2005

Maternal and Fetal Medicine Division Offers First-Trimester Screening for Down Syndrome

Points to Remember

• Increasingly, families want a safe and effective prenatal screening test as early as possible in pregnancy to indicate risk of Down syndrome.
• First-trimester screening is a noninvasive and more accurate alternative to secondtrimester standard blood test screens for Down syndrome.
• If the noninvasive screen indicates a high risk for Down syndrome, the diagnosis can be confirmed by invasive studies such as chorionic villus sampling or amniocentesis, which carry a small risk of miscarriage.
• Mayo Clinic Division of Maternal and Fetal Medicine offers first-trimester screening to pregnant patients who wish screens for Down syndrome.

Scope of Problem

Pregnant women in the United States now commonly request aneuploidy (chromosome) screening. This is true not only among women traditionally counseled to seek testing -- those aged 35 years or older who are at increased risk for bearing children with chromosomal birth defects, particularly Down syndrome -- but among women younger than 35 years as well.

This trend presents new clinical challenges to physicians who do not specialize in high-risk pregnancies or maternal and fetal medicine. These challenges include providing the earliest and most reliable test results about the developing fetus, especially screens for Down syndrome. Between 2% and 4% of live-born infants in the United States have some sort of clinical birth defect. Offering comprehensive, advanced care before, during, and after delivery in a single clinical setting minimizes stress to the family.

Standard Screening and Its Limitations

The association between low α-fetoprotein (AFP) levels and Down syndrome was reported in 1984 and launched the era of maternal serum screening. First triple, then quadruple blood serum screening tests were developed. These tests screen biochemical characteristics of blood. The four components measured by the quadruple screen are AFP, unconjugated estriol, b-human chorionic gonadotropin (β-HCG), and inhibin A levels. This screen correctly detects chromosomal abnormalities about 75% of the time. However, it cannot be performed until week 15 to week 20 of the pregnancy. Many families consider this too late to make the emotional adjustments necessary for the possibility of bearing a child with special needs, to arrange support and counseling, or to preserve privacy and the ability to terminate the pregnancy safely. As a result, there is a demand for a noninvasive Down syndrome screen that can be performed before week 15.

First-Trimester Screening

Safe, noninvasive Down syndrome screening can now be performed at 11 weeks 0 days to 13 weeks 6 days of pregnancy. This test combines information from 4 sources:

1. Maternal age
2. An ultrasound that evaluates fetal nuchal translucency, which gives a measure of the thickness of the back of the fetus's neck
3. Blood serum tests of maternal pregnancy associated plasma protein A
4. Maternal blood serum levels of β-HCG.

For best results, first-trimester screening should be performed at medical centers with high-volume obstetrics practices because this assures that an integrated multispecialty medical team is interpreting the test results. The Mayo Clinic Division of Maternal and Fetal Medicine has performed approximately 500 first-trimester screenings since fall 2004, when Mayo Clinic became one of the first centers to use this technique.

If first-trimester screening results show a high maternal risk for bearing a child with Down syndrome, then definitive, invasive tests such as chorionic villus sampling and amniocentesis can be performed. Both carry a small risk of miscarriage.

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Advantages of First-Trimester Screening

First-trimester screening can be performed earlier -- at week 11 versus week 15. It is noninvasive and therefore safe for both mother and fetus. Studies have shown it is more accurate than previous methods. For example, a multicenter study of 8,514 women reported in the New England Journal of Medicine in 2003 found that first-trimester screening detected Down syndrome in 85.2% of affected cases. Thus, failure to detect Down syndrome (a false-negative reading) occurred in about 15% of cases. This compares favorably with the second-trimester test's sensitivity of identifying Down syndrome in approximately 65% of cases, a false-negative rate of about 35%.

Another advantage of firsttrimester screening is that it can help reduce the number of women who expose themselves and their fetuses to the small risks of miscarriage associated with the invasive diagnostic tests for Down syndrome -- amniocentesis and chorionic villus sampling.

Disadvantages

First-trimester screening is not widely available and requires experienced ultrasonographers and clinicians. Because the accuracy of the screening depends on the integrity of the ultrasound imaging of fetal nuchal transparency measurements, ultrasonographers need to receive certification and ongoing training to standardize their techniques and measurements. An editorial accompanying the 2003 study in the New England Journal of Medicine noted that differences in sonogram reading as small as 0.1 mm may mean the difference between a positive and a negative result. The editorial emphasized that the need for precise, expert, and ongoing training limits the availability of first-trimester screening.

Candidates for First-Trimester Screening

First-trimester screening is appropriate for pregnant women of all ages. It is especially useful for women aged 35 years or older who face a significantly higher risk of bearing a child with Down syndrome.