Alpha-Fetoprotein (AFP) is a protein produced primarily by the developing fetus, initially by the yolk sac and later by the fetal liver. A small amount of this protein crosses the placenta and enters the mother’s bloodstream. The maternal serum AFP (MSAFP) test is a routine, non-invasive blood test offered during the second trimester of pregnancy. It functions as a screening tool to assess the likelihood of the fetus having certain birth defects or genetic conditions. This test is often performed as part of a multi-marker screening panel, such as the triple or quad screen.
Understanding the AFP Maternal Screening
The AFP screening is typically offered between the 15th and 20th weeks of gestation, with the 16th to 18th week considered the optimal time. Measuring AFP levels during this window is important because the protein’s concentration in maternal blood changes rapidly as the pregnancy progresses. Accurate gestational dating is therefore crucial for proper interpretation, as miscalculating the age can lead to an apparently abnormal result.
To standardize results across different laboratories and gestational ages, the test result is reported as a Multiple of the Median (MoM). The MoM compares an individual patient’s AFP level to the median AFP level found in a large population of pregnancies at the exact same week of gestation. For example, a result of 1.0 MoM indicates the patient’s AFP level is exactly the median for that week.
A MoM of 1.0 represents the center of the normal range, normalizing the data regardless of the absolute concentration of AFP. Adjustments are also made based on factors such as maternal weight, race, and insulin-dependent diabetes, as these variables influence AFP concentration. The AFP test is a screening tool designed to assess risk, and an abnormal MoM result does not function as a diagnosis.
Interpreting Results Above the Normal Range
An AFP result is considered elevated, or screen-positive, when the MoM is above a certain cutoff, typically 2.5 MoM for a singleton pregnancy. The primary concern associated with a high AFP level is the increased risk for Open Neural Tube Defects (ONTDs), such as spina bifida and anencephaly. In these conditions, the fetal neural tube fails to close completely, allowing AFP to leak into the amniotic fluid and subsequently into the mother’s circulation.
Elevated AFP can also signal abdominal wall defects, including gastroschisis or omphalocele, where fetal organs protrude outside the body, causing AFP leakage. A high MoM may also indicate a multiple gestation pregnancy, such as twins or triplets, since multiple fetuses produce the protein.
Other Causes of High MoM
Other factors that can cause a high result include underestimation of the pregnancy’s age, placental abnormalities, or a threatened miscarriage. Unexplained elevations in AFP, even without a structural defect, have been associated with an increased risk for adverse pregnancy outcomes. These outcomes include preeclampsia, intrauterine growth restriction, and preterm delivery.
Interpreting Results Below the Normal Range
Conversely, an AFP MoM significantly lower than the median, generally below 0.75 MoM, is considered a screen-positive result. The primary concern with a low AFP level is an increased risk for certain chromosomal abnormalities. Specifically, a low AFP MoM, when combined with abnormal levels of other markers in the quad screen, is characteristic of Trisomy 21 (Down syndrome).
Low AFP levels are also associated with Trisomy 18 (Edwards syndrome), a less common but more severe chromosomal disorder. These conditions typically involve lower production or transfer of AFP into the maternal bloodstream. Similar to high results, an error in estimating gestational age can lead to a low MoM if the pregnancy is less advanced than initially thought. A very low AFP MoM has also been linked to an increased risk of fetal loss or miscarriage, even without a chromosomal anomaly.
Next Steps After an Abnormal Result
Receiving an abnormal AFP MoM result indicates a need for additional evaluation, though most screen-positive results ultimately lead to the birth of a healthy baby. The immediate next step is often a high-resolution ultrasound to confirm gestational age and assess fetal anatomy. This imaging can correct dating errors, which are the most common cause of abnormal MoM results, or visually identify structural issues like a neural tube defect.
If the ultrasound confirms dating and identifies no clear cause, further non-invasive testing, such as Non-Invasive Prenatal Testing (NIPT), may be offered to screen for chromosomal conditions like Trisomy 21. If the risk remains elevated, a definitive diagnostic procedure like amniocentesis may be recommended. This invasive test analyzes amniotic fluid for AFP and acetylcholinesterase, an enzyme that confirms the presence of an open neural tube defect. Consulting with a healthcare provider and a genetic counselor is recommended to understand the specific risks and make informed decisions about further testing.