Autoimmune disorders complicate pregnancy
Pregnancy and autoimmunity are a potentially hazardous combination. But with the right guidance and therapy, these women can become healthy mothers.
In the past, women with autoimmune diseases were frequently counseled against conceiving. Today, more and more women with a range of autoimmune conditions are enjoying healthy pregnancies. To help guide clinicians toward a happy result with these patients, The Clinical Advisor spoke with experts, Michael Lockshin, MD, professor of medicine and obstetrics-gynecology at the Weill Medical College of Cornell University in New York City, and Laurence Mack, MD, an obstetrician/gynecologist with a special interest in high-risk obstetrics in Massapequa, N.Y. Here is what they had to say.
Q: What are the most common autoimmune disorders affecting women of childbearing age?Dr. Lockshin: Rheumatic diseases, such as lupus and rheumatoid arthritis; thyroid diseases, such as Hashimoto's and Graves; and type 1 diabetes.
Dr. Mack: There are also some rarer diseases clinicians should be aware of, including scleroderma; Sjögren's syndrome; and antiphospholipid antibody syndrome, a condition characterized by the presence of antiphospholipid antibodies in the blood. Though women with this condition don't have active disease, they may develop clotting problems down the road. It's important to note that women who suffer from one autoimmune disease are also at risk for another.
Q: Are there any autoimmune diseases that are likely to be exacerbated during pregnancy? Do any autoimmune diseases remit at that time?Dr. Lockshin: About two thirds of pregnant women with rheumatoid arthritis get better during pregnancy and flare after delivery. Whether or not this happens depends on how different the fetus is from the mother, genetically speaking. The more the fetus resembles the father genetically, the more likely the mother is to go into remission.
In the past, some clinicians believed that patients with lupus flared excessively during pregnancy. But this is controversial; many pregnancy complications, like toxemia, are easily mistaken for lupus.
Q: Are autoimmune diseases ever a contraindication for pregnancy?Dr. Lockshin: Not on the basis of diagnosis—only on the basis of individual issues. In more than 20 years of practice, I've told only two women to avoid pregnancy. One had uncontrollable BP, was taking cyclophosphamide, and was nearing the point of needing dialysis for kidney failure. I didn't think a baby would survive. The other patient had severe heart disease, and I doubted whether she'd be able to withstand pregnancy.
Dr. Mack: We used to counsel women with autoimmune diseases to refrain from having children, but now we discuss the risks and benefits and generally allow patients to make the final decision. That said, patients who've had lupus with a hypertensive flare in a previous pregnancy would probably be contraindicated for another pregnancy. Pregnancy in these women may have serious repercussions. They can lose their sight, have a stroke, or even die.
Q: Why is it riskier for women with autoimmune disease to get pregnant?Dr. Lockshin: There are two big issues: One is potential organ damage. For example, some autoimmune diseases cause kidney disease and high BP. The other issue of potential concern is whether the woman has an autoantibody that could harm the fetus.
Q: Is it more difficult for a woman with autoimmune disease to conceive?Dr. Lockshin: In general, women who are ill have more difficulty conceiving than those who are healthy. Certain types of illness, including thyroid disease, can make conception particularly difficult. Occasionally, a woman has antibodies against ovary or other reproductive-system components that make it less likely she'll conceive. However, it usually is not that difficult for a woman to get pregnant if she is reasonably healthy and hasn't had recent exposure to medication that interferes with conception. The two profoundly significant medications that women with autoimmune disease might be taking are cyclophosphamide, which basically kills the ovaries, and methotrexate, which causes spontaneous abortion.
Q: What maternal health complications commonly occur during each trimester in women with autoimmune disease?Dr. Lockshin: It depends on which organ systems are involved. Kidney disease and heart disease can pose problems throughout pregnancy. Thyroid conditions are generally manageable during each trimester if they're recognized and followed properly. In rheumatic or joint conditions, joint problems can worsen. Women with joint damage often hurt more and have more difficulty as pregnancy progresses. High BP generally emerges later in the pregnancy. There's also the issue of multiple gestation. I have seen very sick women trying to carry a triplet pregnancy. A multiple gestation can put any woman at risk, but for women with an autoimmune disease, it's even more hazardous.
Q: For mothers with autoimmune disease, are there common fetal health implications?Dr. Lockshin: Low birth weight and prematurity are risks anytime a pregnant woman is ill. Oftentimes, kidney disease is the underlying problem. In patients with lupus and rheumatic diseases, there are two dangerous autoantibodies—the antiphospholipid antibody, which can end up killing a fetus (usually in the second trimester), and the anti-Sjögren's syndrome A/anti-Sjögren's syndrome B antibody, which can damage the baby's heart.
Dr. Mack: Antibodies and antigens join to form a floating immune complex, which circulates in maternal blood and can clog the filter of the placenta, causing it to become partially blocked. If the amount of nutrients crossing the fetal membrane decreases, the baby will be smaller. These moms have to be watched—especially in the late second and entire third trimester—for early placental dysfunction. Trouble starts when a woman develops placental vasculitis, an inflammation of the capillaries. WBCs come in and try to clean up the problem, but they heal by scarring. This often leads to cell death within the placenta and decreases placental function. Women with vasculitis are at increased risk of preterm delivery and small-for-gestational-age infants.
Q: What is the likelihood that a fetus will develop its mother's autoimmune condition?Dr. Lockshin: In myasthenia gravis, which is a fairly rare disease, the mother's antibodies can cause transient neonatal myasthenia.
Dr. Mack: A condition known as congenital lupus can be passed from mother to child, but it is a rarity. However, there is an increased likelihood that a fetus will have a genetic predisposition for developing the mother's condition later on as an adult.
Q: How would you advise a patient with autoimmune disease to prepare for pregnancy?Dr. Mack: It's important for any patient with autoimmune disease to find a really good obstetrician before conceiving. These patients should come in for an office visit in advance of pregnancy. The obstetrician should then contact a rheumatologist or specialist and ask for a patient evaluation, stating the patient's intent to become pregnant.
Q: Is the timing of pregnancy a significant factor?Dr. Lockshin: It's best for these patients to become pregnant when they're in remission. Obviously, the healthier they are, the better.
Dr. Mack: Younger is always better. If a woman is at increased risk for clot formation as well as vasculitis and preterm delivery, it is not a good idea to delay childbearing for 10 or 15 years, especially because women older than 35 are already at risk for clot formation.
Q: Are there particular dietary or lifestyle recommendations that can help avert pregnancy problems in women with autoimmune disease?Dr. Lockshin: Women need to be as healthy as possible. We advise diabetics to limit sugar and other carbohydrates, but we don't generally offer specific dietary advice to patients with other autoimmune conditions.
Dr. Mack: Not really. We don't know how the autoimmune system reacts to dietary changes. These patients are told the same things as everyone else—don't gain too much weight, eat a well-balanced diet, and exercise.
Q: Can a woman continue to take medication for an autoimmune condition while pregnant?Dr. Lockshin: When women ask if it's safe to stay on their medications, I say “I don't know,” because there is no information available. Many medications have not been examined in pregnancy because drug companies don't want to give experimental drugs to pregnant women. Often, the only data available are from animals. That said, cyclophosphamide and methotrexate are absolutely forbidden during pregnancy. Additionally, women should not use anti-inflammatory drugs in the latter stages of pregnancy because these agents can damage the baby's heart and kidneys. In early pregnancy, however, these drugs are probably fine. We're quite comfortable prescribing drugs like prednisone. With rheumatic diseases, we frequently prescribe hydroxychloroquine.
Thyroid medications and insulin are also safe. There is some uncertainty about immunosuppressant drugs, but by and large, it is probably better for a woman to continue such medication and not risk a flare than to discontinue it. One of the worst scenarios occurs when a woman finds out she's pregnant and stops her medications cold, only to have the disease explode.
Dr. Mack: We give pregnant women steroids, but we don't like to prescribe high doses except in bursts. The strategy entails giving a burst and getting the autoimmune flare under control. Steroids should not be given on a chronic basis in high doses before 16 weeks' gestation because they can cause congenital anomalies.
Q: From the primary-care clinician's standpoint, how does pregnancy care differ for patients with autoimmune disease?Dr. Lockshin: We generally recommend that these patients be followed in a high-risk clinic. Their care is really disease- and patient-specific. Partnership between the clinician monitoring the disease and the obstetrician/gynecologist is crucial. Physician assistants or nurse practitioners should refer pregnant autoimmune patients to a high-risk obstetrician/gynecologist who is likely to collaborate with a specialist.
Dr. Mack: The typical obstetrician/gynecologist generally refers a patient with autoimmune disease to a maternal fetal-medicine specialist. These patients need a tremendous amount of monitoring, including blood-flow evaluations and sonograms every two weeks during the latter stages of pregnancy. Most should be delivered at 38 weeks.
Q: Are there particular concerns about delivery in a woman with autoimmune disease, and is there a greater likelihood of cesarean delivery?Dr. Lockshin: Certainly. That is one of the reasons these women are under high-risk observation. Occasionally, maternal problems force early cesarean delivery, but most cesareans are performed because of fetal distress. If a patient with rheumatoid arthritis has severe hip disease, we might plan for a cesarean—joints that don't move well (particularly hips) make labor and delivery extremely difficult. Hip joints are part of the mechanism that allows the pelvis to spread. Special precautions must be taken to bring a woman with bilateral hip disease through labor.
Dr. Mack: At 38 weeks, there is a smaller chance than at 40 weeks that the cervix will be ripe and able to undergo successful induction of labor. There is a much greater chance of failed induction, thereby necessitating a cesarean.
Q: Are there postpartum health concerns or recommendations for women with autoimmune disease?Dr. Lockshin: The clinician who is monitoring the patient's primary illness should certainly be actively involved in her postpartum care. Issues will often come up concerning breastfeeding and the resumption, continuation, and changing of medication regimens.
Dr. Mack: Autoimmune diseases can flare. What is necessary, especially following the drop in estrogen levels after delivery, is to remain up to date on the patient's progress and refer her back to her rheumatologist or other specialist when necessary.
Q: Can these patients breastfeed even if they are taking medication?Dr. Lockshin: The safety of breastfeeding depends on many factors. There are medications you don't want mothers to take, but there are also quite a few, including many that are used to treat rheumatic diseases, that are perfectly safe.
Dr. Mack: Unless there are specific contraindications, almost all my autoimmune patients breastfeed if they want. There are really no good studies of breastfeeding in patients with autoimmunity, but antibodies do pass through the nipple. The bottom line is that although it is not really known whether these patients should or should not be breastfeeding, there has not been enough bad news to rule it out. For that reason, it is difficult to recommend against breastfeeding.