The Biomarker Handbook is a curated series that seeks to provide readers with insights on each biomarker we cover in our blood test packages and its relation to our body.
Detection of beta Human Chorionic Gonadotropin (hCG) hormone forms the basis of most pregnancy diagnostic tests. In fact, most of the home pregnancy test strips rely on the presence of beta hCG in urine. It is an ideal biomarker of pregnancy since it rises rapidly and consistently in early pregnancy. Detection and monitoring of early pregnancy are vital for safe health outcomes of both the baby and the mother.
In this article the hCG mentioned is the beta subunit, and the terms beta hCG and hCG are used interchangeably.
What is beta-hCG?
hCG is a hormone produced by the placenta of a pregnant woman. Early in pregnancy, the level of hCG increases in the blood and is eliminated in the urine. A pregnancy test detects hCG in the blood or urine and confirms or rules out pregnancy.
The levels of beta hCG can be first detected in blood at around ten days after conception and about 12-14 days in urine. The levels reach a peak of about 100,000 mlU/mL at approximately ten weeks gestation, then begin declining at the twelfth week, when the placenta is fully formed and can maintain the pregnancy. They remain stable from about the 20th week at approximately 20,000 mlU/mL throughout pregnancy. After a delivery, miscarriage or termination of pregnancy, beta hCG levels decline, and after 4-6 weeks, they are no longer detectable. In a non-pregnant adult female, the levels are less than 1.0mIU/mL.
Outside of pregnancy, beta hCG may be released by abnormal tissues, tumors, and cancers, making an hCG test a useful tumor biomarker for diagnosis and treatment monitoring. When used as a tumor biomarker, high levels of the hormone are suggestive of germ cell tumors such as choriocarcinomas, ovarian and testicular cancers.
Why track beta-hCG levels?
There are two methods of testing the hormone, either qualitative or quantitative. The qualitative test checks the presence of beta hCG while the quantitative test assesses the actual levels of the hormone.
The levels of beta hCG are measured in milli-International Units per milliliter (mIU/mL). HCG levels of more than 5mIU/ml are considered positive for pregnancy. However, if the levels are tested too early in pregnancy, they may indicate false-negative results (meaning that result of the test shows negative for pregnancy but it is inaccurate since it is too early in pregnancy to detect this level of hCG) and should be repeated a few days later.
Beta hCG levels are checked to:
- Confirm pregnancy – other than routine pregnancy care, doctors routinely utilize beta-hCG tests to detect early pregnancy to allow discretion of use of radiological procedures like x-rays and proper prescription of drugs to avoid teratogenic effects.
- Diagnose abnormal pregnancy – along with progesterone tests and obstetric ultrasound, beta hCG levels help to diagnose an ectopic pregnancy, monitor a failing pregnancy and follow up after a miscarriage.
- Screen for fetal defects – in the first and second trimesters, beta hCG test is used together with other tests to screen for chromosomal abnormalities such as Down Syndrome and Edwards Syndrome. You should visit your obstetrician early as possible to perform this screening test.
- Detecting multiple pregnancies- although not a confirmatory test, beta hCG levels tend to be 30 to 50% higher (though this is not a rule). Usually a confirmatory ultrasound is necessary. The normal range of hCG during pregnancy can be very varied.
What do abnormal test results mean?
Abnormal levels of hCG are associated with poor pregnancy outcomes. In case of unsatisfactory figures, the test should be repeated within 48 to 72 hours to see if there are any changes.
Very high levels of hCG may be detected in Gestational Trophoblastic Disease (GTD), in which the levels may continue to rise past the first trimester. In a normal pregnancy, the levels of hCG reach a plateau in the late first trimester and have a steady state in second and third trimesters.
Studies also suggest that levels of beta hCG are twice as much in Down’s Syndrome. Slightly raised levels (5-8mIU/ml) of beta-hCG may also be noticed in healthy post-menopausal women, without an increasing pattern.
Low levels of hCG are often indicative of a failing pregnancy. The reduced levels are associated with ectopic pregnancies, possible miscarriage or blighted ovum. It is, however, important to note that some women have had low levels of hCG and continued to have a healthy pregnancy and baby.
In an ectopic pregnancy, beta hCG levels usually rise at a slower rate than usual. A repeat test done 48-72 hours apart shows a suboptimal rise or fall, less than the expected doubling. A level of 1,500mIU/mL or more and a transvaginal ultrasound showing no intrauterine gestational disc is also indicative of an ectopic pregnancy.
In a miscarriage, the levels sharply decline, and if they do not fall to undetectable levels, it is suggestive that there is hCG-secreting tissue still left in the uterus and needs to be removed via dilation and curettage.
As you can see, there are many potential life threatening causes of an abnormal hCG level in your blood. This abnormal level should be confirmed by an ultrasound performed by your obstetrician. It would be prudent to visit your obstetrician for first prenatal visit as soon as possible if you have any concerns about the pregnancy. Otherwise if the pregnancy is confirmed and you do not have any symptoms or blood results indicating an abnormal pregnancy, then the first prenatal visit can be 6 – 7 weeks from the first day of your last menstrual period, according to an obstetrician.
Signs and symptoms to watch out for
Signs and symptoms of abnormal beta hCG levels are related to the underlying causes, but sometimes, there may be no apparent manifestations.
Common signs of a miscarriage include
- Vaginal bleeding
- Passing of blood clots or grayish tissue from the vagina
- Persistent abdominal pain
In case of a blighted ovum, one may have minor abdominal pain and minimal vaginal spotting or bleeding. It occurs very early in pregnancy, and most women may not even notice it. A blighted ovum usually results in a miscarriage.
In an ectopic pregnancy, the pregnancy is usually similar to a normal one, but as it progresses, one may experience:
- Abdominal pain that worsens with movement or straining
- Vaginal bleeding
- Weakness, dizziness, and fainting
- Shoulder pain
- In case of excessive bleeding, signs of shock may be present
How to balance the levels of beta-hCG
Unfortunately, there is no scientifically proven way of lowering or increasing beta hCG levels without treating the underlying causes and factors. In the case of high levels because of an ectopic pregnancy, methotrexate is injected to stop the proliferation of fetal cells if the pregnancy is detected early. In other instances when rupture is a risk or has happened, the treatment is through a laparoscopic or laparotomy surgery to remove the ectopic tissue and repair the fallopian tube.
In a miscarriage, the doctor may choose to let it progress naturally until the body expels all the fetal tissue, use medication or surgically treat by dilatation and curettage (D&C). In a molar pregnancy or GTD, D&C is preferred to remove the molar tissue, followed by hCG monitoring for six months to 1 year.
When to see the doctor
In addition to abnormal routine lab results, any ongoing signs and symptoms of abnormal hCG levels should be reported to a specialist. Most of the conditions are best in detected and treated early – it could mean safe intervention or lifelong complications.
The signs include:
- Any vaginal bleeding
- Lower abdominal pain
- Cessations of signs and symptoms of pregnancy
- Passing of fetal tissue or clots
Is there any further testing required?
When screening the levels of beta hCG, it is customary for the doctor to carry out other tests, for an accurate diagnosis. For instance, in a suspected ectopic pregnancy, a transvaginal ultrasound scan to visualise the reproductive system is required. Likewise, an obstetric ultrasound is useful in diagnosing a blighted ovum, as it confirms an empty gestational sac in the uterus.
For chromosomal abnormalities, pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency tests are carried out along with hCG in the first trimester. In the second trimester, alpha-fetoprotein (AFP), unconjugated estriol, and inhibin A screening tests are done together with hCG to screen for Down’s and Edwards syndromes.
In pregnancy, beta hCG stands out as a serum biomarker for assessing early pregnancy wellness. It is useful in confirming pregnancy, detecting early pregnancy complications like ectopic implantations and in screening for congenital disabilities. Therefore, tracking the levels of beta hCG is essential for every pregnant woman.
In normal pregnancies, at the first prenatal visit, the doctor will confirm the pregnancy. In addition, further tests are carried out including: weighing, urine, measuring blood pressure, and haemoglobin determination. The doctor will draw blood to determine your blood group and rhesus factor and further tests will be carried out to screen for HIV and rubella, along with other potentially dangerous diseases. The focus of this appointment, however, is mainly on the advice. The doctor will discuss possible risks and give advice regarding nutrition and other pregnancy related issues, and you will have the opportunity to ask the questions that you have regarding your pregnancy.
If you want to learn tips on how to care for your body and your baby during pregnancy, read our lifestyle article here!
Interested in other biomarkers? Check out the rest of The Biomarker Handbook.
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