Genetic Screening: Accuracy and Results

How accurate is genetic screening? 

It’s normal to have questions about the accuracy of a screening result, given that screening tests are not able to give a definitive diagnosis and instead indicate an increased risk or probability. If you receive a high-risk screening result, how likely is it that your pregnancy truly has the condition you were positive for? 

The answer to this question is a little less straightforward than you might think and involves several statistical concepts, including sensitivity, specificity, and positive predictive value. Sensitivity refers to the ability of a screening test to correctly flag an individual as screen-positive (or “high risk”) if they have the condition. In other words, a highly sensitive screen has a high detection rate; there are very few false negatives in which cases of disease are missed by the screen. Specificity refers to the ability of a screening test to correctly label an individual as screen negative (or “low risk”) if they do not have the condition. A highly specific screening test will have very few false positives, so those without the condition will rarely be flagged as screen-positive.  

If prenatal genetic screening results come back as screen-positive or indicate an increased risk, then positive predictive value (PPV) is an important statistic to consider. In the context of prenatal screening, PPV refers to the likelihood that a screen-positive result is a “true positive” and the pregnancy has the condition being screened. For example, if you receive a screen-positive NIPS result for Down syndrome with a 90% PPV, this means there is a 90% likelihood that the pregnancy has Down syndrome and a 10% chance the pregnancy does not have Down syndrome. If you receive a screen-positive NIPS result for trisomy 18 with a 20% PPV, this means there is a 20% chance the pregnancy has trisomy 18, and an 80% chance that the pregnancy does not have trisomy 18. A higher PPV means a higher chance of the pregnancy being diagnosed with the condition after a positive screening result. 

What are the next steps if you receive a high-risk genetic screening result? 

1. Review your results with your healthcare team: If your genetic screening reveals an increased risk for a genetic condition during pregnancy, it’s important to speak with your healthcare team so you can gather information, learn about your options for follow-up testing, and make an informed decision about next steps. A consultation with a genetic counselor can help you understand your result in the context of your unique pregnancy… and help you process the emotions that come with a screen positive or “high risk” result. 
2. Consider prenatal diagnostic testing: Because screening tests are not able to definitively diagnose a condition, it is possible for false positives to occur. Confirming prenatal screening results through diagnostic testing is always recommended before making any irreversible decisions about a pregnancy. Prenatal diagnostic testing can be performed through chorionic villus sampling (CVS) in the first trimester or through amniocentesis in the second trimester. CVS testing involves the collection of a placental tissue sample and is typically done between 10-14 weeks gestation. In amniocentesis, a sample of the amniotic fluid is obtained for analysis, and testing is typically done between 15-22 weeks gestation. Both CVS and amniocentesis can provide a clear “yes” or “no” result for chromosome conditions like Down syndrome. Because amniocentesis and CVS are invasive procedures, they are associated with a risk of pregnancy loss (miscarriage). However, with advances in ultrasound technology and provider expertise, the risk is generally <1% (estimates range from approximately 1 in 300 to 1 in 1,000). 

How do I know if genetic screening is right for me? 

The decision of whether to pursue prenatal genetic screening is a personal one, and not all families will choose the same path. For some, being able to screen for genetic conditions early in pregnancy helps give them peace of mind, while others may feel that genetic screening would provide more information than they want to know. Speaking with a healthcare provider like a genetic counselor can help you decide whether prenatal genetic screening is right for you and empower you during your pregnancy journey.

- Authored by Kelly Miller, MS, LCGC | Genetic Counselor

Please note: JunoDx.com and the materials and information it contains are not intended to, and do not constitute medical or other health advice or diagnosis and should not be used as such. You should always consult with a qualified physician or health professional about your specific circumstances.