B8. Prenatal diagnostics II. (non-invasive methods)

Page created on December 23, 2021. Last updated on January 17, 2022 at 20:12


Non-invasive prenatal diagnostics are the first-line investigations for screening for foetal genetic disorders. Multiple non-invasive methods exist:

  • Ultrasound
  • Cell-free DNA
  • Combined tests
  • Biophysical profile

In general, it’s recommended that all women should be offered prenatal diagnostics should they wish. However, the conditions for which the diagnostics are paid for by the state differ from country to country. In general, women with a higher risk for foetal genetic disorders (family history, age > 35) are recommended prenatal diagnostics and will have it paid for by the state. (At least in Norway, I could not find specific information regarding Hungary)


Ultrasound is widely used during pregnancy. How often it’s performed differs from country to country. This overview will follow the lecture. Routine ultrasound scans are not considered prenatal diagnostics but included here anyway.

Ultrasound is not only used as a screening tool for genetic disorders and birth defects, but also for other purposes, as seen below. Three ultrasound investigations are recommended routinely during pregnancy:

  • First trimester scan/ “First genetic ultrasound” – week 11-14
    • Can detect major foetal anomalies
    • Re-estimate gestational age and due date based on CRL
    • Detect foetal heartbeats – to confirm vitality
    • Look for presence of nasal bone
    • Examine nuchal translucency
    • Identify multiple gestations
  • Second trimester scan/ “Second genetic ultrasound” – week 18-20
    • Can detect both major and minor anomalies
    • Measure foetal biometry – BPD, HC, AC, FL
    • Re-estimate gestational age and due date based on BPD
    • Evaluate all organs (heart, face, palate, spine, limbs, stomach, kidneys)
    • Evaluation of placenta appearance and position
    • Measure amniotic fluid index
  • Third trimester scan/ “Foetal well-being ultrasound” – week ~32
    • Same as second trimester scan + evaluation of umbilical artery flow by Doppler

More frequent ultrasound investigations may be indicated in case of high-risk pregnancy or abnormal findings.

Nuchal translucency (NT) is a measure of the thickness of a translucent (fluid-filled) region in the nuchal region of the foetus. A thickness of > 3 mm is abnormal, and is associated with trisomies, especially Down syndrome.

During second and third trimester scans, multiple foetal parameters are measured (foetal biometry):

  • Crown-rump length (CRL) – length from top of head to end of buttocks
  • Biparietal diameter (BPD) – diameter of the head from one ear to another
  • Femoral length (FL) – length of the femoral bone
  • Abdominal circumference (AC) – largest circumference of the foetal abdomen
  • Head circumference (HC)

To estimate the due date, either CRL (first trimester) or BPD (second trimester) is plugged into an algorithm. To estimate the foetal weight (in the third trimester), multiple parameters are taken into account.

The amniotic fluid index (AFI) is a tool to assess the volume of amniotic fluid. It’s described in topic B14.

Cell-free DNA and combined test

Some (cell-free) foetal DNA circulates in the maternal blood. As such, a simple blood test of the mother can give genetic information about the foetus. More specifically, cell-free foetal DNA (cffDNA) can be used to detect trisomies 21, 13, and 18. cffDNA testing is also called non-invasive prenatal testing (NIPT).

A so-called “combined test” is a combination of ultrasound and blood test. More specifically, it involves three examinations:

  • First trimester ultrasound
  • Maternal PAPP-A
  • Maternal free hCG

The results of the combined test can estimate a risk for trisomies 21, 13, and 18.

As both cffDNA and combined test are screening tests, positive tests are not diagnostic and must be followed up by invasive methods (AC/CVS) to confirm the findings.

Other genetic screening tests (triple test, quad test) exist as well, which take additional parameters (AFP, oestriol, inhibin A, etc.) into account, and may give information on the risk for other defects as well, like neural tube defects and abdominal wall defects. However, these are not as widespread in Europe and were not included in lecture.

Biophysical profile

A biophysical profile is a test which can be used to estimate the risk of prenatal foetal death in the second half of the pregnancy. Its main indication is a nonreactive nonstress test. It involves the use of ultrasound and a non-stress test to assess different parameters, score each of them, and add them up to a final score between 0 and 10. The following parameters are included, and 0 points is given if the parameter is abnormal, and 2 points if normal:

  • Foetal movement
  • Foetal tone
  • Foetal breathing
  • Amniotic fluid volume
  • Nonstress test

A score of 8 – 10 is normal. A score of 4 or less is usually an indication for delivery.

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