Original Research
Obstetrics
The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies

https://doi.org/10.1016/j.ajog.2015.09.078Get rights and content

Background

Antiphospholipid syndrome is defined by the combination of thrombotic events and/or obstetric morbidity in patients who have tested positive persistently for antiphospholipid antibodies. With good treatment, approximately 70% of pregnant women with antiphospholipid syndrome will deliver a viable live infant. However, current management does not prevent all maternal, fetal, and neonatal complications of antiphospholipid syndrome.

Objectives

This observational, retrospective, single-center cohort study aimed to assess pregnancy outcome in women with antiphospholipid antibodies who were treated with hydroxychloroquine in addition to conventional treatment during pregnancy.

Study Design

One-hundred seventy pregnancies in 96 women with persistent antiphospholipid antibodies were analyzed: (1) 51 pregnancies that occurred in 31 women were treated with hydroxychloroquine for at least 6 months before pregnancy, and the therapy continued throughout gestation (group A); (2) 119 pregnancies that occurred in 65 women with antiphospholipid antibodies that were not treated with hydroxychloroquine were included as controls (group B).

Results

Hydroxychloroquine-treatment was associated with a higher rate of live births (67% group A vs 57% group B; P = .05) and a lower prevalence of antiphospholipid antibodies–related pregnancy morbidity (47% group A vs 63% B; P = .004). The association of hydroxychloroquine with a lower rate of any complication in pregnancy was confirmed after multivariate analysis (odds ratio, 2.2; 95% confidence interval, 1.2–136; P = .04). Fetal losses at >10 weeks of gestation (2% vs 11%; P = .05) and placenta-mediated complications (2% vs 11%; P = .05) were less frequent in group A than group B. Pregnancy duration was longer in group A than group B (27.6 [6-40] vs 21.5 [6-40] weeks; P = .03). There was a higher rate of spontaneous vaginal labor in hydroxychloroquine-treated women compared with group B (37.3% vs 14.3%; P = .01).

Conclusions

Despite the heterogeneity in the 2 groups in terms of systemic lupus erythematosus prevalence and previous pregnancy history, our results support the concept that women with antiphospholipid antibodies may benefit from treatment with hydroxychloroquine during pregnancy to improve pregnancy outcome. The addition of hydroxychloroquine to conventional treatment is worthy of further assessment in a proper designed randomized controlled trial.

Section snippets

Methods

This was an observational, retrospective, single center cohort study. All the records of women who attended the Lupus & Antiphospholipid Pregnancy clinic from January 2008 to July 2014 were searched. All the pregnancies in women with persisting aPL were identified.

aPL positivity was defined according to the current classification criteria and confirmed at least 12 weeks apart1 in all the included women before the index pregnancy. Women with equivocal or unconfirmed aPL positivity were excluded

Results

Treatment with hydroxychloroquine was well tolerated, and no side-effect was reported. No patients suspended treatment with hydroxychloroquine during the follow-up period.

As indicated in Table 1, women who were treated with hydroxychloroquine had a significant higher prevalence of SLE (64.5% in group A vs 7.7% in group B; P < .001), which is consistent with the higher frequency of antinuclear antibodies and extractable nuclear antigens antibodies that were observed in group A (P < .001).

Comment

To the best of our knowledge, this study is the first to provide clinical evidence from a large cohort that supports a beneficial effect of hydroxychloroquine on pregnancy outcome in women with aPL.

In our study, hydroxychloroquine was well tolerated, and no serious side-effects were observed.

The main serious effects that are associated with hydroxychloroquine exposure are very rare and involve cardiac and retinal toxicities.31 Cardiac toxicity remains controversial; in the largest prospective

References (36)

  • A. Mekinian et al.

    The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study

    Autoimmun Rev

    (2015)
  • V. Pengo et al.

    Update of the guidelines for lupus anticoagulant detection: Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis

    J Thromb Haemost

    (2009)
  • A. Mekinian et al.

    Obstetrical APS: Is there a place for hydroxychloroquine to improve the pregnancy outcome?

    Autoimmun Rev

    (2015)
  • X.X. Wu et al.

    Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression

    Am J Obstet Gynecol

    (2011)
  • J.H. Rand et al.

    Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers

    Blood

    (2008)
  • E. Papadopolous et al.

    Antiphospholipid antibodies and venous thrombosis (VT) in SLE

    Arthritis Rheum

    (1999)
  • K. Bramham et al.

    Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome

    Lupus

    (2010)
  • A. Tincani et al.

    Treatment of pregnant patients with antiphospholipid syndrome

    Lupus

    (2003)
  • Cited by (143)

    • Effect of hydroxychloroquine and chloroquine on syncytial differentiation and autophagy in primary human trophoblasts

      2022, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      Overall, the effects of HCQ on hCG production, cytotrophoblast fusion, autophagy, differentiation-related genes, and JAK2 signaling were milder than those of CQ. HCQ is commonly prescribed in pregnant women with systemic lupus erythematosus or antiphospholipid antibody syndrome [24,25]. Recently, several clinical trials have been underway to test whether HCQ could lower recurrent pregnancy loss and improve pregnancy outcomes [63–65].

    • Rheumatic diseases and reproductive outcomes

      2022, Immunology of Recurrent Pregnancy Loss and Implantation Failure: Volume 3
    View all citing articles on Scopus

    The authors report no conflict of interest.

    Cite this article as: Sciascia S, Hunt BJ, Talavera-Garcia E, et al. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol 2016;214:273.e1-8.

    View full text