Natriuretic Peptide Biomarkers in Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy, encompassing gestational hypertension and pre-eclampsia, represent a leading cause of maternal and perinatal morbidity worldwide. Natriuretic peptides—principally atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), along with their N-terminal fragments (NT-proANP and NT-proBNP)—are cardiac hormones that regulate vascular tone, natriuresis and fluid balance. During a healthy pregnancy, physiological changes in plasma volume and cardiac output lead to modest elevations in these biomarkers. In contrast, pregnancies complicated by hypertension often show marked perturbations in natriuretic peptide levels, reflecting increased ventricular stress, altered proteolytic processing by enzymes such as corin, and changes in receptor expression within the utero-placental circulation. Recent investigations have illuminated dynamic shifts in early-pregnancy NT-proBNP as a predictor of later hypertensive complications, while mechanistic studies have explored ANP’s influence on endothelial function under pre-eclamptic conditions. These biomarkers are now being integrated into multimodal risk-stratification algorithms alongside angiogenic factors and uric acid, with the aim of improving early diagnosis, guiding therapeutic decisions and optimising maternal–fetal outcomes.

Research from Nature Portfolio

Recent studies have evaluated early-pregnancy NT-proBNP levels as a predictive tool for hypertensive disorders manifesting after 35 weeks of gestation. Large retrospective cohorts have demonstrated that women with higher NT-proBNP concentrations in the first trimester exhibit a substantially lower risk of developing gestational hypertension or pre-eclampsia in late pregnancy. A defined cutoff of approximately 60 pg/mL showed high negative predictive value and sensitivity, suggesting that NT-proBNP might serve as an accessible screening marker to rule out subsequent hypertensive complications when measured early in gestation. These findings pave the way for prospective validation and integration into routine antenatal care pathways.

Natriuretic Peptide Biomarkers in Hypertensive Disorders of Pregnancy publication trend

The graph below shows the total number of articles in natriuretic peptide biomarkers in hypertensive disorders of pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Gestational hypertension: New-onset maternal blood pressure elevation (≥140/90 mmHg) after 20 weeks’ gestation without proteinuria or end-organ dysfunction.

Pre-eclampsia: A hypertensive disorder of pregnancy characterised by high blood pressure and multisystem involvement, including proteinuria, placental insufficiency or organ impairment.

Atrial natriuretic peptide (ANP): A cardiac-derived hormone that promotes vasodilation and natriuresis, released in response to atrial stretch.

N-terminal pro-brain natriuretic peptide (NT-proBNP): The inactive fragment of proBNP cleaved in the myocardium, serving as a stable plasma biomarker of ventricular stress.

Mid-regional pro-atrial natriuretic peptide (MR-proANP): A surrogate fragment of proANP with prolonged half-life, used for quantifying ANP precursor release.

Corin: A cardiac serine protease that processes proANP and proBNP into active natriuretic peptides and is also expressed in the uterus during pregnancy.

References

1. Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia. International Journal of Molecular Sciences (2023).
2. Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation. Scientific Reports (2024).
3. High Serum Adrenomedullin and Mid-Regional Pro-Atrial Natriuretic Peptide Concentrations in Early Pregnancy Predict the Development of Gestational Hypertension. Diagnostics (2024).
4. Predictive Model for Preeclampsia Combining sFlt-1, PlGF, NT-proBNP, and Uric Acid as Biomarkers. Journal of Clinical Medicine (2023).