What is the purpose and procedure of maternal serum testing (MST) during pregnancy?

Maternal Serum Testing in Pregnancy

Maternal serum testing is a critical screening tool performed during pregnancy to identify pregnancies at risk for fetal open neural tube defects (ONTDs), anencephaly, and chromosomal abnormalities such as trisomies 21 and 18, allowing for early intervention and improved pregnancy outcomes. 1

Purpose of Maternal Serum Testing

• Maternal serum alpha-fetoprotein (MSAFP) screening identifies pregnancies at risk for open neural tube defects (ONTDs) and anencephaly, with detection rates of 75-90% for ONTDs and 95% for anencephalics 1
• Multiple marker screening (MMS) identifies pregnancies at risk for chromosomal abnormalities, particularly Down syndrome (trisomy 21) and trisomy 18 1
• MSAFP screening may also detect approximately 85% of ventral wall defects 1
• Early identification of these conditions allows for informed decision-making regarding additional testing, pregnancy management, and preparation for potential complications 1

Types of Maternal Serum Testing

First Trimester Screening (11-14 weeks)

• Includes nuchal translucency (NT) measurement via ultrasound, pregnancy-associated plasma protein A (PAPP-A), and human chorionic gonadotropin (hCG) or free beta-hCG 2
• Detection rate of approximately 70% for Down syndrome with a 5% false-positive rate 2

Second Trimester Screening (15-20.9 weeks)

• Triple Test: Measures MSAFP, hCG, and unconjugated estriol (uE3), with approximately 65% detection rate for Down syndrome 1, 3
• Quadruple (Quad) Test: Adds dimeric inhibin-A (INH-A) to the triple test, increasing detection rate to approximately 75% for Down syndrome in women under 35 years and over 80% in women 35 and older 1, 4

Optimal Timing and Procedure

• MSAFP screening for neural tube defects is optimally performed between 16-18 weeks gestation, but can be done between 15-20.9 weeks 1
• Multiple marker screening (MMS) should be performed between 15-20.9 weeks of gestation 1, 4
• The laboratory must be informed of the exact gestational age at the time of sample collection for accurate interpretation 1, 4
• If gestational age changes by 2 or more weeks after ultrasound examination, test results must be reinterpreted 1
• If a sample was drawn before 15 weeks, a new sample should be collected at the appropriate gestational age 1, 4

Factors Affecting Test Accuracy

• Test accuracy improves when the laboratory is informed of:
  • Maternal weight
  • Race (particularly Caucasian or Black/African American)
  • Presence of insulin-dependent diabetes
  • Number of fetuses
  • Family history of neural tube defects 1, 4
• Ultrasound dating of pregnancy reduces false-positive rates and increases detection rates 1, 4

Interpretation of Results

• MSAFP results are reported as multiples of the median (MoM) 1
• Cut-off levels for ONTD screening are 2.0-2.5 MoM in singleton pregnancies and 4.0-5.0 MoM in twin pregnancies 1
• For Down syndrome screening, typically lower levels of AFP and uE3, with higher levels of hCG and INH-A are observed 1
• For trisomy 18 screening, all three analytes (AFP, hCG, uE3) are typically low, with detection rate of at least 70% 1

Follow-up for Abnormal Results

• For elevated MSAFP results, genetic counseling and additional testing such as targeted ultrasound examination and amniocentesis are recommended 1
• For positive screening results for trisomy 21 or 18, genetic counseling and amniocentesis should be offered 1
• A common protocol for abnormal MSAFP includes:
  • Second serum specimen evaluation (if indicated)
  • Counseling
  • Ultrasonography
  • Karyotyping
  • Amniocentesis (if indicated) 1

Patient Education and Informed Consent

• Before testing, patients should be fully informed about the procedure and its implications 1, 5
• Educational materials appropriate for the population should be available to patients, with accurate clinical and incidence data clearly stated in lay language 1
• Prenatal MSAFP screening should be voluntary, and the patient's decision should be documented 1, 5
• Comprehensive counseling should include information about the benefits, risks, and limitations of the tests and possible outcomes 1, 5

Common Pitfalls to Avoid

• Not providing adequate counseling regarding screening options and the benefits, risks, and limitations of different tests 2
• Failing to reinterpret test results if gestational age is revised 1, 4
• Not following up on abnormal results promptly 2
• Performing the test outside the validated window (15-20.9 weeks for second trimester screening) 1, 4
• Overlooking the importance of providing accurate information about maternal factors that affect test interpretation 1, 4

By understanding the purpose, procedure, and interpretation of maternal serum testing, healthcare providers can better guide patients through this important screening process, leading to improved pregnancy outcomes and informed decision-making.