What is the purpose and recommended timing of a maternal serum screen (MSS) for a pregnant individual?

Maternal Serum Screen: Purpose and Timing

Primary Purpose

Maternal serum screening (MSS) is a blood test performed during pregnancy to detect fetuses at increased risk for open neural tube defects (ONTDs), anencephaly, Down syndrome (trisomy 21), and trisomy 18. 1

The screening serves as a risk assessment tool, not a diagnostic test, and identifies pregnancies requiring further evaluation through genetic counseling, targeted ultrasound, or amniocentesis. 1

Optimal Timing

The American College of Medical Genetics recommends offering MSAFP screening optimally between 16 to 18 weeks gestation. 1, 2

• Testing can be performed between 15 and 20.9 weeks, though accuracy is highest at 16-18 weeks. 1
• If a sample is drawn before 15 weeks, a new sample must be obtained with corrected gestational age. 1
• AFP levels increase by 10-15% per week during the second trimester, making accurate gestational age critical for interpretation. 2

Screening Components

Second Trimester Multiple Marker Screening

The quad screen (AFP, hCG, uE3, and INH-A) should be offered to all women unless amniocentesis is already indicated based on history, age, or prior first trimester screening. 1, 2

• Triple screen (AFP, hCG, uE3): Detects approximately 65% of Down syndrome cases. 1, 3
• Quad screen (adds INH-A): Detects approximately 75% of Down syndrome in women under 35 years and over 80% in women 35 and older, with a 5% false-positive rate. 1, 2
• Trisomy 18 detection: At least 70% detection rate using three analytes (AFP, hCG, uE3), which are typically all low in affected pregnancies. 1

Neural Tube Defect Detection

MSAFP screening detects 75-90% of open neural tube defects and 95% of anencephaly cases. 1, 4

• Cut-off levels are 2.0-2.5 MoM for singleton pregnancies and 4.0-5.0 MoM for twin pregnancies. 1
• MSAFP screening may also detect 85% of ventral wall defects. 1
• Elevated AFP values above 2.0-2.5 MoM may indicate neural tube defects, ventral wall defects, or other complications. 2

Critical Information for Accurate Interpretation

The laboratory must be informed of the following factors to adjust MoM levels correctly: 1

• Gestational age at sample collection
• Maternal weight
• Race (Caucasian or Black/African American)
• Presence of insulin-dependent diabetes (AFP levels are lower on average in women with IDDM) 1
• Number of fetuses
• Family history of ONTD

If gestational age changes by 2 or more weeks after ultrasound examination, test results must be reinterpreted. 1

Relationship to First Trimester Screening

Women who have elected first trimester screening and/or CVS should still be offered MSAFP screening between 16-18 weeks gestation for neural tube defect detection. 1, 5

• First trimester screening (NT, PAPP-A, hCG at 11-14 weeks) detects approximately 85% of Down syndrome with combined markers but does not screen for neural tube defects. 2, 5
• Integrated screening combining first and second trimester markers provides the highest sensitivity and cost-effectiveness. 1

Counseling and Informed Consent Requirements

Before obtaining the specimen, patients must be fully informed about the procedure, its implications, and indicate willingness to be tested through documented consent. 1

• Prenatal MSAFP screening must be voluntary, as some couples may not want to face dilemmas posed by abnormal results for religious or ethical reasons. 1
• Genetic counseling and educational materials should be available to review different screening tests, including information about Down syndrome, trisomy 18, ONTDs, and the benefits, risks, and limitations of testing. 1
• Discussions should address possible outcomes and available options. 1

Follow-up for Abnormal Results

Patients with positive second trimester screening results should receive genetic counseling and be offered amniocentesis. 1, 2

• When incorrect gestational age, multiple gestation, and fetal demise have been excluded by ultrasound, prompt consultation or referral to a center with level II ultrasound and amniocentesis capabilities is required. 1
• Both high and low MSAFP values may predict serious birth defects or adverse pregnancy outcomes. 1
• Some centers may proceed directly to expert sonography for very elevated results rather than obtaining a second sample, particularly when pregnancy is relatively advanced. 1

Special Populations

CVS and amniocentesis should continue to be offered to women 35 years and older for diagnosis of aneuploidy, regardless of screening results. 1

• All women should have the option of invasive diagnostic testing regardless of maternal age or screening results. 2, 5
• For twin pregnancies, standard screening protocols apply with adjusted cut-off values. 1

Common Pitfalls to Avoid

• Failing to reinterpret results when gestational age is revised by 2 or more weeks. 1
• Not obtaining a new sample when initial draw was before 15 weeks. 1
• Inadequate counseling about screening limitations—MSS only screens for trisomies 21 and 18, not other aneuploidies like trisomy 13 or Klinefelter syndrome. 1
• Not providing timely information about options in the event of a positive test. 6
• Overlooking the need for MSAFP screening in women who had first trimester screening, as it remains necessary for neural tube defect detection. 1, 5