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What is a Double Marker test?

A double marker test, also known as a dual marker test, is a blood test that evaluates the amount of free beta-human chorionic gonadotropin (HCG) and pregnancy-associated plasma protein-A (PAPP-A) levels. This test is performed during the first trimester of the pregnancy, from the ninth to the thirteenth week.

It is helpful in detecting chromosomal anomalies and developmental deformities such as Down’s syndrome, neural tube defect or spina bifida in the growing or developing a foetus.

  1. Why is a Double Marker test performed?
  2. How do you prepare for Double Marker test?
  3. How is a Double Marker test performed?
  4. What do Double Marker test results indicate?

A double marker test is performed as a routine test in pregnant woman during their first trimester (between the ninth to the thirteenth week) to rule out developmental anomalies in the foetus.

Women who are at a higher risk of having babies with Down’s syndrome or neural tube defects should not skip this test. These risk factors include:

  • Old age: The older the age of conception, the higher are the chances that the foetus would have chromosomal abnormalities
  • A child with birth defects: A history of a child having these chromosomal anomalies increases the risk
  • Carrier parents: Parents who are carriers of gene translocations could transmit them to the baby
  • Mothers having type 1 diabetes (insulin-dependent diabetes)
  • Obese mothers

A double marker test is performed along with an ultrasound. Blood samples are evaluated for free beta-HCG and PAPP-A, while ultrasound is performed to measure foetal length for determining the gestational age. No specific preparations are needed for the test.

A double marker test involves two procedures:

  • Blood test: A blood sample will be taken from a vein in your arm by inserting a small needle; a momentary pricking pain may be felt when the needle goes in the vein. There is a minimal risk of pain, light-headedness and bruising at the site of injection associated with the test. However, at most times, these symptoms disappear quickly. Rarely, an infection may occur at the site of withdrawal of blood.
  • Ultrasound: Ultrasound performed (ideally at the twelfth week) helps in evaluating the thickness of the fluid behind the baby’s neck, this is known as nuchal translucency. It also determines the baby’s age.

Beta HCG levels are measured as milli-international units per millilitre (mIU/mL), while PAPP-A is measured as multiples of the median (MoM).

Normal results: Beta HCG levels of 25,700-2,88,000 mIU/mL indicate normal results, while the normal value for PAPP-A is 1 MoM.

The normal result of a double marker is indicated by stating ‘Screen negative’, which signifies a low risk of chromosomal abnormalities.

Abnormal results: Abnormal results are indicated by stating ‘high risk’, which means signifies the chances of chromosomal defects.

Low levels of PAPP-A and high levels of beta HCG along with increased space at the foetal neck indicate the presence of an extra chromosome in the foetus. This increases the chances of Down’s syndrome or Edwards syndrome in the baby.

It is important to note that a double marker test is only a screening tool. Confirmation of the diagnosis is achieved by performing chorionic villus sampling (CVS) in the first trimester or with the help of amniocentesis in the second trimester. Since both these tests are invasive and carry some level of risk of miscarriage or injury to the foetus, they are not used for screening.

Results of the double marker test are highly dependent on the interpretation of the nuchal translucency, as the gestational age plays a vital role in interpreting results of beta-HCG and PAPP-A. If the gestational age is not determined accurately, it can lead to false-positive or false-negative reporting.

Disclaimer: All results must be clinically correlated with the patient’s complaints to make a complete and accurate diagnosis. The above information is provided from a purely educational point of view and is in no way a substitute for medical advice by a qualified doctor.

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  1. Center for Disease Control and Prevention [internet], Atlanta (GA): US Department of Health and Human Services; Data and Statistics on Down Syndrome
  2. Trisomy 18 Foundation. What is trisomy 18?. Dale City, Virginia.
  3. Center for Disease Control and Prevention [internet], Atlanta (GA): US Department of Health and Human Services; Diagnosis of Birth Defects
  4. American College of Obstetricians and Gynecologists. Prenatal Genetic Screening Tests. Washington, DC; USA
  5. American pregnancy association. Down Syndrome: Trisomy 21. Irving,Texas [internet]
  6. Pregnancy, Birth and Baby. What are neural tube defects?. Healthdirect Australia [internet].
  7. Department of health. Screening tests in the first 3 months of pregnancy. Government of Western Australia [internet].
  8. Lab tests online. What to expect when having a blood test. American Association for Clinical Chemistry [internet].
  9. American pregnancy association. Human Chorionic Gonadotropin (hCG): The Pregnancy Hormone. Irving,Texas [internet]
  10. S. Shiefa .First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome. Indian J Clin Biochem. 2013 Jan; 28(1): 3–12. PMID: 24381414