De novo antineutrophil cytoplasmic antibody-associated vasculitis in pregnancy: a systematic review on maternal, pregnancy and fetal outcomes

Abstract

Background De novo antineutrophil cytoplasmic antibody-associated vasculitis typically arises in post-reproductive years, but can occur during pregnancy. Concerns of treatment-related teratogenicity persist, while efficacy and safety of new therapies including intravenous immunoglobulin (IVIG) and rituximab are uncertain. There remains a paucity of maternal, fetal and pregnancy outcome data in these women, and therefore a lack of guidance on safe treatment for clinicians.MethodsWe conducted a systematic review of the literature and a local, retrospective chart review of women with de novo antibody-associated vasculitis (AAV) in pregnancy. Cochrane, Embase and PubMed databases and relevant conference abstracts were searched. Patient demographics, clinical presentation, management and outcomes (maternal, fetal and pregnancy-related) were analyzed.ResultsTwenty-seven cases of de novo AAV in pregnancy were included. Women presented were from 5 to 39 weeks' gestation, of which a majority were in the second trimester (median 20 weeks). The median gravida of women was 2 and the median parity was 1. Women were treated with steroids (89%), cyclophosphamide (CYC) (37%), other immunosuppressive agents [azathioprine (AZA), IVIG, plasma exchange (PLEX)] or no therapy (11%). High rates of serious complications, including preeclampsia (29%) and maternal death (7%), were reported; however, most pregnancies resulted in live birth (73%). Prematurity was common; 73% of live births occurred prior to 37 weeks’ gestation and 40% prior to 34 weeks’ gestation. The majority of infants were born in the third trimester (median 34.5 weeks). Rates of pregnancy termination were high (23%) and only one intrauterine death was reported, shortly after initiation of therapy (4%). Congenital abnormalities were rare, with one infant having a solitary, pelvic kidney (6%) after maternal treatment with steroids, CYC and PLEX. Use of PLEX, IVIG and AZA increased after 2005, whereas CYC use decreased. Remission often occurred postpartum (60%).Conclusions De novo AAV in pregnancy can result in uncomplicated pregnancies; however, serious maternal risks exist. Further data on potentially pregnancy compatible therapies such as IVIG and rituximab are needed in this population.

Pregnancy Outcomes in Systemic Vasculitides

“…There is a growing literature about pregnancy outcomes in these patients. AAV may be the most frequently diagnosed vasculitis during pregnancy, mostly prior to the third trimester [ 3 •, 105 ••]. In a study of 110 patients with AAV, the diagnosis was made before conception in 63%, during pregnancy in 29%, and in the postpartum period in 8% of patients.…”

“…Pregnancy outcomes are reportedly often favorable in patients with AAV. Complications are more frequent when the disease is active at conception or develops during pregnancy and in patients with severe major organ damage from previous flares (renal insufficiency, cardiomyopathy) [ 3 , 5 , 8 , 105 ••].…”

“…Preterm birth is one of the most common complications associated with AAV, with an incidence range previously reported of 25–50%, mostly in GPA [ 2 , 7 ••, 21 , 37 ]. A recent study with vasculitis diagnosed during pregnancy showed a preterm birth rate of 73%, whereas two studies, including patients with disease in remission, only showed a rate of 7–9% [ 34 , 105 ••, 107 ].…”

“…Spontaneous miscarriages have a variable incidence, between 4 and 20% of pregnancies [ 2 , 21 , 34 , 105 ••, 106 ••, 107 ]. However, one recent Canadian study in 20 pregnancies with AAV reported no miscarriages [ 7 ••].…”

“…LBW occurred in 10–30% of pregnancies [ 5 , 7 ••, 105 ••, 106 ••]. A case series describing patients in remission prior to conception reported no fetal growth restriction [ 107 ].…”