What are the next steps for a pregnant woman with a positive Alpha-Fetoprotein (AFP) screen?

Management of Positive Maternal Serum AFP Screen

For a minimally elevated AFP (first result), obtain a second serum sample before proceeding to invasive testing, but if the AFP is very elevated or the pregnancy is relatively advanced, proceed directly to ultrasound evaluation without repeat testing. 1

Initial Assessment Algorithm

Determine Need for Repeat Testing

The decision to recollect depends on the degree of elevation and gestational age:

• Minimally elevated AFP (approximately 2.0-2.5 MoM): A second serum sample is most appropriate when there is time for repeat specimen collection 1
• Very elevated AFP: Dispense with second sample and proceed directly to expert sonography, particularly when capable ultrasound is available 1
• Advanced gestational age: Skip repeat testing and move to ultrasound evaluation 1

Confirm Accurate Gestational Dating

Before any further workup, verify gestational age as this is the most common cause of abnormal AFP:

• Wrong dating by LMP is the most frequent cause of abnormal MSAFP levels 2
• Gestational age errors account for approximately 46% of initially low AFP and 15% of initially high AFP cases 2
• If ultrasound reveals a gestational age discrepancy of ≥2 weeks, reinterpret the AFP result using the corrected dating 3
• Maternal serum AFP increases 10-15% per week in the second trimester, making accurate dating essential 4

Systematic Follow-Up Protocol

After Confirming or Repeating AFP

1. Genetic counseling should be provided at each step of the evaluation process 1

2. Level I ultrasound to exclude:

   • Incorrect gestational age 1
   • Multiple gestation (accounts for 16% of elevated AFP cases) 2
   • Fetal demise 1

3. If elevated AFP persists after excluding above causes:

   • Prompt consultation or referral to a center with level II ultrasound capability 1
   • Targeted ultrasound examination for neural tube defects and ventral wall defects 3
   • Consider amniocentesis for amniotic fluid AFP and acetylcholinesterase (AChE) testing 3

Expected Outcomes with Repeat Testing

When a second sample is obtained for initially elevated AFP:

• Approximately 46% will normalize on repeat testing 2
• About 12% will remain elevated on second test 2
• The true false-positive rate for MSAFP screening is approximately 1.4% after appropriate follow-up 5

Critical Considerations

Conditions Associated with Elevated AFP

Fetal structural abnormalities:

• Open neural tube defects detected in 75-90% of cases 3
• Anencephaly detected in 95% of cases 3
• Gastroschisis (very elevated levels) 3
• Omphalocele (normal to elevated) 3

Other fetal conditions:

• Congenital nephrosis (very elevated) 3
• Fetal demise 3

Maternal factors requiring adjustment:

• Lower maternal weight (higher AFP levels) 3
• Race/ethnicity (Black/African American women have higher baseline levels) 3
• Insulin-dependent diabetes (lower AFP levels on average) 1, 3

Common Pitfalls to Avoid

• Do not reclassify screen-positive results to screen-negative based on dating changes unless the revised gestational age differs by at least 10 days 4
• Samples drawn before 15 weeks gestation may give inaccurate results 3
• Maternal anxiety is a serious concern—proper genetic counseling must be implemented, as undue anxiety has led to unnecessary pregnancy terminations 2
• The optimal screening window is 16-18 weeks gestation; testing outside this window increases false-negative rates 1, 5

Documentation Requirements

• Document both the initial and repeat AFP values in mass units and multiples of the median (MoM) 1
• Include maternal weight, race, diabetes status, and accurate gestational age for proper interpretation 3
• Provide risk assessment information specific to the patient's test result, not just the MoM value 1