Mid-trimester biochemical screening

1. What is mid-trimester biochemical screening?

  • Mid-trimester biochemical screening is a screening test performed between 16-20 weeks of gestation for Downs syndrome;
  • The risks are calculated based on the age of the pregnant women and the hormonal levels in the mother’s blood
  • Depending the number of hormones checked, the biochemical screening tests might be called differently:
  1. (i) Alfra-fetoprotein (AFP) and Human chorionic gonadotropin (hCG)- Double test
  2. (ii) AFP, HCG and Unconjugated estriol (uE3)- Triple test
  3. (iii) AFP, HCG, uE3 and Inhibin A- Quadruple test or Quad screen
  • The more hormones are used, the slightly higher detection rates will result but there is also higher cost involved

2. How is the test performed?

  • Taking blood from the mother for the hormonal levels
  • Computer software is used to calculate the risks 

3. How accurate is the test?

  • The detection rates depend on the number of hormones used;
  • It is ~60% for Double test, 66% for Triple test and 80% for Quadruple test;
  • There is a false positive rate of 5%

4. What if the test results are abnormal?

  • Not all women with abnormal results have abnormal babies;
  • It is important to discuss with a specialist in this field to determine the next appropriate option, whether it is NIPT or amniocentesis

5. What other abnormalities can this test screen?

  • A low serum AFP happens in pregnancies with Downs and Edwards syndrome;
  • A high serum AFP (> 2.5MoM) is associated with a higher chance of the following conditions:
  1. (i) Fetal structural malformation such as open neural tube defect and anterior abdominal wall defect;
  2. (ii) Bleeding during pregnancy;
  3. (iii) Hypertensive disorder in pregnancy

6.  How is this test compared with other antenatal screening tests for Downs syndrome?



Mid-trimester (16-20 weeks)

biochemical screening


Detection rate




False positive rate





This article is contributed by Dr. T.N. Danny Leung
Updated on 25.09.2020