Artemisinin combination therapies (ACTs), medications widely used against malaria, are safe to administer to women in their first trimester of pregnancy, according to new research published in PLoS Medicine. ACTs had previously been recommended at that stage of pregnancy only in life-saving circumstances.

The international collaboration was led by first authors Stephanie Dellicour of the Liverpool School of Tropical Medicine, UK, and Esperança Sevene of the Manhiça Health Research Centre/Eduardo Mondlane University, Maputo, Mozambique, and senior author Andy Stergachis of the University of Washington School of Pharmacy and School of Public Health. The research team released the largest meta-analysis of all observational studies to date showing there was no difference in the risk of miscarriage, still births or major birth defects associated with the use of artemisinins anytime during the first trimester, compared with quinine.

“Our results show that artemisinins can now be formally considered for first trimester treatment,” said Stergachis, professor of pharmacy and global health. “While there is more work to be done in terms of monitoring birth defects, the available evidence suggests that the benefits of using this class of antimalarial are likely to outweigh any adverse outcomes.”

Malaria is more common and more severe in pregnant women, increasing their risk of miscarriage and other adverse outcomes. The potential harm of malaria in pregnancy requires prompt treatment, and the World Health Organization currently recommends ACTs for pregnant women in the second or third trimesters.

Until now, though, data was limited about ACTs' safety and effectiveness in the first trimester.  The findings may result in reconsideration of guidelines regarding artemisinins.

“We have been able to show that artemisinins, which we know to improve outcomes in malaria, are as safe to use in the first trimester as quinine, which is currently recommended but needs to be taken three times per day for seven days," said Liverpool’s Feiko ter Kuile, head of the Malaria in Pregnancy Consortium. "Quinine is associated with transient side effects such a ringing in the ears and dizziness, leading women not to complete their treatment course and risking inadequately treating their malaria. The artemisinin-based combinations are more efficacious, much better tolerated and can be taken over three days.”

The team analyzed data from 30,618 pregnancies involved in five earlier studies. They examined the records of women who had taken artemisinins for malaria, including during the first trimester of pregnancy. In malaria-endemic countries, many early pregnancies are exposed to artemisinins because women taking the therapy are not aware they are pregnant or do not report an early pregnancy.

The research effort was coordinated through the Malaria in Pregnancy Consortium, established in 2007 at the Liverpool school to improve the control and prevention of malaria in pregnancy. The consortium is funded through a grant from the Bill & Melinda Gates Foundation.