Clinical Information

Maternal serum screening has historically been used in obstetric care to identify pregnancies that may have an increased risk for certain birth defects, such as Down syndrome and trisomy 18. Screening in the second trimester has been available in some version (ie, alpha fetoprotein [AFP] test, triple screen, quad screen) for decades. Screening in the first trimester became an established alternative over the last decade.

More recently, sequential screening, which has an improved detection rate as compared to either first- or second-trimester screening, has become a standard option. Sequential screening has a higher detection rate because information about a pregnancy is collected in both trimesters, which provides a greater opportunity for detecting problems.

Sequential Maternal Screening, Part 1, Serum involves an ultrasound and a blood draw. The ultrasound measurement is of the back of the fetal neck, where fluid tends to accumulate in babies who have chromosome conditions, heart conditions, and other health problems. This measurement, referred to as the nuchal translucency (NT), is difficult to perform accurately. Therefore, NT data is accepted only from NT-certified sonographers. Along with the NT measurement, a maternal serum specimen is drawn and 1 pregnancy-related marker is measured (pregnancy-associated plasma protein A: PAPP-A). The results of the ultrasound measurement and blood work are then entered, along with the maternal age and demographic information, into a mathematical model that calculates Down syndrome and trisomy 18 risk estimates.

If the result from the first-trimester Sequential Maternal Screening, Part 1, Serum indicates a risk for Down syndrome that is higher than the screen cutoff, the screen is completed and a report is issued. In that event, the patient is typically offered counseling and diagnostic testing (ie, either chorionic villus sampling or amniocentesis). When the screen is completed after Sequential Maternal Screen Part 1, a neural tube defect (NTD) risk is not provided. For a stand-alone NTD-risk assessment, order MAFP / Alpha-Fetoprotein (AFP), Single Marker Screen, Maternal, Serum.

If the risk from the first trimester is below the established cutoff, an additional serum specimen is drawn in the second trimester for Sequential Maternal Screen, Part 2, which includes tests for AFP, unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A. Once that specimen is processed, information from both trimesters is combined and a report is issued. If results are positive, the patient is typically offered counseling and diagnostic testing (ie, amniocentesis).

Nuchal Translucency (NT):

The NT measurement, an ultrasound marker, is obtained by measuring the fluid-filled space within the nuchal region (back of the neck) of the fetus. While fetal NT measurements obtained by ultrasonography increase in normal pregnancies with advancing gestational age, fetuses with Down syndrome have larger NT measurements than gestational age-matched normal fetuses. Increased fetal NT measurements can, therefore, serve as an indicator of an increased risk for Down syndrome. 

Pregnancy-Associated Plasma Protein A (PAPP-A):

PAPP-A is a 187-kDA protein comprised of 4 subunits: 2 PAPP-A subunits and 2 pro-major basic protein (proMBP) subunits. PAPP-A is a metalloproteinase that cleaves insulin-like growth factor-binding protein-4 (IGFBP-4), dramatically reducing IGFBP-4 affinity for IGF1 and IGF2, thereby regulating the availability of these growth factors at the tissue level. PAPP-A is highly expressed in first-trimester trophoblasts, participating in regulation of fetal growth. Levels in maternal serum increase throughout pregnancy. Low PAPP-A levels before the fourteenth week of gestation are associated with an increased risk for Down syndrome and trisomy 18.