Managing Lupus in Pregnancy Draws on Evidence, Judgment

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.