oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Alpha-fetoprotein (AFP) is the major protein of fetal serum but it is usually undetectable after birth. AFP is made by the yolk sac of the fetus, enters the amniotic fluid and crosses the placenta into the maternal circulation. See also the separate article Tumour Markers.
Conditions which may have raised levels of alpha-fetoprotein
- Hepatocellular carcinoma: alpha-fetoprotein (AFP) levels are abnormal in 80% of patients and exceed 1,000 ng/ml in 40% of affected patients. The level may drop to normal after surgical resection.
- Nonseminomatous germ cell tumours.
- Other gastrointestinal cancers: occasionally cause elevations of AFP but rarely to greater than 1,000 ng/ml:
- AFP may also be raised in patients with lung cancer.
- Cirrhosis: patients may have abnormal AFP values, although usually less than 500 ng/ml.
- Viral hepatitis.
- Ataxia telangiectasia.
- Pregnancy is associated with elevated AFP levels, particularly if the pregnancy is complicated by a spinal cord defect or other abnormality:
- Maternal serum AFP test results, interpreted according to the gestational age, are often reported in terms of multiple of the median (MoM). Because the median is calculated from tests of other women's pregnancies at the same gestational age, in effect MoM is independent of gestational age. A typical normal range is 0.5 to 2.0 or 2.5 MoM.
- Raised levels of maternal AFP at 16-18 weeks of gestation are found in fetal neural tube defects.
- Amniotic fluid AFP and acetylcholinesterase concentrations can be used to differentiate between open ventral wall defects (gastroschisis and omphalocele) and open neural tube defects.
- Where AFP levels are raised but there is no fetal abnormality, there may be greater risk of obstetric complications.
Screening for neural tube defects and trisomy
See also separate articles Prenatal Diagnosis and Antenatal Screening for Down's Syndrome.
Alpha-fetoprotein (AFP) screening is a simple maternal blood test, performed at around 15 weeks of gestation, that can detect increased risk to the fetus of certain genetic abnormalities such as:
- Open neural tube defects, eg spina bifida.
- Down's syndrome.
- Other chromosomal abnormalities, eg trisomy 18.
- Defects in the abdominal wall of the fetus - omphalocele.
Altered AFP levels, either too high or low compared with normal amounts, can indicate whether a woman is carrying a baby with a chromosomal problem or certain birth defects. A pregnant woman's AFP levels decrease soon after birth. However, midtrimester anomaly scanning may replace serum screening.
Hepatocellular carcinoma (HCC)
Chronic hepatitis B infection may cause HCC. In conjunction with abdominal ultrasonography, it is recommended that AFP be measured at six-monthly intervals in patients at high risk of HCC (especially those with liver cirrhosis related to hepatitis B or hepatitis C).. However, a Cochrane review concluded that it is uncertain whether screening is worthwhile. A Health Technology Assessment concluded that the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a six-monthly basis. However, when costs are taken into account, it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml.
Serum concentrations of AFP variably elevated during liver injury have been suggested to be of prognostic importance in acute liver failure, with higher values being associated with improved outcome. AFP values change dynamically during acute liver failure. In a large prospective study, higher absolute values of AFP did not predict a favourable outcome, but a rising level of AFP over the first three hospital days frequently indicated survival.
Diagnostic aid in premature rupture of membranes (PROM)
A recent study looked at prolactin, AFP and beta human chorionic gonadotrophin (beta-hCG) as effective markers in vaginal fluid for diagnosing PROM. AFP had the greatest accuracy (94% sensitivity and specificity) and could be an ideal marker for diagnosing PROM in equivocal cases.
Further reading & references
- Johnson PJ; The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis. 2001 Feb;5(1):145-59.
- Sturgeon CM, Lai LC, Duffy MJ; Serum tumour markers: how to order and interpret them. BMJ. 2009 Sep 22;339:b3527. doi: 10.1136/bmj.b3527.
- Krantz DA, Hallahan TW, Sherwin JE; Screening for open neural tube defects. Clin Lab Med. 2010 Sep;30(3):721-5. Epub 2010 Jun 15.
- Loft AG, Hogdall E, Larsen SO, et al; A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the Prenat Diagn. 1993 Feb;13(2):93-109.
- Chandra S, Scott H, Dodds L, et al; Unexplained elevated maternal serum alpha-fetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol. 2003 Sep;189(3):775-81.
- Canick JA, MacRae AR; Second trimester serum markers. Semin Perinatol. 2005 Aug;29(4):203-8.
- Huang T, Alberman E, Wald N, et al; Triploidy identified through second-trimester serum screening. Prenat Diagn. 2005 Mar;25(3):229-33.
- Kooper AJ, de Bruijn D, van Ravenwaaij-Arts CM, et al; Fetal anomaly scan potentially will replace routine AFAFP assays for the detection of neural tube defects. Prenat Diagn. 2007 Jan;27(1):29-33.
- Wun YT, Dickinson JA; Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in Cochrane Database Syst Rev. 2003;(2):CD002799.
- Thompson Coon J, Rogers G, Hewson P, et al; Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and Health Technol Assess. 2007 Sep;11(34):1-206.
- Schiodt FV, Ostapowicz G, Murray N, et al; Alpha-fetoprotein and prognosis in acute liver failure. Liver Transpl. 2006 Dec;12(12):1776-81.
- Shahin M, Raslan H; Comparative Study of Three Amniotic Fluid Markers in Premature Rupture of Membranes: Prolactin, Beta Subunit of Human Chorionic Gonadotropin, and Alpha-Fetoprotein. Gynecol Obstet Invest. 2006 Dec 7;63(4):195-199.
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Dr Hayley Willacy
Dr Colin Tidy
Dr John Cox