Over half of all pregnant women world-wide are at risk for malaria, but little is known about possible consequences for the neurodevelopment of children exposed to malaria in pregnancy, researchers said.
They report a causal link between pre-natal exposure to malaria and subsequent neurocognitive impairment in offspring in a mouse model of experimental malaria in pregnancy.
The research also identifies some of the molecular mechanisms involved.
Kevin Kain, from the University of Toronto, Canada, and colleagues examined neurocognitive function in mice of normal birth weight that had been exposed to - but not themselves infected with - malaria in the uterus.
These neurocognitive impairments are associated with decreased tissue levels of major neurotransmitters (serotonin, dopamine, and norepinephrine) in specific regions of the brain, researchers said.
Pushing the technology by imaging blood vessels in the uterus, the researchers also saw changes in neurovascular development in the brain of malaria-exposed mouse foetuses.
Because a specific immune system factor called C5a had previously been linked to both neurodevelopment and adverse birth outcomes after malaria-exposure in pregnancy, the researchers next tested whether C5a signalling played a role in the link between malaria during pregnancy and neurocognitive impairment they discovered.
In other words, mothers with defective C5a signalling that had malaria in pregnancy gave birth to malaria-exposed pups without detectable neurocognitive abnormalities.
These results "highlight a novel mechanism by which malaria in pregnancy may alter the neurocognitive development of millions of children prior to birth," researchers said.
"A prospective study is underway to confirm these findings in African children exposed to malaria in utero," they said.
The study was published in the journal PLOS Pathogens.