Diagnostic and predictive role of maternal circulating PlGF levels promising in reduced fetal movements, reveals study
Women presenting with reduced fetal movements (RFM) have an increased risk of adverse pregnancy outcomes and stillbirth. A study assessing the outcome of low-risk pregnancies complicated by isolated RFM at term, found that RFM were independently associated with mild adverse neonatal outcome and higher rates of cesarean de livery due to fetal distress and intrauterine fetal death at admission, compared to the group without RFM occurring prior to gestational week 37. The mechanisms for the association between maternal perception of RFM and stillbirth are not fully understood, but it is hypothesized that placental dysfunction could be a common pathology. In support of this hypothesis, a register-based retrospective cohort study of perinatal deaths found an association between RFM and placental insufficiency, defined as significant placental lesion(s) on pathological examination in cases with stillbirth.
Placenta-associated biomarkers, such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) are present in the maternal circulation during pregnancy. Imbalances in these biomarkers, with low “proangiogenic” PlGF concentrations and high“antiangiogenetic” sFlt-1 concentrations in maternal circulation, are associated with placenta-related pregnancy complications such as pre eclampsia and fetal growth restriction. Placentas from pregnancies with RFM presenting at gestational age (GA) > 36 weeks resulting in adverse delivery outcome have shown increased villous release of sFlt-1 compared to pregnancies without adverse delivery outcome.
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.
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).
In conclusion, predelivery maternal placenta-associated biomarkers from a real-world population of pregnant women at and beyond term presenting with RFM show a lower proangiogenic profile (lower PlGF) in pregnancies with an adverse outcome of likely placental cause. Placenta associated biomarkers can potentially help to more precisely target RFM pregnancies at risk of adverse delivery outcome of a likely placental cause. Authors consider this study to be an important contribution to the concept that RFM is a marker of placental insufficiency.
Source: S. Bowe et al; European Journal of Obstetrics & Gynecology and Reproductive Biology 307 (2025) 34–42
