Prenatal Genetic Screening and Diagnostic Testing

Types of Prenatal Genetic Screening

Important points about GS:

• These are not diagnostic; they cannot confirm or exclude a diagnosis of a genetic or chromosomal condition.
• Negative results are reassuring, however false negative results can occur. Individuals who want to know for sure if their pregnancy has a genetic or chromosomal condition should pursue DT by chorionic villus sampling (CVS) or amniocentesis.
• Positive results indicate an increased risk for the specified condition. A positive result may indicate an affected fetus, but can also represent a false positive result in a normal pregnancy. Confirmatory DT, such as CVS or amniocentesis, is recommended for positive screening results.

Carrier Screening
Carrier screening analyzes a person’s DNA to see if they are a carrier for a genetic condition. Carrier screening can be performed on a blood sample, saliva sample, or buccal (cheek) swab. Ideally, carrier screening is conducted prior to pregnancy, but screening can also be done during the first and second trimesters.

Carriers of genetic conditions are typically healthy and often do not know they are carriers. If both parents are carriers of the same genetic condition, or in some cases if just the biological mother is a carrier, then there would be an increased risk for their baby to be affected.

Some common genetic conditions screened for include cystic fibrosis, Tay-Sachs disease, sickle cell anemia and fragile X syndrome.

For those found to be at increased risk to have an affected child, reproductive options such as in vitro fertilization with preimplantation genetic testing, egg/sperm donation, or diagnostic testing during pregnancy are available.

Although carrier screening can identify individuals at risk to have a child with a genetic condition, it does not screen for all possible genetic conditions and does not assess risks for chromosome conditions, birth defects, or intellectual disabilities.

More information about carrier screening can be found here: Preconception Genetic Testing

First Trimester Screening
This screen assesses for Down syndrome, trisomy 18 and trisomy 13. Done between 11 and 13 weeks gestation, the measurement of two pregnancy-related hormones obtained from a maternal blood sample are combined with two ultrasound measurements to calculate these risks.

Integrated Screening
This screen assesses for Down syndrome, trisomy 18 and open neural tube defects (like spina bifida). The first part is done between 11 and 13 weeks gestation, during which the measurement of a pregnancy-related hormone is obtained from a maternal blood sample and two ultrasound measurements are recorded. This is followed by the measurement of four pregnancy-related hormones obtained from a maternal blood sample between 15-20 weeks of pregnancy. A final test result is provided at that point.

Sequential Screening
Similar to the Integrated Screen, this screen assesses for Down syndrome, trisomy 18 and open neural tube defects. The patient is given a preliminary risk estimate after completion of the first-trimester analyte and ultrasound screening. If the first-trimester screening result indicates that the risk of a chromosome condition is greater than the laboratory-derived positive screening cutoff, the patient is offered a DT or cell-free DNA screening, and the screening protocol is discontinued. If the patient has a lower risk than the cut-off level, she is informed that she has received a negative screening test result and pursues the second blood draw between 15-20 weeks gestation, after which a final result is provided.

Second Trimester Screening
This screen assesses for Down syndrome, trisomy 18 and open neural tube defects. Done between weeks 15 and 20 weeks, four pregnancy-related hormones are measured from a maternal blood sample. This is not recommended if you have previously pursued either cell-free fetal DNA or first trimester screening.

Alpha-Fetoprotein (AFP) Test
This screen assesses for neural tube defects. It is done between weeks 15 and 20 weeks and measures a single pregnancy-related hormone measured from a maternal blood sample. It is recommended for women who have previously pursued either cell-free fetal DNA or first trimester screen.

A Targeted (or Detailed) Ultrasound
This screen uses sound waves to assess the baby’s anatomy and development. It is typically done between 18 and 20 weeks gestation.

Types of Prenatal Diagnostic Testing

Important points about DT:

• Data suggests that miscarriage rates for chorionic villi sampling (CVS) is ~0.7% while loss rates for amniocentesis are no higher than 0.33%. We recommended that you discuss the center-specific loss rates in prenatal genetic counseling.
• DT performed on samples obtained from either CVS or amniocentesis are typically sent for either chromosome analysis, microarray testing (which can detect deletions and duplications and copy number changes) and, in certain cases, specific genetic conditions. It does not test for all genetic conditions, birth defects or intellectual disabilities.
• The accuracy of results is >99% accurate. Results are typically available 1-2 weeks after testing.

CVS
A small sample of placental tissue (chorionic villi) is obtained either transcervically or transabdominally under ultrasound guidance between 11-13 weeks of gestation.

Amniocentesis (amnio)
A small sample of amniotic fluid is removed by placing a needle into the amniotic cavity under ultrasound guidance after 16 weeks gestation.