Writing in Science Translational Medicine, the team behind the study noted that previous research has identified that malaria can induce arginine deficiency.
The new work, led by researchers from the University of Toronto, found that pregnant women with malaria had lower blood levels of l-arginine than those without the disease and that this was linked to poor pregnancy outcomes.
Malaria-infected women also had a greater risk of their child being stillborn or having a low-birth weight in the prospective study of 340 pregnant Malawians.
The findings prompted the idea that supplementation of the amino acid could reverse the adverse effects of low arginine. To test this theory, the researchers studied the effects in a mouse model of malaria in pregnancy (MIP). They found that pregnant mice given L-arginine deceased the incidence of stillbirth increased birth weight compared with controls.
“We hypothesised that hypoarginaemia contributes to the pathophysiology of MIP and that L-arginine supplementation would improve birth outcomes,“ said lead author Dr. Chloe McDonald.
“In a model of experimental MIP, L-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls,” she added.
Significance
Few safe and effective interventions currently exist to help reduce adverse birth outcomes resulting from MIP. Each year, around 125 million women become pregnant in regions where malaria is endemic and where diets are poor in L-arginine. Therefore, reducing the number of such outcomes is a global health priority, emphasised the researchers.
L-arginine is an important precursor of nitric oxide (NO), which is also depleted in MIP. NO plays a critical role in vascular development of the placenta, the scientists explained.
By using computerised tomography imaging, the researchers found that l-arginine supplemented normalised the formation of blood vessels and promoted vascular development within the placenta.
“These data define a role for dysregulation of NO biosynthetic pathways in the pathogenesis of MIP and support the evaluation of interventions to enhance L-arginine bioavailability as strategies to improve birth outcomes,” concluded McDonald.
Such interventions might have wider applications in other causes of adverse pregnancy outcomes associated with placental insufficiency, the researchers added.
Commenting in a separate article in Science Translational Medicine Focus, Professor James Beeson, a leading authority in the field of MIP, of the Burnet Institute, Melbourne, said:
“The findings by McDonald and co-workers of improved outcomes in a mouse model achieved through l-arginine supplementation are exciting because of the potential simplicity, affordability, and practicality of the intervention. The use of l-arginine to improve NO bioavailability and placental function may be a suitable approach to complement current preventive interventions.”
Source: Science Translational Medicine
Volume 10, issue 431, eaan6007, doi: 10.1126/scitranslmed.aan6007
“Malaria in pregnancy alters l-arginine bioavailability and placental vascular development”
Authors: Chloe R. McDonald et al