Angiogenic Factors in Preeclampsia and Fetal Development

Preeclampsia is a hypertensive disorder of pregnancy in which an imbalance of pro- and anti-angiogenic factors disrupts placental vascular development, with significant implications for maternal health and fetal growth. Central to this imbalance are elevated levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and reduced levels of placental growth factor (PlGF), leading to endothelial dysfunction and placental insufficiency. This dysregulation contributes to impaired uteroplacental blood flow, oxidative stress and inflammation, which in turn can precipitate fetal growth restriction and preterm birth. Angiogenic biomarkers have emerged as predictive tools to stratify risk, guide surveillance and inform timing of delivery. Research continues to elucidate the molecular pathways underlying angiogenic imbalance and to validate novel markers of placental health, with the aim of improving outcomes in both high- and low-risk pregnancies worldwide.

Research from Nature Portfolio

Recent studies have identified circulating serine peptidase inhibitor Kunitz type-1 (SPINT1) as a marker of placental insufficiency and fetal growth restriction. Low maternal plasma SPINT1 concentrations at 36 weeks’ gestation were strongly associated with low birthweight centiles, antenatal Doppler abnormalities and postnatal anthropometric indices of placental dysfunction. A tiered risk model based on SPINT1 levels stratified pregnancies according to the likelihood of delivering infants below the third to twentieth birthweight centiles. These findings were validated across multiple cohorts, highlighting SPINT1’s potential to identify pregnancies at elevated risk of stillbirth and guide late-term surveillance.

Angiogenic Factors in Preeclampsia and Fetal Development publication trend

The graph below shows the total number of articles in angiogenic factors in preeclampsia and fetal development across all publications each year (not limited to Nature Index journals).

Technical terms

Soluble fms-like tyrosine kinase-1 (sFlt-1): An anti-angiogenic receptor fragment that binds vascular endothelial growth factor family ligands, inhibiting placental angiogenesis.

Placental growth factor (PlGF): A pro-angiogenic member of the vascular endothelial growth factor family that promotes placental vascular development.

sFlt-1/PlGF ratio: A clinical index reflecting the balance between anti- and pro-angiogenic factors in maternal circulation.

Fetal growth restriction (FGR): A condition in which the fetus fails to achieve its genetically predetermined growth potential due to placental dysfunction.

Placental insufficiency: A state in which inadequate placental perfusion impairs nutrient and oxygen transfer to the fetus.

Umbilical and uterine artery pulsatility index (PI): Doppler ultrasound measures of blood flow resistance in fetoplacental and maternal vessels used to assess placental perfusion.

References

1. Longitudinal Associations between Ambient Air Pollution and Angiogenic Biomarkers among Pregnant Women in the LIFECODES Study, 2006–2008. Environmental Health Perspectives (2023).
2. Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction. Clinical Science (2023).
3. Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction. Ultrasound in Obstetrics and Gynecology (2024).
4. Pathophysiology of Pre-Eclampsia—Two Theories of the Development of the Disease. International Journal of Molecular Sciences (2023).
5. Circulating SPINT1 is a biomarker of pregnancies with poor placental function and fetal growth restriction. Nature Communications (2020).