Maternal post-absorptive leucine kinetics during late pregnancy in US women with HIV taking antiretroviral therapy: A cross-sectional pilot study

Abstract

Background Despite the success of combination antiretroviral therapy (cART) for the prevention of mother to child transmission of HIV, infants exposed to cART in utero frequently 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 and examine the relationships between maternal leucine kinetics and offspring birth weight and cardiac function. Design 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 3rd trimester 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.

The association between HIV (treatment), pregnancy serum lipid concentrations and pregnancy outcomes: a systematic review

“…The quality of the studies was acceptable. A high risk of bias arose from studies that did not mention [ 28 – 34 ] or control [ 35 – 37 ] for confounders in their analysis (53%, n = 9). Other studies did not provide a definition of outcome (41%, n = 7), [ 28 , 29 , 31 – 33 , 37 , 38 ] used data originating from hospital databases (41%, n = 7) or had missing data (41%, n = 7).…”

“…Two studies measured serum lipid concentrations in all trimesters [ 38 , 40 ]. In two studies serum lipids in HIV-infected and -uninfected pregnant women were compared [ 35 , 40 ]. Cade et al [ 35 ] studied 16 HIV-infected and 14 -uninfected pregnant women who were of similar age, height, weight, and gestational weight gain (GWG) in the third trimester of pregnancy and found serum lipids to be comparable.…”

“…In two studies serum lipids in HIV-infected and -uninfected pregnant women were compared [ 35 , 40 ]. Cade et al [ 35 ] studied 16 HIV-infected and 14 -uninfected pregnant women who were of similar age, height, weight, and gestational weight gain (GWG) in the third trimester of pregnancy and found serum lipids to be comparable. Luzi et al [ 40 ] included 14 HIV-infected (8 (57%) African) and 19 –uninfected (100% Caucasian) pregnant women of similar age and found that TC and LDL-C were significantly higher in the HIV-uninfected group compared to the HIV-infected group in the second and third trimester.…”

“…The lack of HIV-uninfected control groups in the studies included in this review limited our ability to assess the contribution of HIV-infection to changes in serum lipid concentration during pregnancy and the consequences for pregnancy outcome. The only two studies that compared an HIV-infected to an HIV–uninfected group found lipids to be higher in the uninfected group [ 35 , 40 ].…”