Maternal post-absorptive leucine kinetics during late pregnancy in US women with HIV taking antiretroviral therapy: a cross-sectional pilot study.
BACKGROUND
Despite the success of combination antiretroviral therapy (cART) for the prevention of mother to child transmission of HIV, infants exposed to cARTin uterofrequently are born smaller and have mild cardiac abnormalities. The mechanisms responsible for lower birth weight and cardiac abnormalities in children exposed to cART are unclear but could be related to dysregulation of maternal amino acid metabolism during pregnancy. Previous data in HIV(-) women have shown a relationship between abnormal maternal protein metabolism during pregnancy and low infant birth weight and animal data demonstrate a relationship between altered maternal protein metabolism and increased risk for offspring cardiovascular abnormalities.


OBJECTIVE
The objectives of this study were to: characterize post-absorptive maternal leucine kinetics during late pregnancy andexamine the relationships between maternal leucine kinetics and offspring birth weight and cardiac function.


METHODS
Post-absorptive maternal leucine kinetics (evaluated by using stable isotope tracer methodology) in 16 HIV(+) women receiving cART and 14 HIV(-) US women during the 3rdtrimester of pregnancy were compared. Relationships between post-absorptive maternal leucine kinetics, cardiac function (echocardiography) and birth weight were statistically examined.


RESULTS
Maternal plasma leucine concentration (HIV(-): 82.8 ± 10.7 vs. HIV(+): 72.3 ± 13.5 μM, p=0.06) and leucine oxidation rate (HIV(-): 6.1 ± 1.6 vs. HIV(+): 4.9 ± 1.8 μmol/kgBW/min, p=0.03) were lower in HIV+ women compared to controls. Total leucine turnover rate, non-oxidative leucine disposal rate and post-absorptive maternal glucose and palmitate kinetics did not differ between groups. Left ventricular fractional shortening tended to be lower in children born to HIV(+) compared to controls (HIV(-): 42 ± 1 vs. HIV+: 36 ± 5 %, p=0.08) and associated with lower maternal plasma leucine concentration (r= 0.43, p=0.08).


CONCLUSIONS
Preliminary results indicate that post-absorptive maternal leucine metabolism during late pregnancy is mildly altered in HIV+ US women taking cART. The clinical significance of maternal leucine metabolism on adverse infant outcomes is unclear and should be further explored in more expansive studies.
Program in Physical Therapy, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
W Todd
WT
Cade
Department of Pediatrics, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Gautam K
GK
Singh
Department of Physics, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Mark R
MR
Holland
Department of Medicine, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Dominic N
DN
Reeds
Department of Medicine, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
E Turner
ET
Overton
Barnes Jewish Hospital, 1 Barnes-Jewish Hospital Plaza, St. Louis, MO, 63110, USA.
Nancy
N
Cibulka
Program in Physical Therapy, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Karen
K
Bahow
Department of Medicine, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Rachel
R
Presti
Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Andrea
A
Stephens
Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 N. Euclid St., St. Louis, MO, 63110, USA.
Alison G
AG
Cahill
HIV; amino acid; metabolism; nutrition; pregnancy