Should you choose to undergo prenatal screening for Down syndrome?
Once you understand what is meant by having a child with Down syndrome, you can choose whether you want to undergo prenatal screening for Down syndrome or not. Since no treatment is available until now, if your unborn baby is diagnosed with Down syndrome, you need to decide whether you want to continue with the pregnancy or opt for termination of pregnancy.
When termination is not an option because of personal or religious reasons, you may opt out of screening. Still, some couples choose to undergo screening tests to be better prepared for the underlying condition.
It is your choice to undergo screening for Down syndrome or decline it.
What are the prenatal screening tests for Down syndrome and how are these different from diagnostic tests?
Every woman has an age-related risk of having a child with Down syndrome, it increases as the maternal age increases. Using statistical software, developed after research on millions of women around the world, the age-related risk for Down Syndrome is modified by ultrasound findings and blood tests. The results are classified as low-risk, intermediate-risk, and high-risk.
The screening tests cannot tell you whether the baby has Down syndrome or not, but screen you as low/high/intermediate risk for having a child with Down Syndrome.
Low-risk results reduce the possibility of Down syndrome but do not make it zero. High-risk results increase Down syndrome’s probability but need diagnostic tests for confirmation.
The percentage of high-risk cases that will actually have the disease is called the positive predictive value (PPV) of the test.
Screening tests also have a false positive rate – which means that the test classifies a healthy fetus as screen-positive for Down syndrome, and hence, all screen positive cases are recommended to undergo diagnostic tests for confirmation of the suspected disorder.
Let’s discuss various types of screening tests and their pros and cons –
- First trimester combined screening - This test is offered between 11 – 13+6 weeks of pregnancy. It includes ultrasound marker - nuchal translucency (fluid behind baby’s neck); along with levels of two hormones in the mother’s blood (free beta-HCG and PAPP-A).
The test's accuracy depends on the operator's experience, and the criteria followed for measuring the hormones as specified in the protocols provided by the Fetal Medicine Foundation (www.fetalmedicine.org). When done properly, the accuracy of the test is 84-88%, with a false positive rate of 2-3%. The accuracy of the test can be increased by adding ultrasound markers like nasal bone, blood flows across the heart (Tricuspid Doppler) and a tiny vessel in the liver (Ductus venosus Doppler), and/or another hormone in the blood called pLGF. The risks can be provided as a risk at the time of screening (that is, at 11 weeks or 12 weeks whenever the screening was performed) or risk at term (that is at 40 weeks). The risk is different at different gestational age, as around 30% of cases of Down syndrome will have a spontaneous abortion or intrauterine demise as the gestational age advances. The ideal way is to report the risk at term pregnancy or at 40 weeks of gestation.
The classification of the test as high-risk is different in different set-ups and is fixed at 1 in 150 at term in the United Kingdom, where this test was first developed. The definition of high-risk is usually defined by estimating that not more than 5% of women should need to undergo diagnostic tests (CVS or amniocentesis), to detect a maximum number of Down syndrome babies without causing additional harm to healthy pregnancies.
PPV of the high-risk result on combined FTS is around 11%.
Intermediate-risk category came into being after the introduction of another screening test called NIPS (non-invasive prenatal screening test), which is a more accurate screening test for Down syndrome than combined FTS but is costlier, and not cost-effective, if offered by public health system to the whole population.
- NIPS or NIPT (Non-invasive prenatal screening test) - This is a blood test that can be offered to a woman at a gestational age of 10 weeks onwards. The test is based on the fact that some DNA from the placenta crosses into the maternal blood and can be used to ascertain the fetal genetic conditions, as the precursor of both the placenta and baby is the same zygote (or the cell) that is formed by the union of the egg and the sperm that leads to the pregnancy.
The test is highly accurate for Down syndrome with a 99.9% detection rate. One needs to be cautious that maternal blood also contains a lot of free-floating maternal DNA that can lead to incorrect results, especially when the mother herself has a chromosomal aberration or has undiagnosed cancer. This is the reason that all screen-positive cases need confirmation by amniocentesis. Some women may choose to undergo NIPS directly without undergoing combined FTS or they may choose it as a secondary test after high/intermediate-risk on combined FTS or Quadruple test. The main advantage is the low false positive rate (around 0.1%), thereby, fewer women need to undergo invasive test for confirmation of Down syndrome.
- Quadruple marker test – Women who miss first-trimester screening can be offered the Quadruple test between 15 – 21+6 weeks of gestational age, it checks levels of four hormones in the mother’s blood – AFP (alpha fetoprotein), beta-HCG or free beta-HCG, Inhibin-A and uE3 (unconjugated estriol).
The test has around 64% detection rate at a 5% false positive rate. Screen-positive cases can be offered NIPS or amniocentesis after thorough counselling by an expert.
- Anomaly scan – Between 16 – 24 weeks, looking for markers of Down syndrome on ultrasound can detect about 50 – 60% of cases with Down syndrome, depending upon the number of markers used, and operator experience. Combining an anomaly scan with a Quadruple test gives about an 80% detection rate for Down syndrome at a 5% false-positive rate.
Table 1 – Detection rate, positive predictive values, false positive rate of various screening tests –
| Screening Test |
Detection Rate |
Positive predictive value |
False Positive Rate |
| Combined FTS (NT + Dual marker) |
84-88% (screen positive – 1 in 150 at term) |
~ 3 - 4% |
3% |
| FTS with extended US markers (NT+NB+TR+DV+Dual marker) |
93% (screen positive – 1 in 150 at term) |
14% (ACFM, New Delhi, unpublished data) |
1.5% |
| Quadruple marker (Inhibin-A, free b-HCG, uE3, AFP) |
64% (screen positive rate – 1 in 250 at term) |
2.7% |
5% |
| Quadruple marker + Anomaly scan |
80% |
3% |
5% |
| NIPS (cell-free DNA) |
99% |
78.5 – 99% in various studies* |
10 – 15% |
*Ref - Liu S, Yang F, Chang Q, Jia B, Xu Y, Wu R, Li L, Chen W, Yin A, Huang F, Feng S, Li F. Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review. Mol Cytogenet. 2022 Jul 6;15(1):29. doi: 10.1186/s13039-022-00607-z (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261060/)
As evident from the table above, the screening tests are a way of knowing the probability of having a child with Down syndrome, but do not confirm or rule it out. You can read more about diagnostic tests here
