Pregnancy Outcomes Usually Good in Patients With Mild Lupus

Laurie Barclay, MD

June 23, 2015

Pregnant women with inactive or stable mild or moderate systemic lupus erythematosus (SLE) and no specific risk factors seldom have severe flares and have good outcomes, according to findings of a prospective, multicenter cohort study published online June 22 in the Annals of Internal Medicine. Various clinical and laboratory parameters can identify patients at high risk for adverse pregnancy outcomes (APOs).

"Currently, patients with SLE are advised to consider pregnancy during periods of minimal and stable disease," write Jill P. Buyon, MD, from the New York University/Langone Medical Center in New York City, and colleagues from the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE) study. "However, data supporting this advice are based on retrospective or prospective single-center studies involving few patients, have limited generalizability to multiethnic populations, and are controversial."

Using a multiethnic cohort of 385 women with SLE with inactive or stable mild or moderately active disease during the first trimester of pregnancy, the investigators aimed to identify predictors of APOs. These were fetal or neonatal death; birth before 36 weeks' gestation caused by placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age neonate, defined as birth weight below the fifth percentile.

Nearly half (48%) of participants were non-Hispanic white, and 31% had a history of nephritis. The study included women with a singleton pregnancy of up to 12 weeks' gestation. Exclusion criteria were urinary protein–creatinine ratio exceeding 1000 mg/g, serum creatinine level exceeding 1.2 mg/dL, prednisone use exceeding 20 mg/day, diabetes, and uncontrolled hypertension.

Nearly one fifth of the women (19.0%; 95% confidence interval [CI], 15.2% - 23.2%) had one or more APOs. Most of these APOs were small-for-gestational-age neonate (10%) or preterm delivery (9%). Fetal death occurred in 4% and neonatal death in 1%.

Only 2.5% (95% CI, 1.1% - 4.7%) of the women had severe SLE flares in the second trimester, and 3.0% (95% CI, 1.4% - 5.6%) in the third trimester, as determined with the SLE Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA).

Predictors of APOs

Baseline factors associated with APOs were presence of lupus anticoagulant (LAC; odds ratio [OR], 8.32; 95% CI, 3.59 - 19.26), antihypertensive use (OR, 7.05; 95% CI, 3.05 - 16.31), PGA score greater than 1 (OR, 4.02; 95% CI, 1.84 - 8.82), and platelet count (OR, 1.33 [95% CI, 1.09 - 1.63] for each decrease of 50 × 109 cells/L).

Other predictors of APOs were maternal flares, higher disease activity, and smaller increases in C3 level from baseline later in pregnancy. In contrast, being of non-Hispanic white race appeared to protect against APOs (OR, 0.45; 95% CI, 0.24 - 0.84). Anti-double-stranded DNA positivity was not associated with APOs in this study.

The APO rate ranged from 7.8% (95% CI, 3.8% - 13.8%) in women without baseline risk factors to 58.0% (95% CI, 43.2% - 71.8%) in those who were LAC-positive or who were LAC-negative but nonwhite or Hispanic and used antihypertensives. In these high-risk groups, the rate of fetal or neonatal mortality was 22.0% (95% CI, 11.5% - 36.0%) compared with only 3.9% (95% CI, 1.3% - 8.8%) in low-risk women, which is similar to the rate in healthy control participants.

Study limitations include exclusion of patients with high SLE activity, lack of external validation of the predictive models, and inability to address first-trimester losses.

"[I]n the absence of baseline features indicative of risk (LAC-positive, antihypertensive medication use, PGA score >1, Hispanic or nonwhite ethnicity/race, or low platelet count), pregnancy outcomes are highly favorable," the study authors conclude. "Patients with risk factors for APOs should be monitored more closely and considered for future interventional trials to prevent APOs."

Strategies for Pregnancy in Women With SLE

In an accompanying editorial, Bevra H. Hahn, MD, from the David Geffen School of Medicine, University of California, Los Angeles, recommends clinicians use these findings to advise patients with SLE who are considering pregnancy or are already pregnant. Dr Hahn suggests the following strategies:

  • Plan pregnancies to the extent possible, and time them for periods of lowest SLE disease activity.

  • Consider every pregnancy during SLE as high risk, and consult with a high-risk obstetrician for close monitoring of the woman and her infant.

  • Balance the need for tight control of SLE disease activity against the teratogenicity of medications often used to treat SLE and hypertension, such as methotrexate, mycophenolate mofetil, cyclophosphamide, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers.

  • Consider using nonfluorinated glucocorticoids to control SLE disease activity, although there is no evidence that prophylactic therapy with glucocorticoids in women with inactive disease improves fetal outcomes.

  • Consider therapy with low-dose aspirin plus daily heparin for women who are positive for anticardiolipin, particularly those with prior fetal loss or clotting, starting before conception and continuing for 6 weeks after delivery.

"As the PROMISSE investigators point out, they have not yet addressed important questions about fetal prognosis and patient management in women with SLE who habitually abort in the first trimester, those with lupus flares during the first trimester, those with lupus nephritis with heavy proteinuria or renal insufficiency, or those with moderate to severe disease activity at conception," Dr Hahn writes. "Hopefully, data are forthcoming that will guide the counseling and management of such patients."

The National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health supported this study. Some of the study authors reported various financial disclosures involving the Mary Kirkland Center for Lupus Research, Rheuminations, the National Institutes of Health, and/or the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Complete conflict-of-interest information can be found on the journal's website.

Ann Intern Med. Published online June 22, 2015. Abstract

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