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Cite this page: Hill, M.A. (2021, March 7) Embryology Alpha-Fetoprotein. Retrieved from

Original AFP page -


Second Trimester Prenatal Screening for Down's Syndrome in Mainland Chinese Subjects using Double-Marker Analysis of α-fetoprotein and β-human Chorionic Gonadotropin Combined with Measurement of Nuchal Fold Thickness

Ann Acad Med Singapore. 2011 Jul;40(7):315-4.

Liu F, Liang H, Jiang X, Zhang Y, Xue L, Yang C, Cheng J, Liu P, Liu Y, Guo X. Source Department of Clinical Laboratory, the Fourth Affi liated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.


Introduction: This study examines the effectiveness of double-marker analysis for α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) combined with measurement of nuchal fold thickness (NT) in the detection of Down's syndrome (DS) in Mainland Chinese subjects during second trimester prenatal screening. Materials and Methods: We examined pregnant women with a singleton pregnancy between 15 and 21 weeks of gestation who underwent second trimester screening for DS using double-marker analysis for AFP and β-hCG combined with ultrasound measurement of NT. The combined risk of DS was calculated. A cut-off of 1/270 was used to defi ne a pregnancy at high-risk of DS. Amniocentesis was offered to all patients with high-risk pregnancies. Results: Using double-marker analysis for AFP and β-hCG in combination with measurement of NT, the detection rate of DS increased from 66.7% to 77.8% when compared with double-marker analysis alone with similar false-positive rates (4.35%, 4.83% respectively). Using receiver operating characteristic curve (ROC) analysis, we determined that the double-marker analysis combined with measurement of NT exhibited an increased area under the curve (AUC) of 0.835 (95% CI: 0.743 to 0.927) when compared to double-marker analysis alone, which had an AUC of 0.748 (95% CI: 0.635 to 0.860). In addition, both methods were more effective than any other single test such as AFP, free β-hCG or NT measurement. Conclusion: Second trimester prenatal screening using double-marker analysis for AFP and β-hCG combined with measurement of NT is effective for the detection of DS in Mainland Chinese pregnancies.

PMID 21870022


Arch Dis Child Educ Pract Ed. 2011 Aug;96(4):141-7. doi: 10.1136/adc.2011.213181. Epub 2011 May 25.

Murray MJ, Nicholson JC. Source Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, UK.


α-Fetoprotein (AFP) measurements have clinical implications in fetal medicine and, in infants and older children, in detection, differential diagnosis and monitoring of malignant disease. Maternal serum AFP levels constitute part of a multiple-marker test used in early second-trimester screening to predict risk of fetal chromosomal abnormalities. Those individuals with increased risk are offered further definitive diagnostic investigation. Second-trimester screening is now increasingly being superseded by first-trimester screening with other serum markers and ultrasound. As AFP is only produced physiologically during fetal development, elevated serum levels after the first two post-natal years usually indicate the presence of a malignant disease process. Before this time, levels may be purely physiological and therefore serial values should be plotted on a logarithmic chart to ensure that they are falling appropriately, with a typical half-life of ∼5-6 days. If not, further investigation should be undertaken. Serum AFP is raised in a significant proportion of germ cell tumours (GCTs), hepatoblastoma and hepatocellular carcinoma (HCC). In suspected cases of GCT, serum human choriogonadotropin (HCG) estimation should also be performed. For possible intracranial GCTs, both serum and cerebrospinal fluid levels of AFP and HCG should be measured, ideally before neurosurgical biopsy. In malignant conditions, serum AFP may be used for diagnosis, treatment monitoring, surveillance for disease recurrence and prognostication. Immunohistochemistry for AFP using antibody staining is routinely used to assist pathological diagnosis on tissue sections where the differential includes GCT, hepatoblastoma and/or HCC. Elevations of serum AFP also occur in non-malignant conditions such as chronic liver disease.

PMID 21613305


Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants

Exp Biol Med (Maywood). 2001 May;226(5):377-408.

Mizejewski GJ. Source Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany 12201, USA.


Mammalian alpha-fetoprotein (AFP) is classified as a member of the albuminoid gene superfamily consisting of albumin, AFP, vitamin D (Gc) protein, and alpha-albumin. Molecular variants of AFP have long been reported in the biomedical literature. Early studies identified isoelectric pH isoforms and lectin-binding variants of AFP, which differed in their physicochemical properties, but not in amino acid composition. Genetic variants of AFP, differing in mRNA kilobase length, were later extensively described in rodent models during fetal/perinatal stages, carcinogenesis, and organ regeneration. With the advent of monoclonal antibodies in the early 1980s, multiple antigenic epitopes on native AFP were detected and categorized, culminating in the identification of six to seven major epitopes. During this period, various AFP-binding proteins and receptors were reported to inhibit certain AFP immunoreactions. Concomittantly, human and rodent AFP were cloned and the amino acid sequences of the translated proteins were divulged. Once the amino acid composition of the AFP molecule was known, enzymatic fragments could be identified and synthetic peptide segments synthesized. Following discovery of the molten globule form in 1981, the existence of transitory, intermediate forms of AFP were acknowledged and their physiological significance was realized. In the present review, the various isoforms and variants of AFP are discussed in light of their potential biological relevance.

PMID 11393167


Alpha-fetoprotein levels in normal adults

Am J Med Sci. 1992 Mar;303(3):157-9.

Ball D1, Rose E, Alpert E. Author information

Alpha-fetoprotein (AFP) is a fetal specific glycoprotein normally produced primarily by the fetal liver. Normally, AFP levels decline rapidly after birth, reaching undetectable levels (less than 10 ng/ml) within several months after birth. The authors have developed a more sensitive radioimmunoassay, which has allowed them to study low levels of AFP in normal adults and to determine factors which may affect its normal level. Two hundred and seventy normal Houston blood donors were screened for the absence of hepatitis B and normal ALT levels. The mean AFP level was 3.04 ng/ml +/- 1.9 SD. There was a statistically significant higher level in men compared to women (p less than .004). Regression analysis demonstrated a statistically significant increase of AFP levels with age both in men (p less than .05) and in women (p less than .01). These data delineate the normal level of serum AFP in normal adults in the United States. With the normal level now defined, it becomes possible to compare levels in different populations including those exposed to hepatotoxins or hepatocarcinogens in the environment. PMID: 1375809