact of mother-baby friendly initiative plus approach on improving human milk feeding for neonates in hospital: a quality improvement before-and-after uncontrolled study.

Breastfeeding, use of pasteurised donor human milk when mother's own milk is unavailable and kangaroo mother care have independently proven benefits in improving survival of vulnerable sick babies. A triangulated approach called the Mother Baby Friendly Initiative Plus (MBFI+) model, bringing together the combined benefits of these proven interventions, was used to improve exclusive human milk feeding at health facilities through quality improvement and system strengthening approach. This quality improvement before-and-after uncontrolled study enrolled 5343 term and 278 very low birth weight (VLBW) mother-infant dyads. Pre- and post-intervention data were compared to evaluate effect on feeding-related healthcare processes and outcomes. Primary outcome which was incidence of exclusive human milk feeding during hospital stay, improved from 44 to 64.8% (RR 1.47, 95% CI: 1.40-1.55) among term and from 60.5 to 80.7% (RR: 1.33; 95% CI: 1.12-1.59) among VLBW neonates. Neonates receiving extended KMC improved from 43 to 71.1% (RR: 1.65; 95% CI: 1.30-2.10).Conclusion: MBFI+ approach improved exclusive human milk feeding among term and preterm VLBW neonates. What is Known: • Breastfeeding has immense health benefits to sick preterm neonates admitted in NICU. What is New: • Quality improvement approach can lead to system strengthening and can help overcome hindrances to achieve increased breastfeeding rates.

Improving Early Colostrum Feeding in a Tertiary Neonatal Intensive Care Unit: A Quality Improvement Initiative.

Background and Objective: Colostrum feeding is known for its immune benefits for reduction in nosocomial sepsis, necrotizing enterocolitis, and ventilator-associated pneumonias. Colostrum feeding also helps in improving breastfeeding rates and early discharge of vulnerable neonatal intensive care unit (NICU) babies. The objective of this study was to improve early colostrum feeding/oropharyngeal colostrum administration in a busy tertiary NICU in India. Methods: Multiple plan-do-study-act (PDSA) cycles were conducted from January 2020 to September 2020 to improve early colostrum feeding rates in NICU babies to >60%. We tested change ideas such as training of health care personnel, counseling of mothers and families about importance of colostrum expression and feeding, bedside collection of colostrum, safe transportation of colostrum to the NICU, and electronic data handling. Sustainability of the interventions was studied from October 2020 to March 2021 and data were analyzed. Results: Early colostrum feeding rates improved from a baseline of 4.36-68.21% after six PDSA cycles through 9 months. After counseling of mothers and families of NICU babies, rates of breastfeeding and colostrum feeding improved to 98.8% and 97.11%, respectively. The early breast stimulation and colostrum expression rates also improved to 87.28% and 68.2%, respectively. Early colostrum feeding rate was 87.5% after 6 months through the sustainability phase. Conclusions: Quality improvement interventions significantly improved the rate of early colostrum feeding in sick babies admitted to a busy NICU, and the improvement was sustained for 6 months.

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh.

BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Clinical Profile of SARS-CoV-2 Infected Neonates From a Tertiary Government Hospital in Mumbai, India.

OBJECTIVE: To describe the clinical and laboratory profile of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected neonates. METHODS: This is a review of hospital records, conducted in a tertiary care public hospital. Medical records of neonates born from 1 April, 2020 to 31 May, 2020 were reviewed. Women admitted in labor were screened for SARS-CoV-2 infection based on the guidelines issued by Indian Council for Medical Research. Neonates were tested for SARS-CoV-2 infection once mother tested positive, which was after day 2 of life. Demographic, clinical features, laboratory tests and chest radiographs of SARS-CoV-2 infected neonates were reviewed and neonates were telephonically followed up till the age of 2 months. RESULTS: Out of 1229 mothers, 185 tested positive (15.05%); 12 neonates (6.48%) tested positive for SARS-CoV-2 infection. All neonates were exclusively breastfed. Symptoms, if any, were mild and self-limiting. Serum lactate dehydrogenase and liver enzymes were elevated. All neonates were healthy and thriving well on follow-up. CONCLUSION: SARS-CoV-2 infected neonates are mostly asymptomatic and thrive well on exclusive breastfeeding.

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy.

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection.

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.

Prefeeding Oromotor Stimulation Program for Improving Oromotor Function in Preterm Infants - A Randomized Controlled Trial.

OBJECTIVE: To determine effect of Premature Infant Oral Motor Intervention program on oro-motor function and time to full independent wati spoon feeds in preterm infants. METHODS: 30 preterm infants between 28-32 weeks of gestation on full gavage feeds of 150 mL/kg/day were randomized to receive either pre-feed oro-motor stimulation using Premature Infant Oral Motor Intervention (structured stimulation) or sham intervention (unstructured stimulation). RESULTS: Improvement in mean (SD) Neonatal Oro-Motor Assessment Scale (NOMAS) over 7 days from baseline was significantly higher in the study group infants as compared to control group (9.25 (1.73) vs 4.79 (1.52), P=0.001). Infants in the study group reached full independent wati spoon feeds significantly earlier than the infants in control group (4.0 (0.8) d; vs 6.64 (1.0) d; P=0.001). There was significant increase in weight gain after enrolment in infants in study group compared to those in control group. CONCLUSION: Oral stimulation program improves the oro-motor skills and growth velocity in 28-32 week preterm infants. There is decreased transition time from gavage to full independent feeds by mouth.

Hypothermia for encephalopathy in low-income and middle-income countries: feasibility of whole-body cooling using a low-cost servo-controlled device.

Although therapeutic hypothermia (TH) is the standard of care for hypoxic ischaemic encephalopathy in high-income countries, the safety and efficacy of this therapy in low-income and middle-income countries (LMICs) is unknown. We aimed to describe the feasibility of TH using a low-cost servo-controlled cooling device and the short-term outcomes of the cooled babies in LMIC. DESIGN: We recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged <6 hours) admitted to public sector tertiary neonatal units in India over a 28-month period. We administered whole-body cooling (set core temperature 33.5°C) using a servo-controlled device for 72 hours, followed by passive rewarming. We collected the data on short-term neonatal outcomes prior to hospital discharge. RESULTS: Eighty-two babies were included-61 (74%) had moderate and 21 (26%) had severe encephalopathy. Mean (SD) hypothermia cooling induction time was 1.7 hour (1.5) and the effective cooling time 95% (0.08). The mean (SD) hypothermia induction time was 1.7 hour (1.5 hour), core temperature during cooling was 33.4°C (0.2), rewarming rate was 0.34°C (0.16°C) per hour and the effective cooling time was 95% (8%). Twenty-five (51%) babies had gastric bleeds, 6 (12%) had pulmonary bleeds and 21 (27%) had meconium on delivery. Fifteen (18%) babies died before discharge from hospital. Heart rate more than 120 bpm during cooling (P=0.01) and gastric bleeds (P<0.001) were associated with neonatal mortality. CONCLUSIONS: The low-cost servo-controlled cooling device maintained the core temperature well within the target range. Adequately powered clinical trials are required to establish the safety and efficacy of TH in LMICs. CLINICAL TRIAL REGISTRATION NUMBER: NCT01760629.