Pregnancy in Rheumatic Disease Patients
All rheumatologists should be generally familiar with commonly used rheumatic medications in pregnancy. Risk of anti-inflammatory medications is unknown, and so we usually avoid them, especially late in the pregnancy because of concerns about premature closure of the ductus arteriosus. Prednisolone or methylprednisolone is generally used for maternal corticosteroid effect: there is very little placental transfer, although there is a very small risk of oral cleft with first-trimester exposure. Fluorinated corticosteroids pass easily through the placenta and are reserved for fetal treatment effect. Methotrexate is contraindicated, and patients should be off the medication for 3 months before conception. Cyclophosphamide is contraindicated, although it has been rarely used in late pregnancy. Azathioprine is labeled a pregnancy category D drug but is used frequently in clinical practice: it is generally the immunosuppressive of choice during pregnancy. Cyclosporine is also used, more often in transplant patients and less frequently by rheumatologists; it is considered to be a safe alternative, despite risk of hypertension and renal problems. Mycophenolate should not be used during pregnancy. Pregnancy effects of TNF inhibitors are still unknown, but the data are reassuring. The placental transfer of immunoglobulins does not become significant until 16 weeks' gestation, so it seems reasonable to treat at least until the time pregnancy is confirmed. For the RA patient on methotrexate and TNF inhibitors, it is reasonable to stop the methotrexate 3 months before trying to conceive but to continue the TNF inhibitor until they conceive because that can take an unpredictable amount of time. For patients on leflunomide, pregnancy should only be attempted after a washout of the drug with cholestyramine and documentation of absent serum levels of metabolites following the washout procedure. If a patient conceives while on leflunomide, the washout procedure should be performed as soon as possible. Even with early washout, risk of teratogenicity is uncertain, although a recent report suggests it is lower than previously estimated: patients in this situation may be referred to a geneticist who can best define the degree of risk to the fetus. Sulfasalazine is considered safe, but it is prudent to treat with folate supplementation to minimize risk of neural tube defects during pregnancy. There are recent data on the increasing use and benefits of hydroxychloroquine for lupus pregnancy outcome including reduced risk of heart block. Amniocentesis has been suggested to rule out chromosomal abnormalities in patients treated with colchicine during pregnancy, although the necessity for the procedure is uncertain. Heparin or low-molecular-weight heparin is used preferentially in place of warfarin for anticoagulation as these do not cross the placenta. Intravenous immunoglobulin is considered generally safe despite transplacental passage. There are few data on biologics other than the TNF inhibitors, and so these are generally avoided.
Breast-feeding is possible for many patients. Corticosteroids in low dose are considered safe, with administration of the dose more than 4 hours before nursing if possible. Aspirin, heparin, warfarin, hydroxychloroquine, sulfasalazine, and even ibuprofen may be used in patients who are breast-feeding. Ideally, one would like to avoid immunosuppressive medications during this period, although use of azathioprine or TNF inhibitors has been advocated during breast-feeding by some rheumatologists. Breast-feeding may be a concern for the patient with known or suspected osteoporosis, because it may further lower bone density beyond the expected pregnancy-induced decrease and lengthen the time until recovery.
Assessment of rheumatic disease patients considering pregnancy should follow the same general pattern regardless of the specific diagnosis. First, assess for disease activity because if patients are active, this is a poor time to conceive, and they should defer pregnancy and be treated aggressively. When disease has been inactive for 6 months, reassess and also make sure there are no severe manifestations of disease damage that preclude pregnancy such as cardiomyopathy or severe cardiac valve disease, severe pulmonary issues such as pulmonary hypertension or severe interstitial lung disease, serious neurologic manifestations, or renal insufficiency with significantly decreased clearance. If such patients are intent on having a biological child, it may be appropriate to consider the safety of in vitro fertilization process with surrogacy. For patients open to consideration of adoption, this is an alternative option. If disease is inactive, and there is no indication of severe damage, assess the patient's present medical regimen. When current medications are contraindicated, options include taper and discontinuation if disease permits, or a change to permissible medications. Assessment of autoantibodies will determine pregnancy monitoring, whether fetal echocardiograms or nonstress tests, as well as potential additional therapy for antiphospholipid obstetric prophylaxis. Counsel the patient and her partner: knowing what to expect makes a difference. Finally, one cannot effectively discuss planning pregnancy without considering availability and safety of contraception. Oral contraceptives that contain estrogen can be used in lupus if the disease is quiet and if patients do not have antiphospholipid antibodies. For patients who cannot use combined oral contraceptives, the levonorgestrel intrauterine device (the progesterone-containing intrauterine device) is a good option. It is recommended even for nulliparous women, risk of infection is low, and it can remain in place for up to 5 years. It decreases menstrual blood flow, a benefit for patients who are on warfarin because of APS.
Pregnancy in rheumatic disease patients is most often successful when the rheumatologist, obstetrician, and the patient work as a team, with identification and understanding of potential risks particular to the individual patient. In general, planning for a pregnancy in any rheumatic disease patient during a period of well-controlled disease on acceptable medications is likely to yield the best outcome.
Medication Use in Pregnancy
All rheumatologists should be generally familiar with commonly used rheumatic medications in pregnancy. Risk of anti-inflammatory medications is unknown, and so we usually avoid them, especially late in the pregnancy because of concerns about premature closure of the ductus arteriosus. Prednisolone or methylprednisolone is generally used for maternal corticosteroid effect: there is very little placental transfer, although there is a very small risk of oral cleft with first-trimester exposure. Fluorinated corticosteroids pass easily through the placenta and are reserved for fetal treatment effect. Methotrexate is contraindicated, and patients should be off the medication for 3 months before conception. Cyclophosphamide is contraindicated, although it has been rarely used in late pregnancy. Azathioprine is labeled a pregnancy category D drug but is used frequently in clinical practice: it is generally the immunosuppressive of choice during pregnancy. Cyclosporine is also used, more often in transplant patients and less frequently by rheumatologists; it is considered to be a safe alternative, despite risk of hypertension and renal problems. Mycophenolate should not be used during pregnancy. Pregnancy effects of TNF inhibitors are still unknown, but the data are reassuring. The placental transfer of immunoglobulins does not become significant until 16 weeks' gestation, so it seems reasonable to treat at least until the time pregnancy is confirmed. For the RA patient on methotrexate and TNF inhibitors, it is reasonable to stop the methotrexate 3 months before trying to conceive but to continue the TNF inhibitor until they conceive because that can take an unpredictable amount of time. For patients on leflunomide, pregnancy should only be attempted after a washout of the drug with cholestyramine and documentation of absent serum levels of metabolites following the washout procedure. If a patient conceives while on leflunomide, the washout procedure should be performed as soon as possible. Even with early washout, risk of teratogenicity is uncertain, although a recent report suggests it is lower than previously estimated: patients in this situation may be referred to a geneticist who can best define the degree of risk to the fetus. Sulfasalazine is considered safe, but it is prudent to treat with folate supplementation to minimize risk of neural tube defects during pregnancy. There are recent data on the increasing use and benefits of hydroxychloroquine for lupus pregnancy outcome including reduced risk of heart block. Amniocentesis has been suggested to rule out chromosomal abnormalities in patients treated with colchicine during pregnancy, although the necessity for the procedure is uncertain. Heparin or low-molecular-weight heparin is used preferentially in place of warfarin for anticoagulation as these do not cross the placenta. Intravenous immunoglobulin is considered generally safe despite transplacental passage. There are few data on biologics other than the TNF inhibitors, and so these are generally avoided.
Breast-feeding is possible for many patients. Corticosteroids in low dose are considered safe, with administration of the dose more than 4 hours before nursing if possible. Aspirin, heparin, warfarin, hydroxychloroquine, sulfasalazine, and even ibuprofen may be used in patients who are breast-feeding. Ideally, one would like to avoid immunosuppressive medications during this period, although use of azathioprine or TNF inhibitors has been advocated during breast-feeding by some rheumatologists. Breast-feeding may be a concern for the patient with known or suspected osteoporosis, because it may further lower bone density beyond the expected pregnancy-induced decrease and lengthen the time until recovery.
Assessment of rheumatic disease patients considering pregnancy should follow the same general pattern regardless of the specific diagnosis. First, assess for disease activity because if patients are active, this is a poor time to conceive, and they should defer pregnancy and be treated aggressively. When disease has been inactive for 6 months, reassess and also make sure there are no severe manifestations of disease damage that preclude pregnancy such as cardiomyopathy or severe cardiac valve disease, severe pulmonary issues such as pulmonary hypertension or severe interstitial lung disease, serious neurologic manifestations, or renal insufficiency with significantly decreased clearance. If such patients are intent on having a biological child, it may be appropriate to consider the safety of in vitro fertilization process with surrogacy. For patients open to consideration of adoption, this is an alternative option. If disease is inactive, and there is no indication of severe damage, assess the patient's present medical regimen. When current medications are contraindicated, options include taper and discontinuation if disease permits, or a change to permissible medications. Assessment of autoantibodies will determine pregnancy monitoring, whether fetal echocardiograms or nonstress tests, as well as potential additional therapy for antiphospholipid obstetric prophylaxis. Counsel the patient and her partner: knowing what to expect makes a difference. Finally, one cannot effectively discuss planning pregnancy without considering availability and safety of contraception. Oral contraceptives that contain estrogen can be used in lupus if the disease is quiet and if patients do not have antiphospholipid antibodies. For patients who cannot use combined oral contraceptives, the levonorgestrel intrauterine device (the progesterone-containing intrauterine device) is a good option. It is recommended even for nulliparous women, risk of infection is low, and it can remain in place for up to 5 years. It decreases menstrual blood flow, a benefit for patients who are on warfarin because of APS.
Pregnancy in rheumatic disease patients is most often successful when the rheumatologist, obstetrician, and the patient work as a team, with identification and understanding of potential risks particular to the individual patient. In general, planning for a pregnancy in any rheumatic disease patient during a period of well-controlled disease on acceptable medications is likely to yield the best outcome.