Association of Increased Fetal Fraction with Birthweight Discordance and Selective Fetal Growth Restriction: A...

Twin pregnancies are at increased risk for selective fetal growth restriction (sFGR) and birthweight discordance, which contribute to elevated perinatal mortality and morbidity. Early identification of at-risk pregnancies remains challenging, limiting optimal prenatal counselling and timely clinical intervention.

To determine whether fetal fraction (FF) from cell-free fetal DNA (cffDNA) screening correlates with birthweight differences and predicts birthweight discordance and sFGR in twin pregnancies.

This retrospective study included 224 twin pregnancies (both dichorionic and monochorionic twins) that underwent cffDNA aneuploidy screening and delivered at the International Peace Maternity and Child Health Hospital in Shanghai between 2018 and 2021. FF values and neonatal birthweights were collected and analyzed for correlations and predictive accuracy.

FF showed significant positive correlation with inter-twin birthweight differences (β=0.365, 95% CI: 0.122~0.608). For every 1% increase in the FF, the difference in the birthweight between twins increased by 0.365%. A higher FF was significantly associated with an increased risk of birthweight discordance of 20% (adjusted OR: 1.073, 95% CI: 1.009~1.142), 25% (adjusted OR: 1.092, 95% CI: 1.006~1.185), and sFGR (adjusted OR: 1.130, 95% CI: 1.038~1.231). Using ROC analysis, we obtained optimum cut-off points for FFs ≥11.790 and ≥14.800 for birthweight discordance of 20% and sFGR, respectively. Compared with women with FFs of <11.790, there was a 1.091-fold higher risk of birthweight discordance of 20% (adjusted OR: 2.091, 95% CI: 1.218~3.591) when the FF was ≥11.790. There were also significantly increased risks of birthweight discordance of 25% (adjusted OR: 3.045, 95% CI: 1.297~7.149) and sFGR (adjusted OR: 3.526, 95% CI: 1.443~8.618) among women with FFs of ≥14.800.

FF demonstrates strong positive correlation with birthweight differences and represents a novel predictive biomarker for birthweight discordance and sFGR in twin pregnancies. This accessible parameter from routine prenatal screening enables cost-neutral risk stratification and individualized pregnancy monitoring.