Fetal Fraction of Cell-Free DNA and Its Interaction With Maternal Pre-Pregnancy Body Mass Index on Multiple Adverse...

To investigate the relationships between fetal fraction (FF) and multiple adverse pregnancy outcomes and assess its interaction with maternal pre-pregnancy body mass index (BMI).

This cohort study included 10,331 singleton pregnancies undergoing noninvasive prenatal testing (NIPT) at 11-20 gestational weeks. Outcomes included gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small vulnerable newborns (SVN), preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and fetal distress. Logistic regression models were used to assess the associations between FF and adverse pregnancy outcomes, with FF analyzed both as a continuous and binary variable (low FF, defined as < 25th percentile). The interaction of FF and high BMI (defined as BMI ≥ 24 kg/m²) on adverse pregnancy outcomes was examined on both multiplicative and additive scales.

Continuous FF was inversely associated with GDM, HDP, SVN, PTB, LBW, and SGA. Binary low FF was associated with increased risks of HDP, SVN, PTB, and LBW. Additive interaction was observed between low FF and high BMI on HDP (RERI = 2.67, 95% CI: 1.26-4.32; AP = 0.45, 95% CI: 0.24-0.60).

In early pregnancy, lower FF is associated with increased risk of multiple adverse pregnancy outcomes, particularly HDP, SVN, PTB, and LBW. Besides, the effect of low FF on HDP risk may be amplified among women with high BMI.