Patient information: Rheumatoid arthritis and pregnancy

INTRODUCTION

Rheumatoid arthritis (RA) affects 1 percent of the adults in the United States, with more women affected than men. Many women with RA are of childbearing age, which highlights the importance of being prepared for pregnancy, using birth control unless pregnancy is desired, and being monitored frequently during pregnancy.

In many women with RA, disease activity improves substantially during pregnancy. However, some women's RA flares or remains active during pregnancy. It is often necessary to change or modify treatment of RA during pregnancy to control flares and/or to minimize the risks of some RA treatments to the developing fetus.

A number of other topics about rheumatoid arthritis are available separately. (See "Patient information: Rheumatoid arthritis symptoms and diagnosis" and "Patient information: Rheumatoid arthritis treatment" and "Patient information: Disease modifying antirheumatic drugs (DMARDs)".)

CHANGES IN RHEUMATOID ARTHRITIS DURING PREGNANCY

Many changes normally occur during pregnancy that allow a fetus to grow and develop. Some of these changes contribute to the improvement of RA symptoms during pregnancy.

Disease activity during pregnancy — Approximately 80 percent of women with RA notice improvement of RA signs and symptoms during pregnancy. The decrease in disease activity generally starts in the first trimester and lasts for a number of weeks or months into the postpartum period. The severity of a woman's RA before pregnancy cannot predict if she will improve during pregnancy.

It is sometimes difficult to distinguish between the common discomforts of pregnancy and the symptoms of RA. Pregnancy discomforts that are similar to those of RA include the following:

• Fatigue
• Swelling of the hands, feet, or ankles
• Joint pain, especially in the low back
• Shortness of breath
• Numbness or pain in one or both hands (caused by carpal tunnel syndrome of pregnancy)

Pregnancy outcome — Most reports show that there is no increase in stillbirth or miscarriage in women who have RA. However, some medications, particularly high-dose steroids, increase the risk of having a smaller than normal infant and may increase the risk of premature rupture of the membranes (see 'Drugs that may have a small risk of harm' below.

CARE BEFORE PREGNANCY

Women with RA should discuss their desire to become pregnant with a rheumatology or obstetrical care provider before trying to become pregnant.

General recommendations — These recommendations apply to all women who are considering pregnancy, not just those with rheumatoid arthritis.

• All women should take a nutritional supplement containing at least 400 mcg of folic acid. Taking folic acid can reduce the risk of a specific birth defect, called a neural tube defect. Women who have had a child with a neural tube defect should take 1000 mcg of folic acid.

Folic acid should be started before trying to conceive and continued until at least the end of the first trimester. Most prenatal vitamins contain adequate folic acid.

• Women should stop smoking and consuming alcohol or any recreational drugs (eg, marijuana) before trying to become pregnant.
• If a woman takes prescription or non-prescription medications, these should be reviewed with a healthcare provider. Some medications are safe during pregnancy while others are not. In some cases, an alternate medication can be substituted for an unsafe drug.
• Women who take methotrexate should stop it at least one month before trying to conceive; men who take methotrexate should stop it for at least three months. This waiting period is necessary to completely eliminate methotrexate from the body.
• Women who take leflunomide must stop it for at least two years before trying to conceive unless a procedure to eliminate the drug from the body is used. Thus, women who may become pregnant are advised to discuss use of this medication with their arthritis specialist.
• Caffeine intake should be limited to less than 250 mg per day while trying to become pregnant and during pregnancy. Table 1 lists the caffeine content of several common beverages (table 1)

• Blood testing for rubella (German measles), varicella (chicken pox), HIV, hepatitis B, and inherited genes (eg, cystic fibrosis) may be recommended.

Am I ready for pregnancy? — It is common for women with long-term medical problems to be worried about how their health will be affected by pregnancy and parenting. Women with RA often have an improvement in symptoms of pain and fatigue during pregnancy, but then may have a worsening of these problems after delivery. Thus, it is important to consider the changes that a new child may bring, including interrupted sleep, fatigue, stress, and anxiety. Close communication with an obstetric and rheumatology care provider and support from family and friends can help to ease the additional challenges of being pregnant and raising a child.

RHEUMATOID ARTHRITIS TREATMENT DURING PREGNANCY

Some women with RA flare during pregnancy and require treatment. Some medications used in the treatment of RA are not safe during pregnancy. The benefit of any medication must be balanced with the potential risk.

Care during pregnancy — During pregnancy, care of women with RA is usually shared between a rheumatologist and an obstetrical provider. Most pregnant women with RA will be seen every four weeks until 28 weeks of pregnancy. Between 28 and 36 weeks, most women are seen every two weeks. Women are usually seen once per week between 36 weeks and delivery. Some women will need more frequent visits, especially if treatment for an RA flare is required.

At every visit, blood pressure and urine testing will be done. To monitor the fetus' growth during pregnancy, it is important to have an accurate due date. Women who do not remember the date of their last menstrual period or are unsure of when the baby was conceived should have an ultrasound examination to determine their due date. A due date that is calculated by ultrasound examination is most accurate when the examination is performed in the first trimester.

After 10 to 12 weeks of pregnancy, the fetus' heart rate will be measured at every visit. An ultrasound is usually recommended between 18 and 20 weeks of pregnancy to ensure that the fetus is growing and developing normally. Women who require steroids during pregnancy may have an ultrasound to measure the fetus every four weeks after 18 to 20 weeks of pregnancy.

Medications during pregnancy — In general, there are few to no good studies that have evaluated the safety of RA medications during pregnancy. The FDA's classification system (table 2) is meant to be used as a guide and is based on available trials and expert opinions.

Medications that are typically used to treat patients with RA may be divided into three categories: those that should be avoided during pregnancy, those that may have a small risk of harm to the fetus; and those that are probably safe [1].

Drugs to avoid

• Some immunosuppressive medications — Leflunomide, methotrexate, cyclophosphamide, and mycophenolate mofetil should be avoided completely during pregnancy due to a significant risk of fetal harm. If a woman takes one of these medications during pregnancy, she should speak to her clinician immediately.
• Biologic medications — There are insufficient data about the safety of biologic agents in pregnancy. Biologic agents include etanercept, infliximab, adalimumab, anakinra, rituximab, and abatacept. Until more data are available, biologic medications should be avoided in pregnancy whenever possible.

Drugs that may have a small risk of harm

• NSAIDs — Nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Advil®, Motrin®) and naproxen (Aleve®) cross the placenta and can potentially cause harm to the fetus when taken during the third trimester. NSAIDs should also be avoided in patients with fertility issues who are trying to become pregnant because of the risk that NSAIDs interfere with embryo implantation.

A safe alternative to NSAIDs for treatment of pain during pregnancy is acetaminophen (Tylenol®). The recommended dose of acetaminophen is two 375 mg tablets or capsules every 4 to 6 hours as needed. No more than 4000 mg of acetaminophen should be taken per day.

• Aspirin — Women should speak with their obstetric or rheumatology provider about the risks and benefits of aspirin during pregnancy. Aspirin is not usually recommended during the third trimester of pregnancy.
• Prednisone — If RA becomes active during pregnancy, most experts recommend starting treatment with the lowest dose possible of a glucocorticoid medication (most commonly, prednisone). Prednisone crosses the placenta but appears in only small amounts in the infant's blood. Prednisone is considered a class B drug in terms of its risk for pregnancy by the United States Food and Drug Administration (FDA). Other steroids are considered class C. Table 2 describes the FDA rating system for medication risk during pregnancy (table 2).

• - Steroid medications (including prednisone) increase the risk that the infant will have a cleft lip and/or palate (when the lip and/or roof of the mouth are not fused in the middle).
• - Steroids may increase the risk of premature rupture of membranes (breaking the water early) and growth restriction (having a lower birth weight infant).

• Cyclosporine — There is insufficient information about the safety of cyclosporine during pregnancy. Most experts recommend that pregnant women take cyclosporine only if the potential benefits outweigh the potential risks.
• Azathioprine — There are conflicting data about the safety of azathioprine (AZA) during pregnancy. Use of azathioprine is generally limited to women with severe disease who have not responded to other treatments. Men who take AZA should discontinue the medication three months before their partner tries to conceive.
• Sulfasalazine — The risk that sulfasalazine will harm a fetus is thought to be very low. Most experts agree that women with active disease may continue the drug. However, in two studies, harm to the fetus was seen when women were exposed to folic acid antagonists (such as sulfasalazine) in early pregnancy. To address this concern, a folic acid supplement (1000 mcg daily) is recommended before and during pregnancy. Sulfasalazine is generally regarded as safe for use while breastfeeding.

Drugs that are probably safe

• Hydroxychloroquine — Most studies of hydroxychloroquine have found that it is safe to use during pregnancy and breastfeeding. Hydroxychloroquine may play an important role in controlling the underlying disease.

RHEUMATOID ARTHRITIS AFTER DELIVERY

Approximately 90 percent of women with RA experience a flare during the postpartum period, usually within the first three months and particularly after a woman's first pregnancy [2]. Many experts recommend restarting RA medications in the first few weeks after delivery.

Breastfeeding and rheumatoid arthritis activity — It is not clear if breastfeeding increases the risk of an RA flare. The postpartum period is a common time for women with RA to have a flare of the disease, so it is difficult to know if breastfeeding further increases this risk. However, there are numerous benefits of breastfeeding for both women and their infants. For these reasons, women with RA who want to breastfeed are encouraged to do so. (See "Patient information: Deciding to breastfeed".)

Medications and breastfeeding — Many of the same restrictions on medication use during pregnancy apply also to breastfeeding mothers [3]:

• NSAIDs can be used, but aspirin should be avoided.
• Prednisone can be taken in low doses.
• Azathioprine, cyclosporine, cyclophosphamide, methotrexate, and chlorambucil should be avoided during breastfeeding.

The quality of information regarding medication safety in breastfeeding varies. A reliable source of up-to-date information is LactMed, which is available from the National Library of Medicine (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT).

Several topic reviews about breastfeeding are available separately. (See "Patient information: Deciding to breastfeed" and "Patient information: Common breastfeeding problems" and "Patient information: Breast pumps" and "Patient information: Maternal health and nutrition during breastfeeding".)

Birth control and rheumatoid arthritis — Within a few weeks after delivering an infant, it is important to start thinking about birth control. A number of birth control options are available, most of which are safe and effective for women with RA. In most cases, RA should not affect which birth control method a woman chooses.

A full discussion of birth control options is available separately. (See "Patient information: Birth control; which method is right for me?".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: A guide to pregnancy
Patient information: Rheumatoid arthritis symptoms and diagnosis
Patient information: Rheumatoid arthritis treatment
Patient information: Disease modifying antirheumatic drugs (DMARDs)
Patient information: Deciding to breastfeed
Patient information: Common breastfeeding problems
Patient information: Breast pumps
Patient information: Maternal health and nutrition during breastfeeding
Patient information: Birth control; which method is right for me?

Professional Level Information:
Rheumatoid arthritis and pregnancy
Use of immunosuppressive drugs in pregnancy and lactation
Patient information: A guide to pregnancy

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Institute of Arthritis and Musculoskeletal and Skin Diseases

      (www.niams.nih.gov)

• The Arthritis Foundation

      (www.arthritis.org)

• American College of Rheumatology

      (www.rheumatology.org)

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