Ocular toxicity in children exposed in utero to antimalarial drugs: review of the literature

Abstract

Objective: The antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been used for decades to treat rheumatic diseases. CQ is still beneficial for the management of malaria during pregnancy. A growing body of research suggests that antimalarials are safe during pregnancy. There have been concerns about adverse longterm effects, mainly retinal toxicity, in offspring of women exposed to antimalarials during pregnancy. Our objective was to review the published evidence on safety of antimalarials during pregnancy, focusing on ocular toxicity in the offspring.

Methods: Ovid Medline, Embase, and Cochrane Library databases were searched for the period from their inception to May 2010 inclusive with no restrictions on language or year of publication. Randomized controlled trials (RCT) and observational studies examining the safety of CQ or HCQ during pregnancy and reporting on visual function or ocular toxicity in the offspring of exposed women at any point of the followup were eligible for inclusion. The quality of evidence was assessed according to established criteria (the GRADE approach).

Results: Twelve studies with a total of 588 offspring born to mothers treated with CQ or HCQ during pregnancy met the inclusion criteria. Five studies with a total of 251 exposed children reported no clinical visual abnormalities in any case. In an RCT on malaria prophylaxis, visual acuity in 251 infants exposed to CQ in utero did not differ from the placebo group. Detailed ophthalmological examination was performed in 4 studies and normal results were reported in all children (n = 59). Electro-physiological testing using electroretinogram was performed in 3 small cohorts and results were normal in all but 6 infants aged 3-7 months. All 6 children had normal fundoscopy before 4 years of age. Heterogeneity in comparison groups and in outcome measures precluded formal metaanalysis.

Conclusion: Current evidence suggests no fetal ocular toxicity of antimalarial medications during pregnancy. The clinical significance of early electroretinogram anomalies reported in a small subset of infants remains to be established. Larger followup studies are warranted to confirm low risk of ocular toxicity in children following antenatal exposure to antimalarial medications.