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

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 throug...

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Autores principales: Smithmyer, Megan E., Mabula-Bwalya, Chileshe M., Mwape, Humphrey, Chipili, Gabriel, Spelke, Bridget M., Kasaro, Margaret P., De Paris, Kristina, Vwalika, Bellington, Sebastião, Yuri V., Stringer, Jeffrey S.A., Price, Joan T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317322/
https://www.ncbi.nlm.nih.gov/pubmed/34320947
http://dx.doi.org/10.1186/s12884-021-03965-5
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author Smithmyer, Megan E.
Mabula-Bwalya, Chileshe M.
Mwape, Humphrey
Chipili, Gabriel
Spelke, Bridget M.
Kasaro, Margaret P.
De Paris, Kristina
Vwalika, Bellington
Sebastião, Yuri V.
Stringer, Jeffrey S.A.
Price, Joan T.
author_facet Smithmyer, Megan E.
Mabula-Bwalya, Chileshe M.
Mwape, Humphrey
Chipili, Gabriel
Spelke, Bridget M.
Kasaro, Margaret P.
De Paris, Kristina
Vwalika, Bellington
Sebastião, Yuri V.
Stringer, Jeffrey S.A.
Price, Joan T.
author_sort Smithmyer, Megan E.
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-021-03965-5.
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spelling pubmed-83173222021-07-28 Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study Smithmyer, Megan E. Mabula-Bwalya, Chileshe M. Mwape, Humphrey Chipili, Gabriel Spelke, Bridget M. Kasaro, Margaret P. De Paris, Kristina Vwalika, Bellington Sebastião, Yuri V. Stringer, Jeffrey S.A. Price, Joan T. BMC Pregnancy Childbirth Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-021-03965-5. BioMed Central 2021-07-28 /pmc/articles/PMC8317322/ /pubmed/34320947 http://dx.doi.org/10.1186/s12884-021-03965-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Smithmyer, Megan E.
Mabula-Bwalya, Chileshe M.
Mwape, Humphrey
Chipili, Gabriel
Spelke, Bridget M.
Kasaro, Margaret P.
De Paris, Kristina
Vwalika, Bellington
Sebastião, Yuri V.
Stringer, Jeffrey S.A.
Price, Joan T.
Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title_full Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title_fullStr Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title_full_unstemmed Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title_short Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study
title_sort circulating angiogenic factors and hiv among pregnant women in zambia: a nested case–control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317322/
https://www.ncbi.nlm.nih.gov/pubmed/34320947
http://dx.doi.org/10.1186/s12884-021-03965-5
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