Elevated serum sFlt-1 at 18-20 weeks in advanced maternal age: a key difference from younger pregnancies

Advanced maternal age (AMA) is associated with preeclampsia (PE). Although serum sFlt-1 levels at term are lower in PE cases among AMA women compared to those in PE cases among non-AMA women, evidence from mid-pregnancy remain limited. Since the clinical phenotype of PE has not yet emerged at 18-20 weeks of gestation, assessing angiogenic markers during this period may lead to a better understanding of the pathophysiology of PE. We retrospectively analyzed singleton pregnancies delivered at The University of Tokyo Hospital between January 2022 and March 2024. Serum sFlt-1 and PlGF levels were measured at 18-20 weeks of gestation, and their associations with PE were assessed based on maternal age (<35 years: non-AMA; 35-44 years: AMA). In non-AMA pregnancies, serum sFlt-1 levels tended to be lower in PE cases compared to normotensive (NT) cases. Conversely, in AMA pregnancies, PE cases showed significantly higher serum sFlt-1 levels and sFlt-1/PlGF ratios than NT cases. Serum PlGF levels did not differ significantly between any of the groups. These findings highlight differences in PE-associated markers between AMA and non-AMA pregnancies at mid-pregnancy. Clarifying these differences is essential for optimizing early risk stratification and management strategies in AMA populations.