TH new.pptx therapeutic hypothermia neonatology

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1. Adjuvant Erythropoietin therapy along with Therapeutic Hypothermia as primary mode of treatment in Hypoxic Ischemic Encephalopathy : A randomized control trial Randomized Control Trial – MGMCH Jaipur, India Dr Sehajdeep Singh 3 rd year DM Resident

2. AIM and OBJECTIVES To assess the efficacy of Erythropoietin as an adjuvant neuroprotective agent along with therapeutic hypothermia in neonates with Hypoxic Ischemic Encephalopathy at Neonatal unit of Mahatma Gandhi Medical College and Hospital , Jaipur .

3. STUDY DESIGN Eligible neonates with HIE randomized to receive either TH alone or TH + EPO using block randomization. EPO administered at 1000 IU/kg within 6 hours of life and then every 48 hours for a total of 6 doses. The control group will receive placebo saline injections. Both groups received standard NICU care.

4. INCLUSION CRITERIA: All babies admitted to the NICU fulfilling the criteria Therapeutic Hypothermia which are as below : 1) Gestational age ≥ 36 weeks 2) Less than 6 hours old 3). A pH of 7.0 or less or a base deficit of 16 mmol per liter or more in a sample of umbilical cord blood or any blood during the first hour after birth. If the pH is between 7.01 and 7.15 , a base deficit is between 10 and 15.9 mmol per liter , or a blood gas is not available, additional criteria are required. These include an acute perinatal event (e.g., late or variable decelerations, cord prolapse, cord rupture, uterine rupture, maternal trauma, hemorrhage , or cardiorespiratory arrest) and either a 10-minute Apgar score of 5 or less or assisted ventilation initiated at birth and continued for at least 10 minutes. 4) Moderate to severe encephalopathy on clinical examination

5. EXCLUSION CRITEIA Impossibility of getting controlled hypothermia before 6 hours of life Chromosomal or significant congenital abnormality Predictable surgery in the first 3 days of life Uncontrolled collapse Head trauma with or without skull fracture Preterm Babies < 36 weeks

6. METHODOLOGY All babies admitted in NICU fulfilling the inclusion and exclusion criteria were enrolled in the study. The Study conducted in two phases. Phase I was the recruitment phase for 15 months followed by phase II ( Follow up phase )where all recruited babies have undergone developmental assessment by using Denver Developmental Screening Test II at 6 months of age.

7. In TH + EPO group : Recruited babies were randomized to Therapeutic Hypothermia (72 hours) and iv Inj. Erythropoietin(1000IU/Kg) every alternate day for 6 doses (12 days) In TH group : Babies received only Therapeutic Hypothermia (72 hours) Primary outcomes 1. Incidence of ischemic brain injury on MRI (days 3–7) and compared between groups.
2. Neurodevelopmental status at 6 months assessed by Denver Developmental Screening Test II (DDST-II) scores. Secondary Outcomes

8. Table: Baseline Demographic & Perinatal Characteristics Variable TH + EPO (n=10) TH only (n=10) p In-born delivery, n (%) 4 (40) 5 (50) 0.48 Male sex, n (%) 6 (60) 5 (50) 0.67 Birth-weight, g (mean ± SD) 3100 ± 300 3050 ± 280 0.72 Gestational age, wk (mean ± SD) 38.5 ± 1.0 38.6 ± 0.9 0.81 10-min Apgar ≤ 5, n (%) 2 (20) 3 (30) 0.56 Sarnat stage III, n (%) 2 (10) 2 (10) 1.00 Time-to-cooling start, h (median [IQR]) 3.0 [2.5–3.5] 3.1 [2.6–3.7] 0.70 Cord blood pH (mean ± SD) 6.97 ± 0.10 6.93 ± 0.11 0.80 Base deficit, mmol/L (mean ± SD) 14.2 ± 4.0 14.8 ± 4.2 0.75

9. Table: Respiratory Support & Temperature Parameter TH + EPO (n=10) TH only (n=10) p Respiratory distress, n (%) 7 (70) 8 (80) 0.65 Hypothermia < 36 °C, n (%) 5 (50) 5 (50) 1.00 Invasive ventilation, n (%) 6 (60) 5 (50) 0.70 NIPPV, n (%) 2 (20) 2 (20) 1.00 None, n (%) 2 (20) 2 (20) 1.00

10. Table: Early Clinical Endpoints Endpoint TH + EPO (n=10) TH only (n=10) p Seizures needing AED, n (%) 2 (20) 3 (30) 0.65 Days to full enteral feeds (median [IQR]) 7 [6–8] 8 [7–9] 0.52 Need for inotropes, n (%) 4 (40) 2 (20) 0.25

11. Table: Length of Stay & Survival Outcome TH + EPO (n=10) TH only (n=10) p NICU stay, days (mean ± SD) 13.0 ± 4.0 14.0 ± 4.5 0.68 Total hospital stay, days (median [IQR]) 16 [14–18] 17 [15–19] 0.55 Survival to discharge, n (%) 10 (100) 9 (90) 0.31 Survival at 6 months, n (%) 10 (100) 9 (90) 0.31 Death/mod-sev disability, n (%) 1 (10) 2 (20) 0.40

12. Table: DDST-II at 6 Months Domain TH + EPO (n=10) TH only (n=10) Mean diff (95% CI) p Personal-Social 95 ± 13 94 ± 14 +1 (–5 to +7) 0.85 Gross Motor 93 ± 14 92 ± 15 +1 (–6 to +8) 0.88 Fine Motor 94 ± 12 93 ± 13 +1 (–5 to +7) 0.82 Language 94 ± 14 93 ± 12 +1 (–7 to +8) 0.80 Any domain < 85, n (%) 2 (20) 3 (30) 0.60

13. Table: MRI Brain Injury Grading (NICHD scale) Grade TH + EPO (n=10) TH only (n=10) p No injury 4 5 0.80 Mild (1–1A) 3 3 1.00 Moderate (2–2A) 2 2 1.00 Severe (3) 1 1.00 Grades: 0 none; 1A–1B mild; 2A–2B moderate; 3 severe. The NICHD (National Institute of Child Health and Human Development)MRI score classifies HIE-related brain injurybased on involvement of the cortex, basal ganglia, thalamus, internal capsule, PLIC and Cerebral hemispheric devastation

14. Chart: Adverse Events Source: Trial manuscript【7†source】

15. Summary • Baseline characteristics and outcomes were similar between groups • No statistically significant benefit of adding EPO to TH in this cohort • Findings align with larger multicenter trials (NEAT, HEAL) • Consider larger sample size and longer follow-up in future work Source: Trial manuscript【7†source】