Poster Presentation First Malaria World Congress 2018

Could a triple-hit hypothesis explain the pathway from malaria in pregnancy to adverse child neurodevelopmental outcomes? (#323)

Harriet L. S. Lawford 1 , Mary C. Ghazawy 1 , Tessa R. Donaldson 2 , Jack Donaldson 3 , Samudragupta Bora 1
  1. Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia
  2. Department of Psychology, University of Canterbury, Christchurch, New Zealand
  3. Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

Each year, millions of pregnant women in malaria-endemic areas are at risk of Plasmodium falciparum infection and the development of placental malaria. Whilst the neurodevelopmental consequences of cerebral malaria in children have been widely documented in recent years, there has been little focus on the impact of placental malaria on child neurodevelopment. This is critical to address, given that placental malaria has frequently been associated with adverse birth outcomes including preterm birth, low birthweight and intrauterine growth restriction, which themselves are well recognized independent risk factors for adverse short-term and long-term neurodevelopment. Furthermore, the additive effects of prenatal environmental and sociocultural factors on child neurodevelopment remain poorly understood. Hence, we propose a Triple-Hit Hypothesis to explain the potential pathway from placental malaria to poor child neurodevelopmental outcomes. As per our hypothesis, placental infection and dysfunction represent the first-hit that leads to direct activation of immune-inflammatory factors and oxidative stress in utero, and consequently adverse neurodevelopment. The severity of maternal malaria infection represents the second-hit, wherein the risk of poor neurodevelopment is indirectly impacted by the increased likelihood of adverse birth outcomes associated with infection. Finally, associated risk factors for placental malaria including poverty, malnutrition and lack of access to quality healthcare, represent the third-hit in this developmental pathway. Taken together, these multiple hazards culminate in a unique fetal phenotype, where not only do we expect to see the adverse birth outcomes commonly associated with placental malaria, but also adversities including increased risks of neurological, cognitive and behavioral deficits that may impact the quality of life in this high-risk population.