Maternal Serum Alpha-Fetoprotein (MSAFP) screening is a common prenatal blood test offered to assess the risk of certain conditions during pregnancy. Alpha-fetoprotein (AFP) is a protein naturally produced by the developing fetus, primarily in the liver and yolk sac. A small amount of this protein crosses the placenta and enters the pregnant person’s bloodstream, where its level can be measured. It is important to understand that this test is a screening tool, designed to identify pregnancies that may be at an increased statistical risk, and is not a definitive diagnostic test.
Defining the Screening and Administration
The Maternal Serum Alpha-Fetoprotein test is typically performed during the second trimester of pregnancy. The optimal gestational window for accurate measurement is generally between 15 and 20 weeks, with the highest sensitivity often cited between 16 and 18 weeks of gestation. Accurate dating of the pregnancy is necessary for the correct interpretation of the results, as AFP levels naturally rise and fall throughout the pregnancy.
The AFP measurement rarely stands alone and is often conducted as part of a larger panel, historically known as the Triple Screen or Quad Screen. These multiple marker screenings include other substances like human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and sometimes inhibin A. While the Quad Screen provides a more comprehensive risk assessment, the AFP value remains the specific marker used to evaluate the risk for certain structural defects.
The purpose of this test is to calculate a statistical risk score. This score compares the measured AFP level to the median AFP level of all pregnancies at the exact same gestational age. The resulting value helps healthcare providers determine if the pregnancy falls into a higher-risk category that warrants further investigation.
Conditions Identified by MSAFP Screening
The primary structural conditions the MSAFP marker is used to screen for are Open Neural Tube Defects (NTDs), which are malformations of the central nervous system. These defects occur when the neural tube, which forms the brain and spinal cord, fails to close completely during the first few weeks of development. High levels of AFP are strongly associated with NTDs such as spina bifida and anencephaly.
In cases of an open defect, AFP leaks directly from the fetal cerebrospinal fluid into the amniotic fluid, causing an elevation in the maternal bloodstream. The screening also helps assess the risk for other structural issues, including abdominal wall defects like omphalocele and gastroschisis, which also lead to elevated results.
Conversely, a lower-than-expected AFP value, when considered alongside the other markers in a multiple screen, suggests an increased risk for certain chromosomal abnormalities. The most commonly screened-for condition in this category is Trisomy 21, also known as Down Syndrome. In pregnancies affected by Trisomy 21, the median MSAFP level is typically reduced compared to normal pregnancies.
Interpreting High and Low Marker Values
The quantitative result of an MSAFP screening is expressed using a metric called Multiples of the Median (MoM). This value represents the ratio of the measured AFP concentration in the maternal blood to the established average (median) value for that specific week of gestation. For example, an AFP level of 2.0 MoM means the measured value is twice the median for that week.
An elevated AFP result is defined as a level greater than 2.5 MoM, which indicates an increased statistical risk for an Open Neural Tube Defect. However, the most frequent explanation for an elevated MoM is an inaccurate estimation of the gestational age. Multiple gestations, such as twins or triplets, also naturally cause a higher AFP reading because there are two or more sources of the protein contributing to the mother’s blood.
A low AFP value is a finding that raises the statistical risk for a chromosomal abnormality like Trisomy 21. Laboratories adjust the MoM calculation based on specific maternal factors, including weight, race, and the presence of insulin-dependent diabetes, to ensure accuracy before determining the final risk score.
An abnormal MoM does not confirm a diagnosis, but instead suggests that the risk has crossed a predefined threshold. Even with an elevated MoM, the likelihood of a fetus having an NTD is low, and in many cases, the high reading remains unexplained. Furthermore, unexplained elevations in AFP have been associated with an increased risk for later pregnancy complications, such as preeclampsia or fetal growth restriction, which may prompt additional monitoring.
Follow-Up Procedures After Abnormal Results
A screen-positive result requires a referral for further evaluation. The follow-up process typically begins with a high-resolution or Level II ultrasound examination. This detailed ultrasound is used to confirm the exact gestational age and to check for the presence of multiple fetuses, which are common explanations for an elevated AFP.
The targeted ultrasound allows specialists to examine the fetal anatomy, specifically looking for physical signs of neural tube defects or other structural anomalies. If the ultrasound reveals a structural issue, or if the initial screen was positive for a chromosomal risk, invasive diagnostic testing may be offered. The ultrasound can often provide reassurance without the need for an invasive procedure.
Amniocentesis is the definitive diagnostic test that can be performed following an abnormal MSAFP screening. This procedure involves withdrawing amniotic fluid, which can be tested directly for high concentrations of AFP and the enzyme acetylcholinesterase, confirming an open NTD. The fluid sample can also be used to perform a karyotype or chromosomal microarray analysis to diagnose Trisomy 21 or other chromosomal conditions.
The decision to proceed with an invasive diagnostic test is a personal choice, as these procedures carry a risk of complications, including miscarriage. Genetic counseling is offered alongside these tests to ensure the parents understand the risks and the implications of any diagnostic findings. The goal of all follow-up is to move from a statistical risk assessment to a clear diagnosis or to provide reassurance.