Planning and managing pregnancy in lupus patients
The inability to have a child can cause irreparable harm to the quality of life of women who want a child. This fact does not change when a woman is diagnosed with lupus. Telling a woman with lupus that she cannot have a child can be devastating to her life plan, dreams, and satisfaction in life. Lupus takes a lot from young women. It should be our role, as rheumatologists, to ensure that almost any woman with lupus who wants to have a family can do so. To do so means making some hard choices, some easy choices, and a big dose of planning.
Any unplanned pregnancy is at higher than normal risk for birth defects, pregnancy termination, and preterm birth [1,2,3]. These risks increase significantly when the unplanned pregnancy happens in a woman with lupus, particularly if she is taking a teratogen or has active rheumatic disease . An important approach to improving lupus pregnancy outcomes, therefore, is to avoid unplanned pregnancies. This means talking about, and emphasizing the importance of, contraception as a vital component of lupus management.
Managing contraceptive risk in women with lupus
The main concern for contraceptive risk in women with lupus should be the risk of thrombosis related to estrogen. Several well-designed randomized trials published more than a decade ago confirmed that estrogen-containing birth control pills did not lead to lupus flares in women with mild to moderate disease activity [5,6]. We know, however, that estrogen therapy significantly increases the risk for thrombosis . As women with lupus, and especially women with antiphospholipid syndrome, are at particularly high risk for clots, it may be wise to avoid estrogen-containing contraceptives in some of these women.
Fortunately, the majority of contraceptives available today do not contain estrogen. The most effective forms of contraceptive currently available include the intrauterine device (IUD) and implantable progesterone. Both of these contraceptives are placed and removed by a clinician and remain in place for 3 to 5 years, depending on the type and the woman’s desire for pregnancy. The IUD and implant are both long-acting and reversible and are strongly recommended contraceptives for young women with lupus who are not planning pregnancy . Somewhat less effective options include depot medroxyprogesterone acetate; a progesterone injection given every 12 weeks, and progesterone only pills. Emergency contraception, or Plan B, also only contains progesterone and can be considered safe in women with lupus. These pills must be taken within 72 hours of unprotected sex to be effective and can be purchased over the counter, without a prescription, in the USA. Plan B can even be ordered online.
Timing conception to avoid high-risk pregnancy
The key reason for planning pregnancy in women with lupus is the risk for birth defects from three commonly used rheumatic medications: methotrexate; mycophenolate; and cyclophosphamide. Exposure to these drugs in the first trimester leads to a chance of pregnancy loss of up to 40% [9,10,11]. Methotrexate is actually the least likely of these to cause birth defects, with an estimated 7–10% of infants exposed to the drug born with a defect . On the other hand, about 25% of mycophenolate- or cyclophosphamide-exposed infants will be born with a birth defect [10,11]. Avoiding conception while on these three medications will decrease pregnancy loss and birth defects in women with lupus, but clear discussions with patients are essential to decrease these risks.
The most complicated and high risk pregnancies are in women with active nephritis. These patients are at higher risk for long-term renal damage, and their offspring are at risk for long-term complications from prematurity. Once nephritis is well controlled, however, a woman’s chances of a healthy pregnancy and baby significantly improve; helping women understand this is key to improving pregnancy outcomes. Women need to understand why delaying pregnancy is important - they need to know which parameters matter (low proteinuria), which medications are safe and important to continue, and how this makes it more likely that they will have a healthier baby. Simply forbidding pregnancy is not an effective approach to this discussion.
Fortunately, there are good data supporting the use in pregnancy of several common medications used to manage lupus. Hydroxychloroquine and azathioprine (AZA) are both considered compatible with pregnancy – they do not appear to increase the risk of birth defects or pregnancy loss .
If patients maintain control of lupus, they are more likely to have a healthy baby. Some women are very hesitant to take any medications during pregnancy, thinking that sacrificing their own health is helpful to their baby. For women with active lupus, however, forgoing treatment is likely worse for their baby. I impress on many of my patients that taking these medications is the best way to have a healthy baby.
Managing lupus during pregnancy
Once a woman with lupus is pregnant, rheumatologists still need to play an important role. Just as a rheumatologist would not be very good at delivering a baby, most obstetricians are not good at accurately assessing and treating lupus. Too many non-rheumatologists attribute every symptom to lupus, leading to unnecessary prednisone tapers. It would be much better to have the rheumatologist involved and serving as the arbiter of lupus activity. If identifying lupus activity in pregnancy seems complicated, I suggest this simple approach: if a sign or symptom wouldn’t be lupus outside of pregnancy, it isn’t lupus in pregnancy. So, back pain – not lupus! Migraines – not lupus! Most gastrointestinal issues – not lupus! Morning stiffness in the joints – lupus! Red raised rash after sun exposure – lupus! You get the picture.
Managing active lupus in pregnancy is best achieved, in the short run, with moderate doses of prednisone. My goal is the lowest dose of prednisone for the shortest time. Prednisone can prompt hypertension, diabetes, and weight gain, all important contributors to pregnancy complications. They may also be associated with preterm birth and preeclampsia, causing long term complications for offspring. If prednisone is needed, I generally also start or increase AZA to avoid overuse of prednisone.
Aspirin is now recommended by the US Preventive Health Task Force and the American College of Obstetrics & Gynecologists to decrease the risk of preeclampsia in women with lupus. Women with lupus should start aspirin 81 mg per day by week 12 (end of the first trimester) [13,14].
It is worth reminding women to take a prenatal multivitamin - these can be purchased without prescription and should be started prior to pregnancy, if possible. While folic acid is particularly important, so are multiple other vitamins in these pills.
Finally, I think that all women with lupus should at least have a consultation with a high-risk obstetrician (that is a maternal–fetal medicine specialist or perinatologist). Different obstetric teams work in different ways, and much of the day to day monitoring of pregnancy can be done by a regular obstetrician. Having a maternal–fetal medicine physician weigh in increases the likelihood that proper monitoring will be completed and medications continued.
In conclusion, I feel it is our job as rheumatologists to help women with lupus to live their fullest lives. This means being open to managing pregnancy, even under less than ideal circumstances. Planning early to avoid pregnancies during periods of active nephritis or teratogen use will go a long way towards limiting pregnancy loss, birth defects, and the long-term impact of preterm delivery. Effective planning demands having open, honest, frequent, and accurate conversations about pregnancy planning and management. Enabling these conversations is a gift to women with lupus.
- Gong R, Wang ZP, Gao LJ et al. A case-control study of the effects of pregnancy planning on neural tube defects and its primary preventive measures. Birth Defects Res A Clin Mol Teratol 2010 88: 737–742.
- Finer LB, Zolna MR. Declines in Unintended Pregnancy in the United States, 2008-2011. N Engl J Med 2016; 374: 843–852.
- Orr ST, Miller CA, James SA, Babones S. Unintended pregnancy and preterm birth. Paediatr Perinat Epidemiol 2008; 14: 309–313.
- Sammaritano LR. Management of Systemic Lupus Erythematosus During Pregnancy. Annu Rev Med 2017; 68: 271–285.
- Petri M, Kim MY, Kalunian KC et al. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353: 2550–2558.
- Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005; 353: 2539–2549.
- Beyer-Westendorf J, Bauersachs R, Hach-Wunderle V, Zotz RB, Rott H. Sex hormones and venous thromboembolism - from contraception to hormone replacement therapy. Vasa 2018; doi: 10.1024/0301-1526/a000726. [Epub ahead of print]
- Andreoli L, Bertsias GK, Agmon-Levin N et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 2017; 76: 476–485.
- Weber-Schoendorfer C, Chambers C, Wacker E et al. Pregnancy outcome after methotrexate treatment for rheumatic disease prior to or during early pregnancy: a prospective multicentre cohort study. Arthritis Rheumatol 2014; 66: 1101–1110.
- Sifontis NM, Coscia LA, Constantinescu S et al. Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 2006; 82: 1698–1702.
- Alarfaj AS, Khalil N. Fertility, ovarian failure, and pregnancy outcome in SLE patients treated with intravenous cyclophosphamide in Saudi Arabia. Clin Rheumatol 2014; 33: 1731–1736.
- Götestam Skorpen C, Hoeltzenbein M, Tincani et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; 75: 795–810.
- ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. Obstet Gynecol 2018; 132: e44–52.
- LeFevre ML. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. Preventative Services Task Force recommendation statement. Ann Intern Med 2014; 161: 819–826.