Genetic Screening: The Brave New World?


by Susan Dammann RN LAS, Medical Specialist

Recent advances in prenatal testing have afforded physicians and parents the opportunity to screen for abnormalities with a greater degree of accuracy, while identifying a broader range of disorders than ever before.
With this additional knowledge come both the opportunities to seek further testing and to better prepare for the birth of a child with a possible birth defect. Tragically, the increased prevalence of these tests does come with a deadly downside, and has already resulted in a higher number of children who are aborted because of a possible birth defect.

Technology today is taking us into even deeper uncharted waters, presenting greater challenges and opportunities as we consult with clients in the pregnancy center setting. Let’s take a look at some of what is currently available as well as what is on the horizon.

The Quad Marker Screen

Between 15 and 20 weeks of pregnancy, it is common practice for a pregnant woman to be offered the Quad Marker Screen test, as it can only be performed within this certain window of time. The test is optional, and due to uncertainties surrounding the test results, a woman may opt out of the test.

The Quad Marker Screen is a blood test that screens substances in the mother’s blood for problems in the development of the fetus’s brain and spinal cord, called “open neural tube defects”, as well as genetic disorders such as Down syndrome. The Quad Marker Screen can predict approximately 75-80% of open neural tube defects and approximately 75% of Down syndrome cases in women under 35 years old, and over 80% in women age 35 years and older.

The Quad Marker Screen does not diagnose, but rather, predicts the likelihood of a certain problem occurring, determining if a woman is at higher or lower risk of carrying a baby with a birth defect. The test involves no risk to the baby, as a blood sample is taken only from the mother.

Four substances (hence “Quad” Marker Screening) normally found in the baby’s blood, brain, spinal fluid and amniotic fluid are tested:

  1. Alpha-fetoprotein (AFP): a protein produced by the baby’s liver
  2. Human Chorionic Gonadotropin (hCG): a hormone produced by the placenta
  3. Inhibin-A: a hormone produced by the placenta
  4. Unconjugated Estriol (UE): a protein produced in the placenta and in the baby’s liver

The normal amounts of these substances in the mother’s bloodstream change during pregnancy. High AFP levels may indicate an open neural tube defect in the baby, or could indicate that the fetus is older than was originally thought. The numbers could also indicate that the woman is having twins.

An increased risk of a baby having Down syndrome is indicated by higher than normal levels of hCG and Inhibin-A, and lower levels of the hormone estriol.

Can normal test results guarantee a healthy baby? No, a normal result is not a guarantee, but it is a strong indication of health, achieving an accuracy rate of over 98 percent, according to WebMD:

Out of 1,000 pregnant women, approximately 50 will have quad marker screen results that indicate an increased risk for having a baby with a birth defect. Of those women, only one or two will actually have a baby with an open neural tube defect. About 40 women will have quad marker screen results that show an increased risk for having a baby with Down syndrome and one or two will actually have a baby with Down syndrome.

Among the general medical community it is recommended that a woman have the test if:

  • The mother is age 35 or older when the baby is due
  • The family has a history of birth defects
  • The mother has had a previous child with a birth defect
  • The mother was diagnosed with type 1 diabetes prior to her pregnancy

Comparing Testing Limitations, Risks

Test results outside the normal range do not necessarily mean there is a problem with the pregnancy. It is a test that only assesses the risk of having a baby with a birth defect, and can be followed up with additional testing, such as amniocentesis or ultrasound.

The Quad Marker Screen has a false positive rate of 20% when a cut of 1:190 is used. When a positive result is obtained, an amniocentesis may be recommended to help confirm or negate the results. Amniocentesis is very accurate in diagnosing Down syndrome, serving as a “gold standard” predictor, though the fetal loss rate from amniocentesis is about 1:200 or 0.5%.

As we encounter women in our centers who have received negative (suggesting a possible problem) quad test results, or who may be considering having the testing done due to risk factors in their history, and who may gravitate towards aborting if a negative prenatal diagnosis is obtained, this information may help to alleviate some of their initial concerns and equip you to knowledgeably offer support during this potentially difficult time.

Cell-free DNA and Whole Fetal Genome

In 1997, scientists discovered that cell-free fetal DNA could be isolated from maternal blood. Using this technology a screening test was developed to identify 3 trisomies -- trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). New technology now exists for four prenatal genomic screenings that analyze cell-free fetal DNA circulating in maternal blood, offering an early method for detecting certain fetal chromosomal abnormalities. Chromosomal aberration screening can be done between 8 and 10 weeks.

One common test is the MaternT21. The test takes about 7 days to return results, and is 99.8% accurate. It works by sequencing gene fragments of the fetus that are in the maternal blood system.

"It is pretty darn remarkable that there are 4 simple blood tests capitalizing on the cell-free DNA from the fetus in that 1 tube of maternal blood, from which we can determine chromosomal aberrations and gender as well as a whole lot more in terms of sequencing the fetal genome," writes Dr. Eric Topol, Editor-in-Chief of Medscape.1

Susan Klugman, MD, Director of Reproductive Genetics at Montefiore Medical Center in New York City, writes:

In accordance with the American College of Obstetrics and Gynecology (ACOG) guidelines, it is only recommended for high-risk women at the present time. In New York State, the noninvasive prenatal screening test can only be used according to those guidelines. High-risk women are those with:

  • Advanced maternal age (> 35 years);
  • A positive triple or quadruple or first-trimester screen;
  • A structural finding on ultrasonography suggesting aneuploidy;
  • A previous trisomy birth;
  • A known balanced translocation in a parent or the parent of the partner.

For now, noninvasive prenatal screening definitely has a place in prenatal genetic assessment. Women can get reassurance that their unborn babies don't have 1 of the 3 trisomies (13, 18, and 21) or a sex-chromosome disorder, if the screen includes that.2

Cell-free fetal DNA Prenatal Screening is highly sensitive and specific, noninvasive prenatal screening, not a diagnostic test, meaning that if the test is positive for a fetal trisomy, the woman will have to undergo invasive testing if she wants confirmation. According to Klugman, cost varies by laboratory and insurance, in the range of $800 to $3,000, but many laboratories cover most of this cost except for a few hundred dollars.

Screening results do not address the presence or absence of other genetic disorders or diseases that might be present, nor does it assure parents their infant will not have other birth defects. It does not screen for neural tube defects.

Some women may desire to undergo this testing, feeling that obtaining additional information about chromosomal conditions before the birth of the baby will help them feel more prepared. Others may choose this screening with an intent of considering abortion if a chromosomal condition were to be identified.

Katie Stoll, a genetics counselor at Group Health Cooperative in Seattle, has spoken to the issue:

[W]ithout a doubt, some women are making pregnancy termination decisions on the basis of screening results alone. One laboratory presented some preliminary outcomes data at a genetics meeting recently showing that some women were terminating on the basis of noninvasive screening results alone.3

The Present Ethical Dilemna

Cell-Free DNA Technology may make Whole Fetal Genome/Exome Sequencing Possible

Since it is now possible to sequence a fetal genome, Dr. Topol identifies the major ethical concern that needs to be addressed as the technology advances and the possibilities multiply:

[T]he question I really want to bring up is, where do we draw the line? Now that we can sequence a fetal genome, when are we going to start doing that and not just screen for big chromosomal aberrations of trisomies and aneuploidy? This is something that will perhaps engender the biggest bioethical issues of the future. (emphasis added) What do we say is an appropriate finding from sequencing -- whether it is an exome of the fetus or whole genome -- that constitutes criteria for early termination of pregnancy?4

Stoll, likewise, raised the issue in her article:

I am concerned that our technology already has outpaced our ability to offer this testing in a way that empowers truly informed decisions and meaningful information for our patients. There are so many genetic variations that we do not know how to interpret even when we find them in pediatric and adult patients. Is a variant of uncertain significance harmful or beneficial? We often do not know.

Having this level of genetic information prenatally, when we understand so little of what it means, is bound to cause confusion, anxiety, and fear. When used in a way that supports individual needs and values, prenatal testing is incredibly powerful. However, as it becomes more routine and, at the same time, more complex, we run the risk of burdening patients with information that may do more harm than good.5

Arthur L. Caplan, Ph.D., NYU Langone Medical Center, sees a huge concern on the horizon:

The ability to draw cells from the mom's blood will quickly become a test that is used on 100% of pregnant women. I would be surprised if it does not become the standard of care… More testing means that more women may find problems with their fetuses. This test can be performed much earlier than amniocentesis, possibly enabling fetal screening at 7 to 9 weeks. Many people worry that this will lead to more pregnancy terminations. Women who would not have had testing before this will undergo testing, and some may discover things about their fetus that they will not accept, be it a birth defect or some other disease risk factor. Because it is earlier, the burden of abortion may seem morally more acceptable to women than having an abortion much later in pregnancy.6

We can only imagine what these developments will mean long-term for the clients who come into your center. It surely seems probable that as more women are tested with these increasingly definitive tests, the pressure from the medical community to abort would increase as we have already seen for children with Down syndrome. More women may also view abortion as their best—or only—choice as they consider the possibility of giving birth to a child with a negative diagnosis.

As our Savior commanded, let us stay alert and watch and pray, and be ready to minister to these women who will so desperately need our support and love.

1. Eric J Topol, MD, "Topol Predicts Genomic Screening Will Replace Amniocentesis," Medscape, November 2013.
2. Susan Klugman, MD, "The Pros and Cons of Noninvasive Prenatal Screening," Medscape, November 07, 2013.
3. Katie Stoll, MS "Noninvasive Prenatal Screening: A genetics counselor's Perspective" Medscape, November 08, 2013.
4. Topal, "Genomic Screening."
5. Stoll, "Prenatal Screening."
6. Arthur L. Caplan, Ph.D. "Will New Genetic Tests Lead to More and earlier Abortions?" Medscape October 29, 2013.