By Jessica Chapman, M.D.
This past week I was asked to discuss the topic of pregnancy and rheumatic diseases. This is a major issue as many people that develop autoimmune disease are young women. If you so happen to be one of those young women and you thought that pregnancy was out of the question for you because of your illness… think again.
For the most part, most women with autoimmune disease can have successful pregnancies. That is, with careful plan and coordination between your doctors.
It’s extremely important to have a frank discussion with your rheumatologist before thinking about conceiving. If you have a hematologist, nephrologist, pulmonologist, cardiologist, or any other specialist that also plays a role in caring for your autoimmune, then they should be involved as well. It’ll also me crucial for you to establish care with a high risk OB-GYN. I did say that it is possible to have a successful pregnancy, but it won’t be your average type of pregnancy. All this should be done between 6 -12 months prior to attempting conception.
The following are typically recommended.
- For best outcome, conception should be attempted during periods of low disease activity.
- All high risk or teratogenic medications should be replaced with low risk medications. This one can be tricky at times. Remember that most of the medication have very very long washout periods. So just because you stopped methotrexate a week ago, it’s still there lingering.
- You should be assessed for high risk autoantibodies. These include SSA (anti-Ro) and SSB (anti-La) antibodies as well as all the antiphospholipid antibodies.
- If you plan on breastfeeding, the choice of medication should also factor into the decision.
SSA and SSB antibodies
These antibodies are typically associated with Sjogren’s syndrome but can also be present in a variety of different conditions such as lupus and rheumatoid arthritis. It’s important to know whether you have these antibodies because they increase the chance of neonatal lupus. Maternal SSA and SSB antibodies can passively transfer in utero to the baby. The risk is small, 1-2% of cases but the risk significantly increases in women who have already borne a child with neonatal lupus.
Children that are born with neonatal lupus may have a rash, liver problems, and low blood cell counts but thankfully, these symptoms disappear completely after about six months. I did not find research finding that have neonatal lupus increases the chance of the child developing systemic lupus erythematosus (SLE). Research is research and things may change with time.
The most dreaded complication of neonatal lupus is complete heart block, which typically occurs at weeks 20 – 22. It’s currently not recommended to use prophylactic steroids to prevent this from happening, but rather to get frequent cardiac monitoring. This is where the high risk OB-GYN comes into play.
There are three types of antiphospholipids: lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoproteins. The presence of these antibodies, particularly at high titers, are associated with something called the antiphospholipid syndrome. People that have this condition are higher risk of developing bother arterial and/or venous blood clots. Other complications include: miscarriage, stillbirth, pre-term delivery, and preeclampsia. In an effort to try to prevent some of these complications, women that have antiphospholipids typically treated with prophylactic “pregnancy-safe” blood thinners.
High risk medications
Because it would be completely and utterly unethical to conduct a randomized controlled study on pregnancy outcomes and exposure to disease modifying agents (DMARDs), the vast majority of evidence regarding the safety of medications during pregnancy comes from animal models. There are also a few registries that capture human data. As we all know, not all pregnancies are necessarily planned and for some women having active disease may be worse for the baby or the mother, so the benefits of the medication may outweigh the risks. Every situation is unique.
The American College of Rheumatology has a nice table listing medications that typically are used to treat rheumatic conditions. Which is considered safe in pregnancy and breastfeeding. In general the antimalarials, like hydroxychloroquine, are safe as well as azathioprine and sometimes sulfasalazine. Mounting evidence also suggests that the TNF-alpha inhibitors may also be safe, but this isn’t set in stone. Many rheumatologists are still on the fence regarding this one. If a TNF-alpha inhibitor is absolutely required, it may be a good idea to use certolizumab as this medication is pegylated and technically should not cross the placenta. It is VERY important to have a discussion with your rheumatologist regarding your medications!
How does pregnancy affect disease activity?
It all depends on the disease we are talking about. Typically SLE becomes more active during pregnancy, whereas rheumatoid arthritis and psoriatic arthritis tends to improve. Typically vasculitis, polymyositis, dermatomyositis, and systemic sclerosis are unaffected by pregnancy.
High risk clinical situations
HOWEVER, there are a few notable circumstances where pregnancy is risky for both the mother and the child. It’s generally not safe to conceive during a period of very high disease activity. This includes lupus nephritis. It’s generally discouraged to conceive when lupus nephritis is active, but when things are controlled it’s okay with very close monitoring. Patients with lupus nephritis commonly flare, are at higher risk of preeclampsia, and HELLP syndrome during pregnancy but these can be reversed with prompt treatment.
Another very important high risk situation is pulmonary hypertension. This can occur in variety of disease such as systemic sclerosis, SLE, myositis, mixed connective tissue disease, Sjogren’s syndrome, and rheumatoid arthritis. When pulmonary hypertension is caused by an autoimmune disease, we call it connective tissue disease-related pulmonary arterial hypertension. For those who want to get technical, pulmonary hypertension is defined as a mean pulmonary arterial pressure higher than 25 mmHg at rest, associated with a pulmonary capillary wedge pressure lower than 12 mmHg diagnosed by right heart catheterization. Symptoms include:
- Shortness of breath particularly while exercising. Like more than what you would expect. At one point the shortness of breath even when you are at rest.
- Dizziness, passing out.
- Chest pain
- Swollen legs or swollen abdomen (ascites)
- Bluish color
So why is this especially important for pregnancy-related matters?
A study by Qian et al. aimed to evaluate the survival of patient with SLE-associated pulmonary arterial hypertension. This was a systematic review and meta-analysis. They identified 6 studies which included a total of 323 patients. They found that 1-, 3-, and 5-year survival rates were 88%, 81%, and 68% respectively. The more severe the pulmonary hypertension, the worse the outcome. These are not good odds.
High pulmonary hypertension peripartal mortality is not an isolated incident related to SLE alone. It is elevated for all connective tissue disease-related caused of pulmonary arterial hypertension.
We’ve come a long way when it comes to rheumatic diseases and pregnancy. Way back when, it was generally discouraged in practically all circumstances. But things have changed. With careful planning and monitoring, many women with autoimmune diseases can now have safe pregnancies.
Kelley and Firestein’s Textbook of Rheumatology, tenth edition
American College of Rheumatology
Pasut G. Pegylation of biological molecules and potential benefits: pharmacological properties of certolizumab pegol.BioDrugs. 2014 Apr;28 Suppl 1:S15-23.
Moroni G, et al. Maternal outcome in pregnancy women with lupus nephritis. A prospective multicenter study. J Autoimmun. 2016 Nov;74:194-200.
Thakkar V, Lau EM. Connective tissue disease-related pulmonary arterial hypertension. Best Pract Res Clin Rheumatol. 2016 Feb;30(1):22-38.
Qian J, et al. Survival and prognostic factors of systemic lupus erythematosus-associated pulmonary arterial hypertension: A PRISMA-compliant systematic review and meta-analysis. Autoimmun Rev. 2016 Mar;15(3):250-7.