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How Maternal Malaria Reduces Foetal Growth

The discovery of why malaria in pregnancy leads to an increased risk of low birth weight babies could enhance the prospects of neonatal survival in the 85 million pregnancies exposed to malaria globally every year.

Lead researcher Dr Philippe Boeuf of the Burnet Institute said that low birth weight is the main risk factor in about 80% of neonatal deaths. Low birth weight children 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,” Boeuf said. “But we’ve identified the first mechanism that links the two, and this gives us the opportunity to try to improve foetal 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, published in BMC Medicine, demonstrates that inflammation caused by malaria disrupts a signalling pathway called mTOR. This impairs the capacity of the placenta to transport amino acids from maternal blood to the foetus – a major determinant of foetal growth and therefore birth weight.

The focus on mTOR gives scientists the opportunity to design interventions to promote its activity in order to restore the transport of nutrients 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,” Boeuf said.

“The view of most of these interventions has been, well, these women and/or their foetuses 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.”

Boeuf said the next step is to test a range of mTOR activators that are safe to take during pregnancy, initially in vitro, and then eventually in a clinical trial in Papua New Guinea, where low birth weight is highly prevalent and 5000 babies die each year in their first month of life.

Boeuf says that the research findings could also be relevant to inflammation in pregnancy caused by other pathogens.