Can I go straight to an amnio?
In general, we feel that the risks of Down syndrome and other chromosomal abnormalities are too low to warrant the risk, and cost, of an amnio. Therefore, doctors are reluctant to do it, and insurance companies will not reimburse for it.

Can I find out if my baby has Down syndrome?
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 is 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 greater than about 1:290,, you will be encouraged to meet with a genetic counselor and will be offered amniocentesis.

What are the drawbacks to second trimester risk assessment?
The vast majority of patients who “screen positive” with a risk of Down syndrome greater than 1:290 have normal babies. Consider: 200 women are told they are “screen positive” because they have a risk of Down syndrome of 1:200. Of these 200 women, 199, or 99.5%, have unaffected babies. Only one of these 200 babies actually has Down syndrome. That means that 199 women are “needlessly” alarmed; they will choose either to have an amnio, subjecting their fetus to a risk of miscarriage, or they will continue to be worried about this until the birth of the child. This is the problem with the “false positive rate” of serum screening that you may have heard about.

Furthermore, even if you “screen negative” with a risk of Down syndrome less than 1:290 this is not a guarantee that your child has normal chromosomes. For example, a risk of Down syndrome of 1:500 is not the same as a risk of zero. Also, there are other chromosome disorders besides Down syndrome.

The timing of these tests is an issue for many people. Serum screening can only be done after 15 weeks, and modification of the risk by ultrasound is done after 16 weeks. Since it takes another 2 weeks after an amniocentesis to obtain the results, couples who choose amniocentesis after second trimester risk assessment may not obtain definitive results until 20 weeks.

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 earliest that we feel it can be done with minimal risk to the baby.

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?
As is the case in second trimester risk assessment, most women who “screen positive” have normal babies. 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.

Insurance companies do not cover ERA. Therefore, we have to ask women that are interested in ERA to pay for this themselves. At this time, the cost of the ultrasound is $325. We bill the insurance companies for the blood work, in lieu of a second trimester serum screen. If the pregnancy is found to be at increased risk of Down syndrome, all further tests (ultrasound, amniocentesis) will be billed to the insurance company.

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.

What do we need to think about to help us make a decision?
Before you agree to have a screening 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. These couples should have neither ERA nor second trimester risk assessment. Therefore, although it’s difficult, we advise our patients to think about these questions before they agree to undergo screening:

• 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 screening, will I worry about this until the baby is born?