Alpha-fetoprotein (AFP) is a major protein produced by a developing baby during pregnancy. This substance is a glycoprotein, a protein molecule with an attached sugar component. AFP serves as a biomarker, meaning its level in the pregnant person’s bloodstream indicates the baby’s development. Measuring this protein is part of standard prenatal screening offered during the second trimester. The concentration of AFP changes predictably throughout gestation, making its measurement a useful, though non-diagnostic, tool for assessing the likelihood of certain developmental differences.
The Biological Role of Alpha-Fetoprotein
The alpha-fetoprotein molecule is primarily synthesized by the fetal liver and the yolk sac early in development. It is the dominant plasma protein in the fetus, serving a function similar to albumin in an adult’s blood. AFP acts as a transporter, binding to and carrying various substances throughout the fetal circulation.
AFP transports hormones, such as estrogen, as well as essential compounds like fatty acids and bilirubin. The protein moves from the fetal circulation into the surrounding amniotic fluid. A small amount of AFP then crosses the placenta and enters the pregnant person’s bloodstream, where it is measured. The measurement of this maternal serum AFP (MSAFP) provides an indirect look at the protein’s levels within the fetus.
AFP Measurement in Prenatal Screening
The AFP test is performed via a simple blood draw from the pregnant person, typically between the 15th and 20th weeks of gestation. Testing during this window is significant because AFP concentration rises and falls at set times, making accurate gestational dating necessary for correct interpretation. The most accurate results are usually obtained between the 16th and 18th weeks.
AFP measurement is rarely performed in isolation and is often integrated into a multi-marker screening test, commonly known as the Triple or Quad screen. These tests combine AFP results with measurements of other fetal and placental hormones, such as human chorionic gonadotropin (hCG), estriol, and sometimes inhibin A.
The laboratory result is not reported as a simple concentration but is calculated as a Multiple of the Median (MoM). This MoM value compares the individual’s AFP level to the median AFP level found in a large population of pregnancies at the same gestational age. A result that falls outside the established normal range is considered abnormal and suggests an increased risk for further investigation.
Understanding Abnormal AFP Levels
An AFP result significantly higher than the population median is most commonly associated with open neural tube defects (NTDs). These defects occur when the fetal spine or brain does not close completely during early development. This allows excess AFP to leak into the amniotic fluid and subsequently into the maternal bloodstream. Conditions like spina bifida and anencephaly are the primary NTDs detected by elevated AFP.
High AFP can also be linked to other structural issues, such as abdominal wall defects where the baby’s organs protrude outside the body. However, the most frequent explanation for an elevated AFP level is simply an incorrect estimation of gestational age. Since AFP levels rise steadily, being further along than initially thought can artificially inflate the result.
Conversely, a significantly lower-than-median AFP level is associated with an increased chance of certain chromosomal abnormalities. The most recognized of these is Trisomy 21 (Down syndrome) and sometimes Trisomy 18 (Edwards syndrome). An abnormal AFP screen is a risk indicator and not a definitive diagnosis of any condition.
Follow-Up Diagnostic Testing
Following an initial abnormal AFP screening result, the first step is usually to verify the accuracy of the test and pregnancy dating. A repeat blood test may be ordered, but a detailed ultrasound examination is the most common next procedure. The ultrasound confirms gestational age, rules out multiple fetuses (which naturally elevate AFP levels), and checks for visible structural defects.
If the ultrasound confirms correct dating and does not identify the cause of the abnormal level, more invasive diagnostic testing may be offered. Amniocentesis, typically performed after 15 weeks of gestation, involves sampling the amniotic fluid. This fluid can be tested directly for AFP and acetylcholinesterase, a substance also elevated with open NTDs.
Fetal cells obtained from the amniotic fluid can also be analyzed for chromosomal abnormalities like Down syndrome, providing a definitive diagnosis. The distinction between the screening test (assessing risk) and the diagnostic test (confirming a condition) is paramount for understanding the results. The majority of abnormal AFP screening results are ultimately determined to be false positives after further investigation.