Disclosures: Peter H Schur, MD Nothing to disclose. Bonnie L Bermas, MD Nothing to disclose. David S Pisetsky, MD, PhD Consultant/Advisory Boards: Lilly [Lupus]; Pfizer [Lupus]; Genzyme [Anti-DNA]; Isis [Anti-DNA]. Charles J Lockwood, MD, MHCM Nothing to disclose. Monica Ramirez Curtis, MD, MPH Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Systemic lupus erythematosus (SLE) occurs frequently in women of childbearing age. Although patients with SLE are as fertile as women in the general population, their pregnancies may be associated with complications. The prognosis for both mother and child is best when SLE has been quiescent and when renal disease in remission for at least six months prior to the pregnancy Thus, contraception and family planning are particularly important for women with SLE. Maternal health and fetal development should be monitored frequently during pregnancy. If possible, delivery should occur in a controlled setting. In addition, many women with SLE should be followed by an obstetrician knowledgeable in high-risk pregnancies .
Patients with SLE with one or more of the following features should be followed by an obstetrician experienced in management of high risk pregnancies :
●Prior history of poor obstetric outcomes
●Interstitial lung disease
●Evidence of active lupus
●High-dose glucocorticoid therapy
●Antibodies to Ro/La (predisposing to neonatal lupus)
The following characteristics are associated with high maternal and fetal risk :
●Severe pulmonary hypertension (mean pressure >50 mmHg)
●Restrictive lung disease (forced vital capacity <1 liter)
●Chronic renal failure (creatinine >2.8 mg/dL)
●Active renal disease
●History of severe preeclampsia or HELLP syndrome
●Stroke within the previous six months
●Severe lupus flare within the previous six months
If any of the listed high risk factors for poor maternal/fetal outcomes are present, a decision to pursue pregnancy should be carefully considered and made with an awareness of the potentially serious consequences.
Four major issues unique to pregnant patients with SLE and their children are discussed in this review of pregnancy in women with SLE:
●Exacerbation of the disease
●Fetal loss, intrauterine growth retardation, and preterm delivery (often in the setting of antiphospholipid antibodies)
Issues related to menstrual function, menopause, estrogen replacement therapy, and the use of oral contraceptives in women with systemic lupus erythematosus are presented separately. (See "Menstrual function, menopause, and hormonal contraceptives in women with systemic lupus erythematosus".) Issues related to pregnancy in patients with impaired renal function are also presented in more detail elsewhere. (See "Pregnancy in women with underlying renal disease".)
EXACERBATION OF SLE — In the past, exacerbation of SLE occurred in over 50 percent of patients during pregnancy. Flares occurred during all three trimesters with approximately equal frequency and often in the immediate postpartum period. However, the incidence of exacerbation during pregnancy and the postpartum period has been progressively diminishing in the past few decades.
The reduction in rates of SLE flares could be a result of reporting bias, of a difference in the way one defines a flare during pregnancy, or of improved disease control. Some investigators believe that the rate of flares during pregnancy may be similar to the frequency of exacerbation while not pregnant, while other researchers maintain that pregnancy is a time of vulnerability to increased disease activity [3-7]:
●One study prospectively evaluated 40 pregnancies in 37 women with SLE . Flare occurred in 24 (60 percent) of the pregnancies. Comparison of the rates of flare in the same patients after delivery and in nonpregnant patients with SLE showed a significant increase in the rate of flare during pregnancy. Flares presented most commonly as constitutional symptoms, renal disease, or involvement of the skin and joints. Similar findings were found in another prospective study of 68 patients with SLE .
●In contrast, a second case-control study found that lupus flares occurred in similar percentages of pregnant and control patients . In this report, active SLE at study entry was not predictive of flare in either control or pregnant patients, but patients with inactive lupus at presentation were less likely to experience a flare .
The frequency of exacerbation (or persistently active disease) varies with the state of disease activity at conception, ranging from 7 to 33 percent in women who have been in remission for at least six months and from 61 to 67 percent in women who have active disease at the time of conception [9,10]. As noted above, however, it is not clear if these disease flares are due to pregnancy or to spontaneous fluctuations in the course of the disease.
On the other hand, there is general agreement that SLE pregnancy outcomes are more likely to be complicated. In one prospective study, increased rates of hypertension during pregnancy, preterm delivery, unplanned cesarean delivery, postpartum hemorrhage, and maternal venous thromboembolism were all more frequent in women with SLE than others ; fetal growth restriction and neonatal deaths were also more often seen in association with SLE . Disease flares may also occur in association with hormone manipulation for in vitro fertilization [13,14].
RENAL DISEASE — Patients with organ damage at the time of pregnancy may have difficulty since pregnancy imposes an added burden on malfunctioning organs. This phenomenon is particularly important in patients with renal disease.
Lupus nephritis — Pregnancy in women with lupus nephritis is associated with an increased risk of fetal loss (up to 75 percent) and with worsening of the renal and extrarenal manifestations in most [9,10,15] but not all  studies.
Although the incidence is not high, severe renal exacerbations can occur [10,17]. As a result, during preconception counseling women with lupus nephritis should be encouraged to delay pregnancy until the disease can be rendered inactive for at least six months [9,10]. While the risk of adverse effects upon the fetus are minimized if conception and pregnancy occur in the absence of glucocorticoids or other immunosuppressive drugs, it may be preferable in some patients to continue glucocorticoids at the lowest effective dose and/or to cautiously use azathioprine.
Patients with preexisting hypertension, proteinuria, and azotemia are at increased risk for renal exacerbations . The approach to therapy of a flare of lupus nephritis is discussed below. (See 'Treatment recommendations' below.)
Pregnancy following renal transplantation — Women with SLE who have received renal transplants have pregnancy outcomes that are remarkably similar to those of other transplant recipients. This was the conclusion of a study of 38 women with SLE and 274 women who had received renal transplants and who did not have lupus . The course of 60 pregnancies in women with SLE and of 374 pregnancies that occurred in other renal transplant recipients included the following:
●Live births in 77 versus 76 percent of the pregnancies
●Miscarriages and/or still births in 17 versus 16 percent
●Therapeutic terminations of pregnancy in 10 versus 8 percent
The incidence of hypertension, gestational diabetes, and rates of Cesarean delivery were all lower in the patients with SLE than in the other transplant recipients. Prematurity and low birth weight affected many infants of both groups.
Management of pregnancy following renal transplantation is discussed separately. (See "Pregnancy in women with underlying renal disease", section on 'Pregnancy in the renal transplant recipient'.)
Preeclampsia — Preeclampsia is a frequent complication of pregnancy in SLE, occurring in approximately 13 percent of patients . Among women with renal disease, the incidence may be much higher (66 percent in one study) . It is often difficult to distinguish preeclampsia from lupus nephritis or a lupus flare . Furthermore, preeclampsia is more likely to occur in patients with antiphospholipid antibodies (aPL), diabetes mellitus, or a prior episode of preeclampsia . Preexisting thrombocytopenia may also be a risk factor . Preexisting hypertension, though a risk factor for preeclampsia in the general population, was not confirmed as a risk factor in women with SLE in a small retrospective study . (See "Preeclampsia: Clinical features and diagnosis".)
Laboratory testing may be, but is not always, useful in distinguishing preeclampsia from nephritis or a lupus flare:
●Lupus nephritis is often associated with proteinuria and/or an active urine sediment (red and white cells and cellular casts), whereas only proteinuria is seen in preeclampsia.
●Flares of SLE are likely to be associated with hypocomplementemia and increased titers of anti-DNA antibodies; in comparison, complement levels are usually but not always normal or increased in preeclampsia [3,15,24-26].
●Thrombocytopenia, elevated serum levels of liver enzymes and uric acid, and decreased urinary excretion of calcium are more prominent in preeclampsia than lupus nephritis. However, thrombocytopenia may also be seen in association with aPL, thrombotic thrombocytopenic purpura, and immune thrombocytopenia, each of which may complicate pregnancy in women with SLE.
FETAL LOSS — Although fetal losses approaching 50 percent have been noted in pregnant patients with SLE [3,27,28], subsequent studies suggest that pregnancy losses may be decreasing. This was illustrated in a study of published pregnancy outcomes from different time periods .
●1960 to 1965 - The mean rate of fetal loss was 43 percent.
●2000 to 2003 - In one center, the rate was 17 percent.
However, in a multiethnic population with SLE in North America, the rate of fetal losses and stillbirths was reported in 2008 to be 45 percent . The risk of fetal loss is increased in women with hypertension, active lupus , or lupus nephritis [3,8,30] and in those with hypocomplementemia, elevated levels of anti-DNA antibodies, antiphospholipid antibodies, or thrombocytopenia [24,32]. Anti-DNA antibodies may potentiate pregnancy loss by cross reacting with laminin, a molecule critical for placenta implantation .
Role of antiphospholipid antibodies — The principal antiphospholipid antibodies (aPL) measured for clinical purposes are anticardiolipin antibodies (aCL) and lupus anticoagulants (LA). Although the presence of aPL does not necessarily predict fetal loss , patients with SLE and aPL appear to be at increased risk for spontaneous miscarriage compared with those without these autoantibodies. A review of 10 studies of 554 women with SLE found that fetal demise was more common in those with aPL (38 to 59 percent versus 16 to 20 percent in those without such antibodies), LAs (36 versus 13 percent), or aCL (39 versus 18 percent) . Fetal loss typically occurs after 10 weeks gestation . (See "Pregnancy in women with antiphospholipid syndrome".)
It is possible to decrease the risk of fetal loss during subsequent pregnancies in these patients. Thus, all pregnant women with SLE who have had an obstetrical history suggestive of antiphospholipid syndrome (recurrent first trimester pregnancy losses or pregnancy loss after the first trimester) should be tested for the presence of aPL (eg, lupus anticoagulants and aCL). The clinical manifestations, diagnosis, and management of women with aPL who are contemplating pregnancy or who are pregnant are discussed in more detail separately. (See "Pregnancy in women with antiphospholipid syndrome" and "Diagnosis of the antiphospholipid syndrome".)
NEONATAL LUPUS — Neonatal lupus is a passively transferred autoimmune disease that occurs in some babies born to mothers with anti-Ro/SSA and/or anti-La/SSB antibodies; many of these women do not have lupus or other autoimmune disease, although they frequently develop such a disease during follow-up. The most serious complication in the neonate is complete heart block, which occurs in approximately 2 percent of such pregnancies. Isolated skin rash occurs in a similar percentage. The pathogenesis, clinical manifestations, screening, prevention, and treatment of neonatal lupus are discussed in detail separately. (See "Neonatal lupus".)
Neonatal lupus accounts for 90 to 95 percent of cases of heart block occurring in utero or in the neonatal period and for 60 to 90 percent of congenital complete heart block. Once a woman has given birth to an infant with congenital heart block, the recurrence rate of congenital heart block is about 15 percent; another 6 percent have an isolated rash consistent with neonatal lupus. Maternal use of hydroxychloroquine (HCQ) may be associated with reduced rates of the cardiac manifestations in the newborn, including congenital heart block and isolated cardiomyopathy, and maternal HCQ use is also associated with a decreased risk of recurrence of cardiac neonatal lupus in subsequent pregnancies [36,37]. (See "Neonatal lupus", section on 'Preemptive treatment'.)
Women with anti-Ro/SSA and anti-La/SSB may have detectable amounts of these antibodies in breast milk, but there is no evidence that neonatal lupus results from breast feeding .
OTHER CONSEQUENCES OF SLE — SLE does not confer risks for other identifiable congenital abnormalities. Learning disabilities, however, may be more frequent in offspring of SLE mothers, especially in male children .
Patients with SLE have a greater incidence of spontaneous and iatrogenic premature delivery (three times that of patients without SLE). Prematurity and intrauterine growth restriction are associated with glucocorticoid dose, renal complications, hypertension, antiphospholipid antibodies, preeclampsia, or premature rupture of membranes . Severe disease flares were associated with an increased risk of prematurity in one study .
The risk of preterm delivery may be decreasing. A slight decrease in preterm delivery from 1980 to 2002 was noted in a review of published pregnancy outcomes , decreasing from 37.3 to 32 percent. This improvement may be due to the increased recognition and improved treatment of the antiphospholipid syndrome, which can affect many women with SLE.
BREAST FEEDING — Breast feeding is feasible for most women with SLE. However, some medications may enter breast milk. A database of information regarding the use of individual drugs during lactation is provided by the United States Library of Medicine (LactMed drug and lactation data base) . Information available in the database suggests that short-acting NSAIDs, antimalarials, low-dose prednisone (less than 15 to 20 mg/day), warfarin, and heparin are safe for the nursing infant, as little or no active drug is secreted in breast milk.
Limited data are available regarding the safety of biological disease modifying antirheumatic drugs (eg, etanercept, infliximab, adalimumab, rituximab, abatacept) during lactation. However, these agents have high molecular weights, and limited absorption would be expected when these agents are ingested by an infant or child. Published information on these agents is summarized in the LactMed database and is also discussed elsewhere. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
TREATMENT RECOMMENDATIONS — There are two issues related to therapy of women with lupus who become pregnant: monitoring of disease activity in both asymptomatic and symptomatic patients and treatment of active disease.
Monitoring — Mothers should be assessed for disease activity at least once each trimester and more often if they have active lupus. The schedule for monitoring includes:
First visit — At the first visit after (or at which) pregnancy is confirmed, the following investigations are recommended :
●Physical examination, including blood pressure
●Renal function (glomerular filtration rate, urinalysis, urine protein/urine creatinine ratio)
●Complete blood count
●Anti-Ro/SSA and anti-La/SSB antibodies
●Lupus anticoagulant (LA) and anticardiolipin antibody (aCL) assays
●Anti-double stranded DNA antibodies
●Complement (CH50, or C3 and C4)
●Uric acid level
In the absence of any historical features of the antiphospholipid syndrome (APS) (eg, recurrent pregnancy loss, venous or arterial thromboembolism), we recommend that patients with SLE and high levels of aCL or the presence of an LA receive low-dose aspirin therapy, although the data regarding the management of these patients are equivocal. Women with lupus and the APS require more frequent monitoring than those with SLE alone. (See "Pregnancy in women with antiphospholipid syndrome".)
Women who have antibodies to Ro/SSA and/or La/SSB should undergo fetal monitoring for heart block during the time of pregnancy when they are at risk of its development. There is no therapeutic intervention proven to prevent progression, although early detection may improve outcome. The monitoring and management of fetal heart block are reviewed in detail separately. (See "Neonatal lupus", section on 'Treating fetal heart block'.)
Monthly during the first two trimesters — A platelet count (or CBC) is recommended on a monthly basis .
End of each trimester — The following are recommended at the end of each trimester of pregnancy :
●Glomerular filtration rate, urine protein/urine creatinine ratio
●Anticardiolipin antibodies (aCL)
●Complement (CH50 or C3 and C4)
During the last trimester of pregnancy
●In complicated pregnancies (eg, preeclampsia, hypertension, fetal growth restriction, fetal heart block), the fetus should be monitored at least weekly using either the biophysical profile score (see "The fetal biophysical profile") or nonstress test (if no heart block) with amniotic fluid assessment. (See "Nonstress test and contraction stress test".)
●Women who show evidence of increased serologic activity but who remain asymptomatic should be monitored more closely. We do not initiate therapy for serologic findings alone. (See "Pregnancy in women with antiphospholipid syndrome".)
●If fetal growth restriction is noted, then umbilical artery Doppler ultrasonography is recommended to monitor fetal well-being. Information from umbilical artery Doppler ultrasonography helps guide decision making regarding timing of delivery and has been proven to reduce perinatal mortality in this setting. (See "Doppler ultrasound of the umbilical artery for fetal surveillance".)
Postpartum — Some women will experience exacerbations of SLE in the postpartum period. Those who have had active disease at conception and those with significant end-organ damage are at greater risk of disease flares, and they have a poorer prognosis than those who have inactive disease prior to pregnancy . Thus, periodic assessment of disease activity is warranted postpartum. The following laboratory tests are recommended following an uncomplicated delivery :
●Urinalysis, urine protein/urine creatinine ratio
●Renal function if the urinalysis is abnormal
●Complete blood count
●Anti-double stranded DNA (anti-dsDNA)
●Complement (CH50, or C3 and C4)
Treatment of postpartum women with active SLE is the same as that of nonpregnant women. However, women who are breast feeding may have to stop doing so, depending upon which medications are needed. (See 'Breast feeding' above.)
Treating active lupus — Treatment of SLE during pregnancy is associated with some unique problems. Consideration must be given to the following issues:
●Medications used to treat SLE may cross the placenta and cause fetal harm. Thus, the risks and benefits of treatment during pregnancy must be repeatedly weighed against the risk of activity of SLE having a deleterious effect on the mother and the fetus [44,45]. As noted earlier, the use of immunosuppressive drugs during pregnancy is discussed in detail separately. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
●Nephritis in pregnancy requires special consideration because of its potential morbidity and possible confusion with preeclampsia. (See 'Renal disease' above.)
Medication use — Medications that are typically used to treat patients with SLE may be divided into four categories:
●Drugs with a moderate to high risk of fetal harm
●Drugs that may be used selectively during pregnancy
●Drugs with minimal fetal and maternal risk
●Drugs with an unknown level of risk
The most commonly used medications are reviewed briefly below. Other medications and a detailed discussion of the use of specific antiinflammatory and immunosuppressive medications in pregnancy are presented elsewhere. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
Moderate to high risk of fetal harm — Medications with a high risk of causing birth defects should be avoided during conception and pregnancy. These include:
●Mycophenolate mofetil — Mycophenolate should not be used during pregnancy. It is listed as a category D drug (positive evidence of risk) for use in pregnancy by the FDA due to increases in both first trimester pregnancy loss and congenital malformations (table 1). (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Mycophenolate mofetil'.)
Azathioprine can be substituted for mycophenolate prior to and during pregnancy, or, alternatively, glucocorticoids may be used at the lowest dose that controls disease activity. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Azathioprine and 6-MP'.)
●Cyclophosphamide — Cyclophosphamide should not be used during pregnancy, unless there is no alternative available for life-threatening disease affecting the mother. Fetal loss is a likely outcome of cyclophosphamide administration during pregnancy, as a result of cyclophosphamide toxicity, severe disease, or a combination these factors. In one retrospective review of four such pregnancies, there were no live births . (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Cyclophosphamide'.)
●Methotrexate — Methotrexate is teratogenic and should not be used during pregnancy. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Methotrexate'.)
●Warfarin — Warfarin or related anticoagulants are teratogenic when used in early pregnancy. Cautious use after the first trimester has been suggested by some authors . However, these drugs cross the placenta and result in fetal anticoagulation; thus, there is a risk of fetal hemorrhage.
Heparin is generally safe but must be discontinued prior to delivery to reduce the risk of postpartum hemorrhage or of intra- or postoperative bleeding should Cesarean delivery be required.
Selective use allowed during pregnancy — The following drugs are potentially safe during pregnancy, but certain limitations apply to their use. NSAIDs, glucocorticoids, and azathioprine are included in this category. They each have a small risk of causing fetal harm, but their use may be acceptable if needed to control manifestations of SLE during pregnancy. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
●NSAIDs — Use of NSAIDs or aspirin near the time of conception or during early pregnancy can interfere with implantation. Thus, these agents should be avoided during a conception cycle and early pregnancy. An exception would be use of low-dose aspirin, if needed for lupus associated antiphospholipid syndrome (APS). Use of NSAIDs in the third trimester may cause premature closure of the ductus arteriosus and inhibition of labor. Indeed, use of indomethacin is one of several approaches to inhibiting preterm labor, but use of indomethacin or any other NSAID for more than 48 hours should be accompanied by fetal sonographic monitoring for signs of tricuspid regurgitation that could indicate unwanted constriction of the ductus. (See "Pregnancy in women with antiphospholipid syndrome" and "Inhibition of acute preterm labor" and "Spontaneous abortion: Risk factors, etiology, clinical manifestations, and diagnostic evaluation" and "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'NSAIDs and aspirin'.)
●Glucocorticoids — Glucocorticoids are relatively safe to use during pregnancy. Prednisone, prednisolone, and methylprednisolone cross the placenta at very low concentration whereas dexamethasone and betamethasone reach the fetus at higher concentration. Human and animal studies have suggested an increased risk of cleft palate in offspring exposed to glucocorticoids in utero. Maternal and fetal adverse effects of glucocorticoids are discussed in detail separately. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Glucocorticoids'.)
Summarized briefly, they include:
•An increased risk of cleft palate in children
•Premature rupture of membranes
•Intrauterine growth restriction
Steroid side effects in the mother may be reduced by recommending a low salt diet (to prevent weight increase and hypertension), an exercise program (to prevent bone loss and depression), and calcium and vitamin D supplementation (to prevent osteoporosis) .
●Azathioprine — Azathioprine may be used very cautiously. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Azathioprine and 6-MP'.)
●Cyclosporine — Teratogenicity data regarding the use of cyclosporine in humans are derived primarily from organ transplant recipients. When weighed against the risk of rejection, the risk to the fetus is generally judged to be acceptable. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Cyclosporine'.)
Minimal fetal and maternal risk — NSAID use during early and late pregnancy and antimalarial drug use throughout pregnancy are probably safe.
●NSAIDs in late first and in second trimester — NSAIDs are generally safe during the latter part of the first and during the second trimester but should be discontinued in the last trimester of pregnancy. (See 'Selective use allowed during pregnancy' above and "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'NSAIDs and aspirin'.)
●Antimalarial drugs — The safety of use of antimalarial drugs is uncertain. Though there is considerable experience with these drugs for malarial prophylaxis, there has been one report of ocular and ototoxicity in three children in a single family in which the mother had SLE and was taking chloroquine during the pregnancies . However, data from observational studies of the infants of patients with SLE and other rheumatic disorders who received antimalarials during pregnancy suggest that these agents are safe [49-52]. Patients who discontinue hydroxychloroquine prior to, or during, pregnancy are more likely to have exacerbations of SLE . (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Hydroxychloroquine'.)
Among a group of 52 clinicians experienced in treating patients with SLE (median of 75 patients per year) and in participating in the management of pregnancy in such patients (four to five per year per clinician), 69 percent of respondents to a survey reported that they continued antimalarial drugs in at least some patients during pregnancy . A slightly smaller proportion reported advising breast feeding during continued use of these agents postpartum.
Unknown level of risk — Use of biologic antirheumatic drugs such as B cell targeted antibodies (eg, rituximab) and T-B cell costimulation blockers (eg, abatacept) is discouraged in part because of a lack of data on safety of their use during pregnancy. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Unknown risk'.)
Renal disease — Signs of a renal flare include renewed activity of the urine sediment and an increase in the plasma creatinine concentration. In comparison, an isolated elevation in protein excretion is a common, probably hemodynamically mediated finding in all glomerulopathies during pregnancy and should not necessarily be considered a finding of increased lupus activity. (See "Pregnancy in women with underlying renal disease".)
Patients with a significant flare of lupus nephritis should be treated with high-dose prednisone and antihypertensive medication (eg, hydralazine, methyldopa, and calcium channel blockers, but not angiotensin converting enzyme inhibitors or some beta blockers). There is little if any experience with pulse methylprednisolone in pregnancy, and its effects on the fetus are unknown. Cyclophosphamide is contraindicated during pregnancy, but azathioprine can be used cautiously. In addition, the fetus should be delivered as soon as possible [10,44].
Thrombocytopenia — Thrombocytopenia during lupus pregnancies may have multiple causes, including antiplatelet antibodies, toxemia, and antiphospholipid antibodies [44,45]. Treatment includes high-dose prednisone and intravenous immune globulin .
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they 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 patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient information: Systemic lupus erythematosus and pregnancy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The prognosis for both mother and child is best when systemic lupus erythematosus (SLE) has been quiescent for at least six months prior to the pregnancy. Renal disease should be in remission for at least six months prior to conception. Patients should have their disease control maintained by use of medications compatible with pregnancy. Care by an obstetrician experienced in the management of high risk pregnancies is particularly desirable for women with one or more of the following: a history of poor obstetric outcomes, renal or cardiac involvement, pulmonary hypertension, interstitial lung disease, active lupus, high-dose glucocorticoid therapy or use of immunosuppressives, antiphospholipid antibodies/syndrome, antibodies to Ro/La, and multiple gestation. Characteristics associated with high maternal and fetal risk have been identified. (See 'Introduction' above.)
●The incidence of SLE exacerbation with pregnancy, which may occur at any time during the pregnancy or the postpartum period, has progressively decreased in the past few decades, especially in those in remission at the beginning of pregnancy; this improvement may be related to a combination of factors. The frequency of exacerbation (or persistently active disease) is greater in patients with active disease at the time of conception. (See 'Exacerbation of SLE' above.)
●Pregnancy in women with lupus nephritis is associated with an increased risk of fetal loss and with worsening of the renal and extrarenal manifestations of SLE. Pregnancy outcomes following renal transplantation for lupus nephritis are similar to those of other transplant recipients. Preeclampsia is a frequent complication of pregnancy in SLE; the incidence may be higher among women with active renal disease. Laboratory testing is sometimes useful in distinguishing preeclampsia from nephritis or a lupus flare. (See 'Renal disease' above and 'Lupus nephritis' above and 'Pregnancy following renal transplantation' above and 'Preeclampsia' above.)
●The rate of fetal loss is increased in pregnant women with SLE, but it has improved in the past few decades. Risk is increased in women with hypertension, active lupus, or lupus nephritis and in those with hypocomplementemia, increased anti-DNA antibodies, antiphospholipid antibodies, and thrombocytopenia. (See 'Fetal loss' above and 'Role of antiphospholipid antibodies' above.)
●Neonatal lupus is a passively transferred autoimmune disease that occurs in some babies born to mothers with anti-Ro/SSA and/or anti-La/SSB antibodies; many of these women do not have lupus or other autoimmune disease, although they frequently develop such a disease during follow-up. (See 'Neonatal lupus' above and "Neonatal lupus".)
●Maternal SLE is also associated with an increased risk of premature delivery and intrauterine growth restriction. There may be an increased risk of learning disabilities in the offspring, especially in males. (See 'Other consequences of SLE' above.)
●Breast feeding is feasible for most women with SLE. However, some medications may enter breast milk. (See 'Breast feeding' above and "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
●Mothers should be assessed for disease activity at least once each trimester and more often if they have active lupus. The specific testing needed depends upon the stage of pregnancy, the presence of complications (eg, preeclampsia, hypertension, fetal growth restriction, fetal heart block), and the level of disease activity. Periodic assessment of disease activity is also warranted postpartum. (See 'Monitoring' above and 'First visit' above and 'Monthly during the first two trimesters' above and 'End of each trimester' above and 'During the last trimester of pregnancy' above and 'Postpartum' above.)
●Particular attention should be given to several issues in the course of treating SLE during pregnancy, including the relative fetal and maternal risks and benefits of specific medications being used for SLE; the presence and management of nephritis; and the risk of preeclampsia and of antiphospholipid antibodies or thrombocytopenia. (See 'Treating active lupus' above and 'Medication use' above and "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
- Mintz G, Niz J, Gutierrez G, et al. Prospective study of pregnancy in systemic lupus erythematosus. Results of a multidisciplinary approach. J Rheumatol 1986; 13:732.
- Ruiz-Irastorza G, Khamashta MA. Lupus and pregnancy: ten questions and some answers. Lupus 2008; 17:416.
- Lockshin MD. Pregnancy does not cause systemic lupus erythematosus to worsen. Arthritis Rheum 1989; 32:665.
- Petri M, Howard D, Repke J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis Rheum 1991; 34:1538.
- Urowitz MB, Gladman DD, Farewell VT, et al. Lupus and pregnancy studies. Arthritis Rheum 1993; 36:1392.
- Meehan RT, Dorsey JK. Pregnancy among patients with systemic lupus erythematosus receiving immunosuppressive therapy. J Rheumatol 1987; 14:252.
- Lockshin MD, Reinitz E, Druzin ML, et al. Lupus pregnancy. Case-control prospective study demonstrating absence of lupus exacerbation during or after pregnancy. Am J Med 1984; 77:893.
- Ruiz-Irastorza G, Lima F, Alves J, et al. Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies. Br J Rheumatol 1996; 35:133.
- 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.
- Yasmeen S, Wilkins EE, Field NT, et al. Pregnancy outcomes in women with systemic lupus erythematosus. J Matern Fetal Med 2001; 10:91.
- Clowse ME. Lupus activity in pregnancy. Rheum Dis Clin North Am 2007; 33:237.
- Guballa N, Sammaritano L, Schwartzman S, et al. Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum 2000; 43:550.
- Erkan D, Sammaritano L. New insights into pregnancy-related complications in systemic lupus erythematosus. Curr Rheumatol Rep 2003; 5:357.
- Julkunen H, Kaaja R, Palosuo T, et al. Pregnancy in lupus nephropathy. Acta Obstet Gynecol Scand 1993; 72:258.
- Tandon A, Ibañez D, Gladman DD, Urowitz MB. The effect of pregnancy on lupus nephritis. Arthritis Rheum 2004; 50:3941.
- Moroni G, Quaglini S, Banfi G, et al. Pregnancy in lupus nephritis. Am J Kidney Dis 2002; 40:713.
- Kong NC. Pregnancy of a lupus patient--a challenge to the nephrologist. Nephrol Dial Transplant 2006; 21:268.
- McGrory CH, McCloskey LJ, DeHoratius RJ, et al. Pregnancy outcomes in female renal recipients: a comparison of systemic lupus erythematosus with other diagnoses. Am J Transplant 2003; 3:35.
- Nossent HC, Swaak TJ. Systemic lupus erythematosus. VI. Analysis of the interrelationship with pregnancy. J Rheumatol 1990; 17:771.
- Repke JT. Hypertensive disorders of pregnancy. Differentiating preeclampsia from active systemic lupus erythematosus. J Reprod Med 1998; 43:350.
- 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.
- Egerman RS, Ramsey RD, Kao LW, et al. Hypertensive disease in pregnancies complicated by systemic lupus erythematosus. Am J Obstet Gynecol 2005; 193:1676.
- Rothfield NF. SLE: Pitfalls to avoid when managing special problems. J Musculoskel Med 1987; 4:47.
- Buyon JP, Cronstein BN, Morris M, et al. Serum complement values (C3 and C4) to differentiate between systemic lupus activity and pre-eclampsia. Am J Med 1986; 81:194.
- Buyon JP, Tamerius J, Ordorica S, et al. Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy. Arthritis Rheum 1992; 35:55.
- Julkunen H, Jouhikainen T, Kaaja R, et al. Fetal outcome in lupus pregnancy: a retrospective case-control study of 242 pregnancies in 112 patients. Lupus 1993; 2:125.
- Petri M, Allbritton J. Fetal outcome of lupus pregnancy: a retrospective case-control study of the Hopkins Lupus Cohort. J Rheumatol 1993; 20:650.
- 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.
- Andrade R, Sanchez ML, Alarcón GS, et al. Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI) [corrected]. Clin Exp Rheumatol 2008; 26:268.
- Clowse ME, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum 2005; 52:514.
- Clowse ME, Magder LS, Witter F, Petri M. Early risk factors for pregnancy loss in lupus. Obstet Gynecol 2006; 107:293.
- Qureshi F, Yang Y, Jaques SM, et al. Anti-DNA antibodies cross-reacting with laminin inhibit trophoblast attachment and migration: implications for recurrent pregnancy loss in SLE patients. Am J Reprod Immunol 2000; 44:136.
- Melk A, Mueller-Eckhardt G, Polten B, et al. Diagnostic and prognostic significance of anticardiolipin antibodies in patients with recurrent spontaneous abortions. Am J Reprod Immunol 1995; 33:228.
- McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49:193.
- Izmirly PM, Kim MY, Llanos C, et al. Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 2010; 69:1827.
- Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126:76.
- Askanase AD, Miranda-Carus ME, Tang X, et al. The presence of IgG antibodies reactive with components of the SSA/Ro-SSB/La complex in human breast milk: implications in neonatal lupus. Arthritis Rheum 2002; 46:269.
- 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.
- Johnson MJ, Petri M, Witter FR, Repke JT. Evaluation of preterm delivery in a systemic lupus erythematosus pregnancy clinic. Obstet Gynecol 1995; 86:396.
- Drugs and lactation database (LactMed) of the United States National Library of Medicine http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT (Accessed on March 15, 2012).
- Lockshin MD, Sammaritano LR. Lupus pregnancy. Autoimmunity 2003; 36:33.
- Andrade RM, McGwin G Jr, Alarcón GS, et al. Predictors of post-partum damage accrual in systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (XXXVIII). Rheumatology (Oxford) 2006; 45:1380.
- Boumpas DT, Fessler BJ, Austin HA 3rd, et al. Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann Intern Med 1995; 123:42.
- Lockshin MD, Harpel PC, Druzin ML, et al. Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient. Arthritis Rheum 1985; 28:58.
- Clowse ME, Magder L, Petri M. Cyclophosphamide for lupus during pregnancy. Lupus 2005; 14:593.
- Bermas BL, Hill JA. Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 1995; 38:1722.
- Buchanan NM, Toubi E, Khamashta MA, et al. Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases. Ann Rheum Dis 1996; 55:486.
- Al-Herz A, Schulzer M, Esdaile JM. Survey of antimalarial use in lupus pregnancy and lactation. J Rheumatol 2002; 29:700.
- Parke AL, Rothfield NF. Antimalarial drugs in pregnancy--the North American experience. Lupus 1996; 5 Suppl 1:S67.
- Klinger G, Morad Y, Westall CA, et al. Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet 2001; 358:813.
- Costedoat-Chalumeau N, Amoura Z, Duhaut P, et al. Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group. Arthritis Rheum 2003; 48:3207.
- Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006; 54:3640.