Lupus and Pregnancy - Can They Go Together ?

T. Flint Porter, MD MPH and D. Ware Branch, MD
Reprinted from Lupus Foundation of America, Lupus News Volume 20 No 5 Winter 2000

1. How will pregnancy affect my lupus ?
   Introduction.
   Lupus is close to 10 times more common among women than among men, and it is often diagnosed during the childbearing years. Not infrequently, women with lupus are faced with the difficult decision of whether or not to become pregnant. In some cases, lupus can have a negative effect on pregnancy. In others, the course of lupus may be influenced by pregnancy. Although there are some exceptions, the majority of women with lupus can have successful pregnancies and experience the profound reward of having children.
   Naturally, the idea of pregnancy in women with lupus may cause a large amount of anxiety for the patient, her family, and her physician. Women with lupus seeking advice about pregnancy typically have four questions.
   1. How will my pregnancy affect my lupus ?
   2. How will lupus affect me and my baby during pregnancy ?
   3. What lupus treatments are safe during pregnancy ?
   4. How is prenatal care different in women with lupus ?
   In this article, we will answer these questions and, we hope, easy many of the concerns about lupus and pregnancy.

   Lupus flares.
   There is understandable concern about whether or not pregnancy is associated with and increases risk of lupus exacerbation's, more commonly known as flares. This is a difficult question for several reasons. First, determining whether or not a pregnant woman with lupus is having a flare can be difficult because many of the signs and symptoms of flares are also part of normal, uncomplicated pregnancies. These include fatigue and joint discomfort.
   In addition, common complications of pregnancy - for example, preeclampsia, and a hypertensive disorder in pregnancy that may be associated with serious maternal and fetal consequences - may mimic a lupus flare. Reports from the 1950s through the early 1970s suggested that women with lupus were placing themselves at substantial risk for flares during pregnancy. One such study found that the risk of lupus flare was three times greater in the first 20 weeks of pregnancy, and six times greater in the first eight weeks postpartum, than in the eight months prior to conception. Other studies suggested that the rate of pregnancy loss, including stillbirth, among women with lupus was high. Taken together, these concerns led many lupus patients and physicians to the opinion that women with lupus should not become pregnant.
   Fortunately, more recent studies of women with lupus show that the frightening conclusions of these early studies were misleading. More recent studies, which include 300 pregnancies, show that while lupus flares are fairly common during pregnancy - between 15 percent and 65 percent of closely followed women with lupus will have a flare during pregnancy, depending upon how one defines a flare - most flares are mild to moderate in severity and quite manageable. Flares also occur in non-pregnant lupus patients followed over the same period of time, and some studies found no difference in rate of lupus flare when comparing pregnant and non-pregnant women. Furthermore, in studies that used strict criteria for flares ( which would necessarily exclude women who were having normal complaints of pregnancy ), the rate of flares was low ( 13 percent ). It is generally agreed that women with uncontrolled disease activity at the time of conception are more likely to have lupus flares during pregnancy than those lupus in remission.

   Lupus nephritis.
   Women with lupus nephritis ( kidney damage related to lupus ) appear to be at more risk during pregnancy than women without kidney disease. Women with a history of kidney damage may be concerned that pregnancy will worsen renal function and increase the risk of pregnancy - related complications. In particular, there is concern that the risk of preeclampsia, also known as toxaemia, is higher in women with lupus nephritis. Recent studies confirm that pregnancy is more complicated in women with lupus nephritis. However, the majority of women with lupus nephritis have a satisfactory pregnancy outcome. Like uncomplicated lupus, disease activity at the time of conception may be a key factor in predicting outcome. Women with well - controlled lupus nephritis appear to have a lower risk of kidney deterioration during pregnancy. Overall, published case series suggest that no more than 10 percent of women with lupus kidney disease suffer permanent deterioration of their kidney function in association with pregnancy. Serious lupus flare leading to death is rare. Occurring in less that 2 percent of cases reported within the last 30 years.

2. How will lupus affect my pregnancy for me and my baby ?
   Pregnancy Loss.
   Several studies have found that the rate of overall pregnancy loss in women with lupus is between 10 percent and 22 percent ( for comparison, the rate in women without lupus is about 15 percent ). Many of these losses occur as miscarriages before the 12th week from the last menstrual period. However, 5 percent to 10 percent of the pregnancy losses in women with lupus occur in second or third trimesters of pregnancy ( after 13 weeks gestation ). Women with lupus who are at particular risk for pregnancy loss are those who also have another disorder known as antiphospholipid syndrome ( APS ). This syndrome, which can also occur in women without lupus, is associated with a high rate of fetal death unless the patient is treated during pregnancy with heparin, a blood thinner. The diagnosis of APS is made when women have positive tests for antiphospholipid antibodies and a history of recurrent pregnancy loss, stillbirth, or blood clots.
   Three other factors contribute to the rate of pregnancy loss in women with lupus. First, women who have active disease at the time of conception have twice the risk of pregnancy loss as women with controlled disease, again emphasising the need to plan pregnancy during lupus remission. Second, women who have the onset of their lupus during pregnancy experience a loss in about one - third of cases. Finally, women with active lupus nephritis have an increased risk of pregnancy loss.

   Preeclampsia.
   As mentioned previously, this is one of the most common complications in all pregnancies, whether or not women have lupus. Preeclampsia can cause damage to the mother's central nervous system, kidneys, liver and blood. In its most severe forms, women may develop seizures, stroke, kidney failure, liver damage and rupture, serious bleeding disorders, or even die. The cause of preeclampsia remains elusive. As yet, the only known cure is fetal delivery. About one-third of women with lupus develop preeclampsia in some form. Fortunately, most cases are mild and occur late in pregnancy so that delivery represents few serious consequences for mother of baby.
   Some lupus patients are at greater risk for preeclampsia than others. Women with active lupus often require steroids for treatment, and there is evidence that steroid use may increase the rate of preeclampsia. Women with kidney damage from any cause tend to be at risk for preeclampsia, and women with lupus nephritis are no exception. One study reported that 70 percent of women with lupus nephritis developed preeclampsia. Furthermore, it occurred earlier in pregnancy and was more severe than in women without lupus nephritis. Women with antiphospholipid syndrome have a similar risk of early onset, severe preeclampsia.

   Preterm birth.
   About one-third of babies born to mothers with lupus are delivered pre-term - before 37 weeks' gestation. Preterm birth in women with lupus is largely due to obstetric and medical complications which may place mother and/or baby at risk. However, there is some evidence that women with lupus have an increased risk of preterm rupture of membranes which predisposes to preterm birth. One study found that 40 percent of preterm deliveries in women with lupus occurred following preterm rupture of membranes.

   Fetal growth impairment
   ( Babies small for gestational age ) is reported in nearly 25 percent of pregnancies complicated by lupus. The presumed cause for this is poor placental function. Preeclampsia and antiphospholipid syndrome also are linked to poor placental function and fetal growth impairment. Women with lupus nephritis have an increased rate of fetal growth impairment as compared to lupus patients with normal kidney function.

   Neonatal lupus erythematosus ( NLE ).
   Is a rare condition of the fetus and neonate which can affect the skin, heart, and blood. The diagnosis of NLE is confirmed by testing for auto-antibodies associated with the condition, specifically ant-SS-A/Ro and anti-SS-B/La. These antibodies readily cross the placenta and cause immune-mediated damage in fetal tissues. Interestingly, only about half of mothers who deliver an infant with NLE carry the diagnosis of lupus themselves.
   Skin rash the most common type of neonatal lupus is also the most mild and most easily treated type. The rash is similar to the rash of adult lupus. It appears within the first several weeks after deliver and lasts for up to six months before clearing.
   Heart abnormalities associated with NLE are congenital complete heart block ( CCHE ) and endocardial fibroelastosis. These are much less common than the skin rash but certainly more detrimental. CCHB causes a slow fetal heart rate ( bradycardia ) which usually appears between 16 weeks' and 25 weeks' gestation. It can eventually lead to overwhelming fluid accumulation in spaces throughout the fetal body, a condition known as hydrops fetalis, and fetal heart failure.
   In utero treatment has been attempted with steroids and other agents. The current practice is for the mother to receive steroids, which can cross the placenta once the diagnosis of congenital complete heart block due to NLE is made. Steroid treatment does not eliminate the heart block condition, but it does limit further heart damage. This approach is being examined in a registry of cases by Dr. Jill P. Buyon, at the Hospital for Joint Diseases in New York City. Because CCHB is permanent, a pacemaker may have to be implanted in the baby to ensure survival.
   The blood abnormalities of neonatal lupus are less well established but may include anaemia and deficiencies in other blood components.
   Among all mothers with lupus, the risk of NLE is less than 5 percent. It the anti-SSA/Ro antibody is present, the risk of neonatal lupus with only skin lesion is about 15 percent, and the risk of CCHB is very low. The most important risk factor is a history of a previous affected foetus; the recurrence is approximate 25 percent for skin lesions and 10 percent to 15 percent for congenital complete heart block.

3. What lupus treatments are safe during pregnancy ?

   Glucocorticoids, commonly referred to as steroids, form the mainstay of treatment for lupus during pregnancy. In general, the doses of glucocorticoids used in pregnancy are similar to those used in non-pregnant patients. Prednisone, the most common type used is converted to a relatively inactive form by the placenta. This protects the foetus from adrenal suppression and results in a very low risk for birth defects. Other glucocorticoids are not easily made inactive by the placenta, and so should not be administered chronically during pregnancy.
   There are several adverse side effects to glucocorticoids including weight gain, stretch marks, acne, hair growth, suppression of the immune system, bone damage, and stomach ulcers in the mother. The combination of pregnancy and glucocorticoids likely increases the possibility of maternal diabetes during pregnancy. There is also is some evidence that long-term glucocorticoid use, especially at higher doses, adds to the likelihood of preeclampsia and fetal growth impairment. Because of these risks, it is recommended that glucocorticoids by given only to treat the symptoms of lupus.

   Cytotoxic drugs. Three immunosuppressive drugs - azathioprine, methotrexate, and cyclophosphamide - are used in the treatment of lupus outside of pregnancy. Limited data suggests that azathioprine does not cause birth defects in humans, but is associates with fetal growth impairment and impaired neonatal immunity. Ideally, patients should not be treated with azathioprine during pregnancy unless the benefits clearly outweigh the risks.
   Methotrexate and cyclophosphamide have been associated with birth defects in humans. They should be avoided completely during the first trimester and used only in unusual circumstances thereafter.
   Anti-malarial drug such as chloroquine and hydroxychloroquine ( Plaquenil ) cross the placenta and have been reported to cause fetal eye and ear abnormalities. However, most infants born to women taking these drugs during pregnancy appear normal suggesting that these risks are small.

   Non-steroid drugs. The most common types of analgesics ( pain relievers ) used in lupus are non-steroidal anti-inflammatory drugs ( NSAIDs ). Unfortunately, these readily cross the placenta and may cause serious fetal and neonatal side effects, the most common of which is kidney dysfunction. In addition they may be associated with disruption of fetal circulation with serious consequences. Given these risks full-dose aspirin and NSAIDs should be avoided in pregnancy especially after the first trimester. Acetaminophen and codeine should be used as alternatives for pain relief.

4. How is prenatal care different in women with lupus ?
   Prepregnancy.
   A woman with lupus who is considering pregnancy should discuss the problems addressed above with her obstetrician and rheumatologist. Ideally, she should be in remission, and should discontinue cytotoxic drugs and NSAIDs prior to conception. She should also be tested prior to pregnancy for evidence of anaemia or thrombocytopenia, underlying kidney disease, antiphospholipid antibodies, and anti-Ro/SSA and anti-La/SSB antibodies.

   Prenatal.
   Once pregnant, the patient with lupus should be seen by a physician at least every two weeks in the first and second trimesters, and every week thereafter. She should be questioned about signs or symptoms of lupus activity and have her urine examined for evidence of blood or protein. She should notify her physician immediately if she develops a sign of lupus flare between visits. Frequent blood draws are unnecessary as long as she remains asymptomatic. After 20 weeks' gestation, the physician and patient should be alert for the development of preeclampsia and fetal growth impairment. Fetal ultrasonography should be performed every 4 - 6 weeks starting at 18 - 20 weeks' gestation. Fetal surveillance ( daily fetal movement counts and periodic fetal testing ) should begin at 30 - 32 weeks' gestation. Earlier and more frequent fetal assessment is necessary in patients with lupus flare, lupus nephritis, hypertension, proteinuria, clinical evidence of fetal growth impairment, or antiphospholipid syndrome.

   Labour and delivery.
   The careful watch for lupus flare, preeclampsia and fetal impairment should be continued during labour and delivery. Labour and delivery and caesarean section normally result in the production of natural steroids from the adrenal gland. However, women who have received glucocorticoid medication within the last year may not respond appropriately, and extra "stress doses" of glucocorticoids should be given. Preeclampsia and fetal growth impairment are common obstetric concerns, and their management is not specifically altered because of the lupus. Neonatology support may be needed at delivery if neonatal lupus is suspected.

   Postnatal.
   Traditionally, the postpartum period was felt to be a time of particular risk for lupus flare. Recent data indicates that flares are just as likely in the first and second, and third trimesters as they are postpartum. There should be careful vigilance for the development of lupus flares postpartum and they should be treated in the same manner as in the non-pregnant state. Maintenance medications should be restarted immediately following delivery; at similar doses as during the pregnancy. Further medication adjustments can be handled in the outpatient settings.

1. Disease activity at the time of conception can adversely impact pregnancy outcome and the risk of lupus flare. Women with lupus who are considering pregnancy should achieve the best possible control of the disease prior to attempting conception.
2. Women with lupus nephritis must carefully weigh their reproductive needs against the modest increased risk that pregnancy might pose to their health. While the risk today is lower than reported in the past, permanent kidney damage may develop during pregnancy.
3. Women with antiphospholipid syndrome are at substantial risk for pregnancy loss, especially in the second and third trimesters. Treatment with heparin ( usually along with low-dose aspirin ) improves pregnancy outcome.

Disclaimer :
The Lupus Group of WA ( Inc ) does not recommend or endorse any products, drugs, treatments, procedures, medical or health professional in this article. We suggest you discuss this information with your doctor or specialist.