Patient education: Systemic lupus erythematosus and pregnancy (Beyond the Basics)
- Bonnie L Bermas, MD
Bonnie L Bermas, MD
- Associate Professor of Medicine
- Harvard Medical School
SYSTEMIC LUPUS ERYTHEMATOSUS OVERVIEW
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect various organs of the body. With the exception of women who have had prior treatment with cyclophosphamide, women with systemic lupus erythematosus do not appear to have reduced fertility. Women with lupus are at higher risk for pregnancy complications such as preeclampsia and premature delivery, and those with antiphospholipid antibodies have an increased risk of miscarriage and stillbirths. The outcomes for both mother and child are best when systemic lupus erythematosus has been under good control for at least six months before pregnancy and when kidney disease is in remission.
This topic review discusses the preparation for and care of systemic lupus erythematosus during pregnancy. Other topics about lupus are available separately. (See "Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)".)
SYSTEMIC LUPUS ERYTHEMATOSUS AND PREGNANCY
Treatment of systemic lupus erythematosus has become more successful over the past few decades, making pregnancy a viable option for most women with this disorder. Seven to 33 percent of women whose disease has been in remission for at least six months prior to pregnancy will experience a flare of lupus symptoms during pregnancy. This flare rate is comparable to the flare rate of non-pregnant women. By contrast, more than 60 percent of women with active systemic lupus erythematosus at the time of conception will have a flare during pregnancy. Women undergoing in vitro fertilization may also have an increased risk of a disease flare during ovulation induction [1,2]. (See "Pregnancy in women with systemic lupus erythematosus".)
Pregnancy complications — Pregnancy complications that occur more commonly in women with systemic lupus erythematosus include high blood pressure, preeclampsia, preterm delivery, emergent Cesarean section, excessive bleeding after delivery, or blood clots in the leg or lung. There is a higher incidence of miscarriage and fetal loss, especially in women with coexisting antiphospholipid syndrome. Infants born to women with systemic lupus erythematosus have a higher risk of being born prematurely and having a low birthweight.
Preeclampsia — Preeclampsia is the medical term for a pregnancy complication that causes high blood pressure in the mother after 24 weeks of pregnancy. Another name for preeclampsia is toxemia. Preeclampsia occurs in up to 20 percent of women with systemic lupus erythematosus. It may occur even more frequently among women with kidney disease, antiphospholipid antibodies, diabetes mellitus, or prior episodes of preeclampsia (66 percent in one study) .
The treatment of preeclampsia is for the woman to deliver her infant. Delivery may be delayed for a day or two in some women with preeclampsia who are less than 34 weeks pregnant in order to give treatment with certain steroids that speed fetal lung development. The steroids are given in two doses 24 hours apart. This treatment significantly reduces the infant’s risk of lung complications related to prematurity. However, delivery should not be delayed if the mother or infant’s life is in danger. (See "Patient education: Preterm labor (Beyond the Basics)".)
Fetal loss — Fetal loss is defined as the death of a fetus after 10 weeks of pregnancy. The risk of fetal loss is increased in women with high blood pressure, active lupus, or lupus nephritis and in those with low complement levels, elevated levels of anti-DNA antibodies, antiphospholipid antibodies (including anticardiolipin antibodies and lupus anticoagulants), or a low platelet count. In one center, approximately 17 percent of women with systemic lupus erythematosus had a fetal loss .
Women with systemic lupus erythematosus should be tested for the presence of antiphospholipid antibodies (eg, lupus anticoagulants and anticardiolipin antibodies). Women with persistent medium or high titers of these antibodies may be at increased risk of fetal loss or other complications. Treatment with low-dose aspirin is often recommended for women with systemic lupus erythematosus who test positive for antiphospholipid antibodies. However, treatment with heparin is generally reserved for those patients with documented prior pregnancy losses or clotting issues.
Preterm delivery — Patients with systemic lupus erythematosus have an increased risk of preterm delivery. Preterm delivery is defined as delivery before 37 weeks of pregnancy. (See "Patient education: Preterm labor (Beyond the Basics)".)
The risk of delivering before term is increased in women with more severe systemic lupus erythematosus, those who require higher doses of glucocorticoids (eg, steroids) during pregnancy, women on certain immunosuppressive medications such as azathioprine and cyclosporine, and women with other pregnancy complications. Careful management of systemic lupus erythematosus during pregnancy can help to decrease the risk of preterm delivery.
Low birthweight infant — Having systemic lupus erythematosus can increase the risk of a low birthweight baby, especially if the woman requires glucocorticoids (steroids); has kidney complications, high blood pressure, antiphospholipid antibodies, or preeclampsia; or experiences premature rupture of membranes (when the water breaks before contractions have begun).
Kidney disease — Women who have damaged organs before pregnancy may have a higher risk of pregnancy complications, because pregnancy increases the workload on organs throughout the body. This is particularly important in women with kidney disease.
Lupus nephritis — Women with active lupus nephritis at the time of pregnancy have an increased risk of fetal loss (up to 75 percent) and worsening of their kidney function during pregnancy. Women with preexisting high blood pressure, protein in the urine, or high levels of blood urea nitrogen and/or creatinine in their blood are at the highest risk for these complications.
Pregnancy after kidney transplantation — Women with systemic lupus erythematosus who have received a kidney transplant have a slightly higher risk of miscarriage compared with women without systemic lupus erythematosus and a kidney transplant, although approximately 77 percent of women go on to deliver a live infant. One-half to two-thirds of these women have a preterm delivery or a low birthweight baby, and there is an increased risk of developing high blood pressure or gestational diabetes during pregnancy or of requiring a Cesarean delivery.
Lupus and newborns
Neonatal lupus — Neonatal lupus is an autoimmune disease that occurs in about 10 percent of babies born to mothers with anti-Ro/SSA and/or anti-La/SSB antibodies. Neonatal lupus is caused by passage of the anti-Ro/SSA and/or anti-La/SSB antibodies from the mother’s bloodstream across the placenta to the developing baby after about the 20th week of pregnancy. Many women who give birth to a baby with the neonatal lupus syndrome have anti-Ro/SSA or anti-La/SSB antibodies but do not have a diagnosis of lupus or another autoimmune disease at the time of their pregnancy.
Signs of neonatal lupus include a red, raised rash on the scalp and around the eyes. The rash almost always resolves by six to eight months of age because the antibodies are cleared out of the infant’s bloodstream; most (90 percent) of these infants do not develop lupus in later years. Infants can also develop elevations in their liver enzymes that also resolve within a few months of birth.
The most serious complication of neonatal lupus is complete heart block, which occurs in approximately 2 percent of newborns whose mothers have SSA (Ro) or SSB (La) antibodies. Heart block occurs when there is partial or complete blockage of electrical flow in the fetus’s heart, causing an abnormally slow heart rate. Women with SSA (Ro) or SSB (La) antibodies often have regular ultrasound monitoring of the fetus’s heart during pregnancy. Ultrasound monitoring of the fetus’s heart is generally started at 16 weeks of pregnancy and is continued until the 26th week of pregnancy. The goal is to detect fetal heart block at an early stage so that the fetus can be monitored frequently to assure that the heart is functioning well and to be able to prepare the fetus for a pacemaker if it is needed when born. There is no proven treatment for fetal heart block prior to birth, although some preliminary studies suggest that women with these antibodies who are taking hydroxychloroquine during pregnancy have a lower risk of these complications.
If a mother gives birth to a baby with neonatal lupus, her risk of having a child with neonatal lupus in a subsequent pregnancy is about 17 percent. (See "Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)" and "Patient education: Sjögren’s syndrome (Beyond the Basics)".)
Birth defects and learning disabilities — Systemic lupus erythematosus does not increase the risk of having a child with birth defects. It is uncertain whether learning disabilities are more frequent in children of women with lupus, as they have been found to be more frequent in one research study but not in another .
CARE BEFORE PREGNANCY
Women with systemic lupus erythematosus should discuss their desire to have a child with a rheumatologist and a high-risk obstetrical provider before trying to become pregnant.
General recommendations — These recommendations apply to all women who are considering pregnancy, not just those with systemic lupus erythematosus.
●All women should take a nutritional supplement containing at least 400 mcg of folic acid (the amount in most multivitamins). Taking folic acid can reduce the risk of a specific birth defect called a neural tube defect. Folic acid should be started before trying to conceive and should be continued until at least the end of the first trimester.
●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 who is knowledgeable in the care of pregnant women with lupus, such as an obstetrician, an obstetric nurse practitioner, or a midwife. Some medications are safe during pregnancy, while others are not. In some cases, an alternate medication can be substituted for an unsafe drug. (See 'Medications during pregnancy' below.)
●Caffeine intake should be limited to less than 200 mg per day while trying to become pregnant and during pregnancy. The table lists the caffeine content of several common beverages (table 1). (See "The effects of caffeine on reproductive outcomes in women".)
●Blood testing for rubella (German measles), varicella (chicken pox), HIV, hepatitis B, and inherited genes (eg, cystic fibrosis) may be recommended.
Preparing for pregnancy with systemic lupus erythematosus
●Women with lupus nephritis are encouraged to delay pregnancy until their disease is inactive for at least six months [6,7].
●Outcomes of pregnancy of women with systemic lupus erythematosus are better in those women who continue hydroxychloroquine during pregnancy. Therefore, women with lupus should be encouraged to continue this medication during pregnancy.
●The use of glucocorticoids (steroids) along with other immunosuppressive medications, such as azathioprine and cyclosporine, may increase the risks of having a small infant or of having preterm premature rupture of membranes (when the water breaks before 37 weeks of pregnancy). In addition, use of glucocorticoids (steroids) during the first trimester may increase the risk of cleft palate. Despite this, glucocorticoids (steroids) may need to be continued to manage the disease (see 'Medications during pregnancy' below). This decision is best made with an experienced rheumatologist and/or obstetrical care provider.
●Other medications can also cause birth defects and should generally be stopped at least three months before getting pregnant. (See 'Medications during pregnancy' below.)
●Men who take methotrexate, mycophenolate mofetil, or cyclophosphamide should stop these medications for at least three months before trying to conceive. This three-month period is necessary to allow for the development of sperm that have not been exposed to these medications. Women who take these medications should wait at least one to three months after stopping these medications before trying to conceive.
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 systemic lupus erythematosus often have a flare of symptoms during pregnancy or shortly after delivery. It is sometimes difficult to distinguish between the common discomforts of pregnancy and the symptoms of lupus. Pregnancy discomforts that are similar to those of lupus include the following:
●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)
●Skin changes (eg, darkening of facial skin)
It is important to consider the changes that a newborn may bring, including interrupted sleep, fatigue, and, for many women, additional stress. Close communication with an obstetric and rheumatology care provider and support from family and friends can help to ease the challenges of being pregnant and of raising a child.
TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS DURING PREGNANCY
During pregnancy, women with systemic lupus erythematosus need regular monitoring of their disease, even if it has been stable, and many women will need treatment of active disease. Care of women with lupus is usually shared during pregnancy between a rheumatologist and a high-risk obstetrician.
Care during pregnancy
The first visit — As soon as pregnancy is detected, most clinicians recommend that women with systemic lupus erythematosus have a complete physical examination, including measurement of blood pressure and blood testing. The blood tests are important to measure kidney function and to determine if antiphospholipid, anti-Ro/SSA, and anti-La/SSB antibodies are present. (See 'Fetal loss' above.)
Women with systemic lupus erythematosus with high levels of antiphospholipid antibodies who have had a prior pregnancy loss or preeclampsia may require treatment with an anticoagulant (eg, a low dose of aspirin and/or heparin) during pregnancy, depending upon their individual situation. This treatment helps to reduce the risk of blood clots and miscarriage.
To monitor the fetus’s growth during pregnancy, it is important to have an accurate date of conception. Women who do not remember the date of their last menstrual period or who 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.
At subsequent visits — Most women with systemic lupus erythematosus will be seen every two to four weeks until 28 weeks of pregnancy.
During the pregnancy, blood and urine testing is recommended to monitor the activity of systemic lupus erythematosus; the frequency of testing depends upon the individual patient. This usually includes measurement of the kidney function (glomerular filtration rate, urine protein/urine creatinine ratio), testing for antiphospholipid antibodies (if testing previously negative), testing of complement levels (CH50 or C3 and C4), and testing for anti-dsDNA antibodies. After 10 to 12 weeks of pregnancy, the fetus’s heart rate will be measured.
An ultrasound is usually recommended between 18 and 20 weeks of pregnancy to ensure that the fetus is growing and developing normally. Regular ultrasounds may be recommended through the remainder of the pregnancy to monitor the fetus’s growth.
After 28 weeks of pregnancy — After 28 weeks of pregnancy, most women will be seen every one or two weeks. At these visits, the woman’s blood pressure and urine will be monitored. Fetal monitoring may include a biophysical profile and nonstress testing.
●Biophysical profile – A biophysical profile (BPP) score is calculated to assess the fetus’s health. It consists of five components, including nonstress testing and ultrasound measurement of four fetal parameters: fetal body movements, breathing movements, fetal tone (flexion and extension of an arm, leg, or the spine), and measurement of the amniotic fluid levels. Each component is scored individually, with two points given for a normal result and zero points given for an abnormal result. The maximum possible score is 10.
The amniotic fluid level is an important variable in the BPP because a low volume (called oligohydramnios) may increase the risk of umbilical cord compression and may be a sign of changes in the blood flow between the baby and mother. Amniotic fluid levels can become reduced within a short time period, even a few days.
●Nonstress testing – Nonstress testing is done by monitoring the baby’s heart rate with a small device that is placed on the mother’s abdomen. The device uses sound waves (ultrasound) to measure the baby’s heart rate over time, usually for 20 to 30 minutes. Normally, the baby’s baseline heart rate should be between 110 and 160 beats per minute and should increase above its baseline by at least 15 beats per minute for 15 seconds when the baby moves.
The test is considered reassuring (called “reactive”) if two or more fetal heart rate increases are seen within a 20-minute period. Further testing may be needed if these increases are not observed after monitoring for 40 minutes.
Delivery — Women who have required glucocorticoids (steroids) to control systemic lupus erythematosus during pregnancy need an increased dose, called a stress dose, during delivery. The increased dose helps the body respond normally to the physical stresses of childbirth.
Most women with lupus are able to have an uncomplicated vaginal delivery. However, since there is an increased risk of premature rupture of the membranes, of a small infant, and of preeclampsia, women with lupus are advised to deliver in a hospital with a neonatal intensive care unit (NICU).
Medications during pregnancy — Medications that are typically used to treat systemic lupus erythematosus 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.
Drugs to avoid — Medications that should be avoided during pregnancy because of the risk of birth defects include:
●Methotrexate – Men and women who take methotrexate should stop one to three months before trying to conceive. This three-month period is necessary to completely eliminate methotrexate from the body.
●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.
If you take one of these medications and become pregnant, talk to your doctor immediately.
Drugs with a small risk of harm — Nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, prednisone, and azathioprine have a small risk of causing fetal harm; their use may be acceptable if necessary to control systemic lupus erythematosus during pregnancy.
●NSAIDs – NSAIDs, such as ibuprofen (Advil, Motrin) and naproxen (Aleve), cross the placenta and can potentially cause harm to the fetus, especially during the third trimester (after 30 weeks of pregnancy). Women who have trouble becoming pregnant should avoid NSAIDs while trying to become pregnant because NSAIDs may interfere with ovulation and embryo implantation.
A safe alternative to NSAIDs for treatment of pain during pregnancy is acetaminophen (Tylenol). A safe dose of acetaminophen is two 325 mg tablets or capsules every four to six hours as needed. No more than 3000 mg of acetaminophen should be taken per day.
●Aspirin – Aspirin crosses the placenta. Low-dose aspirin (less than 160 mg/day) has been used safely in the treatment of pregnant women with the antiphospholipid syndrome. However, increased rates of stillbirth have been reported with aspirin doses greater than 325 mg/day. Women should speak with their obstetric or rheumatology care provider about the risks and benefits of taking aspirin during pregnancy.
●Prednisone – If systemic lupus erythematosus flares during pregnancy, most experts recommend starting prednisone at the lowest dose possible. Prednisone crosses the placenta but appears in only small amounts in the infant’s blood.
•Glucocorticoid (steroids) 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).
•Glucocorticoids (steroids) may increase the risk of premature rupture of membranes (breaking the water early) and of growth restriction (having a lower birthweight infant).
●Azathioprine – There are conflicting data about the safety of azathioprine during pregnancy , although much of the research that has been done in patients who have received organ transplants suggests that this medication does not increase the risk of fetal anomalies. For this reason, use of azathioprine is generally limited to women who require ongoing immunosuppression during pregnancy.
Drugs that are safe during pregnancy
●Antimalarial drugs – There is no evidence that antimalarial drugs, such as hydroxychloroquine, increase the risk of miscarriage or birth defects at normal doses. These medications are safe to use while breastfeeding. Women with systemic lupus erythematosus should be encouraged to continue their antimalarial drugs during pregnancy as they may decrease the risk of flares, help manage the antiphospholipid syndrome, and possibly decrease the risk of neonatal lupus.
SYSTEMIC LUPUS ERYTHEMATOSUS AFTER DELIVERY
Some women will experience a flare of systemic lupus erythematosus after delivery. Women who have had active disease in early pregnancy and those with significant organ damage are at greater risk of disease flares. Thus, regular visits for systemic lupus erythematosus monitoring are recommended postpartum.
Breastfeeding — Breastfeeding is recommended for most women with systemic lupus erythematosus. There is no increased risk of neonatal lupus related to breastfeeding. However, some medications enter breast milk:
●Nonsteroidal antiinflammatory drugs (NSAIDs) can be used, but aspirin should be avoided.
●Prednisone can be taken in low doses under 20 mg/day.
●Antimalarials, warfarin, and heparin appear to be safe while breastfeeding.
●Azathioprine and cyclosporine enter the breast milk in very low concentrations. While, in general, we recommend discontinuing these medications during nursing, their continued use can be considered on a case-by-case basis if necessary.
●Cyclophosphamide and methotrexate 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 education: Deciding to breastfeed (Beyond the Basics)" and "Patient education: Common breastfeeding problems (Beyond the Basics)" and "Patient education: Pumping breast milk (Beyond the Basics)" and "Patient education: Maternal health and nutrition during breastfeeding (Beyond the Basics)".)
Birth control — 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 for patients with lupus which should be discussed with your gynecologist and rheumatologist.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Systemic lupus erythematosus (SLE) (Beyond the Basics)
Patient education: Preterm labor (Beyond the Basics)
Patient education: The antiphospholipid syndrome (Beyond the Basics)
Patient education: Sjögren’s syndrome (Beyond the Basics)
Patient education: Deciding to breastfeed (Beyond the Basics)
Patient education: Common breastfeeding problems (Beyond the Basics)
Patient education: Pumping breast milk (Beyond the Basics)
Patient education: Maternal health and nutrition during breastfeeding (Beyond the Basics)
Patient education: Long-term methods of birth control (Beyond the Basics)
Patient education: Birth control; which method is right for me? (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Diagnosis and differential diagnosis of systemic lupus erythematosus in adults
Overview of the clinical manifestations of systemic lupus erythematosus in adults
Overview of the management and prognosis of systemic lupus erythematosus in adults
Pregnancy in women with systemic lupus erythematosus
The following organizations also provide reliable health information.
●National Library of Medicine
●National Institute of Arthritis and Musculoskeletal and Skin Disease
●American College of Rheumatology
●Lupus Foundation of America
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- Erkan D, Sammaritano L. New insights into pregnancy-related complications in systemic lupus erythematosus. Curr Rheumatol Rep 2003; 5:357.
- Repke JT. Hypertensive disorders of pregnancy. Differentiating preeclampsia from active systemic lupus erythematosus. J Reprod Med 1998; 43:350.
- Clark CA, Spitzer KA, Laskin CA. Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period. J Rheumatol 2005; 32:1709.
- Ross G, Sammaritano L, Nass R, Lockshin M. Effects of mothers' autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatr Adolesc Med 2003; 157:397.
- Hayslett JP. Maternal and fetal complications in pregnant women with systemic lupus erythematosus. Am J Kidney Dis 1991; 17:123.
- Bobrie G, Liote F, Houillier P, et al. Pregnancy in lupus nephritis and related disorders. Am J Kidney Dis 1987; 9:339.
- Nørgård B, Pedersen L, Christensen LA, Sørensen HT. Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish nationwide cohort study. Am J Gastroenterol 2007; 102:1406.
- Sammaritano LR. Therapy insight: guidelines for selection of contraception in women with rheumatic diseases. Nat Clin Pract Rheumatol 2007; 3:273.
- Tandon A, Ibañez D, Gladman DD, Urowitz MB. The effect of pregnancy on lupus nephritis. Arthritis Rheum 2004; 50:3941.
- Chakravarty EF, Colón I, Langen ES, et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol 2005; 192:1897.
- Clowse ME, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol 2006; 107:293.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.