Pregnancy in acquired bone marrow failure syndromes: Antenatal management and maternal and fetal outcomes

Abstract

Aplastic anemia (AA) is an acquired bone marrow failure (BMF) disorder characterized by hypocellular bone marrow and pancytopenia. The pathogenic mechanism is an immune-mediated attack against hematopoietic precursors, and the concomitant detection of a paroxysmal nocturnal hemoglobinuria (PNH) clone, or its emergence over time, is a frequent event. Pregnancy is one of the proposed risk factors for autoimmune disease development and cases of AA in pregnant women were described in numerous case series. [1][2][3][4][5] However, limited data are available on the management of BMFs during pregnancy or on feto-maternal outcomes.We conducted a single-center retrospective cohort study including women with acquired AA and/or PNH, referred to a tertiary center in the United Kingdom over the last 25 years. The study focused on women who experienced either a relapse of known AA or a de novo occurrence of BMF during pregnancy. Demographic, clinical, and disease severity findings according to Camitta criteria 6 were collected.Additionally, information regarding treatment administered before, during, and after each pregnancy, response to AA-treatment, according to RACE trial adopted criteria, 7 as well as feto-maternal outcomes were systematically recorded.Seventy pregnancies occurring in 52 women were included from a cohort of 266 women with BMF followed from 1989 until 2022; 17 patients developed AA de novo during pregnancy, while 28 had a diagnosis of AA predating pregnancy (Table S1). Additionally, seven patients had a hemolytic PNH (two with onset during pregnancy and five with a previous diagnosis).Regarding 17 de novo AA, most presented during the first trimester, 57% versus 36% and 7% in the second and third trimester respectively, with severe presentation in 29% of cases. In seven patients a PNH clone was detected with a median granulocytes clone of 5.2%(1.7-19). During pregnancy, 16 (94%) required blood transfusions and eight (47%) immunosuppressive therapy (IST) with cyclosporin (CSA) (five patients, three responsive) or steroids (three subjects, one responsive). After delivery, spontaneous hematologic improvement occurred in seven subjects (41%), however, 10 (59%) required IST or transplant (5 ATG + CSA ± Eltrombopag; 4 CSA/Androgens; 1 HSCT) all with response. Maternal adverse events (AEs) were observed in 29% of pregnancies, including two peripartum bleedings, one preterm premature rupture of the membrane (PPROM), and a Cesarean scar infection. Three women needed an urgent Cesarean Section (CS) (one for PPROM, two unknown), and three received additional peripartum transfusion support. No spontaneous miscarriages occurred, but fetal