Generality
Alpha-phetoprotein (AFP) is a glycoprotein substance produced from the earliest stages of pregnancy by the yolk sac first and then by the fetus.
During intrauterine life, the unborn child synthesizes AFP especially at the hepatic level, with a marginal contribution from the kidneys and the gastrointestinal tract. After birth, alpha-fetoprotein levels begin to decrease reaching values typical of an adult within a year.
What's this
Alpha-phetoprotein is a protein that is synthesized by the liver and yolk sac during fetal and embryonic development. This protein is present in the plasma of the unborn child in high quantities, starting from the second trimester of pregnancy, so as to be revealed also in the maternal blood.
From the moment of birth onwards, alpha-fetoprotein levels are rapidly reduced, so much so that they are found only in small traces in women and in healthy children.
Currently, the function performed by this protein in adults and during fetal development is still unclear.
The gene responsible for its expression is the AFP gene located on the q arm of chromosome 4.
Why do you measure
In pregnant women, the dosage of alpha-fetoprotein in the blood is used as a screening for any congenital malformations of the neural tube (such as spina bifida or anencephaly). Furthermore, the examination is useful to support the diagnosis of trisomy 21 (or Down syndrome ).
Alphafetoprotein dosage is performed together with estriol and β-hCG; the combination of these three evaluations is called tri-test and is carried out between the fifteenth and twentieth week of pregnancy.
If the fetus has a defect in the closure of the neural tube, it means that there is an opening at the level of the spinal cord, the head or the abdominal wall. These defects cause concentrations higher than the standard AFP to pass through the placenta and find themselves in excess in the maternal blood.
When is it prescribed?
The dosage of alphafetoprotein is prescribed between the 15th and 20th week of pregnancy, in order to assess the risk of having a fetus with malformations or conditions such as, for example, Down syndrome. If the screening is positive, other tests are needed to confirm the diagnosis, such as ultrasound and amniocentesis.
Normal values
Values in the various stages of pregnancy
During intrauterine life, AFP is the main fetal plasma protein and, in this sense, it performs functions similar to those of albumin; its serum concentrations tend to increase until the end of the first trimester, reaching a peak of about 3 mg / mL between the 10th and 13th week of gestation .
Subsequently, the levels of alpha-fetoprotein fall exponentially between the 14th and 32nd week, at the end of which they amount to about 0.2 mg / mL; this descent goes hand in hand with the progressive increase in the synthesis of albumin (which will be the main protein molecule of the plasma), the increase in the blood volume and the decreased hepatic synthesis of alpha-fetoprotein.
Regardless of the amniotic concentrations of AFP, a proportional part of this substance reaches the maternal circulation, partly overcoming the fetal membranes and the uterine decidua (transamniotic pathway) and partly through the transplacental pathway.
During the earliest stages of pregnancy the alpha-fetoprotein appears to diffuse from the fetal circle to the amniotic fluid through the epidermis, which in these phases is not yet keratinized. However, as soon as the fetal kidneys begin to function (towards the end of the first trimester), alpha-fetoprotein enters the urine of the fetus and from there passes into the amniotic fluid.
AFP High - Causes
Studying the trend of alpha-fetoprotein concentrations in amniotic fluid and maternal blood, researchers have discovered a positive correlation between high levels of AFP and some malformative pathologies, especially concerning neural tube defects such as anencephaly (which leads to death of the fetus) and failure to close the neural tube (spina bifida, ie when the vertebrae do not adequately surround the spinal cord).
In fact, usually the amniotic concentration of alpha-fetoprotein is particularly low compared to the fetal plasma concentration. In the presence of a neural tube defect, on the other hand, the continuity solution created between the liquor and the amniotic fluid determines the free passage of large amounts of AFP, so that the amniotic concentration increases significantly (together with the levels of acetylcholinesterase, a specific enzyme of the nervous tissue that under these conditions undergoes a significant increase).
Alphafetoprotein concentrations can also be measured in maternal blood as a simple screening test, in order to identify at-risk pregnancies that need further investigation, including ultrasound. This latter test, in particular, is currently preferred to the determination of alpha-fetoprotein as an early screening test, both due to its not very good sensitivity and to the excellent ability to detect ultrasonographic signs of chromosomopathies .
Levels of alpha-fetorpotein in the maternal serum tend to increase even in the presence of a placental detachment (abruptio placentae) .
In the opposite situation, that is when there are low values of alpha-fetoprotein in maternal blood, the risk of the fetus suffering from Down syndrome is greater.
Thanks to these evidences, the dosage of alpha-fetoprotein in maternal blood is a valid screening tool, to which many women at risk are subjected between the 15th and 21st week of gestation. More specifically, the levels of alpha-fetoprotein are evaluated - in the so - called Tri-Test - together with those of other biochemical markers, such as HCG (human chorionic gonadotropin) and estriol (placental estrogen) unconjugated.
Other times the inhibin A dosage is also included and therefore we speak of Quadruple-Test.
In pregnant women who carry fetuses with Down syndrome, the serum rates of alpha-fetoprotein and unconjugated estriol decrease, while those of human chorionic gonadotropin increase.
Also in this case it is not a question of real diagnostic tests, but of screening tests which - together with the mother's age - allow us to quantify the risk of the fetus suffering from Down syndrome. When this risk proves to be important, pregnant women are directed to appropriate diagnostic tests such as amniocentesis.
Levels of alpha-fetoprotein in the pregnant woman's blood may EXCEED excessively due to:
- Incorrect gestational age, as the reference values vary widely during the various stages of pregnancy
- Threat of abortion
- Intrauterine death (death of the fetus)
- Multiple pregnancy
- Placental detachment
- Neural tube defects, such as spina bifida and anencephaly
- Contamination with amniotic fluid (if the blood sample is taken after amniocentesis or after chorionic villus sampling)
- Hepatic or ovarian maternal neoplasms
- Other rare anomalies
- Physiological increase unrelated to any kind of anomaly
Low AFP - Causes
The values of alpha-fetoprotein may be low in the following cases:
- Gestational age lower than expected (when the date of conception is not known exactly);
- Abortion not yet identified.
In pregnant women carrying fetuses with a chromosomal defect that will cause Down syndrome, the serum rates of alpha-fetoprotein and non-conjugated estriol tend to be low, while those of human chorionic gonadotropin (hCG) and inhibin A increase.
How to measure it
The alpha-fetoprotein test is a laboratory analysis that involves performing a simple blood sample from a vein in the arm. AFP, hCG, Estriol and inhibin A tests can be performed on the same blood sample.
Preparation
For the analysis of the AFP, a fast of at least 8 hours is required, to avoid that the food interferes with the result.
Interpretation of Results
The result should be interpreted by a genetic counselor or clinician, who can explain the meaning of the exam.
The value of alphafetoprotein in the bloodstream is closely dependent on the determination of the gestational age of the fetus . In fact, if the latter had not been calculated precisely by the gynecologist, there is a risk of considering the levels of alpha-fetoprotein too high or low.
In the maternal serum, the concentration of AFP in the blood begins to increase exponentially up to the 32nd week, only to be reduced a few days after the birth.
High values of alpha-fetoprotein in pregnant women may depend on:
- Defects of the neural tube (spina bifida, anencephaly);
- Placenta problem;
- Fetal malformations (chromosomal anomalies);
- Neoplasm or liver disease of the mother.
However, the factors that could raise AFP levels include:
- Incorrect pregnancy dating;
- Twin pregnancy.
Low levels of alpha-fetoprotein may instead be associated with chromosomal disorders. To be precise, a low level of AFP together with an increased level of HCG (bi-test) was associated with an increased risk of Down Syndrome.
In any case, once these abnormal values have been found, the doctor will recommend further tests, such as an abdominal ultrasound or an amniocentesis to measure the levels of alpha-fetoprotein in the amniotic fluid.
