Effect of hydroxychloroquine on pregnancy outcome in patients with SLE: a systematic review and meta-analysis

Objective: Hydroxychloroquine (HCQ) is an antimalarial drug employed in the treatment of systemic lupus erythematosus (SLE). Prior studies reported inconsistent results regarding the association between HCQ use during pregnancy and adverse pregnancy outcomes. This study aimed to evaluate the impact of HCQ on pregnancy-related outcomes in women with SLE.

Methods: We conducted a systematic search for studies associating pregnancy outcomes with HCQ use in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang database and VIP from inception to 22 September 2022. Random or fixed effect models were used to estimate the pooled effect based on I² measurement of heterogeneity.

Results: Twenty-one studies were included, encompassing 929 and 1031 patients in HCQ and non-HCQ groups, respectively. We found that HCQ use was significantly associated with reduced risks of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (second trimester: mean difference (MD) -1.80, 95% CI -2.46 to -1.13; third trimester: MD -2.30, 95% CI -3.31 to -1.29), flare (OR 0.57, 95% CI 0.33 to 0.97), preterm birth (OR 0.57, 95% CI 0.46 to 0.72), intrauterine growth retardation (IUGR) (OR 0.48, 95% CI 0.31 to 0.72), gestational hypertension (OR 0.19, 95% CI 0.08 to 0.42), pre-eclampsia (OR 0.46, 95% CI 0.29 to 0.72). In contrast, a positive correlation was observed between full-term birth and HCQ use (OR 2.01, 95% CI 1.52 to 2.65). However, the result for disease flare exhibited high heterogeneity (p=0.01, I²=59%). In addition, publication bias was detected in the meta-analysis of full-term birth using the Egger's test.

Conclusions: This meta-analysis offers a comprehensive assessment of the relationship between disease activity, pregnancy-related outcomes and HCQ use, providing supportive evidence for the therapeutic effectiveness of HCQ in pregnant women with SLE.

Prospero registration number: CRD42022374468.