Integration and application of new approach methodologies in assessing the developmental hazards: Case study with an antimalarial drug

Malaria in pregnancy remains a major public health issue capable of causing significant adverse perinatal outcomes. Due to Plasmodium sequestration in the placenta (placental malaria), and the immunosuppression during pregnancy, malaria represents a substantial risk for both the mother and fetus.

Placental malaria occurs in 16%–63% of pregnant women (Darmstadt et al., 2011) with malaria and is the leading global cause of maternal anemia, low birth weight, preterm delivery, stillbirths, and miscarriages (Goldenberg et al., 2010). Each year, approximately 30–35 million women become pregnant in malaria-endemic areas of Africa, and similar numbers of women can be exposed to malaria in Asia, Oceania, and South America (Chico & Cano, 2019; World Health Organization (WHO), 2021). Unfortunately, due to a shortage of safety data on pregnant women for most of the currently recommended antimalarial drugs, there are limited treatment options for this vulnerable population, particularly in the first trimester. This highlights the need for continued improvement and development of novel antimalarial medicines with no developmental effects (teratogenicity). Over the past decades, novel antimalarials have been developed. Unfortunately, a number of these have shown to be teratogenic in preclinical animal models.

To view the full article, please visit the Wiley Online Library website.