Paroxysmal nocturnal haemoglobinuria in pregnancy–a systematic review with meta analysis

The co-occurrence of Paroxysmal nocturnal haemoglobinuria (PNH) and pregnancy has traditionally been associated with poor feto-maternal outcomes. Eculizumab, a terminal complement inhibitor, is often used in pregnant patients, but the drug is not universally available. We therefore present the first systematic review with meta-analysis of outcomes in 190 pregnancies from 135 PNH patients, comparing those receiving eculizumab and those not. We searched PubMed for studies reporting on pregnancy outcomes in PNH. Thirty-five papers were selected for inclusion, the majority of which were case studies or small series. Eculizumab was used in 131 pregnancies. There was one maternal death reported in a woman who did not receive eculizumab. A higher rate of fetal survival was observed in pregnancies where eculizumab was used (82%) than those when it was not (69%). Miscarriage (< 24 weeks gestation) occurred twice as often in women not receiving eculizumab. Intrauterine death (≥24 weeks gestation), maternal thrombosis, bleeding (both antepartum and postpartum), and pre-eclampsia were over-represented in PNH pregnancies but did not significantly differ between treatment groups. Premature birth (< 37 weeks’ gestation) was observed in 32% of eculizumab pregnancies and 44% of non-eculizumab pregnancies. We conclude that Eculizumab appears to be safe and benefits pregnant women with PNH.