Alpha-Fetoprotein Screening – Prenatal diagnosis and invasive techniques to monitor the fetus.

The value of alpha-fetoprotein (AFP) in detecting neural tube defects was recognized over 30 years ago. AFP is a glycoprotein synthesized by the fetal yolk sac, gastrointestinal tract, and liver. When the fetal integument is not intact, markedly elevated levels of AFP occur in the amniotic fluid and maternal serum.

Alpha-Fetoprotein Antibody Monoclonal (SP154) (MA5-16321)

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Hence, elevated AFP levels are associated with neural tube defects, such as anencephaly and spina bifida, and abdominal wall defects. Other causes of high AFP levels include renal anomalies, decreased maternal weight, and multiple gestation. Conversely, low AFP levels are associated with chromosomal trisomy, fetal demise, and increased maternal weight. Inaccurate estimation of gestational age is the most common reason for an abnormal AFP value.

AFP screening is recommended for all pregnant women in order to help detect those among the generalpopulation who may require further diagnostic evaluation. In most regions of the United States, AFP is combined with two additional analytes produced by the placenta, human chorionic gonadotropin (hCG) and unconjugated estriol (uE3). These markers, commonly referred to as the triple screen, can be done from 15 to 22 weeks gestation, but are most accurate between 16 and 18 weeks gestation.


The triple screen is designed to identify pregnancies complicated by neural tube defects, trisomy 18, and trisomy 21. An increased hCG value is the most sensitive marker for detecting trisomy21, while low hCG levels are associated with trisomy 18. Levels of uE3 are decreased in pregnancies affected by trisomy 21 and trisomy 18. Of the markers, only AFP has value in screening for neural tube defects. Absolute values of the three serum analytes are converted to multiples of the median (MoM) and used to calculate a woman’s age-related risk of fetal anomaly. Gestational age, maternal race, and maternal weight are also factors used to adjust the level of risk.

Maternal serum AFP screening can detect about 90% of anencephaly cases and 80% of all open spinabifida cases. The three serum analytes combined detect 60–70% of trisomy 21-affected fetuses with a false positive rate of 5%. Ongoing research aims to improve detection rates using better combinations of maternal erum markers. Inhibin A, free hCG, and plasma protein A (PAPP-A) are among the serum analytes proposedeither to increase screening sensitivity or to allow detection earlier in gestation.

Appropriate diagnostic testing after positive screen result depends on the analyte levels. For AFP, a MoMvalue greater than 2.0–2.5 is considered abnormal. Next an ultrasound examination is done to rule out inaccurate estimation of gestational age as a source of error. Because elevated AFP levels persist with neural tube defects, a repeat maternal serum measurement is sometimes obtained.

If the AFP remains elevated and gestationalage is confirmed, the patient should be referred for a high-resolution ultrasound. When performed by an expert, ultrasound can detect nearly all cases of anencephaly and spina bifida. Amniocentesis may also be utilized to assess karyotype, amniotic fluid AFP, and acetylcholinesterase.


Trisomy 21 screening uses a series of age-specific risk cutoff levels for each triple screen analyte. Many labs select a risk cutoff of 1 in 270, the risk of a 35-yearold woman for carrying a fetus with trisomy 21. Amniocentesis and detailed ultrasound are offered to women whose triple screen values place them in an at-risk group. Although triple screening is noninvasive and does not physically harm the mother or fetus, receiving abnormal results can cause great emotional stress.

Awareness of congenital anomalies in the fetus leads to ethically complex decisions like whether to terminate the pregnancy or not. Before prenatal serum marker screening is done, women should understand how the test may affect them. Counseling should include explanations of the accuracy of the test, the conditions detectable by screening, and the follow-up diagnostic testing recommended for a high-risk screen.

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