Intrauterine Growth Restriction in Babies Born to Cameroonian HIV-Positive Women: Identification of Possible Mechanisms Responsible for Low Birth Weight

HIV increases the risk of intrauterine growth restriction (IUGR), which results in the delivery of low birth weight (LBW) babies, who are 40 times more likely to die during their first year of life. However, the mechanism(s) for IUGR among HIV-exposed newborns remain unknown. In addition to socioeconomic and cultural factors, several hypotheses have been proposed to explain the biological component of IUGR. These include reduced 1) placental angiogenesis and vasculogenesis, 2) production of fetal growth hormones, and 3) transportation of nutrients. The first two hypotheses were examined in this investigation. To evaluate altered vessel formation, placental plasma levels of angiopoietins, ANG-1 and ANG-2, and galectin-13 were measured. Levels of insulin-like growth factor-1 (IGF-1) and one of its binding proteins, IGFBP-1, were measured to evaluate growth hormone dysregulation. In this case-control study, 21 HIV-positive and 30 HIV-negative pregnant mothers were recruited at delivery in the Central Hospital of Yaoundé, Cameroon, Africa. Results showed that biomarker levels in HIV-negative women were similar to literature values for healthy adults; but no significant differences were observed among the different groups. However a statistically significant (p=0.028) declining pattern of galectin-13 levels was noted as the severity of HIV infection increased. Overall, our results suggest that decreased angiogenesis and reduced production of growth factors may not cause LBW, but the dysregulation of maternal vascular development may play a role. Further studies using additional biomarkers are needed to identify the combination of social, economic and biological risk factors that increase the risk of HIV-associated LBW babies.Microbiolog

Impact of HIV-1 infection on the IGF-1 axis and angiogenic factors in pregnant Cameroonian women receiving antiretroviral therapy.

Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria