Can I go straight to CVS or amniocentesis?
Yes. This option is available for women who desire maximal reassurance that their child has normal chromosomes.

Can’t you tell if the baby has Down syndrome from a blood test or by ultrasound?
No. However, we can do second trimester risk assessment after 15 weeks. A maternal blood sample is obtained for measurement of 3 or 4 substances. The “triple test” measures AFP, estriol, and HCG. The “quad test” also measures inhibin, and is slightly better than the triple test at estimating the probability that the baby has Down syndrome. Both the triple test and the quad test are also called the second trimester serum screen, or the AFP screen. Measuring the AFP concentration also helps to identify fetuses with certain structural abnormalities such as spina bifida, and occasionally the screen will identify an increased risk of trisomy 18.

Based on a combination of the mother’s age and the second trimester serum screen, the probability of Down syndrome is calculated. For example, the result could be 1:1000 or 1:10. Thus, this is not a diagnostic test; rather it is only an estimate of the risk. At many centers, including MGH, this risk can be modified by findings on a second trimester ultrasound, usually done after 16 weeks, that is often called a structural survey. If the risk of Down syndrome is low enough, you may decide not to have an amnio.

What are the drawbacks to second trimester risk assessment?
Only an amniocentesis is definitive: even a very low risk of Down syndrome isn’t the same as no risk. Amniocentesis also detects chromosomal disorders other than Down syndrome.

Women who decide to have an amnio after second trimester risk assessment receive the results two or more weeks later than those who choose to go directly to amnio. All of this waiting and worrying can be difficult. Finally, some women who choose not to have an amnio after risk assessment may continue to worry about this until the baby is born.

Is there a way to obtain risk assessment earlier in pregnancy?
Yes. We call this ERA which stands for Early Risk Assessment. ERA is performed between 11.5-14 weeks and involves an ultrasound to measure the nuchal translucency (the fluid in the back of the neck of the fetus). At the same time, a maternal blood sample is obtained. Based on a combination of the mother’s age, the size of the nuchal translucency and the levels of the two proteins (free beta hCG and PAPP-A) in maternal blood, the probability for Down syndrome is calculated, similar to second trimester risk assessment. ERA is followed by an ultrasound after 16 weeks to look for structural abnormalities.

The nuchal translucency is typically very tiny, only 1 to 2 mm. It takes special training and expertise to make this measurement accurately. The Fetal Medicine Foundation has played a leading role in standardizing the precise way this measurement should be made and interpreted. They provide certification to those who have had additional training, have demonstrated the ability to make this measurement to their satisfaction, and submit their data on a regular basis for ongoing analysis and quality review. We feel that only when the nuchal translucency is measured by someone with Certification by the Fetal Medicine Foundation can you be confident that the calculated risk of Down syndrome is accurate.

How does ERA compare to second trimester risk assessment?
Since ERA is earlier than second trimester risk assessment, and most women get reassuring news, they will be reassured several weeks earlier. Women who choose to have an amnio can have it done at 15 weeks, the same gestational age as those who go directly to amnio.

We think ERA provides an estimate of risk of both Down syndrome and other chromosome abnormalities that is a bit more accurate than either the triple screen or the quad screen.

Finally, measurement of nuchal translucency will occasionally provide an indication of a structural or genetic problem.

Can you combine ERA with second trimester risk assessment?
This is a very complex issue. To do this properly, we would have to withhold the information from ERA until after the second trimester screening results are back. This defeats the major advantage of ERA, earlier diagnosis. Therefore, we recommend that women who choose ERA do not have second trimester serum screening.

Occasionally there are findings on the ultrasound done after 16 weeks that make us reconsider the need for amniocentesis.

What are the drawbacks of ERA?
They include the drawbacks of second trimester risk assessment: only after an amniocentesis can we be certain that the fetus does not have Down syndrome or any other chromosomal abnormality. In addition, second trimester risk assessment has been in use longer in the United States, and is considered the “standard of care” by the American College of Obstetricians and Gynecologists. Although ERA is somewhat newer, it has been used for several years in Europe, and recent American studies have confirmed the European experience. ERA requires registration for prenatal care prior to 14 weeks. Some people are concerned about the cost of additional ultrasounds, and that sufficient expertise for measurement of the nuchal translucency is not widely available.

ERA does not screen for many structural abnormalities, including spina bifida. Therefore, we urge all women who have been screened by ERA to have a second trimester structural survey after 16 weeks. We feel that this makes serum AFP screening for abnormalities like spina bifida unnecessary. Although there are some birth defects that can be detected by second trimester AFP screening but be missed by ultrasound, these are exceedingly uncommon.

Rarely, a fetus will have a large nuchal translucency, but the chromosomes and the rest of the structural survey are normal. This fetus is at increased risk of being affected by a genetic syndrome of some type, but we can often say nothing further until after the child is born, and perhaps not even then. This can be a difficult situation for the prospective parents.

Do I have to choose one of these tests?
No. Many women opt not to have any testing for fetal chromosome disorders.

What do we need to think about to help us make a decision?
Before you agree to have a test, you should think about what you will do with the information. Many couples would not have an amniocentesis under any circumstances. They would not undergo pregnancy termination if the fetus is affected, and/or they do not accept the risk of miscarriage of a normal fetus associated with amniocentesis. Therefore, although it’s difficult, we advise our patients to think about these questions:

• Is this information I want to know prior to delivery?
• How do I feel about pregnancy termination?
• How do I feel about raising a disadvantaged child? What impact will this have on my family? Who will care for an adult with special needs when I am no longer able?
• How do I feel about a miscarriage?
• If I decide not to have testing, will I worry about this until the baby is born?

The maximal extent that the findings from ERA can reduce the risk of Down syndrome is by a factor of 10, based on your age. So if you will be 40 years old at delivery, ERA can reduce the risk of Down syndrome at most from 1:100 to 1:1000. If a 40 year old woman feels that 1:1000 is still too high a risk, she should go straight to CVS or amnio.

Overall, it is important to remember that all of these tests are optional. It is entirely your choice. Discussing these options with your obstetrician or genetic counselor is recommended.