Screening for Fetal Chromosomal Abnormalities

Publication Date: October 1, 2020
Last Updated: March 14, 2022


Prenatal genetic screening (serum screening with or without nuchal translucency [NT] ultrasound or cell-free DNA screening) and diagnostic testing (chorionic villus sampling [CVS] or amniocentesis) options should be discussed and offered to all pregnant women regardless of maternal age or risk of chromosomal abnormality. After review and discussion, every patient has the right to pursue or decline prenatal genetic screening and diagnostic testing. (A)

If screening is accepted, patients should have one prenatal screening approach, and should not have multiple screening tests performed simultaneously. (A)

Cell-free DNA is the most sensitive and specific screening test for the common fetal aneuploidies. Nevertheless, it has the potential for false-positive and false-negative results. Furthermore, cell-free DNA testing is not equivalent to diagnostic testing. (A)

All patients should be offered a second-trimester ultrasound for fetal structural defects, since these may occur with or without fetal aneuploidy. Ideally this is performed between 18 and 22 weeks of gestation (with or without second‐trimester maternal serum alpha‐fetoprotein). (A)

Patients with a positive screening test result for fetal aneuploidy should undergo genetic counseling and a comprehensive ultrasound evaluation with an opportunity for diagnostic testing to confirm results. (A)

Patients with a negative screening test result should be made aware that this substantially decreases their risk of the targeted aneuploidy but does not ensure that the fetus is unaffected. The potential for a fetus to be affected by genetic disorders that are not evaluated by the screening or diagnostic test should also be reviewed. Even if patients have a negative screening test result, they may choose diagnostic testing later in pregnancy, particularly if additional findings become evident such as fetal anomalies identified on ultrasound examination. (A)

Patients whose cell-free DNA screening test results are not reported by the laboratory or are uninterpretable (a no‐call test result) should be informed that test failure is associated with an increased risk of aneuploidy, receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing. (A)

If an enlarged nuchal translucency or an anomaly is identified on ultrasound examination, the patient should be offered genetic counseling and diagnostic testing for genetic conditions as well as a comprehensive ultrasound evaluation including detailed ultrasonography at 18–22 weeks of gestation to assess for structural abnormalities. (A)

The use of cell-free DNA screening as follow-up for patients with a screen positive serum analyte screening test result is an option for patients who want to avoid a diagnostic test. However, patients should be informed that this approach may delay definitive diagnosis and will fail to identify some fetuses with chromosomal abnormalities. (B)

In clinical situations of an isolated soft ultrasonographic marker (such as echogenic cardiac focus, choroid plexus cyst, pyelectasis, short humerus or femur length) where aneuploidy screening has not been performed, the patient should be counseled regarding the risk of aneuploidy associated with the finding and cell-free DNA, quad screen testing, or amniocentesis should be offered. If aneuploidy testing is performed and is low-risk, then no further risk assessment is needed. If more than one marker is identified, then genetic counseling, maternal–fetal medicine consultation, or both are recommended. (B)

No method of aneuploidy screening that includes a serum sample is as accurate in twin gestations as it is in singleton pregnancies. This information should be incorporated into pretest counseling for patients with multiple gestations. ()

Cell-free DNA screening can be performed in twin pregnancies. Overall, performance of screening for trisomy 21 by cell-free DNA in twin pregnancies is encouraging, but the total number of reported affected cases is small. Given the small number of affected cases it is difficult to determine an accurate detection rate for trisomy 18 and 13. (B)

Because preimplantation genetic testing is not uniformly accurate, prenatal screening and prenatal diagnosis should be offered to all patients regardless of previous preimplantation genetic testing. (B)

The use of multiple serum screening approaches performed independently (eg, a first-trimester screening test followed by a quad screen as an unlinked test) is not recommended because it will result in an unacceptably high positive screening rate and could deliver contradictory risk estimates. (C)

In multifetal gestations, if a fetal demise, vanishing twin, or anomaly is identified in one fetus, there is a significant risk of an inaccurate test result if serum-based aneuploidy screening or cell-free DNA is used. This information should be reviewed with the patient and diagnostic testing should be offered. (C)

Patients with unusual or multiple aneuploidies detected by cell-free DNA should be referred for genetic counseling and maternal–fetal medicine consultation. (C)

Recommendation Grading



Screening for Fetal Chromosomal Abnormalities

Authoring Organization

Publication Month/Year

October 1, 2020

Last Updated Month/Year

January 9, 2023

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Adult

Health Care Settings

Ambulatory, Laboratory services, Outpatient

Intended Users

Nurse midwife, genetics, nurse, nurse practitioner, physician, physician assistant


Assessment and screening

Diseases/Conditions (MeSH)

D025063 - Chromosome Disorders, D000081182 - Noninvasive Prenatal Testing


chromosomal abnormalities, chromosomal disorder, prenatal screening