Toxic Elements Disrupts Angiogenic Balance in Pathogenesis of Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and fetal morbidity and mortality, with emerging evidence indicating that trace element imbalances may play a role in their pathogenesis. This study aims at detecting association between heavy metals (Ni, As, Hg, Al, Pb, and Cd), angiogenic markers (PlGF and sFlt-1), their ratio (sFlt-1/PlGF) and risk of developing HDP. This prospective case-control study was conducted at the Department of Obstetrics and Gynecology in collaboration with the Department of Biochemistry at a North Indian tertiary care center. It included 203 pregnant women (HDP) and 199 normotensive pregnant controls. Serum trace elements were analyzed using ICPMS (Nexion 1000, Perkin Elmer), while sFLT-1 and PlGF were analyzed on Cobas e-series 6000 (Roche Diagnostics) using commercially available kits from the same manufacturer. The sFlt-1/PlGF ratio was also calculated. Women with HDP had significantly higher serum Ni (p < 0.017), As (p = 0.001), and Hg (p = 0.001) levels. The median sFlt-1/PlGF ratio was significantly higher in Q4 (50.27; IQR: 14.85-134.68) than in Q1 (34.61; IQR: 17.65-141.58) (p = 0.025). With HDP as the outcome, serum levels of Ni (β = 4.47; p = 0.001), As (β = 0.08; p = 0.001), and Hg (β = 0.51; p = 0.011) were significant risk factors. The Gaussian process classifier and BKMR analysis revealed that Ni, As, and Hg increased the probability of HDP. WQS regression further confirmed Ni as the predominant contributor (94%) to HDP risk, with Hg (1.4%) contributing only moderately. Elevated levels of Ni, As, and Hg were significantly associated with a higher risk of HDP and angiogenic biomarkers.