First Trimester Screen, Hyperglycosylated hCG (h-hCG)

A negative screen means it is unlikely the fetus has either Down syndrome or trisomy 18. But a negative screen does not guarantee the birth of a healthy baby. The demographic information provided at the time of testing is used in calculating the patient’s Down syndrome and trisomy 18 risk. Please check the demographic information to ensure accuracy of calculated results.

The first trimester screening test screens only for Down syndrome and trisomy 18. Guidelines recommend neural tube defect screening be performed in the second trimester.¹ The Maternal Serum AFP test (test code 5059) is available for this purpose.

Most patients with negative screening tests choose not to proceed with a diagnostic test.

A positive Down syndrome screen result means there is an increased risk for the fetus to be affected with Down syndrome or other chromosome abnormalities. The demographic information provided at the time of testing is used in calculating the patient’s Down syndrome and trisomy 18 risk. Please check the demographic information to ensure accuracy of calculated results.

Guidelines recommend counseling women with a positive screening test. Such counseling may include a discussion of the significance of the screening results and diagnostic testing options (eg, chorionic villus or amniocentesis testing) and/or noninvasive prenatal screening (NIPS; test code 92777 or 91933[NY]). Guidelines do not recommend repeating Down syndrome positive screening tests.

A positive trisomy 18 result means there is an increased risk for the fetus to be affected with trisomy 18 or other chromosome abnormalities. The demographic information provided at the time of testing is used in calculating the patients Down syndrome and trisomy 18 risk. Please check the demographic information to ensure accuracy of calculated results.

Guidelines recommend counseling women with a positive screening test. Such counseling may include a discussion of the significance of the screening results and diagnostic testing options (eg, chorionic villus or amniocentesis testing) and/or noninvasive prenatal screening (NIPS; test code 92777 or 91933[NY]). Guidelines do not recommend recalculating incorrect estimated date of delivery/gestational age or repeating trisomy 18 positive screening tests.

The gestational age is calculated from the crown rump length (CRL) provided, using criteria derived from the Fetal Medicine Foundation. If the CRL is not provided, the gestational age is derived from the estimated date of delivery (EDD) and the collection date provided and is an exact calculation by calendar days. Gestational wheels may be inaccurate by several days or more.

Note that the gestational age is reported in decimal weeks. For example, 11 weeks 4 days is reported as 11.6 weeks.

It is appropriate to change the gestational age or EDD when the data used for screening are substantially above or below that determined by ultrasound. In case of a positive screen for trisomy 18, however, guidelines recommend against changing the gestational age or EDD (see Question 3.)

The earliest EDD calculated by ultrasound should be used for dating purposes.² An ultrasound derived EDD is most accurate when determined in the first trimester. Accuracy decreases with advancing gestational age. For example, accuracy of an ultrasound EDD is ±7 days in the first trimester and ±10 days in the second trimester.

If a first trimester ultrasound EDD is available and the gestational age used for screening is within the EDD ±7 days, the gestational age should not be changed for screening purposes. If the gestational age used for screening is outside the ultrasound EDD range, it may be appropriate to change the gestational age used for screening.

If you want to change the EDD/gestational age used for a specific patient’s screening test, please contact your local Quest Diagnostics business unit or call Quest Genomics Client Services at 866-GENE-INFO. If the revised gestational age is between 10.0 to 13.9 weeks gestation, we can calculate and report new risks. If the revised gestational age is <10.0 weeks, we cannot calculate new risks. Consider submitting a second specimen for screening, collected when the patient is between 10.0 to 13.9 weeks gestation. If the revised gestational age is >13.9 weeks gestation, we cannot calculate new risks, and a more accurate risk assessment cannot be provided. Consider submitting a second specimen for second trimester screening (ie, Penta Screen or Quad Screen) when the patient is between 15.0 to 22.9 weeks gestation (preferably 16 to 18 weeks).

The web calculator is a tool that allows you to add nuchal translucency (NT) data acquired after a patient’s sample was submitted for screening and get revised Down syndrome and trisomy 18 risks. It can be used only for this test (test code 16020 or 16969[NY]).

Access the calculator at http://gocalc.QuestDiagnostics.com and perform the following steps:

1. Enter the UNIKEY code for the patient, the sonographer’s ID number, and the patient’s last name. Note that the sonographer must be on file with the lab prior to using the calculator tool.
2. Enter the NT value when prompted.
3. Review the revised risks provided by the calculator.
4. Add forwarding information when prompted so the revised final report can be sent to the primary physician as well as the client doing the NT measurement.

Please call Quest Genomics Clients Services at 866-GENE-INFO to discuss this case with a genetic counselor. Documentation of the abnormality in the family may enable a more specific risk assessment or indicate whether additional studies should be performed. 

A cutoff of 1 in 270, the risk of a 35-year old, is used to determine if a pregnancy is screen negative or screen positive for Down syndrome. This cutoff is used regardless of the patient’s age, since it’s the historical cutoff for offering diagnostic testing (amniocentesis).

When counseling a pregnant patient, it may be helpful to compare her age-related risk (ie, pre-test risk) with her screen-derived risk (post-test risk) and the general population risk (1 in 600-800 live births). This allows the patient and her partner to better understand her risk of carrying a Down syndrome-affected fetus and to weigh it against the risks and consequences of amniocentesis.

There is no consensus as to exactly what constitutes a low PAPP-A value in first trimester screening. However, low PAPP-A levels have been associated with low birth weight, reduced fetal growth, hypertension, pre-eclampsia, pre-term labor, and fetal demise. When a physician considers a patient’s PAPP-A to be low, he/she usually treats her as if she has a high risk pregnancy and follows her more closely as the pregnancy progresses.

Prenatal screening in twin pregnancies is complex. The serum markers can be measured in a patient with a twin gestation and then divided by corresponding medians for unaffected singleton pregnancies to calculate multiple of medians (MoMs) which are then adjusted for twins in order to provide a pseudo-risk for Down syndrome. This calculation accounts for the presence of two fetuses, and also takes into account the nuchal translucency measurement of each specific fetus. The result is a pregnancy-specific pseudo-risk, rather than a fetus-specific risk.

Prenatal screening in twin pregnancies is complex. A trisomy 18 risk assessment is not calculated for twin gestations due to insufficient screening marker data from affected twin pregnancies