From the Guidelines
The gestational age at which the serum alpha-fetoprotein (AFP) is measured has the greatest influence on determining its predictive value for neural tube defects. Serum AFP screening is most accurate when performed between 16 and 18 weeks of gestation, with optimal timing around 16-18 weeks 1. Testing too early or too late can significantly reduce the test's predictive value. This timing is critical because AFP levels naturally change throughout pregnancy, with concentrations rising until about 32 weeks and then declining. When interpreting AFP results, values must be adjusted for gestational age using multiples of the median (MOM) rather than absolute values. Additionally, other factors that can affect AFP levels and potentially lead to false positives include multiple gestation, underestimated gestational age, fetal death, and certain maternal conditions like diabetes. Understanding the relationship between gestational age and AFP levels is essential for proper interpretation of test results and appropriate counseling regarding the risk of neural tube defects. Some key points to consider when interpreting AFP results include:
- The optimal time for NTD screening is at 16 to 18 weeks gestation 1
- Testing can be done between 15 and 20.9 weeks, but the laboratory should be informed of the gestational age at the time the sample was drawn for an accurate interpretation 1
- Ultrasound dating of the pregnancy reduces the false-positive rate and increases the detection rate of ONTDs 1
- The test is most accurate if the laboratory is also informed of maternal weight, race, presence of insulin-dependent diabetes, number of fetuses, and family history of ONTD 1. It is worth noting that while an older study from 1989 discussed the use of MSAFP screening for various conditions 1, the most recent and highest quality study from 2004 provides the most relevant guidance on the use of AFP screening for neural tube defects 1.
From the Research
Factors Influencing Predictive Value of Serum Alpha-Fetoprotein for Neural Tube Defects
The predictive value of an increased serum alpha-fetoprotein (AFP) concentration for neural tube defects is influenced by several factors, including:
- The population being screened, with the predictive value varying depending on the risk level of the population 2
- The use of routine ultrasonography before amniocentesis, which can identify anencephaly and reduce the predictive value of an elevated AFP 2
- The presence of other factors that can cause elevated AFP levels, such as fetal blood contamination 3 or abdominal wall defects 4
- The sensitivity and specificity of the ultrasound examination in detecting neural tube defects, with a sensitivity of 90% or higher allowing for a revised risk estimate to be calculated 5
Key Considerations
When interpreting the results of an increased serum AFP concentration, it is essential to consider the following:
- The risk of false positives, which can be high in low-risk populations 2
- The potential for other conditions to cause elevated AFP levels, such as multivitamin/folic acid supplementation 6
- The importance of ultrasound examination in detecting neural tube defects and revising the risk estimate 5
- The need for genetic counselors to reconsider the recommendation of routine AFP screening in low-risk maternal populations 2