S5624 Neonatal Acute Liver Failure From Gestational Alloimmune Liver Disease: Distinct Outcomes in Two Infants

Introduction: Gestational alloimmune liver disease (GALD) is rare but the leading cause of neonatal acute liver failure (NALF), triggered by maternal alloantibodies against fetal hepatocytes. This causes complement mediated hepatocyte injury and systemic iron overload. Despite advances in imaging and immunotherapy (IVIG, exchange transfusion), GALD remains under-recognized and often fatal without timely treatment. We present 2 cases highlighting variability in presentation, diagnostic challenges, and outcomes. Case Description/Methods: Case 1: A 36-week boy born via vaginal delivery for maternal preeclampsia, discharged home on day of life (DOL) 2. On DOL 13, he presented with fussiness and hypothermia but was discharged with reassurance. He returned the next day with jaundice, hypoglycemia (39 mg/dL), and shock. Labs showed total bilirubin 34 mg/dL, international normalized ratio (INR) >8, and ammonia 119 µmol/L. He was admitted to PICU and treated with exchange transfusion, IVIG, and plasma exchange for presumed GALD. Buccal biopsy was negative; magnetic resonance imaging (MRI) on DOL 25 showed diffuse siderosis. He developed multiorgan failure and necrotizing enterocolitis. Care was withdrawn on DOL 36. Postmortem autopsy confirmed GALD. Case 2: A 32 + 1-week girl born via Cesarean section for oligohydramnios, requiring CPAP and presenting with blueberry muffin lesions. On DOL 1, she developed hypotension, acidosis, and pneumothorax. She received steroids, vasopressors, and IVIG on DOL 2. Liver dysfunction progressed (bilirubin 23.5 mg/dL, INR 2.9). Buccal biopsy on DOL 8 confirmed GALD. She received 2 additional IVIG doses and 1 exchange transfusion. Complications included MSSA bacteremia, gastrointestinal bleeding, and renal failure requiring ultrafiltration. She stabilized and was transferred for transplant evaluation. Discussion: These cases illustrate the critical importance of early detection and prompt treatment. In Case 1, late presentation (DOL 14) contributed to delayed diagnosis and poorer outcome. Diagnostic delays are common, as GALD may be misattributed to metabolic, infectious, or genetic etiologies. While buccal biopsy is minimally invasive, it may yield false negatives in early or preterm infants due to insufficient or immature glandular tissue. MRI serves as a valuable non-invasive tool for confirmation. The standard treatment involves IVIG, with or without exchange transfusion; therapeutic plasma exchange remains investigational. Maintaining a high index of suspicion is essential for improving survival and reducing the need for liver transplantation.