‘Malaria in pregnancy causes cognitive defects in offspring’

CAN malaria be the reason why children in Sub Saharan Africa have slower cognitive development than their counterparts from the West?
New research shows a causal link and reveals the mechanisms by which malaria in pregnancy alters the neurocognitive development of millions of children prior to birth.

Although there are some 125 million pregnancies worldwide at risk of malaria infection every year, little was known about the effect maternal malaria may have on the neurodevelopment of the unborn child.

What this new research – published in PLOS Pathogens by a team from the University of Toronto, Canada – shows is that given how the environment in the uterus profoundly impacts on the development of a person, malaria in pregnancy does lead to neurocognitive impairment of offspring.

The research team wanted to know if there was a causal link between malaria in pregnancy and neurocognitive impairment and, if this was the case, what mechanisms were causing this to occur, with particular reference to previous research on the mechanism known as “C5a signaling.”

To reach their findings, the researchers used a mouse model of experimental malaria in pregnancy.
As low birth-weight and fetal malaria mechanisms also affect neurodevelopment, these were eliminated from the experiment as possible complicating factors.

In this experiment, young mice exposed to malaria in pregnancy were found to have impaired learning, impaired memory and showed depressive-like behavior throughout their lives.

These impairments and behavior changes caused by malaria in pregnancy, it was found, were associated with lower levels of serotonin, dopamine, and norepinephrine – the major neurotransmitters in specific regions of the brain.

The excessive production of C5a – a potent inflammatory peptide – has already been identified in previous studies as a critical mediator of placental and fetal injury in a noninfectious mouse model of spontaneous miscarriage.

C5a has also been linked to both neurodevelopment and adverse birth outcomes after malaria exposure in pregnancy. For this reason, the researchers then tested whether C5a signaling played a role between malaria in pregnancy and neurocognitive impairment in the developing offspring.

In their tests, the researchers found that disrupting maternal C5a signaling in pregnant mice exposed to malaria restored neurotransmitter levels. The result was that neurocognitive defects in the mice offspring were completely rescued, thus indicating the role of C5a in the processes.

These results, the researchers say, “highlight a novel mechanism by which malaria in pregnancy may alter the neurocognitive development of millions of children prior to birth.”

They add: “A prospective study is underway to confirm these findings in African children exposed to malaria in utero. It is essential to identify preventable risk factors that can be modified to decrease the risk of developmental delay in children. This study suggests that malaria in pregnancy is one such factor that can be targeted. … in order to improve cognitive development and school performance in malaria-endemic regions.”