E.W. "Al" Thrasher
Status: Funded - Open
Manimaran Ramani, MD, MPH, MSHA, MSHQS
BACKGROUND: Long-term neurodevelopmental disability in survivors of birth asphyxia is a major burden for children, families, and communities worldwide, especially in low- and middle-income countries. Infants born in LMICs are at high risk for birth asphyxia and developing neonatal sepsis/meningitis, increasing the risk for neurodevelopmental disability. GAP: Preclinical evidence shows that azithromycin, an antibiotics with anti-inflammatory effect has neuroprotective benefits in hypoxic-ischemic and other forms of brain injury. This study will determine whether azithromycin, a safest and effective antibiotics for intrapartum prophylaxis that reduces maternal sepsis, also have neuroprotective benefits in infants with hypoxic-ischemic encephalopathy and survive birth asphyxia. HYPOTHESIS: Among survivors of birth asphyxia (≥ 34 weeks of gestation) born in low-resource settings, intrapartum azithromycin increases the Bayley Scales of Infant Development, Third Edition (BSID-III) Cognitive Composite Score (CCS) at 24 (±1) months corrected age compared to children born to mothers exposed to placebo METHODS: This will be follow-up study of 420 children with birth asphyxia whose mothers were randomized to either azithromycin or placebo during labor in the Azithromycin-Prevention in Labor Use Study (A-PLUS trial). Children will undergo neurodevelopmental assessment at 24 ±1 correct age. RESULTS: Pending. IMPACT: This research will determine whether intrapartum azithromycin (a widely available low-cost therapy increasingly used for all low- and high-risk deliveries in low-resource settings to reduce perinatal infections) can be repurposed as a neuroprotective therapeutic strategy to improve neurodevelopment in birth asphyxia survivors. If azithromycin improves neurodevelopmental outcomes in children after birth asphyxia, this study could be a cornerstone for governmental policy, parental decision making, and obstetrical counseling regarding the decision to take azithromycin in pregnancies in low-resource settings for reducing both perinatal infections and neurodevelopmental impairment.