Which among the following is the safest antimalarial drug during pregnancy?

Proguanil is a prodrug; only its triazine metabolite, cycloguanil is a selective inhibitor of the bifunctional plasmodial dihydrofolate reductase-thymidylate synthetase that is crucial for parasite de novo purine and pyrimidine synthesis. Proguanil is considered safe for use during pregnancy. It is remarkably safe when used in conjunction with other antimalarial drugs such as chloroquine, atovaquone, tetracyclines, and other antifolates. Quinine appears to be safe in pregnancy and is used commonly for the treatment of pregnancy-associated malaria but there is increased risk of hypoglycemia. There are increased rate of stillbihs with mefloquine use, especially during the first trimester. Pregnancy should be avoided for 3 months after mefloquine use because of the prolonged t1/2 of this agent. At high doses, pyrimethamine is teratogenic in animals, and in humans the related combination, trimethoprim-sulfamethoxazole, may cause bih defects. Ref: Vinetz J.M., Clain J., Bounkeua V., Eastman R.T., Fidock D. (2011). Chapter 49. Chemotherapy of Malaria. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e.