Mosha Dominic, Mazuguni Festo, Mrema Sigilbert, Sevene Esperanca, Abdulla Salim, Genton Blaise
Ifakara Health Institute, Rufiji HDSS, P,O Box 40, Rufiji, Tanzania.
Malar J. 2014 May 27;13:197. doi: 10.1186/1475-2875-13-197.
There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy.
Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery.
2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]).
Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.
关于青蒿素在孕早期的安全性资料有限。因此，由于动物研究中显示的胚胎 - 胎儿毒性，世界卫生组织不建议将其作为孕早期疟疾的一线治疗药物。本研究评估了孕早期意外暴露于蒿甲醚 - 本芴醇（AL）的孕妇的分娩结局，并与同期暴露于其他抗疟药物或未用药的孕妇进行比较。
从孕产妇保健诊所或每月的家访（人口监测）中招募孕周小于20周的孕妇，并进行前瞻性随访直至分娩。
共招募了2167名孕妇，其中1783名（82.3%）完成研究直至分娩。319名（17.9%）孕妇在孕早期使用了抗疟药物，其中172名（53.9%）使用了（AL），78名（24.4%）使用了奎宁，66名（20.7%）使用了磺胺多辛 - 乙胺嘧啶（SP），11名（3.4%）使用了阿莫地喹。孕早期暴露于奎宁与流产/死产风险增加（比值比2.5；1.3 - 5.1）和早产风险增加（比值比2.6；1.3 - 5.3）相关，而暴露于AL的孕妇流产/死产风险为（比值比1.4；0.8 - 2.5），早产风险为（比值比0.9；0.5 - 1.8）。在4个暴露组中发现了先天性异常，即仅暴露于AL组（1/164[0.6%]）、仅暴露于奎宁组（1/70[1.4%]）、暴露于SP组（2/66[3.0%]）和非抗疟药物暴露组（19/1464[1.3%]）。
孕早期暴露于AL比暴露于其他任何抗疟药物更为常见。暴露于奎宁与不良妊娠结局相关，而摄入其他抗疟药物则未出现这种情况。由于使用AL和奎宁是根据其可获得性而非疾病严重程度，观察到的效应可能与药物有关而非疾病本身。即便如此，已经可以设想在整个孕期将治疗单纯性疟疾的政策从奎宁改为AL。
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