Motherisk Program, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
J Rheumatol. 2011 Dec;38(12):2504-8. doi: 10.3899/jrheum.110686. Epub 2011 Oct 15.
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.
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).
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.
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.
抗疟药物氯喹（CQ）和羟氯喹（HCQ）已被使用了几十年，用于治疗风湿性疾病。CQ 在怀孕期间仍有益于疟疾的治疗。越来越多的研究表明，抗疟药在怀孕期间是安全的。人们一直担心在怀孕期间接触抗疟药的女性的后代会出现长期不良影响，主要是视网膜毒性。我们的目的是回顾已发表的关于怀孕期间使用抗疟药安全性的证据，重点关注后代的眼部毒性。
从 Ovid Medline、Embase 和 Cochrane Library 数据库中检索了从建立到 2010 年 5 月期间的文献，没有对语言或出版年份进行限制。纳入了随机对照试验（RCT）和观察性研究，这些研究检查了 CQ 或 HCQ 在怀孕期间的安全性，并报告了暴露于母亲的女性在随访期间的任何时间点的后代的视觉功能或眼部毒性。根据既定标准（GRADE 方法）评估证据质量。
共有 12 项研究符合纳入标准，这些研究共纳入了 588 名在母亲怀孕期间接受 CQ 或 HCQ 治疗的后代。其中 5 项研究共纳入了 251 名暴露儿童，在任何情况下均未报告临床视力异常。在一项关于疟疾预防的 RCT 中，251 名在子宫内暴露于 CQ 的婴儿的视力与安慰剂组没有差异。在 4 项研究中进行了详细的眼科检查，所有儿童（n=59）的结果均正常。使用视网膜电图进行了 3 项小型队列的电生理测试，除了 6 名 3-7 个月大的婴儿外，所有结果均正常。所有 6 名儿童在 4 岁之前的眼底检查均正常。由于比较组和结局测量的异质性，无法进行正式的荟萃分析。
目前的证据表明，怀孕期间使用抗疟药物不会对胎儿的眼部造成毒性。在一小部分婴儿中报告的早期视网膜电图异常的临床意义仍有待确定。需要进行更大的随访研究，以证实儿童在产前接触抗疟药物后眼部毒性的风险较低。
