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FeedbackQuantitative Chemiluminescent Immunoassay (CLIA)
- First-trimester screening test for T21 and T18
- Does not include alpha fetoprotein (AFP) for ONTD screening
- Requires nuchal translucency (NT) measurement performed by an ultrasonographer certified by the Fetal Medicine Foundation (FMF) or the Nuchal Translucency Quality Review (NTQR)
Quantitative Chemiluminescent Immunoassay (CLIA)
- First-trimester screening test for T21 and T18
- Requires NT measurement performed by an ultrasonographer certified by the FMF or NTQR
- Risks provided in both first and second trimesters
Quantitative Chemiluminescent Immunoassay
- Second-trimester screening test for T21, T18, and ONTD
- Requires a previously submitted first-trimester specimen, Maternal Screening, Sequential, Specimen #1, hCG, PAPP-A, NT (3000146)
- Requires NT measurement performed by an ultrasonographer certified by the FMF or NTQR
- Risks provided in both first and second trimesters
Quantitative Chemiluminescent Immunoassay (CLIA)
- First-trimester screening test for T21, T18, and ONTD
- Risks determined using a combination of first- and second-trimester serum markers, with or without first-trimester NT measurement
- Risks provided after testing is completed for second-trimester specimen, Maternal Serum Screening, Integrated, Specimen #2, Alpha Fetoprotein, hCG, Estriol, and Inhibin A (3000149)
Quantitative Chemiluminescent Immunoassay
- Second-trimester screening test for T21, T18, and ONTD
- Requires a previously submitted first-trimester specimen, Maternal Serum Screening, Integrated, Specimen #1, PAPP-A, NT (3000147)
- Risks are determined after second-trimester specimen is received, using a combination of first- and second-trimester serum markers with or without first-trimester NT measurement
Quantitative Chemiluminescent Immunoassay
Second-trimester screening test for T21, T18, and ONTD
Quantitative Chemiluminescent Immunoassay
Second-trimester screening test for ONTD
The American College of Obstetricians and Gynecologists (ACOG), American College of Medical Genetics and Genomics (ACMG), and Society for Maternal-Fetal Medicine (SMFM) recommend offering both screening and diagnostic testing for chromosomal abnormalities and neural tube defects (NTD) to all pregnant women. Screening options include maternal serum screening (MSS), cell-free DNA (cfDNA) screening, and ultrasound. Testing is optional; women may decline screening, as well as prenatal diagnosis. High-risk results merit prompt, appropriate follow-up with critical clinical decisions based on diagnostic rather than screening test results. Refer to the ARUP Consult Prenatal Testing for Chromosomal Abnormalities and Neural Tube Defects topic for additional details.
Disease Overview
Incidence
- Open neural tube defects (ONTD): 1/1,400 pregnancies
- Trisomy 21 (T21): 1/660 births
- Trisomy 18 (T18): 1/3,300 births
Background
ONTD: pretest risk is independent of maternal age.
- Most common ONTDs include:
- Spina bifida: variable presentation which includes some degree of paralysis of lower limbs, loss of bowel and bladder control, ventriculomegaly
- Anencephaly: incompatible with life
T21: pretest risk increases with maternal age.
- Caused by an extra chromosome 21 in all cells
- Clinical features include hypotonia, characteristic facial features, developmental delays/intellectual disability, and short stature
T18: pretest risk increases with maternal age.
- Caused by an extra chromosome 18 in all cells
- Clinical features include intrauterine growth restriction, multiple congenital anomalies, and intellectual disability
- High risk for pre- and postnatal mortality
Test Description
MSS uses biochemical markers present in maternal blood to identify pregnancies with a higher risk for ONTDs, T21, and T18. Some of the panel tests require NT measurements obtained by certified sonographers to be provided to the laboratory. Gestational age windows for test components are specific. Please refer to the ARUP First and Second Trimester Screening Options table for more information.
Test Interpretation
Results
NOTE: The cutoff values were selected based on a ≤5% false-positive rate.
| Disorder(s)a | Result | Posttest Risk Cutoff |
|---|---|---|
| Maternal Serum Screen, First Trimester Only (3000145) | ||
|
First Trimester |
||
|
T21 |
Screen positive |
≥1/230 |
|
Screen negative |
<1/230 |
|
|
T18 |
Screen positive |
≥1/100 |
|
Screen negative |
<1/100 |
|
| Maternal Serum Screen, Sequential (3000146 [first trimester] and 3000148 [second trimester]) | ||
|
First Trimester |
||
|
T21 T18 |
Screen positive |
≥1/25 |
|
Screen negative |
<1/25 |
|
|
Second Trimester |
||
|
T21
|
Screen positive |
≥1/110 |
|
Screen negative |
<1/110 |
|
|
T18 |
Screen positive |
≥1/100 |
|
Screen negative |
<1/100 |
|
|
ONTDsb |
Screen positive |
≥1/250 and/or AFP ≥2.5 MoM |
|
Screen negative |
<1/250 and AFP <2.5 MoM |
|
| Maternal Serum Screen, Integrated (3000147 [first trimester] and 3000149 [second trimester]) | ||
|
Second Trimester |
||
|
T21
|
Screen positive |
≥1/110 |
|
Screen negative |
<1/110 |
|
|
T18 |
Screen positive |
≥1/100 |
|
Screen negative |
<1/100 |
|
|
ONTDs |
Screen positive |
≥1/250 and/or AFP ≥2.5 MoM |
|
Screen negative |
<1/250 and AFP <2.5 MoM |
|
| Maternal Serum Screen, Quad (3000143) | ||
|
Second Trimester |
||
|
T21 |
Screen positive |
≥1/150 |
|
Screen negative |
<1/150 |
|
|
T18 |
Screen positive |
≥1/100 |
|
Screen negative |
<1/100 |
|
|
ONTDsb |
Screen positive |
≥1/250 and/or AFP ≥2.5 MoM |
|
Screen negative |
<1/250 and AFP <2.5 MoM |
|
| Maternal Serum Screen, Alpha Fetoprotein (3000144) | ||
|
Second Trimester |
||
|
ONTDsb |
Screen positive |
≥1/250 and/or AFP ≥2.5 MoM |
|
Screen negative |
<1/250 and AFP <2.5 MoM |
|
|
aOther measurements that may indicate areas of increased risk include:
bCutoffs for ONTDs vary as follows:
MoM, multiple of median |
||
Limitations
- For test specific sensitivity, see Supplemental Resources.
- False positives may occur with incorrect gestational age, multiple gestation pregnancies, fetal demise, placental abnormalities, fetal ventral wall defects, fetal conditions not targeted by MSS, or due to other fetal and maternal biological factors.
References
-
32976375
Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin Summary, No. 226. Obstet Gynecol. 2020;136(4):859-867.
-
19915395
Driscoll DA, Gross SJ, Professional Practice Guidelines Committee. Screening for fetal aneuploidy and neural tube defects. Genet Med. 2009;11(11):818-821.
-
27467454
Gregg AR, Skotko BG, Benkendorf JL, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056-1065.
-
31700163
Palomaki GE, Bupp C, Gregg AR, et al. Laboratory screening and diagnosis of open neural tube defects, 2019 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(3):462-474.
-
Smith’s Recognizable Patterns of Human Malformation
Jones KL, Jones MC, Del Campo, M. Smith’s Recognizable Patterns of Human Malformation. 7th ed. Elsevier Saunders; 2013:7-13.