Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jul 28;21(1):534.
doi: 10.1186/s12884-021-03965-5.

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case-control study

Megan E Smithmyer  1 , Chileshe M Mabula-Bwalya  2 , Humphrey Mwape  2 , Gabriel Chipili  2 , Bridget M Spelke  3 , Margaret P Kasaro  2   4 , Kristina De Paris  5 , Bellington Vwalika  4 , Yuri V Sebastião  3 , Jeffrey S A Stringer  3   2 , Joan T Price  3   2   4
Affiliations

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case-control study

Megan E Smithmyer et al. BMC Pregnancy Childbirth. .

Abstract

Background: Maternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway.

Methods: In a case-control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth).

Results: Compared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens.

Conclusions: We present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.

Keywords: HIV; Placental growth factor; Preterm birth; Soluble fms-like tyrosine kinase-1; Stillbirth.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Sample inclusion criteria flowchart. This flowchart describes the criteria used to select the subset of ZAPPS specimens that were included in this analysis as either cases or controls
Fig. 2
Fig. 2
Concentrations of A) sEng B) PlGF and C) sFLT-1 in 57 controls and 57 cases, analyzed using Luminex assays. The threshold for statistical significance was set to p < 0.05, as calculated using Wilcoxon rank-sum
See this image and copyright information in PMC

References

    1. UN Joint Programme on HIV/AIDS (UNAIDS) The gap report. Geneva: UNAIDS; 2014.
    1. Wedi COO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Perinatal outcomes associated with maternal HIV infection: A systematic review and meta-analysis. Lancet HIV. 2016;3:e33–48. doi: 10.1016/S2352-3018(15)00207-6. - DOI - PubMed
    1. Obimbo MM, Zhou Y, Mcmaster MT, Cohen CR, Qureshi Z, Ong’ech J, et al. Placental structure in preterm birth amongst HIV positive versus negative women in Kenya. JAIDS J Acquir Immune Defic Syndr. 2018;1. doi:10.1097/QAI.0000000000001871. - PMC - PubMed
    1. Kalk E, Schubert P, Bettinger JA, Cotton MF, Esser M, Slogrove A, et al. Placental pathology in HIV infection at term: a comparison with HIV-uninfected women. Trop Med Int Heal. 2017;22:604–613. doi: 10.1111/tmi.12858. - DOI - PubMed
    1. Conroy AL, McDonald CR, Gamble JL, Olwoch P, Natureeba P, Cohan D, et al. Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV. Am J Obstet Gynecol. 2017;217:684.e1–684.e17. doi: 10.1016/j.ajog.2017.10.003. - DOI - PMC - PubMed

Substances