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Association Between Cell-Free Fetal DNA and Placenta Accreta Spectrum: A Retrospective Cohort Study
Tianyue Zhang1,2, Pingping Li1,2, Donghao Liu2,3
1Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
The Journal of Obstetrics and Gynaecology Research
|June 14, 2026
Summary
Cell-free fetal DNA (cffDNA) levels show a nonlinear association with placenta accreta spectrum (PAS) but have limited standalone diagnostic ability. Combining cffDNA with other factors may improve prenatal diagnosis of PAS.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Prenatal Diagnostics
Background:
- Prenatal diagnosis of placenta accreta spectrum (PAS) is crucial for reducing maternal and neonatal complications.
- Current imaging methods for PAS lack perfect reliability.
- Maternal serum cell-free fetal DNA (cffDNA) has been suggested as a potential biomarker for PAS.
Purpose of the Study:
- To investigate the association between cffDNA levels measured via noninvasive prenatal testing (NIPT) and PAS.
- To evaluate the diagnostic performance of cffDNA in identifying PAS.
- To assess the incremental value of cffDNA when combined with other clinical factors.
Main Methods:
- Retrospective study of 81 PAS patients and 810 controls who underwent NIPT.
- Clinical data and cffDNA levels were collected and analyzed.
- Multivariable logistic regression, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curves were used to assess the association and discriminative performance.
Main Results:
- Elevated cffDNA levels were significantly associated with PAS (OR=1.98).
- RCS analysis revealed a nonlinear, J-shaped association between cffDNA and PAS.
- While cffDNA alone had limited discrimination (AUC=0.573), its incremental value in a combined model was not significant.
Conclusions:
- CffDNA exhibits a nonlinear association with PAS but is not a reliable standalone biomarker.
- CffDNA may offer adjunctive value when integrated with clinical and imaging data for PAS diagnosis.
- Further research is needed to optimize the use of cffDNA in prenatal PAS assessment.