Healthy pregnancy possible, especially if disease in remission

Analysis of preterm births, newborn weight, and disease flares in 78 women

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Rates of preterm delivery, lower-than-normal birth weight, and maternal disease flares are higher among pregnant women with ANCA-associated vasculitis (AAV) than in the general population, according to a review study.

Despite this, “most pregnancies resulted in healthy newborns and manageable, non-life-threatening flares of AAV,” the researchers wrote, suggesting that “pregnancy in this population can be successful, mainly when conception is achieved during remission.”

The study, “Pregnancy outcomes in ANCA-associated vasculitis patients: A systematic review and meta-analysis,” was published in the journal Joint Bone Spine.

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AAV is caused by the production of antibodies that mistakenly target proteins at the surface of certain immune cells, leading them to erroneously cause inflammation and damage to small blood vessels.

In the past, pregnancy was not advised for women with AAV, partly due to the potential risks of cyclophosphamide, an immunosuppressive therapy commonly used in AAV and linked to toxicity and reduced fertility.

“Better management of immunosuppressive drug use before, during and after pregnancy, as well the replacement of [cyclophosphamide] by rituximab (RTX) as first-line therapy, have led to a more optimistic approach indicating pregnancy as a realistic perspective for these patients,” the researchers wrote.

However, no systematic review has been undertaken to assess the frequency of unfavorable pregnancy outcomes among women with AAV.

Researchers in Greece searched for studies published up until September 2022 reporting on pregnancies and complications in women with AAV. Complications evaluated by these scientists were preterm delivery (before 37 weeks of gestation), a lower-than-normal newborn weight, and disease flares in the mother.

A total of six studies, involving 78 pregnant women and 92 pregnancies, were included in the meta-analysis, which combines the results of multiple scientific studies.

Women’s median age ranged from the late 20s to 34 across these studies. Most had granulomatosis with polyangiitis (GPA), the most common type of AAV, while the remaining patients had eosinophilic granulomatosis with polyangiitis (EGPA), the rarest type.

All women had stopped cyclophosphamide treatment prior to conception, and most were treated with low to medium doses of glucocorticoids and azathioprine during pregnancy.

In 72.8% of the pregnancies, the women were in disease remission at the time of conception. Those with active disease had mostly mild manifestations.

Complications more common than among public at large, but not overly serious

Preterm delivery occurred in 18% of the pregnancies, and underweight/smaller babies were reported in 20% of cases.

AAV relapse was reported in 28% of pregnant women, occurring at distinct times during pregnancy. None of the relapses were life-threatening, and most were managed by increasing doses of glucocorticoids and azathioprine. Plasma exchange, a blood-cleaning procedure, was used in more severe and refractory cases, the study noted.

Common flare manifestations among GPA patients were subglottic stenosis (a narrowing of the windpipe), crusting rhinitis (a nasal condition characterized by crusting), and impaired kidney function. A worsening in asthma was most common among those with EGPA.

Overall, the rates for preterm delivery, low birth weight, and disease relapse “appear to be much higher compared to the general population,” the researchers wrote, adding that in Europe, preterm delivery is reported in 5% to 9% of cases and low birth weight in 5%.

Notably, “no notable distribution of relapses across the three trimesters was observed in the analyzed studies, highlighting the need for increased vigilance throughout overall pregnancy course,” the team wrote.

Preterm delivery and low birth weight were more common in women who experienced severe disease relapses, especially those with worsening kidney function and high blood pressure.

“Despite the lack of validated [AAV] activity scores in the majority of the studies included in the analysis, it appears that stable disease before conception contributed to favorable outcomes and absence of relapse in the largest part of patients” studied, the team wrote.

Moreover, while preterm delivery, lower-than-normal birth weight, and disease flares occurred more frequently than usual, most pregnancies were successful, resulting in healthy newborns.

“To the best of our knowledge, this is the first meta-analysis for pregnancy outcomes in patients with AAV,” the researchers wrote, adding that larger studies, especially those following patients over time, are needed to confirm these findings.

“Guidelines on the management of pregnant women with [whole-body blood vessel inflammation] would help clinicians approach these patients in a more holistic manner,” they added.