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Elevated Maternal Serum AFP (MSAFP) During the Second Trimester

Author: Michael T. Mennuti, MD

Editor: Elizabeth A. Ferries-Rowe, MD

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Alpha-fetoprotein (AFP) is produced by the fetal yolk sac and liver. Levels rise during the second trimester. Values are expressed as MoMs (multiples of the median) for each specific week of gestation, and values greater than 2.5 MoMs are generally considered elevated. MoMs are typically corrected for maternal weight, race, and diabetes. MSAFP is often elevated when there is an open fetal defect such as spina bifida, anencephaly, or an abdominal wall defect. The median MSAFP is reduced about 25% in women carrying a fetus with Trisomy 21 when compared to pregnancies with a normal chromosomal complement.

Measurement of MSAFP at 16 weeks was initially used to screen for open neural tube defects, although second trimester ultrasonography now appears to be more sensitive than MSAFP in the detection of these defects. Testing between 15- and 18-weeks’ gestation is preferred as sensitivity is highest.  It is also commonly used as one of the analytes in first and second trimester serum aneuploidy screening. Errors in dating which underestimate the gestational age may result in false positive elevations. Multiple gestations also cause elevations of MSAFP. The level of alpha-fetoprotein is much higher in fetal than maternal blood (on the order of 50,000:1), so fetal-to-maternal bleeding can markedly elevate MSAFP.  An association between placenta accreta spectrum and unexplained elevated second trimester MSAFP has been reported by numerous investigators. Extremely high MSAFP levels can result from a rare germ cell tumor.

Patients with an elevated MSAFP should be initially evaluated with ultrasonography. If errors in dating are found, the MSAFP result should be reinterpreted using the new gestational age or, when the sample was drawn outside of the appropriate gestational age range the test may need to be redrawn. Elevated levels of MSAFP should prompt careful anatomic evaluation for open defects of the spine or abdominal wall. Intracranial anatomic changes (e.g. “lemon sign”, “banana sign”) associated with spina bifida should be evaluated.  Targeted ultrasonography should also be used to examine the placental attachment to the uterus.  Amniocentesis to measure amniotic fluid AFP may be considered. Improvements in ultrasonography have largely supplanted the value of performing amniocentesis primarily to measure amniotic fluid AFP.

An association between unexplained elevated MSAFP and stillbirth has been reported. When corrected for low birth weight, however, elevated AFP does not appear to be an independent risk factor for stillbirth. There are no recommendations for increased antenatal surveillance based on an isolated elevated AFP.

Further Reading:

American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice, Society for Maternal-Fetal Medicine. Indications for Outpatient Antenatal Fetal Surveillance: ACOG Committee Opinion, Number 828. Obstet Gynecol. 2021 Jun 1;137(6):e177-e197. doi: 10.1097/AOG.0000000000004407. PMID: 34011892.

Practice Bulletin No. 187: Neural Tube Defects. Obstet Gynecol. 2017 Dec;130(6):e279-e290. doi: 10.1097/AOG.0000000000002412. PMID: 29189693. Accessed November 2022.


Original approval June 2010; Revised September 2016; Reaffirmed March 2018; Revised and renamed September 2019; Revised November 2022.


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