Malaria in pregnancy alters l-arginine bioavailability and placental vascular development

McDonald, Chloe R., Cahill, Lindsay S., Gamble, Joel R., Elphinstone, Robyn, Gazdzinski, Lisa M., Zhong, Kathleen J. Y., Philson, Adrienne C., Madanitsa, Mwayiwawo, Kalilani-Phiri, Linda, Mwapasa, Victor, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617, Sled, John G., Conroy, Andrea L. and Kain, Kevin C. (2018) 'Malaria in pregnancy alters l-arginine bioavailability and placental vascular development'. Science Translational Medicine, Vol 10, Issue 431, eaan6007.

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Abstract

Reducing adverse birth outcomes due to malaria in pregnancy (MIP) is a global health priority. However, there are few safe and effective interventions. l-Arginine is an essential amino acid in pregnancy and an immediate precursor in the biosynthesis of nitric oxide (NO), but there are limited data on the impact of MIP on NO biogenesis. We hypothesized that hypoarginemia contributes to the pathophysiology of MIP and that l-arginine supplementation would improve birth outcomes. In a prospective study of pregnant Malawian women, we show that MIP was associated with lower concentrations of l-arginine and higher concentrations of endogenous inhibitors of NO biosynthesis, asymmetric and symmetric dimethylarginine, which were associated with adverse birth outcomes. In a model of experimental MIP, l-arginine supplementation in dams improved birth outcomes (decreased stillbirth and increased birth weight) compared with controls. The mechanism of action was via normalized angiogenic pathways and enhanced placental vascular development, as visualized by placental microcomputerized tomography imaging. 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.

Item Type:	Article
Subjects:	WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WQ Obstetrics > Pregnancy > WQ 200 General works WQ Obstetrics > Pregnancy Complications > WQ 240 Pregnancy complications (General)
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1126/scitranslmed.aan6007
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	13 Mar 2018 09:55
Last Modified:	07 Sep 2018 01:02
URI:	https://archive.lstmed.ac.uk/id/eprint/8359

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