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Placental Cell-Free DNA
Aka: Placental Cell-Free DNA, Fetal Cell Free DNA, Cell-Free DNA, Noninvasive Prenatal Testing, NIPT
- See Also
- Antenatal Screening
- Aneuploidy Screening
- First Trimester Education
- Second Trimester Education
- Pregnancy Risk Assessment
- Trisomy Findings on Fetal Ultrasound
- Nuchal Translucency
- Second Trimester Ultrasound
- Indications
- Congenital defect screening in pregnancy (e.g. Trisomy 21, Trisomy 18, Trisomy 13, Sex ChromosomeAneuploidy) AND
- High risk women for child with congenital defects
- Maternal Age 35 years or older
- Ultrasound findings at higher risk of Aneuploidy
- Prior chromosomal defect in pregnancy (esp. Trisomy 21, Trisomy 18, Trisomy 13)
- Positive results on First Trimester Combined Screening or Second Trimester Quad Maternal Screen Panel
- (2015) Am J Obstet Gynecol 212(6):711-6 [PubMed]
- Mechanism
- Placental DNA fragments circulate in maternal blood as Fetal Cell-Free DNA
- Maternal serum is collected and Fetal DNA is isolated and amplified
- Fetal DNA distribution from each Chromosome is quantified, therefore able to predict Aneuploidy
- Protocol
- Obtain sample after 10 weeks gestation
- Testing earlier than 10 weeks may obtain too little fetal DNA to characterize accurately (see low fetal fraction below)
- Confirm positive results with invasive testing (Chorionic Villus Sampling or Amniocentesis)
- Efficacy: Trisomy 21
- Test Sensitivity: 99.7%
- Test Sensitivity in Twin Pregnancy: 99%
- Negative Predictive Value >99% regardless of age
- False Positive Rate is 0.04% (contrast with rates of 3-5% for Quad Screen)
- Positive Predictive Value (PPV) changes significantly with advancing maternal age
- Age 20 years old PPV: 68% (Trisomy 21Prevalence 1 per 1177)
- Age 25 years old PPV: 71% (Trisomy 21Prevalence 1 per 1040)
- Age 30 years old PPV: 78% (Trisomy 21Prevalence 1 per 700)
- Age 35 years old PPV: 89% (Trisomy 21Prevalence 1 per 296)
- Age 40 years old PPV: 97% (Trisomy 21Prevalence 1 per 86)
- Efficacy: Trisomy 18
- Test Sensitivity: 78.9 to 97.9%
- Test Sensitivity in Twin Pregnancy: 85%
- False Positive Rate: 0.01 to 0.04%
- Causes: Low Fetal Fraction (results too low to report)
- Testing earlier than 10 weeks gestation
- Obesity
- Low Fetal Fraction in 10% who weigh >100 kg
- Low Fetal Fraction in 51% who weigh >160 kg
- Causes: Abnormal Cell-Free DNA with Normal Invasive Testing
- Placental Mosaicism
- Maternal Aneuploidy
- Occult Maternal Malignancy
- References
- Gil (2017) Ultrasound Obstet Gynecol 50(3): 302-14 [PubMed]
- LeFevre (2020) Am Fam Physician 101(8):481-8 [PubMed]
- Liao (2017) Prenat Diagn 37(9): 874-82 [PubMed]
- Norton (2015) N Engl J Med 372(17): 1589-97 [PubMed]