Management of Elevated Alpha-fetoprotein in Pregnancy
The best next step for a 38-year-old pregnant female with an elevated alpha-fetoprotein (AFP) level on her quad screen is to obtain an ultrasound. 1, 2
Rationale for Ultrasound as First Step
Elevated maternal serum alpha-fetoprotein (MSAFP) requires a systematic approach to determine the underlying cause. The American Society of Human Genetics (ASHG) specifically recommends ultrasonography as the initial step in management for patients with elevated MSAFP levels 2. This approach allows for:
- Confirmation of gestational age (incorrect dating is a common cause of falsely elevated MSAFP)
- Exclusion of multiple gestation
- Ruling out fetal demise
- Detection of neural tube defects (which cause 75-90% of elevated MSAFP)
- Identification of ventral wall defects (which account for 85% of elevated MSAFP)
- Assessment of placental abnormalities 1, 2
Management Algorithm
Ultrasound first: Perform detailed ultrasound to identify potential causes of elevated MSAFP
- If ultrasound shows incorrect dating → recalculate MSAFP based on corrected gestational age
- If ultrasound identifies multiple gestation → adjust interpretation of MSAFP (cut-off levels for twins are 4.0-5.0 MoM)
- If ultrasound detects fetal anomaly → provide appropriate counseling and management
Amniocentesis consideration: Only after ultrasound has been performed and either:
- Identified an abnormality requiring confirmation
- Failed to explain the elevated MSAFP 2
Important Considerations
Ultrasound limitations: While ultrasound is the appropriate first step, it's important to note that it has limitations. Studies show that ultrasound alone may miss some anomalies. Research indicates that ultrasound has approximately 83% sensitivity for detecting anomalies in patients with elevated MSAFP 3.
Risk stratification: The risk of fetal anomalies increases with higher MSAFP levels:
- MSAFP < 3.0 MoM: 0.93% risk of anomalies
- MSAFP > 7.5 MoM: 56% risk of anomalies 3
Pregnancy outcomes: Even with normal ultrasound findings, unexplained elevated MSAFP is associated with:
- 2-4 fold increase in low birthweight
- 10-fold increase in placental abruption
- 10-fold increase in perinatal mortality 4
Why Not Other Options
Amniocentesis (Option A): While amniocentesis may eventually be needed, it should not be the first step due to its invasive nature and associated risks. Ultrasound should precede amniocentesis to potentially identify the cause without invasive testing 2, 3.
Repeat test in 4 weeks (Option B): Guidelines recommend against repeating MSAFP for significantly elevated values and instead suggest proceeding with diagnostic evaluation via ultrasound 2.
Abortion (Option C): This is inappropriate without diagnostic confirmation of a serious fetal anomaly. Elevated MSAFP is a screening test with many potential causes, including benign ones.
Ultrasound provides valuable diagnostic information with no risk to the pregnancy, making it the clear first choice in evaluating elevated MSAFP.