The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally and 11 were diagnosed postnatally: all 11 spontaneous survivors' genotypes had preserved embryonic zeta globin. We compared three groups of patients; Group 1 were prenatally diagnosed and alive at hospital discharge (n=14), Group 2 were prenatally diagnosed and deceased perinatally (n=5), Group 3 were postnatally diagnosed and alive at hospital discharge (n=11). Group 1 had better outcomes than Groups 2 and 3 in resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation correlated with higher neurodevelopmental (Vineland-3) scores (r= -0.72, P=0.02). Preterm delivery after IUT was seen in 3/16 (19%) of patients who continued their pregnancy. When we combined our data with those from two published series, patients who received ≥2 IUTs had better outcomes than those with 0-1 IUT, including resolution of hydrops, delivery ≥34 weeks' gestation, and 5-minute Apgar scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT versus 5/13 of the 0-1 IUT group (OR 2.74; P=0.01). Thus, fetal transfusions enable survival of patients with ATM with normal neurodevelopment even in patients presenting with hydrops. Non-directive prenatal counseling of expectant parents should include the option of IUTs.