Non-Invasive Prenatal Screening (NIPS)

Non-invasive prenatal screening (NIPS) may be used to assess the risk of a pregnant woman’s developing baby (fetus) having a chromosome disorder, such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). It may also be used to identify sex chromosome abnormalities (changes to the number of X or Y chromosomes present). Some laboratories offer additional testing for conditions caused by small segments of missing information on specific chromosomes, called microdeletion syndromes.

You should discuss this and other screening options with your health care practitioner to ensure it is the best choice for you. If you are not certain which prenatal screening or diagnostic test is right for you, it may be a good idea to speak with a genetic counselor.

The non-invasive prenatal screening (NIPS) can be offered during or after the tenth week of pregnancy. Samples collected prior to this time are automatically rejected, so it is important to be certain that the pregnancy is at a minimum of 10 weeks along.

Results may be reported as “low risk” (negative) or “high risk” (positive).

A NIPS result that is reported as “negative” or as “low risk” means that it is unlikely the baby has any of the specific chromosome disorders that were screened. Most NIPS tests evaluate the risk for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), but depending on how your healthcare practitioner ordered the test, it may also include the sex chromosomes (X and Y) and certain microdeletion syndromes.

It is important to remember that NIPS is a screening test, not a diagnostic test, so it is possible that the baby actually has a chromosomal disorder, even though the screening results show low risk (a false-negative result). In addition, NIPS does not screen every chromosome and does not detect the many genetic disorders that are caused by smaller changes in DNA. This means that other chromosome abnormalities or genetic disorders could be present and would not be identified by NIPS.

A NIPS result that is reported as “positive” or “increased/high risk” means that the baby is at an increased risk of having the abnormality identified. It is important to note that, while the test’s ability to correctly identify pregnancies at increased risk of Down syndrome is high, it is not as good at correctly identifying abnormalities of other chromosomes, including 18, 13 and X. It is important to remember that NIPS is a screening test and not a diagnostic test, so it is possible that the baby actually does not have the disorder indicated (false-positive result).

Diagnostic testing can be performed with either chorionic villus sampling (CVS), which samples placental tissue, between the 10th and 13th week of pregnancy, or amniocentesis (amnio), which samples amniotic fluid, after about 16 weeks of pregnancy. Chromosomal analysis by karyotyping or chromosomal microarray is performed on the sample to rule out or confirm a suspected chromosome disorder.

In some cases, the laboratory that performs the NIPS testing will return an “indeterminate” or “no call” result when there is an insufficient amount of cfDNA from the placenta in the mother’s blood sample. There are a number of factors that may affect this measurement, such as the gestational age, the presence of multiple fetuses (e.g., twins) and the mother’s weight. Obese women tend to have a lower concentration of placental cfDNA in their bloodstream.

American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend that women with a “no call” result be offered diagnostic testing using CVS or amniocentesis rather than repeating the NIPS testing (unless the sample was accidentally collected too early in the pregnancy). For mothers who are obese, their health care practitioner may offer a prenatal screen that is less affected by maternal weight than NIPS.

There are different versions of NIPS offered by different laboratories. Healthcare practitioners should be prepared to offer pre- and post-test genetic counseling for the version of NIPS that are chosen for their patients. If there are additional questions about result interpretation, a referral to a maternal-fetal medicine specialist and/or genetic counselor is appropriate.

NIPS that uses cfDNA testing is only one of the options that may be offered for prenatal screening for chromosome disorders and it may not be routinely offered by your health care practitioner. If you are interested in NIPS, you may choose to discuss it as well as other options with your health care practitioner to make an informed decision. You may also be referred to a genetic counselor to help you better understand the limitations and benefits of screening as well as the significance of a “screen positive” versus a “screen negative” result.

Other options include:

• First trimester maternal serum screening—includes an ultrasound exam to measure the thickness of a space at the back of the fetus’s neck (nuchal translucency) and blood tests to measure pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG).
• Second trimester maternal serum screening—includes blood tests for alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol (triple screen) or includes those three tests plus inhibin A (quad screen).
• Integrated screening, which combines first and second trimester screening results.

If any of these screening tests are positive for an increased risk of a chromosomal disorder, the recommendation is to offer diagnostic testing by CVS or amniocentesis. It is not recommended to perform multiple screening tests, so while NIPS is sometimes offered following a positive serum screen result, the appropriate course of action is to offer diagnostic testing.

The screening approach a woman chooses depends on her preferences, what technology is available through her health care practitioner or local hospital, as well as when she first seeks prenatal care.

Ultimately, you should discuss available prenatal screening and diagnostic testing options with your health care provider or a genetics specialist, such as a genetic counselor. Post-test genetic counseling for women with a positive screening or diagnostic result is recommended.

NIPS may be a screening option for you in any of your pregnancies. Since it is the baby’s placental cfDNA that is being assessed, each pregnancy is evaluated separately.

Results are typically available in less than one week, but different laboratories have different result turn-around times, so it is best to check with the lab performing your NIPS.

No. NIPS cannot detect open neural tube defects or abdominal wall defects. Screening for these conditions is typically performed by a detailed ultrasound in the second trimester as well as a second trimester blood test called alpha-fetoprotein (AFP) serum screening (Second Trimester Maternal Serum Screening).

It depends on the type of NIPS your health care practitioner orders and the specific lab that does the testing. Many laboratories routinely offer screening for five chromosomes: 21, 18, 13, X and Y. If this is the case, NIPS will show you the predicted sex of your baby. Remember that false negatives and false positives occur in screening tests. If you do not want to know the predicted sex of your baby, it might be possible for the lab to only report on the sex chromosomes if there is a sex chromosome abnormality (but not if it is a normal male or a normal female). If not, you can request that a note is placed in your file indicating that you do not want to know the baby’s sex.