Burnet Institute researchers have identified the first mechanism linking malaria in pregnancy and the increased risk of delivering low birth weight babies.
This discovery could enhance the prospects of neonatal survival in the 85 million pregnancies exposed to malaria globally every year.
Lead researcher Dr Philippe Boeuf said the study is important because placental malaria is a major cause of low birth weight, which is the main risk factor in about 80 percent of neonatal deaths.
Children born low birth weight are also at a higher risk of intellectual development issues, and are more susceptible in adulthood to chronic diseases such as diabetes.
“Before now, no one understood the link between being infected with malaria in pregnancy and having an increased risk of delivering a low birth weight baby,” Dr Boeuf said.
“But we’ve identified the first mechanism that links the two, and this gives us the opportunity to try to improve fetal growth, and therefore, birth weight.
“Because low birth weight is the main cause of neonatal death, if we improve the birth weight, this could have a significant impact on neonatal survival, and allow a healthier adult life.”
The study was conducted principally by PhD candidate Genelyn Dimasuay in collaboration with colleagues from the University of Colorado Denver, the University of Manchester, and the University of Melbourne, and published in the prestigious BMC Medicine journal.
It demonstrates that inflammation caused by malaria disrupts a signalling pathway called mTOR, which impairs the capacity of the placenta to transport amino acids from maternal blood to the fetus; a major determinant of fetal growth and therefore birth weight.
The focus on mTOR gives scientists the opportunity to design interventions to promote its activity to restore the transport of nutrients to promote fetal growth, and therefore improve neonatal survival and adult health.
“There have been quite a few trials of nutritional supplementation of malaria-exposed pregnant women that had relatively modest impact on birth weight. We think that’s because those interventions haven’t been targeted specifically at mTOR,” Dr Boeuf said.
“The view of most of these interventions has been, well, these women and/or their fetuses are not getting enough nutrients, therefore if we give mothers dietary supplements, that should improve birth weight, but results have largely been inconsistent.
“The approach we are taking is, OK, we know that mTOR inhibition appears to be a driver of low birth weight, so let’s research ways to activate mTOR, and those that show any effect, we’ll take further and hopefully to implementation.”
Dr Boeuf said the next step is to test a range of mTOR activators shown to be safe in pregnancy, initially in vitro, and then eventually in a clinical trial as part of Burnet’s Healthy Mothers, Healthy Babies project in Papua New Guinea, where low birth weight is highly prevalent and 5,000 babies die each year in their first month of life.
Dr Boeuf underlines that the research findings are likely to have broader impact than for malaria-infected women, and could be relevant to inflammation in pregnancy caused by other pathogens.
“In combination with malaria control strategies such as bed nets, we believe that interventions aimed at restoring mTOR activity in the placenta could translate into improved birth weight and, in turn, improved survival and adult health for these tens of millions of pregnancies exposed to malaria every year.”