Getting Started with NIPT

Different laboratories offer different testing menus for NIPT. Most laboratories include screening for
 common autosomal trisomies. Some laboratories will also include screening for sex chromosome aneuploidies. Additionally, some laboratories will offer an expanded menu for NIPT. Please check with your laboratory regarding their specific screening options and determine the most appropriate options for your practice and patients.

Common autosomal aneuploidies

Trisomy 21 — Trisomy 21 (also called Down syndrome) occurs when three copies of chromosome 21 are present instead of two. People with Down syndrome usually have intellectual disabilities that can range
 from mild to severe. Physically, they frequently have low muscle tone and may have heart defects. They may have a shorter lifespan. However, since every person with Down syndrome is a unique individual, not everyone with the condition will have all of the same features.

Trisomy 18 — Trisomy 18 (also called Edwards syndrome) occurs when three copies of chromosome 18
 are present instead of two. People with trisomy 18 have severe intellectual disabilities and birth defects that affect multiple organs. Few babies born with trisomy 18 survive their first year of life.

Trisomy 13 — Trisomy 13 (also called Patau syndrome) occurs when three copies of chromosome 13 are present instead of two. People with trisomy 13 have severe intellectual disabilities and birth defects that affect multiple organs. Few babies born with trisomy 13 survive their first year of life.

Sex chromosome aneuploidies

Monosomy X — Monosomy X (also called Turner syndrome) occurs when only one sex chromosome (the
 X chromosome) is present, and the second sex chromosome is missing. 1-1.5% of all pregnancies have monosomy X. About 99% of these pregnancies will miscarry. About 1 out of every 2000 live-born females has monosomy X. Common features of monosomy X include heart defects and hormone problems which can lead to shorter-than-average height, delayed puberty, and infertility.

Triple X syndrome (XXX) — 47,XXX occurs in about 1 in every 1000 female live births. Many females with 47,XXX do not have any noticeable characteristics. Variable characteristics of 47,XXX include taller-than-average height, learning difficulties, and speech and language delays. Delayed development of motor skills and behavioral and emotional difficulties are also possible.

Klinefelter syndrome (47,XXY) — Klinefelter syndrome occurs in approximately 1 in every 500–1000 male live births. Variable characteristics of Klinefelter syndrome include speech and/or learning difficulties, tall stature, fertility problems, and small testes.

Jacob’s syndrome (47,XYY) — 47,XYY occurs in approximately 1 in every 1000 male live births. Variable characteristics of 47,XYY include delayed development of speech and language skills, learning disabilities, and autism spectrum disorders.

Expanded panel

Microdeletions — Microdeletions are chromosome disorders caused by small missing pieces of chromosome material. They cannot usually be seen by routine methods of chromosome analysis. Microdeletions can occur on any of the 23 pairs of chromosomes. Some occur more commonly in a specific area of a particular chromosome and have been linked to known genetic syndromes. Most occur by chance, rather than being inherited from a parent, and can occur with no prior family history and without other risk factors (eg, advanced parental age).

• 22q11.2 deletion syndrome — 22q11.2 deletion syndrome (also called DiGeorge syndrome, Velocardiofacial syndrome) affects approximately 1 out of every 4000 live births. Signs and symptoms vary, but it can be associated with learning problems, congenital heart defects, and incomplete fusion of the palate (cleft palate). Life expectancy is usually normal.
• 1p36 deletion syndrome — 1p36 deletion syndrome affects approximately 1 out of every 4000–10,000 live births and is associated with characteristic facial features, seizures, and brain and heart defects. Intellectual disability varies. Life expectancy varies, but can be normal.
• Angelman syndrome* — Angelman syndrome (also called 15q11.2 deletion syndrome) affects approximately 1 out of every 12,000 live births. Features of Angelman syndrome include intellectual disability, speech problems, and seizures. Life expectancy is usually normal.
• Prader-Willi syndrome* — Prader-Willi syndrome (also called 15q11.2 deletion syndrome) affects approximately 1 out of every 10,000–25,000 live births and is associated with low muscle tone, morbid obesity, delayed motor and language skills, intellectual disability, and small testes. Life expectancy varies, but is usually normal.
• Wolf-Hirschhorn syndrome (4p- syndrome) — Wolf-Hirschhorn syndrome (also called 4p- syndrome) affects approximately 1 out of every 50,000 live births. Features include growth deficiency, low muscle tone, distinct facial features, intellectual disability, and heart and brain problems. Life expectancy varies.
• Cri du chat syndrome (5p- syndrome) — Cri du chat syndrome (also called 5p- syndrome) affects approximately 1 out of every 20,000–50,000 live births. Features include intellectual disability, speech delay, and a “cat-like” cry. About 10% of babies will not survive the first year of life; for the 90% who survive, life expectancy varies but is usually normal.

*The microdeletion region is the same region for Angelman and Prader-Willi syndromes (15q11.2). NIPT
 will not distinguish between these 2 syndromes. Further testing is necessary.

Rare autosomal aneuploidies

These are chromosomal aneuploidies that occur on chromosome pairs other than chromosomes 21, 18, and 13. Full monosomies usually do not lead to viable pregnancies, but mosaic monosomies have rarely been described in ongoing pregnancies, even leading to live birth. Some laboratories may report only trisomies and not monosomies.

Partial deletions and duplications of 7 Mb or greater

These occur when there are either deletions or duplications of larger segments of genetic material. Duplications involve extra copies of a chromosomal region, which can cause different copy numbers of genes for that chromosomal area. Deletions occur when portions of the chromosome are lost.

PPV refers to the likelihood that a positive screen result is truly positive. If your patient receives a positive result, PPV will tell you the chances that the pregnancy is affected. PPV is also dependent upon prevalence of the condition in the population using the test, as well as on the sensitivity and specificity of the test. Higher prevalence leads to higher PPV.¹

NIPT based on cell-free DNA analysis from maternal blood is a screening test; it is not diagnostic. False-positive and false-negative results do occur. Test results must not be used as the sole basis for diagnosis. Further confirmatory testing is necessary prior to making any irreversible pregnancy decision. A negative result does not eliminate the possibility that the pregnancy has a chromosomal or subchromosomal abnormality. This test does not screen for birth defects such as open neural tube defects, or other conditions, such as autism.¹

A very small fraction of NIPT tests may be inconclusive, or yield a “no result” when there is insufficient fetal DNA detected. A “no result” is likelier in women with high body mass index, pregnancies with a chromosomal abnormality, or twin pregnancies. If a “no result” occurs, it is important to get a conclusive result to rule out any potential chromosomal abnormalities, either through repeat NIPT screening or a confirmatory diagnostic procedure.¹

If your patient receives a positive result from an NIPT screen, it’s important that they understand what it means to have a positive result, the chances that their pregnancy could have the underlying condition, and what their options are. Read our Patient Counseling Guide for insight into effective ways to approach patient conversations about NIPT results and what they mean, and how to assess your patient's options.¹