Background Some countries face restrictions to prescribe Chloroquine (CQ) and Hydroxychloroquine (HCQ) during pregnancy, due to report of ocular toxicity in rodents and potential genotoxicity. The aim of this study was to perform a systematic literature review (SLR) and a meta-analysis of fetal malformation rates under CQ and HCQ (all indications) during pregnancy. In the subgroup of patients suffering from systemic lupus erythematosus (SLE), we performed an analysis of CQ and HCQ efficacy on maternofetal outcomes.
Methods Two independent reviewers searched literature from inception to September 2019 (via Pubmed, Embase and abstracts from ACR and EULAR congresses) for studies that compare fetal malformation rates and pregnancy outcomes of CQ/HCQ versus placebo. A meta-analysis was performed to estimate a global risk difference for malformation rate and pregnancy outcomes, considering a p-value threshold of 5%.
Results From 2835 articles, the literature search revealed 127 articles and abstracts of interest. For the fetal malformation safety analysis, we identified 16 studies fulfilling required criteria. Selected articles include a total of 2068 exposed children of mothers treated by CQ/HCQ for autoimmune diseases or malaria indication, compared to 16294 children in control group. The meta-analysis did not show any differences of malformation rate for patients treated by HCQ compared to non-treated ones (DR=0,00 [-0.01, 0.00]95%; p=0.04, I2=2%)(figure 1).
Regarding pregnancy outcomes in SLE patients, we found 14 studies. The meta-analyses showed a protective effect of HCQ for disease flare (OR=0.48 [0.27, 0.87]95%; p=0.02; I2=56%), prematurity (OR=0.61 [0.40, 0.93]95%; p=0.02; I2=47%), and pre-eclampsia (OR=0.49 [0.59, 1.01]95%; p=0.05; I2=49%). The analyses did not reveal any significant difference for fetal growth restriction or congenital atrioventricular block. The SLR also identified uncontrolled cohort studies suggesting importance of HCQ in preventing lupus flares.
Conclusion Prenatal exposure to CQ or HCQ is not associated with higher rate of congenital abnormalities, and is associated with improvement of maternofetal outcomes.
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