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Certain biomarkers may predict pregnancy complications in women with SLE

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Certain biomarkers may predict pregnancy complications in women with SLE


Women with systemic lupus erythematosus and certain serum biomarkers during pregnancy may be more likely to have adverse pregnancy outcomes, according to recently published research.

Researchers studied 492 pregnant women with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS) enrolled at 12 weeks gestation in a prospective, multicenter study between September 2003 and August 2013 in the U.S. and Canada. The study included 335 women with SLE without antiphospholipid (APL) antibodies, 59 women with SLE and APL, and 98 women with only APL.

Serum was monitored monthly for soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PIGF) and soluble endoglandin (sEng) and for pregnancy complications. A healthy control group of 197 pregnant women was recruited with similar ethnicity to patients and low risk for adverse pregnancy outcomes. Patients were excluded in the presence of 20 mg or higher daily prednisone use, urine protein to creatinine ratio greater than 1,000, urinary erythrocyte casts, serum creatinine greater than 1.2 mg/dL, type 1 or 2 diabetes or blood pressure above 140/90 mm Hg at the time of screening.

Fifty-nine (12%) severe and 49 (10%) moderate adverse pregnancy outcomes occurred within the cohort of patients. At 12 to 15 weeks of gestation, women who had adverse pregnancy outcomes had significantly raised sFlt1, sEng and a high sFlt1 to PIGF ratio, which increased over the duration of the pregnancy. Small but consistent levels and increases of sFlt1, sEng and a high sFlt1 to PIGF ratio were also observed in patients with SLE or APS who did not have adverse outcomes compared to 197 healthy participants who did not have adverse outcomes.

“Given that over 20% of pregnant women with lupus APL experience adverse pregnancy outcomes, the ability to identify patients early in pregnancy, who are destined for poor outcomes, would significantly impact care of this high-risk population,” investigator Jane E. Salmon, MD, of the Division of Rheumatology, Hospital for Special Surgery, and Weill Cornell Medical College, New York, NY, said in a press release.

The presence of lupus anticoagulant, a history of high blood pressure or thrombosis, diastolic blood pressure over 80 mm Hg and high BMI were baseline clinical variables associated with a higher risk for adverse pregnancy outcomes. The use of aspirin appeared to be protective, according to the researchers. – by Shirley Pulawski

Disclosure: Kim reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.



Large proportion of pregnancies in women with SLE are uncomplicated


A large proportion of childbirths to patients with systemic lupus erythematosus occurred without complications, and outcomes were not related to anti-dsDNA antibodies, according to research published in The Annals of Internal Medicine.

“For those patients who had a poor outcome, we were able to identify specific risk factors,” lead study author Jill P. Buyon, MD, director of the division of rheumatology and director of the lupus center at New York University Langone, told Healio.com/Rheumatology in an interview. “Happily, most of the women did do very well with their pregnancies.”

Buyon and colleagues studied the outcomes of 385 pregnant women with systemic lupus erythematosus (SLE) between September 2003 and December 2012 at eight locations in the U.S. and one in Canada. Consecutive pregnant women with up to 12 weeks of gestation were recruited into the PROMISSE study. Eligibility criteria included age between 18 years and 45 years; presence of a single, intrauterine pregnancy; and hematocrit levels above 26%. Exclusion criteria were use of prednisone at doses greater than 20 mg daily, a ratio of protein to creatinine greater than 1,000 mg/g, presence of urine erythrocyte casts, diabetes, serum creatinine above 1.2 mg/dL and blood pressure above 140/90 mm Hg.

Patients underwent a physical examination that included a complete blood count; comprehensive metabolic panel; urinalysis; detection of antibodies including anti-dsDNA, anti-Ro, anti-La, antiphospholipid (aPL) anti-beta-2-glycoprotein I and anticardiolipin; lupus anticoagulant; and C3 and C4 levels.

Disease activity was measured at baseline and follow-up using the Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI), and a flare composite was derived from the composite used in the SELENA (Safety of Estrogens in Lupus Erythematosus, National Assessment) trial.

Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation (not attributable to anatomic malformation, chromosomal abnormalities or congenital infection) or as neonatal death prior to hospital discharge related to prematurity, placental insufficiency or both. Other APOs included preterm delivery before 36 weeks caused by gestational hypertension, placental insufficiency or preeclampsia, or an outcome of small-for-gestational-age neonate (low birthweight).

One or more APOs were observed in 19% of the participants, with fetal death in 4% of the cohort. Neonatal death occurred in 1% of patients, preterm delivery occurred in 9% of patients, low birthweight was present in 10% of the children, and 17 patients had more than one APO. Preeclampsia was observed in 2% of patients after 36 weeks. Severe flares were observed in 2.5% of patients in the second trimester and in 3% of patients in the third trimester.

In patients without aPL antibodies, rates of APOs were 15.4% compared with 43.8% in patients with aPLs and 3% in patients without SLE. Other risk factors included non-white race, hypertension and low platelet counts, according to the researchers.

“Going into pregnancy counseling, the physician can use these parameters to discuss the risks with the patient,” Buyon said. “Helping patients manage their expectations is important. If a patient knows she may have a small baby or a premature baby, she can seek out appropriate care, such as a high-risk obstetrician or a hospital with a center dedicated to premature babies.”

For some patients, finding appropriate care may involve travel and additional research to find appropriate specialists, but Buyon said these steps could mitigate some of the risk, and that future research is needed to understand and mitigate the risk factors identified.

Buyon said that in the past, because of the role estrogen has been believed to play in SLE, many women were advised to avoid pregnancy; however, most of the women in her study had good outcomes. This study builds on some of her earlier work focused on estrogens and birth control medications in women with SLE, she said.

Regarding the role of estrogen, Buyon said there is much to learn.

“Things are more complicated than we have thought,” Buyon said. “As in life, biology is more complex than we can predict.” – by Shirley Pulawski

DisclosuresBuyon reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.

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