Decoding placental dysfunction with a new angiogenic classification of PlGF and sFlt-1

Objective: The ratio between sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (Placental Growth Factor) was recently introduced to aid in the management of hypertensive disorders of pregnancy and fetal growth restriction, but it has limitations. This study proposes a new angiogenic classification of PlGF and sFlt-1 to enhance maternal and fetal risk assessment in pregnancies with suspected placental dysfunction. Study design: A retrospective analysis was conducted on hospitalized singleton pregnancies beyond the 20th week complicated by hypertensive disorders of pregnancy and/or fetal growth restriction. Patients were classified based on sFlt-1/PlGF (low, medium, high, very high) and into the nine possible combinations using PlGF and sFlt-1 gestational age-specific levels: (1) PlGF and sFlt-1 within range; (2) PlGF in range, sFlt-1 < range; (3) PlGF in range, sFlt-1 > range; (4) PlGF < range, sFlt-1 in range; (5) PlGF and sFlt-1 < range; (6) PlGF < range, sFlt-1 > range; (7) PlGF > range, sFlt-1 in range; (8) PlGF > range, sFlt-1 < range; (9) PlGF and sFlt-1 > range. Results: The cohort included 227 patients. The most common categories were 1, 3, 4, and 6. Categories 4 and 6 had a higher proportion of fetal growth restriction, whereas categories 3 and 6, presented a greater risk of severe maternal complications. Category 6 exhibited the highest risk of adverse maternal-fetal outcomes; conversely, category 1 was the category at the lowest risk for complications. Notably, 40 % of patients classified as low or medium risk by the sFlt-1/PlGF were high-risk by our classification. Conclusion: Evaluation of actual PlGF and sFlt-1 levels rather than set cut-off ratios can improve the risk stratification of clinical manifestations of placental pathology.