Pregnancy outcome and safety of breast-feeding in two patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with eculizumab

Background Paroxysmal nocturnal haemoglobinuria (PNH) is associated with increased maternal and perinatal morbidity and mortality due to haemolysis, thromboembolism and prematurity. Management is challenging and has been considered a relative contraindication to pregnancy. Eculizumab (an IgG monoclonal antibody) is standard treatment outside pregnancy. Trials excluded pregnant, women as it could potentially cross the placenta and into breast milk. There has been one report of good outcomes in 7 pregnancies following eculizumab but the safety of breast feeding remains unknown. Cases Two patients with PNH were treated antenatally with eculizumab. Patient A commenced treatment at the end of the first trimester and patient B at 23 weeks. Eculizumab inhibited intravascular haemolysis in both (median LDH decrease 77.2 and 63.9%). Patient A required a dose increase in the third trimester due to breakthrough haemolysis requiring blood transfusions. She had no further complications and delivered a 3.2kg infant at 41 weeks. Patient B developed PET at 36 weeks and was induced at 37 weeks delivering a 2.5kg infant. Eculizumab was continued for 6 months post-partum. Both patients elected to breast-feed. Eculizumab levels were measured in paired breast milk and maternal serum samples at 12 hours and 5 days after the last dose. Although therapeutic serum levels (>35 µg/ml) were measured, no eculizumab was detected in the breast milk. Baby A had no complications by 30weeks of follow-up. Baby B developed neutropenia for which no cause was found by 12 weeks. Conclusions Eculizumab seems to be effective in PNH during pregnancy and is not excreted in breast milk.