{"id":2861,"date":"2019-10-31T18:59:29","date_gmt":"2019-10-31T22:59:29","guid":{"rendered":"https:\/\/www.shortform.com\/blog\/?p=2861"},"modified":"2022-04-14T16:48:42","modified_gmt":"2022-04-14T20:48:42","slug":"genetic-testing-during-pregnancy","status":"publish","type":"post","link":"https:\/\/www.shortform.com\/blog\/genetic-testing-during-pregnancy\/","title":{"rendered":"Genetic Testing During Pregnancy: The 3 Methods"},"content":{"rendered":"\n

Does it make sense for you to undergo genetic prenatal testing? What are the different ways you can do this, and what are their pros and cons? Learn the three methods of genetic testing here.<\/p>\n\n\n\n\n\n\n\n

Why Do Prenatal Genetic Testing?<\/h2>\n\n\n\n

The primary purpose of prenatal screening during pregnancy is to detect chromosomal abnormalities, the most common being Down Syndrome, or trisomy 21. Tests also screen for the rarer Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), both more severe than Down Syndrome with babies rarely surviving their first year. Families at high risk for genetic disorders may also screen.<\/p>\n\n\n\n

The risk of Down Syndrome increases with maternal age, from 1 in 1488 from ages 20-24, to 1 in 746 in ages 30-34, to 1 in 30 for age 45 (a fuller chart is shown later). For some comparison, the risk of a car accident in the next year is 1 in 50, and the risk of being audited in the next year is 1 in 200.
<\/p>\n\n\n\n

There are largely two types of screening: non-invasive (cell-free fetal DNA<\/a>, ultrasound), and invasive (amniocentesis, chorionic villus sampling). Non-invasive tests pose no risk to the fetus but are more prone to false positives and false negatives. In contrast, invasive tests have higher accuracy, but pose a risk of miscarriage (according to Oster, 1 in 800).
<\/p>\n\n\n\n

Spoiling the punchline: cell-free fetal DNA tests have advanced non-invasive screening considerably<\/strong> from the ultrasound days.
<\/p>\n\n\n\n

Plan Ahead Before Screening<\/strong><\/h2>\n\n\n\n

Typically, people consider getting a non-invasive genetic screen first, then depending on the results, they might get an invasive genetic screen.
<\/p>\n\n\n\n

Before getting a screen, it\u2019s useful to consider what you\u2019re going to do based on the news you receive.<\/strong> For some parents, screening may have no point – no matter what they find, they\u2019ll continue with the pregnancy. Then testing would just cause undue anxiety and may be unnecessary.
<\/p>\n\n\n\n

If you do want a genetic testing during pregnancy, then consider what you\u2019ll do if you get a positive or negative result. For instance, if you get a non-invasive test and it comes back negative (things check out as normal), would you get an invasive test anyway to be sure? If so, then you might just skip to the invasive test anyway.
<\/p>\n\n\n\n

Noninvasive Test: Cell-free Fetal DNA<\/strong><\/h2>\n\n\n\n

Cell-free fetal DNA tests use fetal DNA that is circulating in the mother\u2019s bloodstream. 
<\/p>\n\n\n\n

The mother\u2019s bloodstream contains not just fetal cells but also fetal DNA outside of cells. In fact, 10-20% of DNA isolated from maternal plasma is from the fetus. 
<\/p>\n\n\n\n

Theoretically, if the fetal DNA could be isolated fully from the mother\u2019s DNA, then full genomic sequencing could occur. We\u2019re not quite there yet, but bulk defects can still be detected – for instance, if a higher than expected proportion of chromosome 21 is in the mix, there\u2019s a good chance it indicates trisomy 21.
<\/p>\n\n\n\n

The sensitivity (true positive rate, or accurate detection of a disorder) is remarkably high – in one large-scale study, 99.1% of trisomies are detected with this procedure. The false negative rate is also low, at 0.05% (of 146,000 women without Down Syndrome, 61 were given a false positive).<\/p>\n\n\n\n

In essence, if you get a positive result, it\u2019s very likely the child has Down Syndrome; and if it\u2019s negative, it\u2019s very unlikely the test is wrong.
<\/p>\n\n\n\n

If you get a positive result when you\u2019re younger, the chances that the child actually has Down Syndrome are lower as well.
<\/p>\n\n\n\n

(Shortform note: the true positive rate increases with age because the risk increases a lot with age. When the baseline rate is high and the test is positive, chances are better that the test is correct, compared to younger mothers.)
<\/p>\n\n\n\n

Noninvasive Test: Ultrasound + Blood Test<\/strong><\/h2>\n\n\n\n

The newer cell-free fetal DNA test may not be covered by insurance until you\u2019re over 35. In contrast, the more traditional screen consists of an ultrasound to detect nuchal translucency (fluid behind the baby\u2019s neck) and a blood test for hormones in maternal blood (PAPP-A, hCG). 
<\/p>\n\n\n\n

This test\u2019s accuracy is much worse than the cell-free DNA test – it detects only 90% of Down Syndrome cases (vs 99%), and it has a false positive rate of 6.3% (vs 0.05%).
<\/p>\n\n\n\n

An additional second trimester test draws blood and tests for alpha-fetoprotein, hCG, unconjugated estriol, and inhibin A. Combined altogether, the performance improves – up to 97% of Down Syndrome cases are successfully detected.
<\/p>\n\n\n\n

(Shortform note: the author doesn\u2019t comment on the accuracy of combining the cell-free fetal DNA with the noninvasive test, but given the accuracy of the cell-free test, things may not improve by much.)
<\/p>\n\n\n\n

Invasive Test: CVS and Amniocentesis<\/strong><\/h2>\n\n\n\n

Both invasive tests use a needle to extract something from the womb – in chorionic villi sampling (CVS) it\u2019s part of the placenta; in amniocentesis, it\u2019s amniotic fluid. CVS is performed earlier between 10-12 weeks, while amniocentesis is done between 16-20 weeks.
<\/p>\n\n\n\n

The accuracy of both tests is very high (Shortform note: the author doesn\u2019t put numbers to this).
<\/p>\n\n\n\n

The risk of miscarriage is the worrisome part – inserting the needle might hit the fetus or pierce the placenta. Common wisdom puts the risk of miscarriage at 1 in 200.
<\/p>\n\n\n\n

Oster argues this number is outdated and based on research from the 1970s, which found a non-significant increase of miscarriages from 3.2% to 3.5%. With better procedures (using ultrasound to guide the needle), Oster believes the risk of miscarriage is now closer to 1 in 800<\/strong>, if there is any risk at all.
<\/p>\n\n\n\n

However, one factor may increase risk – the popularity of cell-free DNA testing has lowered the need for CVS, and practitioners may become rusty. So if you want to get invasive testing, go to someone who still does them often.
<\/p>\n\n\n\n

Making a Choice<\/strong><\/h2>\n\n\n\n

Now equipped with this information about genetic testing during pregnancy, you can make a choice<\/a> about risks and what you gain.
<\/p>\n\n\n\n

For instance, if you\u2019re 35, get a cell-free DNA test, and receive a negative result, the baby\u2019s risk of Down Syndrome is 1 in 45,109. The invasive test has a chance of miscarriage<\/a> of 1 in 800. Do you think that the risk of unexpectedly having a Down Syndrome child is 56 times worse (45109 \/ 800) than having a miscarriage? If yes, then proceed to the invasive test.
<\/p>\n\n\n\n

For what it\u2019s worth, Oster chose ultrasound screening for her first child at age 31. For her second child at age 35, she believed the risk of miscarriage was less important now that they already had one child, and she chose to have amniocentesis in the second trimester. As Oster stresses, this was her personal choice, not what she dictates for everyone.
<\/p>\n","protected":false},"excerpt":{"rendered":"

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