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Lisa Sammaritano provided a comprehensive review of pregnancy in rheumatic diseases, starting with lupus. Significant lupus activity within 6 mts of conception is associated with a 4-fold increase in pregnancy loss. These are pretty strong statistics, and should be reviewed when counselling patients. Furthermore, those with active disease prior to pregnancy have a 58% risk of flare during pregnancy, compared to 8% in patients who have quiescent disease for 6 mts prior to conception. Hydroxychloroquine protects against lupus flare and should be continued in all lupus patients throughout pregnancy. MMF, methotrexate and cyclophosphamide are contraindicated in pregnancy. If a patient is on MMF, this should be switched to azathioprine for at least 6 months prior to conception. In patients who don't respond to AZA or who don't tolerate it, tacrolimus has been used successfully.
Regardless of disease activity and medications, lupus patients have higher rates of both maternal and fetal complications. Peripartum maternal mortality is 20 times higher in lupus patients compared to the general population. Other potential complications include hypertension, preterm labour, SGA and pre-eclampsia. Predictors of adverse outcomes include a prior history (or currently active) lupus nephritis, concurrent hypertension, active disease, thrombocytopenia, and presence of antiphospholipid antibodies.
The PROMISSE study is a multicentre, observational pregnancy study in patients with SLE and APLA. Over 700 patients have been enrolled and are being actively followed. The majority of patients actually have mostly quiescent disease, which is not significantly active, have no active renal disease and low-dose or no prednisone use. Despite optimal pregnancy conditions, 37% of patients with both SLE and APLA had adverse pregnancy outcomes including preeclampsia, preterm delivery, SGA, and fetal and neonatal death. Baseline risk factors associated with poor outcomes included race (Caucasian protective), global assessment, concurrent hypertension and presence of lupus anticoagulant (LAC). Peripartum factors associated with adverse pregnancy outcomes included low complement (particularly C3) and flare during pregnancy. Those without any risk factors had a low risk of adverse outcome (7%). Fetal loss was increased in those with active nephritis (35% vs 9%). Preeclampsia was 4x more common in SLE patients with a previous history of renal disease. As a result, low-dose ASA is recommended throughout pregnancy in SLE patients with previous renal disease or hypertension. Some advocate for low-dose ASA in all SLE patients through pregnancy, although this is controversial.
One third of patients with lupus also have APLAs, which are associated with maternal (pregnancy loss, preeclampsia, HELLP, thrombosis) and fetal (prematurity, SGA) complications, particularly with positive lupus anticoagulant or triple APL positivity. Although the management of these in pregnancy remains controversial, meta-analysis data suggests that combination of low-dose ASA with heparin is better than ASA alone.
I find the data presented today quite humbling. Even with our best efforts, our patients continue to be at moderate risk. I think it is vital that all lupus patients are followed closely throughout pregnancy, with shared care with the rheumatologist, obstetrician and obstetrical medicine, when available.
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About the Author
Dr. Shahin Jamal
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.
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