Maternal macrovascular and microvascular adaptation in healthy pregnancy, gestational diabetes, and hypertensive disorders of pregnancy.

OBJECTIVE: Healthy pregnancy requires substantial vascular adaptation, yet clinically relevant vascular markers remain poorly defined. This study aimed to characterize longitudinal macrovascular and microvascular profiles during pregnancy and their association with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM). METHODS: A total of 166 nulliparous women were prospectively evaluated at 11-13 and 24-27 weeks' gestation. Vascular function was assessed through arterial applanation tonometry and sublingual dark-field microscopy. Blood pressure (BP) measurements in seated, supine, and standing positions were performed. RESULTS: In healthy pregnancies, BP and arterial stiffness decreased from early to mid-pregnancy, while heart rate increased. Pregnancies that developed HDP showed higher BP and arterial stiffness already in early pregnancy, with a greater increase over time in sitting and upright BP. Microvascular parameters were similar across groups, with a trend toward endothelial glycocalyx thinning in HDP. Upright mean BP and carotid-femoral pulse wave velocity (cfPWV) showed the strongest associations with HDP and enhanced the predictive performance of the FMF score (AUC 0.84 vs. 0.71 for the FMF score alone). Vascular profiles in women who developed GDM largely overlapped with those of healthy pregnancies in cross-sectional group comparisons. However, logistic regressions identified higher second-trimester BP as an independent predictor of GDM occurrence, whereas association with arterial stiffness was inconsistent across vascular indices and adjustment models. CONCLUSION: HDP is characterized by early alterations in arterial stiffness and positional BP responses, which may improve risk stratification when integrated with FMF algorithm. In contrast, GDM was not associated with overt vascular dysfunction.