New Guidelines Recommend Universal Prenatal Screening for Down Syndrome

News Author: Laurie Barclay, MD
CME Author:
Désirée Lie, MD, MSEd

Posted: 1/4/2007

January 4, 2007 -- The American College of Obstetrics and Gynecology (ACOG) recommends that all pregnant women, regardless of their age, be offered screening for Down syndrome, according to new guidelines published in the January issue of Obstetrics and Gynecology.

"Historically, maternal age 35 years or older at the time of delivery has been used to identify women at highest risk of having a child with Down syndrome, and these women have been offered genetic counseling and amniocentesis or chorionic villus sampling (CVS)," write Ray Bahado-Singh, MD, Deborah Driscoll, MD, and colleagues, of the ACOG Committee on Practice Bulletins -- Obstetrics, the ACOG Committee on Genetics, and the Society for Maternal-Fetal Medicine Publications Committee. "Biochemical serum screening for Down syndrome in women younger than 35 years was introduced in 1984, when an association between low maternal serum alpha-fetoprotein (AFP) levels and Down syndrome was reported... The practice of using age cutoffs to determine whether women should be offered screening or invasive diagnostic testing has been challenged."

These guidelines were developed to review and evaluate the best available evidence for the use of ultrasonographic and serum markers for selected aneuploidy screening in pregnancy and to offer practical recommendations for implementing Down syndrome screening in clinical practice.

In recent years, numerous markers and strategies for Down syndrome screening have been developed, as have algorithms combining ultrasound and serum markers in the first- and second trimesters. Various markers have included human chorionic gonadotropin (hCG) and unconjugated estriol used in combination with maternal serum alpha-fetoprotein levels.

Using all 3 markers (triple screen) has a detection rate for Down syndrome of approximately 70%, with a positive screen result in approximately 5% of all pregnancies. Adding inhibin A to the triple test (quadruple screen) improves the detection rate for Down syndrome to approximately 80%.

"Screening with biochemical markers, ultrasonography, or both is being offered increasingly to the entire pregnant population to provide a more accurate estimate of individual Down syndrome risk," the authors write. "Higher sensitivity or detection rates (defined as the percentage of Down syndrome pregnancies identified with a positive test result) at low false-positive rates have led to increased use of screening and a decline in the number of amniocenteses performed."

Another screening procedure is evaluation of nuchal translucency, an early presenting feature of a wide variety of fetal chromosomal, genetic, and structural abnormalities. Guidelines for the systematic measurement of nuchal translucency have been standardized, improving the detection rates for Down syndrome. For screening programs that include nuchal translucency measurement, specific training for a standardized method of measurement and ongoing audits of examination quality are recommended.

An important breakthrough in first-trimester screening for Down syndrome was achieved by expressing the nuchal translucency measurement as a multiple of the median and combining it with free β-hCG and pregnancy-associated plasma protein A (PAPP-A). Maternal serum analytes, PAPP-A, and hCG or free β-hCG are effective for screening in the first trimester, but alpha-fetoprotein levels, unconjugated estriol, and inhibin A are useful only in the second trimester.

Specific guideline recommendations based on good and consistent scientific evidence (level A) are as follows:

  • First-trimester screening using both nuchal translucency measurement and biochemical markers is an effective screening test for Down syndrome in the general population. This screening strategy results in a higher detection rate than does the second-trimester maternal serum triple screen and a comparable rate to the quadruple screen, with the same false-positive rates.

  • For first-trimester screening, measurement of nuchal translucency alone is less effective than is the combined use of nuchal translucency measurement and biochemical markers.

  • Women found to have increased risk for aneuploidy based on first-trimester screening should be offered genetic counseling and the option of chorionic villus sampling or second-trimester amniocentesis.

  • Nuchal translucency measurement for Down syndrome risk assessment should be limited to centers and individuals meeting the criteria for specific training, standardization, use of appropriate ultrasound equipment, and ongoing quality assessment.

  • Women who elect only first-trimester screening for aneuploidy should be offered neural tube defect screening in the second trimester.

"Regardless of which screening tests you decide to offer your patients, information about the detection and false-positive rates, advantages, disadvantages, and limitations, as well as the risks and benefits of diagnostic procedures, should be available to patients so that they can make informed decisions," the authors conclude. "Patients may decline Down syndrome screening because they would not use the information in deciding whether to have a diagnostic test or because they wish to avoid the chance of a false-positive screening test result. The choice of screening test depends on many factors, including gestational age at first prenatal visit, number of fetuses, previous obstetric history, family history, availability of nuchal translucency measurement, test sensitivity and limitations, risk of invasive diagnostic procedures, desire for early test results, and options for earlier termination."

Obstet Gynecol. 2007;109:217-228.