Genetic Experts Update Recommendations on Non-invasive Prenatal Screening

Non-invasive prenatal screening (NIPS) is the most sensitive screening option for Down syndrome, according to an updated position statement recently published by the American College of Medical Genetics and Genomics (ACMG). The position statement recommends that healthcare practitioners inform their pregnant patients about this screening option, regardless of age and whether or not they are at increased risk for carrying a baby with a chromosome disorder.

NIPS, which uses a technique to detect cell-free fetal DNA or cffDNA, analyzes fragments of DNA from the placenta of a developing baby that circulate in the mother's blood. It is performed on a sample of the mother's blood and screens for chromosome abnormalities called trisomies, in which a baby receives an extra copy of a chromosome in addition to the two normally inherited from each parent. In addition to Down syndrome (trisomy 21), NIPS routinely screens for Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13).

ACMG's statement also stresses the importance of patient counseling before and after testing to assist patients in making informed decisions. Whenever a "positive" or "increased risk" fetal screening test result is reported, diagnostic testing, such as chorionic villus sampling (CVS) or amniocentesis, should be offered to confirm the presence of a fetal chromosome abnormality.

According to ACMG, NIPS can replace conventional first trimester and second trimester screening tests to identify pregnancies at increased risk for Down, Edwards, or Patau syndromes. The ACMG position statement cites data from two large studies showing that NIPS is superior to conventional screening tests.

For example, the data showed that NIPS is better able to detect the three trisomies when they are present (better sensitivity) and to rule them out when they are not present (better specificity). Because NIPS is better able to rule out the trisomies, fewer women may need follow-up diagnostic testing. It should be noted that NIPS testing does not detect all chromosomal defects and that diagnostic tests, such as amniocentesis, should remain an option especially for high-risk individuals.

In some cases, the laboratory that performs the DNA analysis will return an "indeterminate" or "no call" result when there is an insufficient amount of cell-free fetal DNA in the maternal blood sample. This can occur, for example, when the woman is obese (>250 lbs) or when the blood sample is collected too early in the pregnancy. ACMG recommends offering diagnostic testing using amniocentesis or CVS following a "no call" NIPS screening result if the maternal blood sample was drawn at an appropriate gestational age. They also recommend offering a screening test other than NIPS in cases of significant maternal obesity.

The utility of NIPS is evolving at a rapid pace. In addition to screening for trisomies of chromosomes 21, 18, and 13, it may be used to identify fetuses at increased risk for sex chromosome abnormalities, such as Turner syndrome and Klinefelter syndrome. Less often, laboratories may use NIPS to screen for trisomy 16, trisomy 22, and triploidy.

Genetic counseling is essential both before and after prenatal screening. Expectant mothers should talk to a genetic counselor or qualified healthcare practitioner who can explain the meaning of the results and discuss the potential risks and benefits of screening and diagnostic testing if it is indicated. Pregnant women may also wish to check with their insurance companies, as not all policies may cover NIPS.