PlGF and sFlt-1, reduced fetal movements and adverse delivery outcome of a likely placental cause: A real world prospective observational study

Objective To assess the association between predelivery maternal placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) and adverse delivery outcome of a likely placental cause in women presenting with reduced fetal movements (RFM) in term and post-date pregnancies. Study design Prospective cohort study conducted in a single tertiary maternity unit from September 2016 to March 2020. PlGF and sFlt-1 were measured in maternal serum (n = 122) from prospectively included women presenting with RFM (gestational age >= 37(+0)). All neonatal and delivery outcomes were externally reviewed, blinded for biomarker results, and judged whether the adverse outcomes were most likely associated with placental dysfunction ("likely placental cause") or not.Predefined gestational age specific reference levels for PlGF, sFlt-1 and sFlt-1/PlGF ratio were used and multiple of the median (MoM) were calculated. Categorical variables were compared using Fisher's exact-test. Means were compared using one-way analysis of variance and medians were compared using the Kruskal-Wallis test. Pairwise comparisons between groups were Bonferroni corrected. Results The pregnancies were assigned into three groups: the "complicated" (likely placental cause, n = 4), the "intermediate" (non-placental/undetermined cause, n = 9) and the "uncomplicated" (no adverse outcome, n = 109). Mean PlGF concentration differed significantly between the three groups (80, 144, and 213 pg/ml, p = 0.004). There was a higher proportion of PlGF levels < 10th centiles in the "complicated" compared to the "intermediate" and "uncomplicated" groups (50 % vs. 22 % and 11 %, p = 0.045). The median MoM of PlGF differed significantly between the three groups (0.43, 0.83 and 1.12, p = 0.006). Conclusion In women presenting with RFM in late pregnancy and beyond term (gestational age >= 37(+0)), a lower predelivery "proangiogenic" PlGF concentration was associated with a composite adverse delivery outcome of a likely placental cause. The diagnostic and predictive role of maternal circulating PlGF levels is promising.