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Elevated Maternal Serum AFP (MSAFP) During the Second Trimester

Author: Michael T. Mennuti, MD

Editor: Timothy Klatt, MD

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Alpha-fetoprotein (AFP) is produced by the fetal 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. Testing between 16- and 18-weeks gestation is preferred as sensitivity is highest.  It is also commonly used as one of the analytes in second trimester serum screening for Trisomy 21. 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. Many experts believe that improvement in ultrasonography has largely supplanted the value of performing amniocentesis primarily to measure amniotic fluid AFP. Testing for fetal-to-maternal bleeding by Kleihauer-Betke staining may be considered, particularly in Rh negative patients.

An association between unexplained elevated MSAFP and low birth weight or poor obstetric outcome has been reported. The value of this association in the management of the patient is limited because of the low sensitivity and low positive predictive value of this finding. There are currently no recommendations to modify pregnancy or delivery management based on finding an unexplained elevated MSAFP in an otherwise normal pregnancy.

Further Reading:

Prenatal Diagnosis. In: Cunningham F, Leveno KJ, Bloom SL, et al; Williams Obstetrics, 25e (2018) New York, NY: McGraw-Hill; . Accessed April 27, 2021.

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


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