Hydroxychloroquine Reduces Incidence of Heartbeat Condition in Newborns
A drug used to treat systemic lupus erythematosus (SLE) significantly reduces the incidence of a rare and sometimes fatal heart condition in newborn babies, a new study from NYU Grossman School of Medicine researchers shows.
The condition, called congenital heart block (CHB), results in a lower than normal heart rate and affects as many as one in 15,000 live births, study investigators say. Normal resting heart rate for newborns, they point out, is 120 heartbeats to 160 heartbeats per minute, but a heart rate below 50 heartbeats per minute can be fatal for a fetus. Of the babies born with low heart rates who survive, about 75 percent will require at least one pacemaker during their lifetime. Some patients might require a heart transplant to survive.
CHB is strongly linked to the presence of immune proteins, or antibodies, in the mother that react with other proteins called SSA/Ro. For mothers with these antibodies, the risk of this heart problem in their babies is low, at 2 percent, but increases ninefold if a previous pregnancy has resulted in heart block.
Reporting in the Journal of the American College of Cardiology online July 13, the NYU Langone Health researchers show that giving the antimalarial drug hydroxychloroquine to pregnant women who previously had a child affected by CHB reduced the likelihood that the condition recurred in a subsequent pregnancy by 50 percent.
"Our study shows hydroxychloroquine as the first, safe, and highly effective drug for preventing pregnant women at risk from having another child with congenital heart block," says study lead author and rheumatologist Peter Izmirly, MD, an associate professor in the Department of Medicine at NYU Langone Health.
Although rare, CHB occurs when the mother's immune system suddenly attacks the heart of the fetus she carries. Researchers say that in about half the cases of CHB, the mother has an autoimmune condition, such as systemic lupus erythematosus (SLE) or Sjogren's syndrome, where the body mistakenly develops antibodies that can identify their own cells' proteins in a similar way they would target those made by invading bacteria. Many women do not even know they have these antibodies until they give birth to a child with CHB.
Hydroxychloroquine, in addition to its effectiveness against malaria, is prescribed for the treatment of SLE. The drug reduces tissue inflammation, the main feature of SLE, and what researchers believe injures the fetal heart, leading to CHB.
Previous research by Izmirly and study senior author Jill Buyon, MD, the Sir Deryck and Lady Va Maughan Professor of Rheumatology in the Department of Medicine at NYU Langone, found that newborns of pregnant women with SLE taking hydroxychloroquine were significantly less likely to develop heart block than newborns of pregnant women who were not taking it. A second study of patient records in the NYU Langone-led National Research Registry for Neonatal Lupus found that the recurrence rate of CHB in pregnant women who were taking hydroxychloroquine was significantly lower, but until the new study, they note, it was not known if hydroxychloroquine likely caused the benefit.
To determine whether hydroxychloroquine was effective in reducing the CHB historical recurrence rate of 18 percent, Izmirly and Buyon monitored pregnant women from across the country who had previously had a child affected by CHB. Study participants were given 400 milligrams of hydroxychloroquine daily, starting in the first trimester.
In 54 women enrolled in the new study, four pregnancies resulted in fetuses with CHB. During the study, the researchers found that nine participants were taking medications that could have potentially enhanced the effectiveness of hydroxychloroquine. The researchers replaced these participants with nine additional pregnant women who were purely on hydroxychloroquine. Among this group, there was one additional case of CHB.
Overall, the recurrence rate of CHB in newborns of women taking hydroxychloroquine was 7.9 percent, compared to the historical recurrence rate of 18 percent.
"Testing for anti-SSA/Ro antibodies is not part of the normal screening of pregnant women, but it should now be considered," says Buyon. "One implication of our findings is that hydroxychloroquine could be effective in preventing CHB in newborns of first-time, pregnant women with anti-SSA/Ro antibodies, which could change the way we evaluate all pregnancies regardless of a mother's health."
Reference: Izmirly, et al. (2020). Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers. Journal of the American College of Cardiology DOI: 10.1016/j.jacc.2020.05.045
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