The Integrated Screen is a two-part screening test that assesses the risk of a baby being born with Down syndrome, trisomy 18, and open neural tube defects (ONTDs). The risk for Smith-Lemli-Optiz syndrome (SLOS) is also reported if the patient is high risk. The first part can be performed between 11 weeks and 13 weeks, 6 days gestation. The second part can be performed between 15 and 22 weeks gestation.
In the first part, ultrasound is used to precisely determine the gestational age of the pregnancy (measure the crown-rump length (CRL)). The ultrasound, performed by a certified sonographer, is also used to measure the nuchal translucency (NT) and assess nasal bone development. A maternal blood sample is drawn to measure the levels of one serum analytes:
- Pregnancy-associated plasma protein (PAPP-A)
In the second part, a second maternal blood sample is taken to measure the levels of serum analytes:
- Alpha-fetoprotein (AFP)
- Total beta-human chorionic gonadotropin (total ß-hCG)
- Unconjugated estriol (uE3)
In pregnancies affected by Down syndrome, the levels of PAPP-A, AFP, and uE3 tend to be lower than normal while the levels of inhibin-A and total ß-hCG are elevated. The NT measurement may also be thicker than normal in an affected pregnancy, and the nasal bone may be underdeveloped (hypoplastic).
In pregnancies affected by trisomy 18, the levels of PAPP-A, AFP, uE3, inhibin-A, and ß-hCG tend to be lower than normal.
In pregnancies affected by ONTDs, such as open spina bifida or anencephaly, the level of AFP tends to be elevated.
Two-part Risk Estimate
Using information from the first and second trimester yields a higher detection rate than a test using information from the first part alone. Additionally, a test using only information from the first trimester cannot assess risk for ONTDs.
What Does a Negative Result Mean?
The result is considered screen negative if the risks for Down syndrome, trisomy 18 and ONTDs are lower than the cut-off used. Typically, after completion of both parts, a cut-off of one in 270 is used for Down syndrome, a cut-off of one in 100 is used for trisomy 18, and a cut-off of one in 104 is used for ONTDs. A patient with a screen negative result is not considered at high risk to have a baby with either Down syndrome or trisomy 18. However, the chance to have a pregnancy with Down syndrome or trisomy 18 is not completely eliminated.
What Does a Positive Result Mean?
A screen positive result for Down syndrome by the Integrated Screen means that the patient has a risk to have a baby with Down syndrome of greater than or equal to one in 270. About 2.15% of patients who have the Integrated Screen receive a screen positive result. A screen positive result for trisomy 18 means that the patient’s risk of having a baby with trisomy 18 is greater than or equal to one in 100 after both parts. A screen positive result for ONTDs means that the patient’s risk of having baby with an ONTD is greater than or equal to one in 104.
A high-risk result for Smith-Lemli-Optiz syndrome (SLOS) will be reported if the patient has a risk of greater than or equal to one in 50. No risk assessment will be provided for this condition if the patient is low risk.
What is the Detection Rate for Down Syndrome, Trisomy 18, and ONTDs?
The Integrated Screen will detect about 95% of singleton pregnancies affected with Down syndrome, greater than 95% of singleton pregnancies affected with trisomy 18, and 85% of singleton pregnancies affected with ONTDs.
What Other Tests may be Offered if an Integrated Screen is Positive?
Depending on the results of the Integrated Screen, additional testing may be offered including a second trimester detailed anatomy ultrasound and prenatal diagnosis (amniocentesis). Genetic counseling is also recommended.