Beyond Diagnostic Cut-Offs: Associations Between the sFlt-1/PlGF Ratio and Perinatal Outcomes in Low-Risk Term...

Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical placental dysfunction even in otherwise low-risk pregnancies. To investigate associations between the sFlt-1/PlGF ratio and maternal and neonatal outcomes in a low-risk term obstetric population, beyond established diagnostic cut-offs. Methods: This prospective cohort study included 87 women with singleton term pregnancies. Serum sFlt-1 and PlGF concentrations were measured at hospital admission before delivery, and the sFlt-1/PlGF ratio was calculated. The primary outcome was estimated blood loss at delivery. Secondary maternal outcomes included postpartum hemoglobin decline, uterine atony, and fibrinogen concentration. Neonatal outcomes included birthweight, umbilical artery pH, and bilirubin concentration. Multivariable regression models were used to evaluate associations between the ln-transformed sFlt-1/PlGF ratio and outcomes after adjustment for prespecified maternal and obstetric covariates. Results: Each doubling of the sFlt-1/PlGF ratio was associated with greater estimated peripartum blood loss (+78.0 mL, 95% CI 42.1-113.9; p < 0.001), a larger postpartum hemoglobin decline (+0.078 g/dL, 95% CI 0.008-0.148; p = 0.030), lower fibrinogen concentration (-20.7 mg/dL, 95% CI -30.5 to -10.9; p < 0.001), and lower neonatal birthweight (-64.6 g, 95% CI -102.0 to -27.2; p = 0.001). No significant associations were observed for uterine atony, premature rupture of membranes, or umbilical artery pulsatility index above the 75th centile. Conclusions: In low-risk term pregnancies, higher sFlt-1/PlGF ratios were associated with greater estimated peripartum blood loss, lower fibrinogen concentrations, and lower neonatal birthweight. These findings support the hypothesis that variation in angiogenic balance may reflect subclinical placental dysfunction even in apparently uncomplicated pregnancies. Further prospective studies are needed to validate these exploratory observations and determine their clinical relevance.