Genetic screening

One question that frequently comes up in my office is whether my pregnant patients should have genetic screening.  This is a really complex issue, and it's also very personal.  I usually lay out the pros and cons of testing, and help my patients decide for themselves whether to have the tests.

First of all, genetic screening should be an optional test.  I don't recommend across the board that all patients have it.  It's important to know what is being tested, and what you will do with that information once the test is completed.

Genetic screening is a way to decide which pregnant patients are at high risk of having a child with chromosome problems, such as Down Syndrome (an extra copy of chromosome 21) or other more serious trisomies (extra copy of either chromosome 13 or 18).  The test is not diagnostic, meaning it does not tell you whether your baby has a chromosome problem or not.  When the results of the test come back, they say something like "positive screen for trisomy 21, risk 1:100".  A positive screen is an arbitrary cutoff point, usually if the risk is greater than that of an average 35 year old woman.  As you can imagine, a positive screen can cause significant anxiety, but since it is a screening test only, there is a high false positive rate, and a diagnostic test such as amniocentesis or chorionic villus sampling is the only way of knowing for sure if your baby is affected.  I think it is important for women to decide ahead of time what they would do if they had a positive screen.  If an amniocentesis is completely out of the question, they may not want to have the screen.  Likewise a negative screen does not completely rule out chromosome problems.  If a woman is at particularly high risk of chromosome problems, such as a history of an affected infant, she may want to skip the screening altogether, and go straight to diagnostic testing.

There are several ways to screen for trisomies.  The earliest results come from what's called "First Trimester Screening".  This involves an ultrasound of the back of the baby's neck, called Nuchal Translucency or NT, between 11 weeks and 13 weeks 6 days gestation, as well as a blood test on the mother to check the levels of specific proteins, PAPP-A and free beta-hCG.

In the second trimester, between 15 and 22 weeks, the Quad test is offered.  This involves checking the mother's blood for 4 different proteins, total hCG, AFP, unconjugated estriol, and Inhibin-A.  There is no ultrasound with the second trimester screen.  This test also provides a screen for open neural tube defects such as spina bifida and anencephaly, where the brain and/or spinal column do not close completely during development.

These tests can be done individually, sequentially, or integrated (confusing, I know).  A large study published in the New England Journal of Medicine in 2005, called the FASTER trial, showed that for a set 5% false positive rate, the detection of Down syndrome was highest, 96%, if the patient had fully integrated screening.  This means the first trimester screen with ultrasound and blood test and the second trimester Quad test were done, and all the results were integrated to give a risk.  Sequential testing refers to the same tests, but results are given after each test is completed, instead of waiting until after the Quad test to integrate the results.

So, if you're still confused, what does this mean?  Bottom line, think about first of all, whether this information is important to you.  Do you want to find out before you have your baby if there are any chromosome problems?  What would you do differently if you found out your baby had a trisomy?  For some women, if they know they will have a baby who has a potentially lethal defect, they would opt to terminate the pregnancy.  For other women, termination would never be an option.  Others may want to know just to be prepared for what will happen when the child is born.  Some women are comfortable not having this information, and would not want to know ahead of time.

The one genetic screen that most women do have during pregnancy is a detailed anatomic ultrasound sometime around 20 weeks of gestation.  Although it can not diagnose genetic problems, major anatomic defects can raise suspicion for chromosome issues and diagnostic testing could be performed then.  There is also a chance that the ultrasound would look totally normal, but the baby has Down syndrome or other chromosome problems.

It's a lot to think about.  With new developments in what we can find out prior to delivery, more complex decisions have to be made.  There are a lot of ethical issues also involved in the discussion.  I believe every person has the right to make an informed decision about what testing they do or do not desire during pregnancy.  I welcome comments or questions related to this topic...