Routine amniotic fluid alphafetoprotein assay: experience with 40,000 pregnancies

Area of Science:

• Prenatal Diagnosis
• Biochemistry
• Genetics

Background:

• Amniotic fluid alphafetoprotein (AFP) and acetylcholinesterase (AChE) are established biochemical markers for fetal abnormalities.
• Elevated levels can indicate open neural tube defects (NTDs) and other serious fetal conditions.

Purpose of the Study:

• To evaluate the diagnostic accuracy of amniotic fluid AFP and AChE levels in identifying open neural tube defects (NTDs).
• To determine the risk of fetal abnormalities associated with specific AFP and AChE levels.
• To assess the false-positive rate and recurrence risk of NTDs.

Main Methods:

• Analysis of 40,000 amniotic fluid samples for AFP and AChE levels.
• Correlation of biomarker levels with confirmed fetal diagnoses, including open NTDs.
• Calculation of risk percentages based on standard deviation (SD) thresholds for AFP and AChE positivity.
• Follow-up assessment of false-positive rates and NTD recurrence risks.

Main Results:

• 0.7% of samples had AFP levels ≥ +3 SD. Risk of NTD or abnormality was 61% at ≥ +3 SD and 87% at ≥ +5 SD.
• Positive AChE increased NTD risk to 84% (≥ +3 SD AFP) and 95% (≥ +5 SD AFP).
• All 93 open NTDs were identified with a true false-positive rate of 1 in 13,000. Recurrence risk was 1.8%.

Conclusions:

• Amniotic fluid AFP and AChE testing is highly effective in detecting open neural tube defects (NTDs).
• Elevated AFP levels, particularly when confirmed by AChE, strongly predict fetal abnormalities.
• The screening protocol demonstrated high sensitivity and a low false-positive rate for NTD detection.