Atovaquone-proguanil exposure in pregnancy and risk for adverse fetal and infant outcomes: A retrospective analysis

Background: Malaria in pregnancy can cause severe maternal and fetal complications. Chloroquine (CQ) and mefloquine (MQ) are recommended for chemoprophylaxis in pregnancy, but are not always suitable. Atovaquone-proguanil (AP) might be a viable option for malaria prevention in pregnancy, but more safety data are needed. Methods: Data for pregnancies and live births among active duty military women, 2003-2014, from the Department of Defense Birth and Infant Health Research program were linked with pharmacy data to determine antimalarial exposure. Multivariable Cox and logistic regression models were used to assess the relationship of antimalarial exposure with fetal and infant outcomes, respectively. Results: Among 198,164 pregnancies, 50 were exposed to AP, 156 to MQ, and 131 to CQ. Overall, 17.6% of unexposed pregnancies and 28.0%, 16.0%, and 6.1% of pregnancies exposed to AP, MQ, and CQ, respectively, ended in fetal loss (spontaneous abortion or stillbirth) (adjusted hazard ratios [aHR] = 1.46, 95% confidence interval [CI] 0.87-2.46; aHR = 1.06, 95% CI 0.72-1.57; and aHR = 0.47, 95% CI 0.24-0.94, respectively). Conclusions: The small number of AP exposed pregnancies highlights the difficulty in assessing safety. While definitive conclusions are not possible, these data suggest further research of AP exposure in pregnancy and fetal loss is warranted. Twitter line: More research on fetal loss following atovaquone-proguanil exposure in pregnancy is warranted.