What is the significance of fetal fraction in non-invasive prenatal testing (NIPT)?

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Last updated: June 2, 2025View editorial policy

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From the Guidelines

Fetal fraction is a crucial parameter in non-invasive prenatal testing (NIPT) that represents the proportion of cell-free DNA in maternal blood originating from the placenta, and its significance lies in its impact on test accuracy and failure rates, as evidenced by studies such as 1. The fetal fraction is essential for interpreting NIPT results, as a minimum threshold is required for reliable testing. According to 1, the chance of test failure due to low fetal fraction varies and is reported to be between 0.9-8.1%. Key factors influencing fetal fraction include:

  • Gestational age, with lower fractions at earlier gestations
  • Maternal conditions, which can affect the amount of cell-free DNA
  • Certain fetal chromosomal abnormalities, such as trisomy 13,18, or triploidy, which may be associated with lower fetal fractions Understanding the significance of fetal fraction helps healthcare providers counsel patients appropriately, especially in cases of test failure or inconclusive results, and guides the decision to offer alternative diagnostic testing options, as suggested by 1. In cases where NIPT results are ambiguous or the test fails, alternative diagnostic approaches like amniocentesis or chorionic villus sampling may be recommended for patients with persistently low fetal fraction, as these methods can provide definitive genetic information about the fetus.

From the Research

Definition of Fetal Fraction

  • Fetal fraction refers to the proportion of cell-free fetal DNA (cffDNA) in the mother's blood that is of fetal origin 2.
  • It is an important factor in non-invasive prenatal testing (NIPT) as it affects the accuracy of the test results 2, 3.

Significance of Fetal Fraction in NIPT

  • A higher fetal fraction is generally associated with more accurate NIPT results 2, 3.
  • A minimum fetal fraction of 4% is often considered necessary for reliable NIPT results 3.
  • Factors that can affect fetal fraction include gestational age, maternal body mass index (BMI), and placental biomarkers 2, 3.

Factors Affecting Fetal Fraction

  • Gestational age: Fetal fraction tends to increase with gestational age 2, 3.
  • Maternal BMI: Fetal fraction tends to decrease with increasing maternal BMI 2.
  • Placental biomarkers: Fetal fraction is associated with certain placental biomarkers, such as free β-hCG, PAPP-A, and PlGF 2.

Clinical Implications

  • Fetal fraction is an important consideration in the interpretation of NIPT results 4, 5.
  • Low fetal fraction can lead to uncertain or false-negative results 3.
  • Healthcare providers should take fetal fraction into account when counseling patients about NIPT results 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy.

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2018

Research

Non-invasive prenatal testing for aneuploidy: current status and future prospects.

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2013

Research

Noninvasive prenatal testing: the future is now.

Reviews in obstetrics & gynecology, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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