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

Ultrasound Obstet Gynecol. 2013 Jul;42(1):15-33. doi: 10.1002/uog.12513.

Abstract

Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis. We review NIPT in the context of established screening and invasive technologies, the range of cytogenetic abnormalities detectable, cost, counseling and ethical issues. Current NIPT approaches involve whole-genome sequencing, targeted sequencing and assessment of single nucleotide polymorphism (SNP) differences between mother and fetus. Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes, and possibly Patau syndrome, in high-risk women. Universal NIPT is not cost-effective, but using NIPT contingently in women found at moderate or high risk by conventional screening is cost-effective. Positive NIPT results must be confirmed using invasive techniques. Established screening, fetal ultrasound and invasive procedures with microarray testing allow the detection of a broad range of additional abnormalities not yet detectable by NIPT. NIPT approaches that take advantage of SNP information potentially allow the identification of parent of origin for imbalances, triploidy, uniparental disomy and consanguinity, and separate evaluation of dizygotic twins. Fetal fraction enrichment, improved sequencing and selected analysis of the most informative sequences should result in tests for additional chromosomal abnormalities. Providing adequate prenatal counseling poses a substantial challenge given the broad range of prenatal testing options now available.

Keywords: Down syndrome; amniocentesis; aneuploidy; chorionic villus sampling; fetal DNA; maternal plasma; screening; sequencing; trisomy.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Chorionic Gonadotropin, beta Subunit, Human / blood*
  • Chromosome Disorders / diagnosis*
  • Chromosomes, Human, Pair 13
  • Down Syndrome / diagnosis*
  • Female
  • Genetic Counseling / trends
  • Genetic Testing / trends
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Maternal Age
  • Nuchal Translucency Measurement / trends
  • Personal Autonomy
  • Pregnancy
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Prenatal Diagnosis* / trends
  • Risk Factors
  • Trisomy / diagnosis*
  • Trisomy 13 Syndrome
  • Ultrasonography, Prenatal
  • alpha-Fetoproteins / metabolism*

Substances

  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • alpha-Fetoproteins
  • Pregnancy-Associated Plasma Protein-A