Abstract:
Background: 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.
Methods: 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.
Results: 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%]).
Conclusion: 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.
