Trimester-Resolved Dynamics of Angiogenic, Haematological, Coagulation and Biochemical Biomarkers and First-Trimester Uterine-Artery Doppler in Pregnancies at Risk of Early-Onset Preeclampsia: A Prospective Comparative Study of Early Diagnosis and Complex

Abstract

Background. Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity driven by defective spiral-artery remodelling, placental ischaemia and generalised endothelial dysfunction. We characterised the trimester dynamics of angiogenic, haematological, coagulation and biochemical biomarkers with first-trimester uterine-artery Doppler, and evaluated the impact of early diagnosis and complex treatment.
Materials and Methods. In this prospective comparative study, 102 pregnant women formed a control group (physiological pregnancy, n=30), an early-diagnosed and complex-treated group (n=32) and an at-risk, untreated group (n=40). Complete blood count, coagulogram, CRP, LDH, urea, creatinine, VEGF, TGF-β2, EGF, sFlt-1, PlGF and the sFlt-1/PlGF ratio were measured each trimester; uterine-artery pulsatility (PI), resistance (RI) and systolic/diastolic (S/D) indices and early ultrasound markers were assessed at 4–12 weeks. Analyses used ANOVA or Kruskal–Wallis with post-hoc correction, linear mixed models and Spearman correlation; α=0.05.
Results. By the third trimester, untreated women showed anaemia (haemoglobin 80.1±6.2 g/L), thrombocytopenia (150.9±14.2×10⁹/L), hypercoagulation (fibrinogen 7.6 g/L; PT shortened 27%), a 5.2-fold CRP rise, LDH 648.9 U/L (2.9-fold) and creatinine 107.4 µmol/L. VEGF, TGF-β2 and EGF fell progressively while the sFlt-1/PlGF ratio rose 10.6-fold versus controls (all p<0.001). First-trimester left uterine-artery PI (1.33) and S/D (4.17) were markedly elevated, and early ultrasound abnormalities were 3–6-fold more frequent in untreated women. All derangements were significantly attenuated by early treatment.
Conclusion. Early-onset PE produces coordinated, severity-graded multisystem biomarker derangement detectable from the first trimester. The sFlt-1/PlGF ratio and uterine-artery Doppler were the strongest discriminators, and early diagnosis with complex treatment markedly limited progression, supporting an integrated first-trimester risk-stratification strategy.