Pregnancy Outcomes Improved in Lupus

Veronica Hackethal, MD

July 12, 2019

Pregnancy outcomes among American women with systemic lupus erythematosus (SLE) have improved during the past 2 decades, according to a nationwide study published online on July 8 in Annals of Internal Medicine.

The authors found substantial improvement in maternal mortality among women with lupus compared to women who did not have lupus. During 1998–2000, maternal mortality was 34 times higher among women with lupus than among the general population. During 2013–2015, the disparity had declined to less than fivefold.

For women with lupus, improvements were seen in other pregnancy outcomes, including preeclampsia, eclampsia, and length of hospital stay; however, rates for these outcomes remained worse compared to women who did not have lupus. Fetal mortality also declined slightly more among women with lupus than among women without, but the results were not statistically significant.

"Our study provides nationwide evidence that SLE pregnancy outcomes have become markedly better in the past 2 decades and continue to improve," write Bella Mehta, MBBS, Hospital of Special Surgery, New York City, and colleagues.

"However, SLE pregnancy risks remain high, and more work is needed to ensure good pregnancy outcomes among women with SLE," they add.

Large Sample Reveals Improvements

Lupus is an autoimmune disease that can affect the kidneys, heart, lungs, brain, and other organs. Women of childbearing age are among the groups at highest risk for lupus.

Thirty years ago, pregnancy was considered to be of such high risk for women with lupus that many physicians counseled against it.

Major changes in the treatment of pregnant women with lupus began in the 1980s. In the past, all medications for lupus were withheld during pregnancy because of fear of harming the fetus. Now, use of hydroxychloroquine (Plaquenil, Concordia Pharmaceuticals) has become standard of care during pregnancy in this population. The drug can decrease the risk for pregnancy-related flares and adverse pregnancy outcomes.

Other advances include use of low-dose aspirin to decrease risk for preeclampsia in high-risk pregnancies and use of heparin and low-dose aspirin to treat pregnancy-related antiphospholipid syndrome, which is relatively common in lupus pregnancies and can increase the risk for death.

Yet, the effects of these advances on pregnancy outcomes in lupus remained unknown. Therefore, Mehta and colleagues conducted a retrospective cohort study. Using data from the National Inpatient Sample (NIS) database, they compared nationwide trends and disparities in maternal and fetal outcomes for pregnant women with and for those without lupus who had pregnancy-related hospitalizations in the United States during the period 1998–2015.

The NIS is the largest publicly available database of inpatient records and represents more than 95% of the US population.

The study included 93,820 pregnant women with lupus and 78,045,054 pregnant women without lupus. The authors pooled data in 3-year intervals.

During the 18-year period included in the study, in-hospital maternal deaths decreased for both groups. Among women with lupus, maternal death declined from 442 per 100,000 admissions in 1998–2000 to <50 in 2013–2015. Among women without lupus, maternal deaths declined from 13 per 100,000 admissions in 1998–2000 to 10 in 2013–2015.

The decline in maternal deaths was significantly greater for women with lupus compared to those without (difference in trends, P < .002).

During this period, rates of preeclampsia or eclampsia decreased significantly among women with lupus compared to women without lupus. For women with SLE, the rate decreased from 9.5% to 9.1%; for women without SLE, the rate increased from 3.3% to 4.1% (P < .001). For women with SLE, non-delivery-related admissions declined from 19.2% to 16.4%; for women who did not have SLE, non-delivery-related admissions declined from 8.4% to 5.5% (P = .002). Hospital length of stay declined for pregnant women with SLE (mean, 4.3 to 3.8 days) but increased for pregnant women who did not have SLE, (mean, 2.5 to 2.7; P < .001).

Rates of cesarean delivery increased significantly in both groups, although the increase was significantly less in women with lupus (with SLE, 34.0% to 40.7%; without SLE, 21.2% to 31.7%; P < .001).

Fetal mortality rates declined for women with SLE (268 deaths per 10,000 deliveries from 1998–2000 vs 153 deaths from 2013–2015) and for women without SLE (72 deaths per 10,000 deliveries from 1998–2000 vs 66 deaths from 2013–2015).

Caution Remains Warranted

"Mehta and colleagues have demonstrated important improvements in maternal and fetal mortality by using one of the few data sets large enough to study these rare events," Megan E. B. Clowse, MD, MPH, Duke University Medical Center, Durham, North Carolina, writes in a linked editorial.

Yet she questions some results, especially the drop in maternal mortality during the last 5 years of the study (from 140 maternal deaths per 100,000 births in 2010–2012 to less than 50 per 100,000 in 2013–2015). It is not likely that improvement in management could explain such a large drop in maternal deaths, she says. Also, analyzing an event as rare as maternal mortality could affect the accuracy of results. Finally, for some of the women, antibody levels may have been elevated without their actually having SLE, which may account for the decrease in the rate of poor outcomes such as preeclampsia.

"For these reasons, I am concerned that the observed decline in maternal mortality may be an artifact, underestimating the ongoing risk of pregnancy for women with SLE," she writes.

In agreement with the authors, Clowse stresses: "Work still must be done, however, regarding preeclampsia and fetal and maternal mortality, each of which is several times more common in women with SLE than in those without the disease."

The study authors have disclosed no relevant financial relationships. Clowse has received grants from GlaxoSmithKline and personal fees from UCB.

Ann Intern Med. Published online July 8, 2019. Abstract, Editorial

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