Pregnancy in Rheumatic Disease Patients

Lisa R. Sammaritano, MD


J Clin Rheumatol. 2013;19(5):259-266. 

In This Article

Lupus Pregnancy

There have been many reports addressing the risk of pregnancy in lupus patients, and we are familiar with hearing about those years when rheumatologists told their lupus patients to never get pregnant because it was too dangerous. Thankfully, those days are gone, but lupus pregnancy still involves more risk than for the average patient without lupus. Degree of risk obviously depends very much on the patient and her particular circumstances. One study, published in 2001, looked at 1.2 million pregnancies in total of which 555 were in lupus patients:[18] adverse outcomes were significantly higher in the patients who had a lupus diagnosis. Maternal morbidity in lupus is estimated to be 20-fold higher in another recent study,[19] and women with lupus still have fewer live births.[20]

A recent study by Clark et al[21] compared pregnancy outcomes in SLE patients over the last 40 years. They looked at 83 of their SLE patients who delivered between the years 2000 to 2003 and then did a literature review to look at prior pregnancy outcomes; adverse outcomes included fetal loss and preterm delivery. In their 83 patients, the pregnancy loss rate was 17% compared with the general population rate of 16% (which includes losses in the first trimester); in contrast, the SLE pregnancy loss rate in the 1960s was 43%. Preterm delivery, however, did not improve significantly: it was 32% in the recent patients versus 37% in the prior literature review. In comparison, preterm delivery occurred in only 9% to 12% in the current general population. The PROMISSE study interim analysis found only a 6% rate of pregnancy loss.[22] However, these patients were enrolled at 12 or even up to 18 weeks, so early losses were not captured. Preterm delivery was close to that in the general population, about 10%.

Looking throughout the literature, there are certain factors that stand out in terms of increasing risk for lupus pregnancy: these include having active disease at the time of conception, having prior or active nephritis, and having antiphospholipid antibodies. In terms of neonatal outcome, high levels of disease activity and higher DNA and lower complement levels in the setting of more active disease have been shown to predict small size and early delivery.[23] Remember this does not mean that eventually there is not a good outcome, but it may mean a more difficult path to that outcome, such as a baby born at 32 weeks with attendant risk of complications due to prematurity instead of at 40 weeks, or a mother with preeclampsia complicating her delivery. Proteinuria, thrombocytopenia, aPL, and hypertension at the first visit have also been shown to be predictors of pregnancy morbidity.[24] Active disease, high titer aPL, and high uric acid were associated with adverse outcomes in the PROMISSE study.[22] Patients with both SLE and aPL antibody are at highest risk for adverse outcome: they have greater than 30% likelihood of adverse primary outcome, whereas for patients with lupus without aPL antibody, that number is about 12% to 13%.

The risk of flare during lupus pregnancy has been estimated at anywhere from 13% to 60%; although still controversial, true risk is probably closer to the lower number. The lowest risk is associated with quiet disease for at least 6 months before conception. History of nephritis or active renal disease increases risk of adverse maternal outcome. The risk of flare can be very difficult to assess in lupus patients, as many pregnancy-related issues can mimic lupus activity, and this is probably a major reason for such widely varying estimates of flare rates. Rates of flare in the PROMISSE study are at the low end of the spectrum; however, these patients were selected for entry into this study and could not have significantly elevated serum creatinine or be on more than 20 mg of prednisone per day.

Pregnancy is challenging when the patient has a history of nephritis, because pregnancy puts a significant stress on patients' kidneys. It is a very important risk factor, both for the pregnancy outcome and for deterioration in renal function in the mother. Precise histology is less important than the degree of renal dysfunction. Lupus patients who have undergone renal transplant do well during pregnancy and may do even better than other transplant patients with other comorbidities. For patients with a high creatinine who want to become pregnant, it may make sense to think about transplanting sooner rather than later. A serum creatinine of 1.6 mg/dL or a clearance of 60 mL/min is often used as a general cutoff for increased level of concern. Exacerbation can occur in up to 40% of patients with prior nephritis, but it is relatively less common for patients to have ongoing renal dysfunction. In addition to decreased creatinine clearance, predictors for adverse renal outcome include hypertension and significant proteinuria.[25,26] It can be very difficult to differentiate lupus renal disease from superimposed preeclampsia, and one may find necessity of treating for both. Clinical symptoms of active lupus support a diagnosis of lupus flare as do elevation in DNA antibody and presence of red cell casts. Complements are not necessarily helpful because they may increase in normal pregnancy or decrease in preeclampsia.

In summary, risk for poor outcome in lupus pregnancy can be estimated to some extent. Inactive lupus at the time of conception is very important in preventing flare. Although the precise likelihood of flare is uncertain, it is probably increased to some extent, and it can occur any time during pregnancy including the postpartum period. Renal insufficiency and hypertension increase risk. Antiphospholipid antibody increases risk. Having severe flare at the beginning or during the pregnancy also is worse both in terms of maternal outcome and fetal outcome. Prepregnancy assessment should include disease activity, related damage, renal function, current medications, and relevant autoantibodies such as aPL and anti–Ro/SS-A and La/SS-B.

Medication use and safety during pregnancy for rheumatic disease patients are discussed in detail below. For patients with SLE, however, continuation of hydroxychloroquine is encouraged to reduce risk of disease flare, and low-dose prednisone is usually substituted for nonsteroidal anti-inflammatory drugs for symptoms of arthralgia or arthritis. Many immunosuppressives are contraindicated during pregnancy, but azathioprine (and cyclosporine) may be continued with low risk of adverse effects. Ideally, the transition to azathioprine from mycophenolate mofetil or methotrexate in advance of pregnancy should be followed by at least 6 months of stable disease before the patient attempts to conceive.

Treatment with corticosteroid is appropriate for active lupus but is not given prophylactically. High-dose corticosteroid increases the risk of morbidity including hypertension, diabetes, infection, and premature rupture of membranes. Finally, some experts suggest low-dose aspirin for pregnant lupus patients, even in the absence of aPL, particularly for the patient with history of renal disease.