Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta‐analysis

Abstract

AIMSThe objective of this meta-analysis was to determine whether gestational use of hydroxychloroquine (HCQ) for autoimmune disorders leads to an increase in the risk for adverse pregnancy outcomes. METHODSMEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from inception to November 21 2014. Studies which reported the outcomes of pregnant women after exposure to HCQ during pregnancy and including a control (unexposed) group were included. Two independent reviewers carried out the review and the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). A random effects method was used to calculate the odds ratios (OR) for the outcomes. RESULTSThe meta-analysis reported no significant increases in rates of major congenital (OR 1.13, 95% confidence interval (CI) 0.59, 2.17), craniofacial (OR 0.62, 95% CI 0.13, 3.03), cardiovascular (OR 1.06, 95% CI 0.29, 3.86), genitourinary (OR 1.38, 95% CI 0.42, 4.53), nervous system malformations (OR 1.81, 95% CI 0.31, 10.52), stillbirth (OR 0.69, 95% CI 0.35, 1.34), low birth weight (OR 0.69, 95% CI 0.21, 2.27) or prematurity (OR 1.75, 95% CI 0.95, 3.24). The rate of spontaneous abortions, however, was found to be significantly increased in HCQ exposed pregnancies (OR 1.85, 95% CI 1.10, 3.13). No significant heterogeneity was detected among the studies for the evaluated outcomes except prematurity. CONCLUSIONSPrenatal exposure to HCQ for autoimmune diseases does not appear to increase the risk of adverse pregnancy outcomes except spontaneous abortion rate, which may be associated with the underlying disease activity (bias by indication) and needs further investigation.

Lysosomal membrane permeabilization and cell death

“…Examples of CADs include the antimalarial agent chloroquine (CQ) and its derivatives, which have been used to treat several human diseases, albeit with severe side effects. Combinations of CQ and other drugs have been developed to treat cancer and autoimmune diseases . CADs have been extensively researched and are being studied as potential anticancer agents, and it has been speculated that CAD treatment may enhance the cellular accumulation of secondarily administered amine drugs .…”

Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage

“…Similarly, cumulative clinical data in pregnant women with autoimmune disorders, such as SLE, have suggested no HCQ‐related adverse effect on the fetus, with the exception of one meta‐analysis that noted an increased rate of spontaneous abortion. However, this analysis was potentially biased by the higher underlying disease activity and older age of the HCQ‐exposed group . Tarfaoui et al analysed the results of nine studies enrolling 246 new‐borns who were exposed to HCQ in utero and screened at birth for ocular damage.…”

Improvement of type 2 diabetes mellitus control with hydroxychloroquine added to triple oral antidiabetis drugs: a case report

“…It is used, either alone or in combination with other agents, in the management of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases [3].…”