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OVERVIEW — Systemic lupus erythematosus (also called lupus or 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 a medication called cyclophosphamide, women with SLE do not appear to have problems with fertility (getting pregnant). However, women with SLE are at higher risk for complications during pregnancy, such as preeclampsia and premature delivery. Additionally, some women with SLE have certain proteins in their blood (called "antiphospholipid antibodies"); the presence of these antibodies increases the risk of miscarriage or stillbirth.
The outcomes for both mother and baby during pregnancy are best when attempting pregnancy is delayed until SLE has been under good control for several months on pregnancy-compatible medications. In particular, kidney disease should be in remission. Working closely with a rheumatologist and obstetrician before and during pregnancy can help reduce the risk of complications and increase the chances of having a healthy pregnancy and delivery.
This topic review discusses the preparation for and care of SLE during pregnancy. A general discussion of SLE is available separately. (See "Patient education: Systemic lupus erythematosus (Beyond the Basics)".)
SYSTEMIC LUPUS ERYTHEMATOSUS AND PREGNANCY — Treatment of systemic lupus erythematosus (SLE) 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 women with SLE who are not pregnant. By contrast, more than 60 percent of women with active SLE at the time of conception will have a flare during pregnancy.
Pregnancy complications — Pregnancy complications that occur more commonly in women with SLE include high blood pressure, preeclampsia, preterm labor, miscarriage, emergency cesarean section, excessive bleeding after delivery, or blood clots in the leg or lung. Each of these is discussed in more detail below.
Infants born to women with SLE have a higher risk of being born prematurely and having a low birth weight.
Preeclampsia — Preeclampsia is the medical term for a pregnancy complication that is characterized by high blood pressure and organ damage in a woman after 20 weeks of pregnancy. It is also called "toxemia." (See "Patient education: Preeclampsia (Beyond the Basics)".)
Preeclampsia occurs in about 15 to 30 percent of women with SLE. It may occur more frequently among women whose SLE is active (causing symptoms) during pregnancy, or in women with kidney disease, antiphospholipid antibodies, diabetes mellitus, or prior episodes of preeclampsia. Given the increased risk of preeclampsia in women with SLE, we recommend taking a daily low-dose aspirin during pregnancy, as this may reduce the risk of preeclampsia.
The only cure for preeclampsia is to deliver the baby. In women who are less than 37 weeks pregnant when preeclampsia develops, delivery can sometimes be delayed if there are no severe features of the disease (eg, very high blood pressure, kidney problems, or symptoms like severe headache, vision problems, abdominal pain, or shortness of breath).
For women who are less than 34 weeks pregnant, doctors sometimes delay delivery for a day or two in order to give treatment with certain types of steroids that speed fetal lung development. These steroids (different from prednisone) are given as injections in two doses 24 hours apart. They significantly reduce the infant's risk of lung complications related to prematurity. However, in some cases (ie, if the mother's or baby's health is at risk), delivery cannot be delayed. (See "Patient education: Preterm labor (Beyond the Basics)".)
Fetal loss — Fetal loss is when a fetus dies after 10 weeks of pregnancy. The risk of fetal loss is increased in women with high blood pressure, active lupus, or lupus nephritis (kidney disease) and in those with certain laboratory abnormalities such as low complement levels, elevated levels of anti-double-stranded DNA (anti-dsDNA) antibodies, antiphospholipid antibodies, and/or a low platelet count.
Women with SLE should be tested for the presence of antiphospholipid antibodies, as higher-than-normal levels of these antibodies may increase the risk of fetal loss (see "Patient education: Antiphospholipid syndrome (Beyond the Basics)"). Daily low-dose aspirin is often recommended for women with SLE who test positive for antiphospholipid antibodies. Some women (who have had pregnancy losses in the past, or are known to have blood clotting issues) require treatment with heparin.
Preterm delivery — Women with SLE have an increased risk of preterm delivery (when the baby is born before 37 weeks of pregnancy). (See "Patient education: Preterm labor (Beyond the Basics)".)
The risk of preterm delivery is increased in women who have more severe SLE, require higher doses of glucocorticoids (steroids) during pregnancy, take certain immunosuppressive medications such as azathioprine and cyclosporine, or have other pregnancy complications. Careful management of SLE during pregnancy can help to decrease the risk of preterm delivery.
Low birthweight infant — Having SLE can increase the risk of a low birthweight baby, especially if the woman requires glucocorticoids; has kidney complications, high blood pressure, antiphospholipid antibodies, or preeclampsia; or experiences prelabor "rupture of membranes" (when the water breaks before contractions have begun).
Kidney disease — Women who have organ damage before pregnancy may have a higher risk of pregnancy complications; this is because pregnancy increases the workload on organs throughout the body. This is particularly true for women with kidney disease.
Lupus nephritis — Women with active lupus nephritis (kidney disease caused by SLE) at the time of pregnancy have an increased risk of fetal loss and worsening of kidney function during pregnancy. Women with preexisting high blood pressure, protein in the urine, or high levels of blood urea nitrogen and/or creatinine (as determined by blood tests) are at the highest risk for these complications.
Pregnancy after kidney transplantation — Women with SLE who have received a kidney transplant have a slightly higher risk of miscarriage compared with women without SLE who have had a kidney transplant, although most go on to have a successful delivery. Of these women, one-half to two-thirds 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 ("c-section").
Lupus and newborns
Neonatal lupus — Neonatal lupus is an autoimmune disease that occurs in about 10 percent of babies born to mothers with certain antibodies called "anti-Ro/SSA" and/or "anti-La/SSB" antibodies. 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 of these infants do not develop SLE in later years. Infants can also develop elevations in their liver enzymes that also resolve within a few months of birth.
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 neonatal lupus 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.
The most serious complication of neonatal lupus is complete heart block, which occurs in approximately 2 percent of newborns whose mothers have anti-Ro/SSA or anti-La/SSB 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 anti-Ro/SSA or anti-La/SSB antibodies often have regular ultrasounds to monitor the fetus's heart during pregnancy. This is generally started at 16 weeks of pregnancy and continues 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 the fetus starts to develop signs of heart block, treatment with dexamethasone, a type of steroid, is often started; however, this treatment is not proven to be effective.
If a mother gives birth to a baby with neonatal lupus, her risk of having another baby with neonatal lupus in a subsequent pregnancy is about 17 percent. (See "Patient education: Systemic lupus erythematosus (Beyond the Basics)" and "Patient education: Sjögren's syndrome (Beyond the Basics)".)
Developmental problems — SLE does not increase the risk of having a child with congenital anomalies. It is uncertain whether learning disabilities are more frequent in children of women with lupus, as studies have yielded conflicting results.
CARE BEFORE PREGNANCY — Women with systemic lupus erythematosus (SLE) who wish to get pregnant should talk with their rheumatologist and a high-risk obstetrical provider before they start trying. Getting the right care before and during pregnancy can help reduce the risk of complications.
General recommendations — These recommendations apply to all women who are considering pregnancy, not just those with SLE.
●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 problem 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 nonprescription medications, these should be reviewed with a health care 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 to 300 mg per day while trying to become pregnant and during pregnancy. The table lists the caffeine content of several common beverages (table 1).
●Blood testing for rubella (German measles), varicella (chicken pox), human immunodeficiency virus (HIV), hepatitis B, and inherited genes (eg, cystic fibrosis) may be recommended.
Preparing for pregnancy with systemic lupus erythematosus
●Women with lupus nephritis (kidney disease related to SLE) are encouraged to delay pregnancy until their disease has been inactive for at least six months.
●Outcomes of pregnancy of women with SLE are better in those women who continue taking hydroxychloroquine during pregnancy.
●The use of glucocorticoids along with other immunosuppressive medications, such as azathioprine and cyclosporine, may increase the risks of having a smaller-than-normal infant or of having preterm premature rupture of membranes (when the water breaks before 37 weeks of pregnancy). Despite this, glucocorticoids 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 problems for a developing baby and should generally be stopped at least three months before getting pregnant. (See 'Medications during pregnancy' below.)
●Certain medications often used to treat SLE are not safe during pregnancy, and should be stopped before conception (see 'Drugs to avoid' below). In particular:
•Men who take cyclophosphamide or thalidomide (a drug sometimes used to treat skin problems related to lupus) should stop these medications for at least three months before trying to get a partner pregnant. This three-month period is necessary to allow for the development of sperm that have not been exposed to these medications.
•Women who take cyclophosphamide or thalidomide should stop these medications for at least three months before trying to get pregnant.
•Women who take methotrexate should wait at least one month, and ideally three months, after stopping this medication before trying to conceive.
•Women who take mycophenolate mofetil should stop this medication six weeks prior to conception.
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 SLE 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. Normal pregnancy discomforts that are similar to those of lupus 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)
●Skin changes (eg, darkening of facial skin)
It is also 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 DURING PREGNANCY — During pregnancy, women with systemic lupus erythematosus (SLE) 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 confirmed, most clinicians recommend that women with SLE 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/or anti-La/SSB antibodies are present. (See 'Fetal loss' above.)
Women with SLE with high levels of antiphospholipid antibodies who have had a prior pregnancy loss or preeclampsia may require treatment with an anticoagulant or "blood thinning" medication (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 SLE will be seen every two to four weeks until 28 weeks of pregnancy. After 28 weeks, the frequency of visits typically increases. (See 'After 28 weeks of pregnancy' below.)
During the pregnancy, blood and urine testing is recommended to monitor the activity of SLE; 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-double stranded DNA (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.
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 to control SLE during pregnancy may need an increased dose, called a "stress dose," during a cesarean section 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 SLE 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 congenital anomalies (problems a baby can be born with) include:
●Mycophenolate mofetil
●Methotrexate – 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.
If you take one of these medications and get 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 SLE during pregnancy.
●NSAIDs – NSAIDs, such as ibuprofen (Advil, Motrin) and naproxen (Aleve), cross the placenta and can potentially cause harm to the fetus after 20 weeks of pregnancy. Women who have trouble becoming pregnant may consider avoiding NSAIDs while trying to become pregnant if disease control is not compromised. NSAIDs may be taken during the second trimester of pregnancy.
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 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 potential benefit of low-dose aspirin in preventing preeclampsia.
●Prednisone – If SLE flares during pregnancy, most experts recommend starting prednisone (a glucocorticoid, or steroid, commonly used in treating SLE) at the lowest dose possible. Prednisone crosses the placenta but appears in only small amounts in the infant's blood.
Glucocorticoids may increase the risk of premature rupture of membranes (breaking the water early) and of growth restriction (having a lower-birthweight infant). They can also increase the risk of pregnancy-induced diabetes and high blood pressure in the mother.
Drugs with unclear risk
●Biologic medications – There are limited data about the safety of biologic agents in pregnancy. Tumor necrosis factor (TNF) inhibitors such as etanercept, adalimumab, and infliximab can be used until week 32 of pregnancy. Biologic agents including rituximab, abatacept, and belimumab may be used up until conception.
Drugs that are safe during pregnancy
●Antimalarial drugs such as hydroxychloroquine do not increase the risk of miscarriage or congenital anomalies at normal doses. These medications are safe to use while breastfeeding. Women with SLE 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.
●Immunosuppressive medications – Azathioprine, cyclosporine, and tacrolimus are considered compatible during pregnancy. There are reassuring data in women who have received organ transplants to suggest that these medications do not increase the risk of fetal anomalies.
CONSIDERATIONS AFTER DELIVERY — Some women will experience a flare of systemic lupus erythematosus (SLE) 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 SLE monitoring are recommended postpartum.
Breastfeeding — Breastfeeding has many benefits for both mother and baby. 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 high-dose aspirin should be avoided.
●Prednisone can be taken. In doses above 20 mg/day, discarding breast milk for the first four hours after taking this medication is recommended.
●Antimalarials, warfarin, and heparin appear to be safe while breastfeeding.
●Azathioprine, cyclosporine, and tacrolimus enter the breast milk in very low concentrations. They may be used in breastfeeding mothers.
●Cyclophosphamide, mycophenolate mofetil, leflunomide, thalidomide, 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.
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: 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 women with SLE; these should be discussed with a 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.
Patient education: Lupus and pregnancy (The Basics)
Patient education: Lupus (The Basics)
Patient education: Lupus and kidney disease (The Basics)
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 (Beyond the Basics)
Patient education: Preterm labor (Beyond the Basics)
Patient education: 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: Health and nutrition during breastfeeding (Beyond the Basics)
Patient education: Long-acting 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.
Clinical manifestations and diagnosis of systemic lupus erythematosus in adults
Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis
Overview of the management and prognosis of systemic lupus erythematosus in adults
Pregnancy in women with systemic lupus erythematosus
Clinical manifestations and diagnosis of systemic lupus erythematosus in adults, section on 'Information for patients'
The following organizations also provide reliable health information.
●National Library of Medicine
(www.medlineplus.gov/healthtopics.html)
●National Institute of Arthritis and Musculoskeletal and Skin Disease
●American College of Rheumatology
●Lupus Foundation of America
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Peter Schur, MD, who contributed to an earlier version of this topic review.
