Q&A: Navigating pregnancy with interstitial lung disease

ByIsabella Hornick

ByAmanda Grant-Orser, BHSc, MBBCh, FRCPC

Fact checked byKristen Dowd

Because interstitial lung disease is often associated with an older patient population, there is limited knowledge on how ILD impacts young women who are pregnant, according to a review published in CHEST.

According to the review authors, younger women can be diagnosed with connective tissue disease-associated ILD, familial pulmonary fibrosis and post-COVID-19 fibrosis, yet there are few studies that include pregnant women when assessing therapeutics.

Quote from Amanda Grant-Orser — *Source: Healio Interviews*

Healio spoke with Amanda Grant-Orser, BHSc, MBBCh, FRCPC, lead author of the review and fellow in the interstitial lung disease program at University of Calgary, to learn more about how ILD impacts women who are pregnant, drugs that are recommended and safe to take during pregnancy and preventive measures that can help ensure positive pregnancy outcomes.

Healio: What prompted you to conduct a literature review on pregnancy outcomes for patients with ILD?

Grant-Orser: There are many areas within ILD where we lack strong evidence to guide clinical decision-making. This review was motivated by a desire to fill an evidence gap. I began this project when I was pregnant myself and felt strongly that patients with ILD who were contemplating pregnancy along with their treating physicians should have data to help guide them through this exciting experience.

Healio: There are several types of ILD. Which types can affect women who may become pregnant, and how prevalent are they in this patient population?

Grant-Orser: Those of childbearing age are most likely to be affected by a connective tissue disease-related ILD. Other forms of ILD, such as idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis, tend to occur among older patients. Although familial pulmonary fibrosis can occur in younger generations, this is a rare diagnosis. There are limited data on the prevalence of ILD among pregnant patients but, overall, it should be considered rare.

Healio: How is pregnancy for a patient with ILD different from pregnancy for an individual without ILD? What extra precautions must patients with ILD take?

Grant-Orser: Like any chronic disease, those with ILD contemplating pregnancy should have a stable disease course prior to pregnancy, be on stable doses of medications and have a multidisciplinary team supporting them throughout their pregnancy. Perhaps the biggest takeaway is that there is more planning involved in the preconception phase to ensure all these factors are in place.

Regarding extra precautions, there may be some medications that have to be changed prior to or immediately after conception is confirmed, and there may be additional vaccine suggestions or different blood work that may need to be monitored compared with a patient who becomes pregnant without a diagnosis of ILD.

Healio: Does the level of ILD disease severity impact pregnancy?

Grant-Orser: This is one of the main questions we were trying to answer with this review. Based on the available evidence, it appears that women with ILD can have safe and healthy pregnancies. However, those with very severe disease, variably defined based on the cohort studied, did have an elevated risk for pregnancy-related adverse outcomes. For example, in the largest cohort published by Clowse and colleagues, where very severe disease was defined as diffusion capacity of the lungs for carbon monoxide of less than 40% or FVC of less than 40%, all seven pregnancies had an adverse pregnancy outcome (including preeclampsia, preterm delivery after spontaneous labor and medically indicated preterm delivery due to maternal disease activity). This is not to say that these women cannot or should not become pregnant, but it is important for clinicians, patients and their loved ones to understand the potential risks of pregnancy and the impact it may have on both mom and baby in order to make the most informed decisions possible.

Healio: Patients with ILD must continue to treat their disease while they are pregnant and lactating, yet you note in the review that pregnancy is an exclusion criterion for ILD drug trials. What are the notable drugs that are recommended and safe to take during pregnancy? How does the lack of trial data for this population complicate treatment?

Grant-Orser: The ILD treatment regime depends on the type of ILD, severity and any drug intolerances or allergies a patient may have. If patients require immunosuppression, drugs that are considered safe include low-dose prednisone and azathioprine. Although there are some associated risks with these medications, they are recommended in the most recent American College of Rheumatology Guidelines, published in 2020, for management of rheumatic disease during pregnancy. Newer biologic medications, such as rituximab, have scant evidence, but some observational data suggest they may be safe. If there are alternatives, better-studied options are preferred.

Often, we see that patients are prescribed newer agents having failed options with more supporting data, which presents a problem when selecting therapy options for pregnant patients. Ultimately, a case-by-case decision is required with a discussion between the health care provider and patient to understand all the risks and benefits of the available options, followed by very close monitoring of therapy. Antifibrotic medications — nintedanib (Ofev, Boehringer Ingelheim) and pirfenidone — are contraindicated in pregnancy and breastfeeding.

A lack of clinical trial data is a big problem not only in ILD, but in many chronic diseases that affect women of childbearing age. It is a complicated issue, but we would be wise to avoid excluding women from trials if pre-trial data suggests no harm.

Healio: In your review, you recommend three preventive measures that pregnant patients with ILD can take: vaccination, infectious disease screening and prophylaxis, and smoking cessation. Are these preventive measures widely utilized in this community and how important are they to successful pregnancy outcomes?

Grant-Orser: Preventative health is a cornerstone of pre-, ante- and post-partum care. Measures such as vaccination against influenza and COVID-19 have shown benefit in this vulnerable patient population. Vaccine coverage rates (VCRs) vary based on geography and vaccine type. For example, a recent study by Baïssas and colleagues found that countries that implement vaccination programs are more likely to have higher VCRs. Another contributing factor is guideline and scientific society endorsement.

There are limited data in the ILD community to determine vaccine uptake, but national guidelines recommend patients with chronic lung disease receive influenza, COVID-19 and pneumococcal vaccines. However, these vaccines for ILD differ from pregnancy-recommended vaccines, again highlighting the importance of a multidisciplinary team to ensure the best standard of care is upheld from both an ILD perspective and a pregnancy perspective.

Healio: What are your recommendations for future studies related to pregnancy in patients with ILD?

Grant-Orser: Future research will ideally provide data on long-term maternal and childhood outcomes for patients with ILD via registry data. In addition, better understanding of the risks and benefits of the newer biologic drugs commonly used in rheumatic diseases will strengthen their safety profile for pregnant and breastfeeding women, expanding the therapy options available to this vulnerable population. Lastly, understanding the effects of sex hormones on ILD is an area already being explored within the field.