The use of hydroxychloroquine (Plaquenil) during pregnancy among women with systemic lupus erythematosus (SLE) was associated with improved fetal outcomes, a single-center French study found.
Among women taking hydroxychloroquine while pregnant, preterm birth (before 37 weeks) occurred in 15.8% compared with 44.2% for women not on the antimalarial agent (P=0.006), according to M.E. Leroux, MD, of La Reunion University Hospital in St. Pierre, and colleagues.
And the rate of intrauterine growth restriction was significantly lower in the hydroxychloroquine-treated group (10.5% versus 28.6%, P=0.03), the researchers reported online in
Action Points
- Note that this observational study suggests that the use of hydroxychloroquine during pregnancy is associated with better fetal outcomes.
- Be aware that the study was observational. Women taking hydroxychloriquine durine pregnancy may engage in other healthful behaviors that lead to better outcomes.
Despite recent improvements in care and multidisciplinary approaches being used, pregnancy remains risky for women with SLE, with
Hydroxychloroquine has been shown to improve maternal disease activity, reducing the frequency of flares and thrombotic events, and continuing the drug during pregnancy However, uncertainty remains as to the effects on fetal events including preterm birth and intrauterine growth restriction.
Accordingly, Leroux and colleagues conducted a retrospective study of 118 women with SLE who delivered after 22 weeks at Bordeaux University Hospital from 2001 through 2011.
A total of 41 of the women had received hydroxychloroquine throughout pregnancy, while 77 were not exposed to the drug.
The women's mean age was 30, and no differences were seen among the hydroxychloroquine-positive and negative groups in tobacco use, body mass index, or socioeconomic factors.
However, the hydroxychloroquine-positive group more commonly had joint (75.6% versus 40.3%, P<0.001), hematologic (43.9% versus 18.2%, P=0.003), and renal (19.5% versus 6.5%, P=0.03) manifestations, suggesting that they had more severe disease.
All women in the hydroxychloroquine group received the drug in dosages of 400 mg/day. They also were on a mean daily dose of prednisone of 11.9 mg, compared with 15.8 mg of prednisone in the hydroxychloroquine-negative group.
Successful live births occurred in 92.7% and 96.1% of the hydroxychloroquine-positive and negative groups, respectively. One pregnancy in a woman not on hydroxychloroquine was terminated because of congenital malformations.
No malformations were observed in the hydroxychloroquine group, and although chloroquine has been associated with teratogenic effects in animal studies when given in high doses, no cases have been reported in humans exposed to hydroxychloroquine.
None of the women on hydroxychloroquine delivered before 32 weeks, while two not receiving the drug did so during disease flares.
There also had been a lower rate of induced preterm birth with hydroxychloroquine use (9.8% versus 27.3%, P=0.006), reflecting "improvement of fetal and maternal health," the authors noted.
No cases of pregnancy-induced hypertension were seen in the hydroxychloroquine-positive group, while nine cases occurred in the negative group (P=0.02).
On multivariate analysis, preterm birth was associated with these factors:
- No hydroxychloroquine exposure, RR 6 (95% CI 1.6-22)
- Vascular manifestations, RR 7 (95% CI 1.8-30.16)
- Preeclampsia, RR 25 (95% CI 3.1-201)
- Premature rupture of membranes, RR 56 (95% CI 5.4-584)
And intrauterine growth restriction was associated with these factors:
- Tobacco use, RR 3.8 (95% CI 1.2-11.6)
- Unplanned pregnancy, RR 6 (95% CI 2.5-18.9)
- Pregnancy-induced hypertension, RR 8.25 (95% CI 1.6-40.3)
The multivariate analysis "seems to suggest that hydroxychloroquine would decrease the rate of preterm delivery independently of its action on SLE itself. This observation may be due to the fact that hydroxychloroquine acts not only on the immune system, but also impacts the coagulation and metabolism pathways," the researchers explained.
"We assume that the antithrombotic effect of hydroxychloroquine may play an important role in reducing low birth weight through improved placental vascularization. This hypothesis requires confirmation in a prospective study where it could be interesting to compare placental histology from hydroxychloroquine-exposed and non-exposed SLE patients," they wrote.
The study supports the use of hydroxychloroquine during pregnancy among women with SLE not only for limiting their risk of disease flare, but also to lower the risk of preterm birth and intrauterine growth restriction, they concluded.
Disclosures
The authors reported no conflicts of interest.
Primary Source
Lupus
Leroux M, et al "Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study" Lupus 2015; DOI: 10.1177/0961203315591027.