29 - Erythropoietin Monotherapy for Neonatal Encephalopathy in Low- and Middle-Income Countries (EMBRACE Pilot trial): 18-Month Outcomes.

Publication Number: 1026.29

Ashwini Thayyil, imperial college london, plymouth, England, United Kingdom; Manjesh Kurupalya Annayappa, IPEU, Bangalore, Karnataka, India; Anchal Dhawan, Imperial College London, London, England, United Kingdom; Laxmikant S. Deshmukh, Government Medical College Aurangabad, Aurangabad, Maharashtra, India; Atul Londhe, Govt Medical College and Hospital, Aurangabad, Aurangabad, Maharashtra, India; Amol Joshi, GMC Chh Sambhajinagar Aurangabad, Aurangabad, Maharashtra, India; Sudhindrashayana R. Fattepur, Karnataka Medical College and Research Institute, Hubballi, Karnataka, India; Swati Amol. Manerkar, Lokmanya Tilak Medical College & General Hospital, Mumbai, Maharashtra, India; Sahana Devadas, BANGALORE MEDICAL COLLEGE, Bangalore South, Karnataka, India; Chinnathambi N. Kamalarathnam, Tamilnadu Medical Services, Chennai, Tamil Nadu, India; Prathik Bandiya, Indira Gandhi institute of Child Health, Bengaluru, Karnataka, India; Stuti Pant, Imperial College London, London, England, United Kingdom; Harini Venkateswaran, Imperial college of London, Chennai, Tamil Nadu, India; Paolo Montaldo, Imperial College London, lONDON, England, United Kingdom; Ismat Jahan, Bangladesh Medical University (Former Bangabandhu Sheikh Mujib Medical University), Dhaka, Dhaka, Bangladesh; Mohammod Shahidullah, Bangladesh Medical University (former BSMMU), Dhaka, Dhaka, Bangladesh; Sadeka Moni C. Choudhury, Bangladesh Medical University, Dhaka, Dhaka, Bangladesh; Sanjoy Kumer Dey, Bangladesh Medical University, Dhaka, Dhaka, Bangladesh; Farah Alobeidi, Imperial College Healthcare NHS Trust, London, England, United Kingdom; P. Ellen grant, Boston Children's Hospital, Boston, MA, United States; Seetha Shankaran, University of Texas at Austin Dell Medical School, Ann Arbor, MI, United States; Sudhin Thayyil, Imperial College London, London, England, United Kingdom; Reema Garegrat, Imperial College London, London, England, United Kingdom

Background: Erythropoietin (Epo) is a promising neuroprotective therapy for neonatal encephalopathy (NE) in low- and middle-income countries (LMICs), where therapeutic hypothermia has limited effectiveness.

Objective: To assess neurodevelopmental outcomes at 18-22 months among infants enrolled in the EMBRACE pilot trial.

Design/Methods: In this double-blind, randomized, placebo-controlled pilot trial, 50 term infants ( < 6 hours old) with moderate or severe NE were enrolled from eight neonatal units in India and Bangladesh. Infants were randomly assigned to receive Epo (500 U/kg/day for 9 days; n = 26) or placebo (n = 24) following informed parental consent. All infants underwent brain MRI before discharge and neurodevelopmental assessment at 18-22 months using the Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-IV). Adverse outcomes were defined as death or moderate/severe disability.

Results: Baseline characteristics were similar between groups (Tabe 1). Death before discharge occurred in 5 infants (19%) in the Epo group and 11 (46%) in the placebo group (Figure 1). MRI brain injury was detected in 18/20 (90%) Epo-treated and in 12/13 (92.3%) placebo-treated infants. At 18-22 months (100% follow up), adverse outcomes occurred in 14 of 26 (54%) in the Epo group and 15 of 24 (63%) in the placebo group. Mortality at 18 months was 38% in the Epo group and 46% in the placebo group (Figure 2). Two infants (both in the Epo group) developed extensive sinus venous thrombosis but had normal neurodevelopmental outcomes.

Conclusion(s): Early and extended Epo therapy with high follow-up rates is feasible in LMICs, although many deaths occurred after hospital discharge. Larger, adequately powered clinical trials are needed to determine the efficacy of Epo on neurodevelopmental outcomes.

Figure 1
Flow chart

Table 1
Baseline data, neonatal outcomes and outcomes at 18 to 22 months


Figure 2
Survival up to 18 months among the Erythropoietin (blue) and the Placebo (red) groups