(McGready et al., 2001). Another study of 287 pregnant Gambian women inadvertently treated (during a mass drug administration) with a single dose of artesunate plus SP during their first, second, or third trimesters of pregnancy found no evidence of obstetric or fetal toxicity compared with women who were not exposed to artesunate plus SP (Deen et al., 2001). There are no published data on the use of artemether-lumefantrine in pregnant or breast-feeding women.

Evidence from Experimental Animals

Studies investigating the possible risks of artemisinins in during the first trimester of pregnancy (when birth defects are most likely to occur), also have been conducted in laboratory animals. In 2001, a WHO report concluded: “Preclinical studies have consistently shown that artemisinin and its derivatives do not exhibit mutagenic or teratogenic activity, but all of these drugs caused fetal resorption in rodents at relatively low doses” (WHO, 2001). More recently, in some experiments in rats and rabbits, but not in others, cardiovascular and limb abnormalities occurred when pregnant animals were given artemisinin doses similar to those used in man. For this reason, in 2002, WHO convened two further meetings of experts who reviewed the animal and human evidence relevant to the use of artemisinins by pregnant women, concluding:

Presently, artemisinin compounds cannot be recommended for treatment of malaria in the first trimester. However, they should not be withheld if treatment is considered to be lifesaving for the mother and other antimalarials are considered to be unsuitable. Because the safety data are limited, artemisinin compounds should only be used in the second and third trimesters when other treatments are considered unsuitable.

There is a need for further evidence of the safety of artemisinin compounds in pregnancy. All pregnant women treated with artemisinin compounds should be carefully followed up to document the pregnancy outcomes and subsequent development of the child and reported to the appropriate authorities. (WHO/RBM/UNDP/World Bank, 2003).

In summary, current data are encouraging but more safety data for the artemisinin derivatives are needed to support use in pregnant women with uncomplicated malaria. In contrast, although there are no published data regarding the treatment of severe malaria in pregnancy with artesunate or artemether, these drugs have been used widely and found effective. In particular, artesunate and artemether are often preferred over quinine and quinidine during pregnancy because they do not induce hypoglycemia, and they are easier to administer (Tran et al., 1996). Nonetheless, if ACTs are widely introduced, tens of thousands of pregnant African women—includ-



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