Background & objectives: Hydroxychloroquine, a medication originally developed for the treatment of malaria, has been used for more than 40 years as an oral disease-modifying anti-rheumatic drug (DMARD) for discoid and systemic lupus erythematosus, as well as rheumatoid arthritis. The drug is used to treat these rheumatic conditions during pregnancy.
In use for any indication, the drug has previously been associated in adult patients with a dose-dependent risk for irreversible retinal damage and severe cardiomyopathy, including ventricular arrhythmias and torsade de pointes. Previous small studies have been reassuring regarding the pregnancy safety of hydroxychloroquine; however, one recent report found an increase in major birth defects at doses ≥400 mg/day.
In 114 women treated with hydroxychloroquine and 455 pregnant women not exposed to hydroxychloroquine, the investigators found no increased risks for preterm birth nor reduced birth weight following treatment with hydroxychloroquine. However, the comparison group consisted of pregnant women without the same underlying rheumatic conditions.
Thus, Chambers et al. set out to examine pregnancy outcomes in women with rheumatic conditions following the use of hydroxychloroquine.
Methods: The researchers selected pregnant women prospectively enrolled in MotherToBaby/OTIS Pregnancy Studies who had been exposed to hydroxychloroquine. Disease-matched and healthy comparison groups without hydroxychloroquine exposure were randomly selected from the same source using a 1:1 ratio. Data were collected through interviews, medical records and dysmorphology examinations. Outcomes were major and minor birth defects, spontaneous abortion, preterm delivery and infant growth.
Results: Between 2004 and 2018, 837 pregnancies met criteria for inclusion, 279 women who had been exposed to hydroxychloroquine and 279 in each comparison group. Sixty pregnancies (7.2%) were lost to follow-up. Among live births, 20/232 (8.6%) with first-trimester hydroxychloroquine exposure had a major birth defect compared with 19/256 (7.4%) in the disease-matched group (odds ratio [OR] 1.18, 95% confidence interval [CI] 0.61, 2.26), and 13/239 (5.4%) in the healthy group (adjusted OR 0.76, 95% CI 0.28, 2.05).
Risks did not differ at doses ≥400 mg/day. No pattern of birth defects was identified. There were no differences in rates of spontaneous abortion or preterm delivery. Growth deficiency measures did not differ in the hydroxychloroquine-exposed vs. disease-matched group, except for the newborn’s head circumference at birth (adjusted OR 1.85, 95% CI 1.07, 3.20).
Conclusions: Chambers et al. found no evidence of an increased risk for structural defects or other outcomes with hydroxychloroquine, with the exception of the newborn’s head circumference at birth. For women treated with hydroxychloroquine, these findings are reassuring.
