Peripartum Changes in Neuroendocrine, Angiogenic, and Inflammatory Biomarkers in Gestational Hypertension

Background: Hypertensive disorders in pregnancy, such as gestational hypertension (GH), pose significant risks to maternal and fetal health, affecting a substantial proportion of pregnancies worldwide. Despite their prevalence, the dynamics of various biomarkers across the peripartum period remain poorly understood, limiting comprehensive insight into their pathophysiology. This study aimed to evaluate changes in neuroendocrine, angiogenic, and inflammatory biomarkers before and after delivery in women with GH and to compare these profiles with those of normotensive controls. Methods: This prospective study included women with singleton vaginal deliveries, assigned to GH and control groups (n = 20 per group). Clinical data were collected, and blood samples (pre- and 2 hours post-delivery) were analyzed for chromogranin A (CgA), catestatin (CST), soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), interleukin-6 (IL-6), and C-reactive protein (CRP). Peripartum changes were evaluated using rank-based repeated-measures analysis. Results: CgA concentrations decreased significantly after delivery in both groups (pTime < 0.001), with comparable peripartum kinetics (pGroup×Time = 0.718; median difference [MD]: 2.3 ng/mL; 95% confidence interval [CI]: –5.4 to 7.8). PlGF concentrations were significantly lower in the GH group (pGroup = 0.002) and declined after birth (pTime < 0.001), with a clinically meaningful trend toward a greater decline in the GH group (MD: 78 pg/mL; 95% CI: 30 to 220). IL-6 increased 10-fold after delivery (pTime < 0.001), with a comparable shift between groups (pGroup×Time = 0.456; MD: 6.9 pg/mL; 95% CI: –9.1 to 21.2). CRP concentrations increased after delivery (pTime < 0.001), with no difference in peripartum kinetics between groups (pGroup×Time = 0.257). Pre-delivery CgA and sFlt-1 were strongly correlated in the control group (rs = 0.636, p = 0.003). Sex-stratified analyses revealed significantly lower IL-6 concentrations in female fetuses within the control group (1.9 vs. 3.6 pg/mL; p = 0.037), and significantly lower PlGF concentrations in female fetuses within the GH group (73 vs. 153 pg/mL; p = 0.039). Conclusions: Our results align with established patterns for angiogenic and inflammatory markers, but these novel neuroendocrine findings require validation in larger groups. Incorporating neuroendocrine regulation into models of GH is a key area for future study. Study Registration: The study has been registered on https://zenodo.org/ (registration number: zenodo. 18958924; registration link: https://zenodo.org/records/18958924).