Pregnancy is a time of emotional stress for many women, and women with systemic vasculitides face substantial additional challenges. Systemic vasculitides are rare rheumatic diseases characterized by inflammation in blood vessel walls, classified according to vessel size, histopathology, and clinical features.1 Pregnancy in people with vasculitis is considered high risk, and experts recommend planning pregnancy when vasculitis is in sustained remission and when on stable pregnancy-compatible immunosuppressants.2 Yet, even in remission, sequelae of prior vasculitis, including hypertension, cardiopulmonary damage, kidney disease, and glucocorticoid toxicity, may especially increase the risk of adverse pregnancy outcomes in this group.3 Most clinicians have limited experience and data to inform optimal management of vasculitis pregnancies. Epidemiologically, pregnancy in vasculitis is a “rare in rare” condition.4 For example, Takayasu arteritis often affects women of reproductive age5 but is one of the rarest forms of vasculitis globally,6 and only 10% of individuals with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are of reproductive age.7 Further, vasculitis subtypes are clinically heterogeneous, posing different potential challenges for conception, pregnancy, and delivery.

For patients with vasculitis, several factors may contribute to uncertainty and anxiety related to pregnancy. First, treatments may be contraindicated (eg, cyclophosphamide, mycophenolate, methotrexate) or be restricted to organ-threatening disease (eg, rituximab) in pregnancy.8 Second, past exposure to cyclophosphamide may diminish ovarian reserve and fertility,9,10 necessitating assisted reproductive technologies (ART) and augmenting psychological stress. Therefore, understanding reproductive health concerns and outcomes in this group represents an unmet need.

In this issue of The Journal of Rheumatology, Sims and colleagues report on the experience of women with a pregnancy after vasculitis diagnosis.11 The investigators conducted 1-on-1 interviews through videoconferencing of 18 women enrolled in the Vasculitis Pregnancy Registry (VPREG). The Vasculitis Patient-Powered Research Network (VPPRN) and the associated VPREG are web-based registries in which patients self-enroll and enter their clinical data directly into a centralized web platform.12 Although diagnoses and data are patient-reported, a prior VPPRN study found that > 90% of participants with self-reported AAV met 1990 American College of Rheumatology (ACR) classification criteria or 2012 Chapel Hill Consensus Conference definitions.1,12,13 This research infrastructure is useful for studying rare conditions, eliminating resource-intensive recruitment and data collection.14 To our knowledge, the cross-sectional qualitative study published here11 is the first to date evaluating the needs and barriers to pregnancy counseling specifically in women with vasculitis.

In their study, the investigators described observing the following 4 predominant themes regarding conception and/or pregnancy: (1) patients needed self-advocacy to initiate conversation about pregnancy and optimize communication between healthcare providers, (2) women sought information about pregnancy from a range of sources, but (3) cited discussions with their family and particularly their physicians as most influential when making decisions about vasculitis treatment, and finally, (4) most women reported term live-birth pregnancies.11

This qualitative study uncovers some important aspects of the reproductive experience of women with vasculitis, particularly the need for patient self-advocacy. Although several studies in other rheumatic diseases have shown the need for self-advocacy regarding reproductive rheumatology care, the participants included in this study displayed a higher level of self-advocacy compared to prior studies.11,15 Indeed, half of the women relied on self-advocacy to coordinate communication among subspecialists, navigating between 2 to 5 specialized physicians during pregnancy (eg, rheumatologists, maternal-fetal medicine specialists, nephrologists, hematologists).11 Some women were quoted as having to “remain vigilant,” “[be] on top of [their] care,” and “be the go-between” with several specialists to receive appropriate management.11 This showcases a potential care gap, as not all pregnant women with vasculitis have the ability—including medical literacy and educational level—as well as the emotional and physical capacity to act as a liaison between healthcare providers. As a result, pregnant women with vasculitis could face inappropriate multidisciplinary management due to communication failure between specialists.

Unfortunately, the study findings are limited by selection bias, which affects the assessment of self-advocacy and its generalizability, and precludes any definitive conclusion about estimates of adverse pregnancy outcomes. Indeed, the current study population included a very selected group of women with vasculitis. As mentioned previously, they were selected through an online platform, in which subjects had to enroll themselves. The study participation rate was low, with approximately 40% of VPREG subjects who were contacted by email expressing any interest in the study.11 Thus, those who agreed to be interviewed and were ultimately included in the study were likely to be more proactive in their prenatal care and advocate for themselves in their interactions with healthcare professionals.

Further, patients with more severe disease activity and/or damage may be less likely to self-enroll in an online registry. This was reflected by a relatively low rate of immunosuppression—roughly half did not use any immunosuppressants during pregnancy.11 It might also partly explain why many participants felt that patients in online vasculitis support groups were too “severely ill” and thus “extraordinarily depressing.”11 This selected group of women with less severe vasculitis might have been less likely to have adverse pregnancy outcomes. It is therefore impossible to conclude a direct causal relationship between the self-advocacy exhibited by study subjects during pregnancy and the risk of adverse outcomes, as loosely implied by the authors.11 We should also be mindful that having a live-birth pregnancy delivered at term does not necessarily equate with the absence of any adverse outcomes, as some pregnancies might have faced other maternal and fetal complications.

We commend the investigators for attempting to evaluate pregnancy outcomes in women with vasculitis, which is a so-far neglected issue in vasculitis research and not an easy task. Not only did the authors report pregnancy outcomes occurring in the 18 interviewed women, but in this same issue of The Journal, Sims and colleagues published outcome data from 76 women with 78 pregnancies enrolled in VPREG, surveyed throughout gestation and postpartum.16 The vast majority of pregnancies (97%) resulted in live births, of which 21% experienced a preterm delivery.16 Among live births, other self-reported pregnancy complications included preeclampsia (25%) and gestational hypertension (21%).16 Similar to their other study,11 this prospective study of a self-enrolled online survey likely suffers from selection bias, as 42% of subjects were lost to follow-up with no information on pregnancy outcomes.16 Thus, estimates are likely conservative, as women with fetal loss would be less likely to be enrolled and those with pregnancy complications more likely to be lost to follow-up; as an extreme example, all cases of maternal mortality would not be captured. In addition, pregnancy outcomes were self-reported, likely contributing to some information bias. In a prior study, roughly 90% of self-reported preeclampsia diagnoses were confirmed by clinician diagnosis, compared to approximately only 60%, according to professional obstetrical definitions.17 Reporting a conservative adverse pregnancy outcome estimate might be counterproductive to efforts advocating for more reproductive research, care, and resources in this vulnerable population.

These 2 studies published concomitantly by the same group11,16 highlight the need for a multicenter prospective cohort study of unselected pregnancies in women with vasculitis, with physician-confirmed diagnoses and outcomes, to precisely and accurately estimate the risk of adverse pregnancy outcomes. In addition, prospective studies should be conducted to evaluate the risk of disease flare in vasculitis pregnancies, with disease activity assessed by physicians. Several patients expressed concerns about disease flare during gestation and shared that this created additional anxiety during pregnancy, which is already a stressful time even for those without vasculitis.11 Subjects also voiced concerns about fertility, with a substantial proportion of women previously exposed to cyclophosphamide.11 Although the authors state that most women conceived without ART, no further information was provided about ART use.11 However, even if the investigators did report specific numbers of ART use, these would have very likely suffered from selection bias as VPREG is a pregnancy registry and does not capture patients who never conceive. Reproductive data collection in prospective vasculitis registries is much needed and essential to integrate biological sex into vasculitis research. In addition, with the development of new therapies specific to the management of vasculitis (eg, avacopan), as well as novel clinical trials evaluating cell therapies with exposure to lymphodepleting agents such as fludarabine, it is imperative to collect reproductive outcomes as part of established and/or new prospective vasculitis registries/cohorts. This will offer evidence-based data to guide clinicians caring for pregnant women with vasculitis.

Thirty years ago, women with vasculitis were advised to avoid pregnancy because of the immense risks for maternal and fetal morbidity and mortality, as well as concerns over drug safety. With advances in vasculitis management and reproductive care, the vast majority of affected female individuals can now consider pregnancy. Although substantial progress has been made in the field of reproductive rheumatology, it is astonishing to realize how recently this occurred. It was only in 2006—less than 20 years ago—that the first consensus paper on antirheumatic drug safety in pregnancy was published.18 A decade later, in 2016, the European Alliance of Associations for Rheumatology (EULAR) presented its first guidelines on the use of antirheumatic drugs during pregnancy and lactation, followed in 2020 by the first ACR guidelines on reproductive health in rheumatic diseases.8,19 Up-to-date best practice guidelines on antirheumatic drug safety in pregnancy and lactation, as well as other aspects of reproductive health, are critical to provide some help in guiding clinicians caring for reproductive-aged women with vasculitis. Yet, very few, if any, of the evidence supporting these recommendations come from studies specific to vasculitis. Moreover, none of these guidelines offer specific recommendations for women with vasculitis.8,19 Similarly, the 2021 ACR/Vasculitis Foundation vasculitis treatment guidelines do not address reproductive health.20-22 Only the Canadian Vasculitis Research Network (CanVasc) made 1 specific statement in its consensus recommendations for the management of AAV. This recommendation was limited to specifying that women with AAV should not consider pregnancy earlier than 6 months after achieving sustained remission and, while pregnant, should be managed in close collaboration with an obstetrician with expertise in this field and/or in high-risk pregnancies.23

To bolster research and management of reproductive health in patients with vasculitis, a potential avenue is capacity building by further training rheumatologists with expertise in this area. The term “reproductive rheumatology” was first coined less than 10 years ago and now designates an emerging new rheumatology subspecialty.24 Reproductive rheumatologists are dedicated to optimizing the management of reproductive health and pregnancies in patients with rheumatic diseases, including vasculitis. They are highly qualified health professionals who can be leaders of multidisciplinary clinics in their respective centers. They can also practice at referral centers and be consulted, remotely or in person, by other professionals caring for patients with vasculitis regarding reproductive health issues. Studies have shown that women with rheumatic diseases, including vasculitis, believe that rheumatologists should be at the center or be the leader of their multidisciplinary care team.11,15 Patients also stressed the need to enhance direct communication between specialists, which could be facilitated by training dedicated reproductive rheumatologists with existing contact and frequent interactions with relevant specialists, and by creating multidisciplinary clinics where reproductive rheumatologists would have a leadership position.11,15

In summary, pregnancy in vasculitis requires well-coordinated care between knowledgeable medical specialists, including those in obstetrics and rheumatology. When communication or coordination between healthcare professionals fail, pregnant patients with vasculitis might be required to self-advocate for their own care, as shown by Sims and colleagues.11 Patients and providers may benefit from tailored resources to facilitate decision making, and more work is needed to determine how to best support patients with vasculitis on their reproductive journeys. One potential solution would be to have more dedicated reproductive rheumatologists, who would be well-poised to act as multidisciplinary care team leaders, connecting the relevant healthcare professionals—hence, connecting the docs—and alleviating the need for patient self-advocacy. As we await further results from VPREG and other prospective vasculitis pregnancy registries, studying reproductive-aged subgroups within larger vasculitis registries may help to characterize disease damage, medication use, and comorbidities relevant to pregnancy in these populations. This will help to anticipate potential reproductive care needs and ultimately improve outcomes.

AM receives junior salary support from the Fonds de recherche du Québec - Santé (FRQS). ÉV receives senior salary support from the FRQS.

The authors declare no conflicts of interest relevant to this article.

See Vasculitis reproductive experience, page 997, and Vasculitis reproductive outcomes, page 1003