Alpha Fetoprotein (AFP, Maternal Serum Alpha Fetoprotein, MSAFP)


Article Author:
Oluwaseun Adigun


Article Editor:
Shailesh Khetarpal


Editors In Chief:
Stephen Leslie
Karim Hamawy


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James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
2/22/2019 8:43:24 AM

Introduction

Alpha-fetoprotein (AFP) is a plasma protein produced by the embryonic yolk sac and the fetal liver. AFP levels in serum, amniotic fluid, and urine functions as a screening test for congenital disabilities, chromosomal abnormalities, as well as some other adult occurring tumors and pathologies. This tumor marker is a glycoprotein encoded by the AFP gene on chromosome 4q25. Prenatal levels in developing human embryo rise from the end of the first trimester and begin to fall after 32 weeks of gestation. Maternal serum AFP forms part of the triple or quadruple screening tests for fetal anomaly.[1][2][3]

Specimen Collection

A blood sample is collected from the vein using aseptic techniques and observing universal precautions. Serum alpha levels are measured either as part of a maternal triple or quadruple screening test or for other diagnostic purposes in non-pregnant female or male patients.

Urine samples collected in plain or universal bottles may also be assayed for alpha-fetoprotein levels, although this may be significantly lower in comparison to serum levels.

Amniocentesis is needed to be able to assay alpha-fetoprotein levels in the amniotic fluid. A diagnostic amniocentesis involves the use of an ultrasound-guided, hollow needle through the maternal anterior abdominal wall into the amniotic cavity to draw out amniotic fluid for AFP immunoassay.[4][5][6]

Procedures

Blood sample collection (phlebotomy):

  1. Introduce yourself to the patient and confirm the patient's name and date of birth.
  2. Explain procedure to the patient, warning patient of possible discomfort from the needle prick.
  3. Position patient appropriately, exposing the upper arm.
  4. Follow hand washing and basic universal precautions.
  5. Tie the tourniquet around the upper arm.
  6. Identify a prominent vein and clean with an alcohol swab.
  7. Introduce the needle attached to a vacutainer.
  8. Remove tourniquet and remove needle after obtaining a sample.
  9. Apply cotton ball to needle site with pressure to stop bleeding. 
  10. Label sample bottles appropriately.
  11. Send a sample for AFP assay.

Procedure for amniocentesis (done from 15 weeks gestation):

  1. Introduce yourself and confirm the patient's identity and gestational age of the pregnancy.
  2. Conduct pretest counseling. This usually includes genetic counseling as well.
  3. Obtain informed consent.
  4. Follow hand washing and universal precautions.
  5. Position patient appropriately.
  6. Clean exposed area of the abdomen.
  7. Use a local anesthetic if necessary.
  8. Carefully introduce the ultrasound-guided, hollow needle through the anterior abdominal wall into the amniotic cavity.
  9. Aspirate 15 ml to 20 ml of amniotic fluid.
  10. Send for AFP assay.

Indications

The following are reasons for AFP assay:

  • Advanced maternal age
  • Previous births with chromosomal or birth defect (e.g., neural tube defects)
  • Family history of chromosomal or birth defects (e.g., downs syndrome,  spina bifida)
  • screening for cancers (e.g., liver, testicular, ovarian)
  • To evaluate progress of anti-cancer treatment

Potential Diagnosis

 Pregnant maternal serum AFP levels elevated:

  • Neural tube defects (e.g., spina bifida, anencephaly)
  • Omphalocele
  • Gastroschisis

Pregnant maternal serum AFP low levels:

  • Down syndrome

Non-pregnant female or male adult AFP elevated:

  • Hepatocellular cancer
  • Metastatic liver cancer
  • Liver cirrhosis
  • Hepatitis
  • Germ cell tumors
  • Yolk sac tumor
  • Ataxia telangiectasia

Normal and Critical Findings

Typical findings include:

  • Alpha-fetoprotein levels in men and non-pregnant women vary for age and race but mostly range from 0 ng/ml to 40 ng/ml.
  • Maternal AFP levels in pregnancy start to rise from about 14th week of gestation up until about 32 weeks gestation. Between week 15 and 20 weeks, levels usually range between 10 ng/ml to 150 ng/ml.
  • Adult blood levels of greater than 200 ng/ml in patients with liver cirrhosis strongly indicate hepatocellular carcinoma.

Interfering Factors

The following have been implicated in false-positive results:

  • Two weeks after radiodiagnosis involving the use of radioactive tracers
  • Multiple gestations
  • Gestational diabetes
  • Cigarette smoking
  • Race (slightly higher levels in black women, and lower in women of Asian descent as compared to whites)
  • AFP levels are also adjusted for weight

Complications

Risks associated with phlebotomy include:

  • Phlebitis
  • Abnormal bruising and bleeding in patients with clotting disorders or those taking blood thinners.

The risk associated with amniocentesis:

  • Miscarriage
  • Preterm delivery

Patient Safety and Education

Phlebotomy for the purpose of blood alpha fetoprotein assay requires little or no preparations as this is largely safe when performed by qualified health workers. However, patients need to be counseled on the possible discomfort from the needle prick, although mostly bearable. Patients must also be asked about their use of blood thinners (e.g., aspirin, warfarin).

Patients must also be given appropriate information regarding possible outcomes and implications of the test.

It is pertinent to explain that this is a screening test. Depending on the outcome, more tests may be ordered for the purpose of establishing a diagnosis. A negative test does not necessarily indicate no risk as very low maternal blood alpha-fetoprotein is associated with an increased incidence of Down syndrome. Hence, a low maternal blood alpha-fetoprotein should also be investigated.

Patients having amniocentesis must be duly counseled about the procedure, as well as, the associated risks. There is a risk of obstetric mishap following amniocentesis; a miscarriage can happen in less than 1% of cases. Some other very rare complications of amniocentesis are preterm labor, infection (amnionitis), iatrogenic trauma, or injury to the developing fetus or mother.

Following amniocentesis patients may experience some cramp-like discomfort in the first few hours but are usually allowed to go home after a short rest. Oral paracetamol (acetaminophen) may be prescribed. Patients should report back to the hospital in case of vaginal bleeding, vaginal discharge, or increasing abdominal cramps.

Clinical Significance

Maternal blood AFP levels often as part of triple (AFP, Estriol, and hCG) or quadruple (AFP, implies Estriol, hCG and Inhibin A) screening test for birth defects. Levels are usually interpreted for age, race, weight, and gestational age. The elevated levels imply a significant risk of having birth defects, hence, further evaluation may be required to assess the level of risk.[7][8]

A significant amount of patients with elevated maternal AFP do not develop birth defects, but there may be an increased risk of obstetric complications like premature rupture of membrane, placenta accreta, increta, and packet.

Low maternal AFP levels may be suggestive of risk for Down syndrome.

In nonpregnant women and men, elevated levels are seen in cancers, especially, liver cancer. Levels greater than 200 ng/ml in cirrhotic patients suggest hepatocellular carcinoma. Elevated alpha-fetoprotein levels can also be found in testicular and ovarian carcinoma.

AFP levels may also be used to evaluate response to anti-cancer therapy.


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Alpha Fetoprotein (AFP, Maternal Serum Alpha Fetoprotein, MSAFP) - Questions

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In which of the following is an elevation of alpha-fetoprotein not seen?



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Which of the following conditions does NOT have an elevated alpha-fetoprotein (AFP) level?



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A 38-year-old pregnant female has been told that she has an elevated serum level of alpha-fetoprotein in her amniotic fluid. What is the next step?



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Prenatal screening done at 17 weeks shows elevated alpha fetoprotein. Which of the following is not in the differential diagnosis?



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Cerebrospinal fluid alpha-fetoprotein may be elevated in which of the following?



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Which of the following is the tumor marker for a yolk sac tumor of the testes?



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For which cancer is alpha fetoprotein a tumor marker?



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A 40-year-old primigravida at 16 weeks gestation had a serum alpha-fetoprotein (AFP) of 300 ng/ml. Which of the following is not a likely fetal cause of elevated AFP?



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Alpha Fetoprotein (AFP, Maternal Serum Alpha Fetoprotein, MSAFP) - References

References

Sharony R,Dayan D,Kidron D,Manor M,Berkovitz A,Biron-Shental T,Maymon R, Is the ratio of maternal serum to amniotic fluid AFP superior to serum levels as a predictor of pregnancy complications? Archives of gynecology and obstetrics. 2016 Apr     [PubMed]
Öztürk H,Erkaya S,Altınbaş S,Karadağ B,Vanlı Tonyalı N,Özkan D, The role of unexplained high serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in the second trimester to determine poor obstetric outcomes. Turkish journal of obstetrics and gynecology. 2014 Sep     [PubMed]
Rood K,Stiller R, Hereditary persistence of alpha-fetoprotein: a rare cause for unexplained alpha-fetoprotein elevations in pregnancy. Connecticut medicine. 2013 Jan     [PubMed]
Gkogkos P,Androutsopoulos G,Vassilakos P,Panayiotakis G,Kourounis G,Decavalas G, Mid-trimester maternal serum AFP levels in predicting adverse pregnancy outcome. Clinical and experimental obstetrics     [PubMed]
Chen CP,Chern SR,Cheng SJ,Chang TY,Yeh LF,Lee CC,Pan CW,Wang W,Tzen CY, Second-trimester diagnosis of complete trisomy 9 associated with abnormal maternal serum screen results, open sacral spina bifida and congenital diaphragmatic hernia, and review of the literature. Prenatal diagnosis. 2004 Jun     [PubMed]
Shipp TD,Wilkins-Haug L, The association of early-onset fetal growth restriction, elevated maternal serum alpha-fetoprotein, and the development of severe pre-eclampsia. Prenatal diagnosis. 1997 Apr     [PubMed]
Benn PA,Horne D,Briganti S,Rodis JF,Clive JM, Elevated second-trimester maternal serum hCG alone or in combination with elevated alpha-fetoprotein. Obstetrics and gynecology. 1996 Feb     [PubMed]
Wenstrom KD,Owen J,Davis RO,Brumfield CG, Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein. Obstetrics and gynecology. 1996 Feb     [PubMed]

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