Abnormal soluble fms-like tyrosine kinase to placental growth factor ratio during pregnancy and subjective memory impairment 3 to 6 years postpartum

BACKGROUND: Preeclampsia is a pregnancy-related disorder characterized by systemic endothelial dysfunction and angiogenic imbalance, most notably elevated levels of soluble fms-like tyrosine kinase-1 and decreased placental growth factor. While preeclampsia has been associated with long-term cardiovascular and cognitive risks, the specific role of angiogenic imbalance in predicting postpartum memory impairment remains unclear. Identifying biomarkers that can anticipate future neurocognitive outcomes may offer opportunities for early intervention and monitoring. OBJECTIVE: To evaluate whether preeclampsia and angiogenic imbalance during pregnancy, defined by a soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥38, are associated with subjective memory impairment 3 to 6 years postpartum. STUDY DESIGN: Cross-sectional study at a tertiary hospital in Barcelona, Spain. Individuals were prospectively recruited during pregnancy and reevaluated 3 to 6 years postpartum. Preeclampsia was defined per American College of Obstetricians and Gynecologists criteria. Angiogenic imbalance during pregnancy was defined as soluble fms-like tyrosine kinase-1/placental growth factor ≥38 (determined between 28 and 40 weeks of gestation). Subjective memory performance was assessed using the validated Memory Failures of Everyday Life questionnaire. Memory impairment was defined as a total Memory Failures of Everyday Life score ≥36. Logistic and linear regression models were used to examine associations, adjusting for relevant confounders. RESULTS: A total of 266 individuals were reevaluated between August 2023 and February 2025. 81 of them (30.45%) had a documented history of preeclampsia. Participants with an elevated soluble fms-like tyrosine kinase-1/placental growth factor ratio during pregnancy showed a higher prevalence of memory impairment (30.0% vs 16.2%, P=.03). In multivariable analysis, angiogenic imbalance remained significantly associated with increased odds of memory impairment (odds ratio=2.18, 95% confidence interval [1.02-4.65], P=.04). In contrast, preeclampsia diagnosis alone was not significantly associated with memory outcomes (odds ratio=1.35, 95% confidence interval [0.70-2.60], P=.37). CONCLUSION: An elevated soluble fms-like tyrosine kinase-1/placental growth factor ratio during pregnancy is associated with an increased risk of subjective memory impairment 3 to 6 years postpartum. These findings highlight the potential utility of angiogenic biomarkers as early indicators of long-term cognitive vulnerability, supporting the need for longitudinal follow-up and targeted preventive strategies in women exposed to angiogenic imbalance during pregnancy.