Hydroxychloroquine significantly decreases the risk of preeclampsia in pregnant women with autoimmune disorders: a systematic review and meta-analysis

Abstract

This meta-analysis aimed to investigate whether hydroxychloroquine (HCQ) intervention could decrease the incidence of preeclampsia and other maternal and fetal outcomes among pregnant women with autoimmune disorders. PubMed, EMBASE, Web of Science, and the Cochrane databases were searched from inception until January 2022. Data on maternal or fetal outcomes of the control and hydroxychloroquine treatment groups were gathered and analyzed. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were determined. Cochran's Q test, I² statistics, leave-one-out analysis, Baujat plot analysis, GOSH plot analysis, and multivariable meta-regression were applied to assess between-study heterogeneity. The meta-analysis was performed using the Stata V.16.1 software. Baujat plot analysis and GOSH plot analysis were performed using the R V.4.0.0 software. Our study included 21 cohort studies and one case-control study with a total of 3948 pregnancies with immune disorders. HCQ treatment significantly reduced the incidence of preeclampsia (OR 0.45, 95% CI 0.33-0.63, p = 0.000, I² 3.68%). After outlier omission, HCQ treatment significantly reduced the incidence of premature delivery (OR 0.84, 95% CI 0.73-0.96, p = 0.01, I² 44.81%) in pregnant women with autoimmune disorders. In sub-group analysis, HCQ also significantly reduced the incidence of gestational hypertension (OR 0.42, 95% CI 0.26-0.68, p = 0.001, I² 49.33%) and preterm birth (OR 0.63, 95% CI 0.48-0.82, p = 0.001, I² 27.63%) in pregnant women with lupus. The heterogeneity of the findings mentioned above was low to moderate. There were no significant differences in the risk of other outcomes, including gestational diabetes, HELLP syndrome, thrombosis, spontaneous abortion, fetal loss, small for gestational age infant (SGA), low birth weight, stillbirth, APGAR score < 7, and congenital malformation. This meta-analysis indicated that HCQ treatment could significantly decrease the incidence of preeclampsia and premature delivery in pregnant women with autoimmune disorders. In addition, HCQ could reduce the risk of gestational hypertension in pregnant lupus patients.

Keywords: Fetal outcomes; Hydroxychloroquine; Maternal outcomes; Preeclampsia; Pregnancy.