# HIF-1α regulated pathomechanism of low birth weight through angiogenesis factors in placental Plasmodium vivax infection

## TL;DR

This study explores how Plasmodium vivax infection in pregnant women leads to low birth weight through changes in placental angiogenesis factors.

## Contribution

The study identifies HIF-1α as a key mediator in the pathomechanism of low birth weight caused by placental Plasmodium vivax infection.

## Key findings

- Plasmodium vivax sequestration is linked to low birth weight through altered angiogenic factors.
- HIF-1α plays a central role in the imbalance of placental angiogenic factors in infected mothers.
- Significant differences in angiogenic factors were observed in placental tissues of infected versus non-infected mothers.

## Abstract

Background: Malaria in pregnancy can lead to placental malaria. The main pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia, due to sequestrations of
Plasmodium falciparum infected erythrocytes in the placenta, but the pathomechanism of placental
Plasmodium vivax infection have not been studied in detail. Hypoxia inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions which interacts with the change and imbalances of many chemical mediators including angiogenic factors, leading to abnormality of fetal growth.

Methods: This study was conducted cross sectionally in Sikka Regency, East Nusa Tenggara Province, Indonesia, currently known as a malaria endemic area with high incidence of low birth weight (LBW) cases. In this study the peripheral and umbilical blood samples as well as placental tissues were collected from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. Blood samples were examined for the presence of parasites by microscopic and polymerase chain reaction (PCR) techniques, while the plasma levels of VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α were determined using enzyme-linked immunosorbent assay (ELISA). The sequestration of infected erythrocytes and hemozoin were determined from placental histological slides and the expression of placenta angiogenic factors were observed by immunofluorescent techniques.

Results: In total, 33 cases had complete data to be analyzed. Of them, there were 19 diagnosed with vivax malaria and none with falciparum malaria. There were significant differences of Δ 10th percentile growth curve of baby’s body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected (p<0.05), but not for VEGF and VEGFR-2 in the plasma.

Conclusions: This study found
Plasmodium vivax sequestration is associated with LBW through the changes and imbalances of angiogenic factors leaded by HIF-1α.