Objective  To systematically evaluate the efficacy and safety of hydroxychloroquine (HCQ) in obstetric antiphospholipid syndrome (OAPS).

Methods  PubMed, Embase, Cochrane Library, Web of Science, SinoMed, Wanfang Data, CNKI, and VIP databases were searched electronically to collect clinical research on HCQ treatment for OAPS from inception to January 31, 2023. Two researchers independently screened the literature,extracted data, and assessed the risk of bias of the included studies, Meta-analysis and GRADE evaluation were performed using RevMan 5.4 software and GRADE Profile 3.6 softwares.

Results  Five cohort studies and three randomized controlled trias (RCTs) were included, with a total of 644 OAPS patients (732 pregnancies). The results of Meta-analysis showed that compared with conventional treatment, HCQ supplementation significantly increased the live birth rate of OAPS (RR=1.29, 95%CI 1.10 to 1.51, P=0.001), the negative conversion rate of lupus anticoagulant (RR=1.29, 95%CI 1.13 to 1.47, P<0.001), the anticardiolipin antibody negative conversion rate (RR=1.27, 95%CI 1.12 to 1.45, P<0.001) and the anti-β2 glycoprotein Ⅰ antibody negative conversion rate (RR=1.31, 95%CI 1.12 to 1.52, P<0.001), the rate of early abortion (<10 weeks) was significantly reduced (RR=0.31, 95%CI 0.10 to 0.93, P=0.04). However, there was no significant difference between the two groups in reducing the rate of premature birth, late abortion (>10 weeks) and the incidence of preeclampsia (P>0.05). In terms of safety analysis, two studies described HCQ adverse effects including skin reactions and dry eyes, symptoms are mild. Three RCTs were used to compare the incidence of adverse reactions between the two groups, the incidence of adverse reaction of HCQ group was lower than that of control group (RR=0.40, 95%CI 0.25 to 0.66, P<0.001), and no serious adverse reactions occurred in both groups. The sensitivity analysis results were robust and reliable. The results of GRADE evaluation showed that the quality of index evidence included in this study were low or very low, with weak recommendations.

Conclusion  HCQ can significantly improve the live birth rate of OAPS and the negative conversion rate of antiphospholipid antibody, and reduce the fetal abortion rate before 10 weeks with fewer adverse reactions, but there is insufficient evidence to reduce the incidence of premature birth, fetal abortion after 10 weeks and preeclampsia. Due to the limited number and quality of included studies, the above conclusions need to be confirmed by more high-quality studies.

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