Fetal Aneuploidy: Screening and Diagnostic Testing


Am Fam Physician. 2020 Apr 15;101(8):481-488.

  Patient information: See related handout on fetal aneuploidy.

Author disclosure: No relevant financial affiliations.

Aneuploidy is the presence of one or more extra chromosomes or the absence of one or more chromosomes. The risk of fetal aneuploidy rises with increasing maternal age. Because fetal aneuploidy can affect any pregnancy, all pregnant women should be offered screening. First-trimester combined screening performed between 10 and 13 weeks' gestation detects 82% to 87% of trisomy 21 (Down syndrome) cases. Second-trimester serum quadruple screening performed between 15 and 22 weeks' gestation detects 81% of trisomy 21 cases. Combinations of these tests include integrated or serum integrated, stepwise sequential, and contingent sequential screenings, all of which improve detection rates compared with each test alone. Fetal cell-free DNA testing (noninvasive prenatal testing) performed at or after 10 weeks' gestation detects more than 99% of trisomy 21 cases, with a lower false-positive rate than traditional first-or second-trimester screening methods. Fetal cell-free DNA testing has similar detection rates in high- and low-risk populations but has lower positive predictive values in younger women. It may be performed as primary screening or as a follow-up test to abnormal findings on first- or second-trimester screenings. Second-trimester ultrasonography has limited utility in aneuploidy screening in women who have already been screened with a first- or second-trimester serum test. Diagnostic tests following a positive screening result include chorionic villus sampling performed between 10 and 13 weeks' gestation or amniocentesis performed after 15 weeks' gestation.

Chromosomal abnormalities affect approximately one in 150 pregnancies1 and are responsible for 50% of early pregnancy losses.2 Aneuploidy is the presence of one or more extra chromosomes or the absence of one or more chromosomes.3 The consequences of fetal aneuploidy vary from incompatibility with life to intellectual and physical disability. Prenatal screening aims to detect the most common forms of aneuploidy compatible with survival beyond early embryologic development into viability. The risk of fetal aneuploidy rises with increasing maternal age. For example, the risk of a woman giving birth to a live newborn with trisomy 21 (Down syndrome) increases from one in 1,480 at 20 years of age to one in 85 at 40 years of age.1 Although the overall birth rate in the United States has declined, the portion of first births to women older than 30 years increased from 23.9% in 2000 to 30.2% in 2014.4,5 Because fetal aneuploidy can affect any pregnancy, all pregnant women should be counseled and offered aneuploidy screening regardless of age.1,6,7


Although the overall birth rate in the United States has declined the portion of first births to women older than 30 years increased from 23.9% in 2000 to 30.2% in 2014.

Fetal cell-free DNA testing (noninvasive prenatal testing), which is generally performed at or after 10 weeks' gestation, can be used to determine the likelihood of trisomies 21, 18, and 13, as well as fetal sex and sex chromosome aneuploidy.

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Clinical recommendationEvidence ratingComments

All pregnant women should be counseled and offered aneuploidy screening regardless of maternal age.1,6,7


Expert consensus guidelines

Fetal cell-free DNA testing (NIPT), which is generally performed at or after 10 weeks' gestation, is superior to first- or second-trimester serum screenings with fewer false positives and higher positive predictive values for trisomies 18 and 21.1,7,17,2332


Systematic reviews and meta-analyses of high-quality diagnostic accuracy studies; NIPT performs similarly in high- and low-risk populations, although positive predictive values are lower in low-risk populations

First-trimester nuchal translucency, NIPT, and first- or second-trimester serum testing can be performed in twin pregnancies.1,7,38


Meta-analysis of diagnostic accuracy studies with limitations; detection rates are lower in twin pregnancies

Women with positive results on aneuploidy screening should be offered referral for invasive diagnostic testing.1,7


Expert consensus guidelines; no screening test, including cell-free DNA, is considered diagnostic

NIPT = noninvasive prenatal testing.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Authors

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NICHOLAS M. LEFEVRE, MD, is a faculty physician at the John Peter Smith Hospital Family Medicine Residency Program and Maternal-Child Health Fellowship, Fort Worth, Tex., and an assistant professor in the Department of Family Medicine at the Texas Christian University and University of North Texas Health Science Center School of Medicine, Fort Worth....

RICHARD L. SUNDERMEYER, MD, FAAFP, is program director of the HealthONE/Sky Ridge Family Medicine Residency Program, Denver, Colo. At the time this article was written, he was a faculty physician at the John Peter Smith Hospital Family Medicine Residency Program and director of the Maternal-Child Health Fellowship.

Address correspondence to Nicholas M. LeFevre, MD, 1500 S. Main St., Fort Worth, TX 76104 (email: nlefevre@jpshealth.org). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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