Project Lead(s): Andrea Conroy
Issue
In sub-Saharan Africa, an estimated 25% of all pregnancies show signs of malaria infection in the placenta at delivery.
During pregnancy, malaria-infected red blood cells preferentially accumulate in the placenta, resulting in maternal anemia, miscarriage, poor fetal growth, preterm birth and stillbirth.
A central component of antenatal care in malaria-endemic regions is the administration of a single dose of safe, effective and long-lasting antimalarial drug at each antenatal visit, starting mid-pregnancy.
However, the emergence of widespread resistance against antimalarial drugs currently used and a lack of safe alternatives threaten the success of these programs.
Solution
The project investigated whether malaria infection in pregnancy is associated with reduced L-arginine levels and whether L-arginine supplementation in an animal model of malaria in pregnancy would improve fetal survival and birth weight.
L-arginine is a conditionally essential amino acid in humans, meaning that it can be produced by the body and does not need to be obtained from the diet in most circumstances. However, if the body is unable to make enough L-arginine to meet metabolic needs, increased dietary consumption of L-arginine or supplementation of L-arginine may be required.
In addition, population survey data were used to assess consumption of L-arginine in Malawian women to understand dietary sources of L-arginine to devise appropriate supplementation/fortification programs.
Outcome
The most significant achievement of the study was to demonstrate that L-arginine improves fetal survival and growth in a preclinical animal model (mice), with no adverse effects
Compared to pregnant mice not exposed to malaria, mice infected with malaria had a 49% decrease in fetal viability. When malaria-infected mice were supplemented with L-arginine in pregnancy, the mice receiving L-arginine had a 23% increase in fetal viability, compared to the group not receiving L-arginine.
L-arginine supplementation had a modest, but statistically significant, effect on increasing fetal weight, with fetuses from mice receiving L-arginine in pregnancy being 4% heavier than those not receiving L-arginine.
Provided the study team can demonstrate an L-arginine supplement improves birth outcomes in a clinical trial, they will begin discussions with stakeholders in Malawi (e.g., the Ministry of Health) to explore the sustainability and financial feasibility of administering an L-arginine nutritional supplement to pregnant women as policy.