A research team has developed a preliminary theoretical screening model combining maternal placental growth factor, cell-free DNA fetal fraction, and prior risk factors to evaluate risk for preterm preeclampsia. The investigation focused on establishing marker distributions across preterm preeclampsia and unaffected pregnancies using testing data gathered during the first trimester.
To build the model, the investigators fitted a bivariate Gaussian marker distribution and maternal prior risk factors to an initial series. Biomarker concentrations were standardized and expressed in multiples of the median using fitted regression equations. Parameters for unaffected pregnancies were calculated directly from the preliminary cohort, whereas parameters representing preterm preeclampsia were derived from published literature or established through specified assumptions.
The preliminary dataset comprised 2,149 women tested between 9 and 14 weeks of gestation, though pregnancy outcome data were not available for the cohort. Log-linear equations for multiples of the median demonstrated a good fit to the observed data following logarithmic transformation of placental growth factor and square-root transformation of cell-free DNA fetal fraction.
The study identified differences in biomarker distributions between singleton pregnancies and the 42 twin pregnancies included in the series. Medians in twins were higher than in singletons for placental growth factor, registering 1.15 multiples of the median compared to 1.00 multiples of the median (P < 0.01). Fetal fraction medians were similarly higher in twins than in singletons, reaching 1.35 multiples of the median versus 1.01 multiples of the median (P < 0.0001).
Statistical modeling demonstrated a strong correlation between log-transformed placental growth factor and square-root-transformed fetal fraction. This correlation was observed in singletons (R = 0.257, P < 0.0001) as well as in twins (R = 0.221), though the association in twins did not achieve statistical significance (P = 0.16). Applying the model retrospectively with a risk cut-off of 1 in 60 for singletons and 1 in 12 for twins classified 10.0 percent of pregnancies as screen-positive.
The authors concluded that the preliminary theoretical model identifies specific parameters requiring refinement before screening efficacy can be established. Further modification in a substantially larger series alongside confirmed pregnancy outcome data is necessary prior to any prospective clinical evaluation of combined placental growth factor and fetal fraction screening for preeclampsia.
Subject of Research: Theoretical first-trimester screening model for preterm preeclampsia combining placental growth factor and cell-free DNA fetal fraction
Article Title: First trimester screening for pre-term preeclampsia combining placental growth factor and cell-free DNA fetal fraction: development of a preliminary theoretical model
Article References: Rabbi, M. L., Meiri, H., Maymon, R., Weiner, C., Zehavi, Y., Abu-Hamed, R., Chaim, A. B., Benveniste-Levkovitz, P., & Cuckle, H. (2026). First trimester screening for pre-term preeclampsia combining placental growth factor and cell-free DNA fetal fraction: development of a preliminary theoretical model. Archives of Gynecology and Obstetrics. https://doi.org/10.1007/s00404-026-08505-0
Image Credits: AI Generated
DOI: 10.1007/s00404-026-08505-0
Keywords: preterm preeclampsia, placental growth factor, cell-free DNA, fetal fraction, first-trimester screening, theoretical modeling, multiples of the median, prenatal screening, First, trimester, screening, pre-term
News Source: Ophelia Keating. (November 9, 2026). Preliminary Theoretical Model Evaluates First-Trimester Screening Markers for Preterm Preeclampsia. Scienmag.
