Down Syndrome Screening Tests: First Trimester Screening (FTS) & NIPT

What are Down syndrome screening tests?

Down syndrome screening tests typically involve a combination of non-invasive tests to determine the risk of the fetus having chromosomal abnormalities.

It's important to note that while early pregnancy assessment screening may provide some information about the risk, a definitive diagnosis is usually confirmed through more invasive diagnostic procedures if deemed necessary.

Who is at risk of having a Down Syndrome baby?

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. While the majority of cases are not inherited and occur spontaneously, certain factors can increase the likelihood of having a baby with Down syndrome. Here are some factors that may contribute to an increased risk:

1. Maternal age:

   • The risk of having a baby with Down syndrome increases with maternal age. While it can occur in women of any age, the incidence is higher in older mothers. The risk becomes more significant after the age of 35 and continues to rise with each year.

2. Paternal age: 

   • Although the impact is not as pronounced as maternal age, there is some evidence suggesting a slight increase in the risk of Down syndrome with advancing paternal age.

3. Previous child with Down syndrome: 

   • Parents who have had one child with Down syndrome have a slightly higher risk of having another child with the condition. However, most cases of Down syndrome occur in families without a history of the condition.

4. Carrier parents: 

   • In a small percentage of cases, one of the parents may be a carrier of a balanced translocation involving chromosome 21. This can increase the risk of having a child with Down syndrome.

5. Genetic variations: 

   • While the vast majority of cases of Down syndrome are not inherited, there are rare instances where a genetic predisposition may increase the risk. This can include certain genetic conditions or variations.

What is non-invasive Down syndrome screening?

Non-invasive Down syndrome screening provides expectant parents with valuable information about the risk of having a baby with Down syndrome without the need for invasive procedures like amniocentesis or chorionic villus sampling.

Two primary non-invasive screening tests for Down syndrome are:

1. First Trimester Screening (FTS)

2. Non-Invasive Prenatal Testing (NIPT) 

It's important to understand that FTS and NIPT are screening tests, not diagnostic tests. Positive results should be confirmed through invasive diagnostic procedures.

What is First Trimester Screening (FTS)?

FTS is a non-invasive method that involves a combination of maternal blood tests and ultrasound measurements performed during the first trimester of pregnancy. This screening is typically conducted between the 11th and 14th weeks of gestation. FTS assesses the risk of chromosomal abnormalities, including Down syndrome. The test involves two main components:

1. Nuchal Translucency (NT) ultrasound measurement: 

   • During the ultrasound, the thickness of the skin at the back of the baby's neck (nuchal translucency) is measured. An increased thickness may indicate a higher risk of Down syndrome.

2. Blood tests: 

   • Maternal blood is analyzed for specific markers, such as pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (hCG). Deviations from normal levels may suggest an increased risk of chromosomal abnormalities.

FTS provides a risk assessment, and if the results indicate a higher likelihood of Down syndrome, further diagnostic tests like amniocentesis or chorionic villus sampling may be recommended for confirmation.

What is Non-Invasive Prenatal Testing (NIPT)?

NIPT is a more advanced and accurate screening method for detecting chromosomal abnormalities, including Down syndrome. Unlike FTS, NIPT is a blood test that can be performed as early as 10 weeks into pregnancy. This test analyzes cell-free fetal DNA (cffDNA) circulating in the maternal bloodstream, providing highly accurate results. The process involves extracting and analyzing fragments of the fetal DNA from the mother's blood. This allows for the detection of abnormalities with a high degree of sensitivity and specificity. 

FAQs

Is it possible to undergo FTS and NIPT at the same time?

Yes, you can undergo FTS and NIPT at the same time. In fact, there are instances where NIPT may not yield a result due to various factors. Given this possibility, we recommend going for FTS, regardless of whether you choose to proceed with NIPT. This approach ensures a comprehensive assessment of fetal health and can provide valuable insights into your pregnancy.

What are the advantages and limitations of FTS?

Advantages of FTS

1. Early detection:

   • FTS is typically performed between the 11th and 14th weeks of pregnancy, allowing for early risk assessment.

2. Non-invasive:

   • FTS is a non-invasive procedure that does not pose a risk of miscarriage, making it a safer option compared to invasive diagnostic tests.

3. Widely available: 

   • FTS is a widely available screening method, making it accessible to many expectant parents during routine prenatal care.

Limitations of FTS

1. False positives:

   • FTS may yield false-positive results, indicating a higher risk of chromosomal abnormalities when the fetus is, in fact, healthy. This can lead to unnecessary anxiety and further invasive testing.

2. False negatives: 

   • FTS may also produce false-negative results, suggesting a low risk when the fetus does have a chromosomal abnormality. This can provide a false sense of security, and abnormalities may go undetected.

3. Not diagnostic: 

   • FTS is a screening test, not a diagnostic test. Positive results require confirmation through invasive diagnostic procedures, such as amniocentesis or chorionic villus sampling.

4. Limited specificity: 

   • While FTS is effective in detecting Down syndrome, it may have limitations in identifying other chromosomal abnormalities or structural anomalies.

5. Operator-dependent: 

   • The accuracy of FTS can be influenced by the skill and experience of the sonographer performing the ultrasound measurements.

6. Limited window:

   • FTS must be performed within a specific window of time (11th to 14th weeks), which may limit its availability for some individuals.

What are the advantages and limitations of NIPT?

Advantages of NIPT

1. Non-invasive: 

   • NIPT is a simple blood test that poses no risk to the fetus or mother, eliminating the potential complications associated with invasive procedures.

2. High accuracy: 

   • NIPT has demonstrated high sensitivity and specificity in detecting chromosomal abnormalities, providing more reliable results compared to traditional screening methods.

3. Early detection: 

   • NIPT can be performed early in pregnancy, allowing expectant parents to make informed decisions earlier in the gestational period.

4. Reduced need for invasive procedures: 

   • Due to its accuracy, NIPT helps minimize the need for unnecessary invasive diagnostic procedures, which carry a small risk of miscarriage.

Limitations of NIPT

1. Non-diagnostic: 

   • While NIPT is a highly accurate and reliable screening method, it is important to note that it is a screening test, not a diagnostic test. Positive results from NIPT should be confirmed through invasive diagnostic procedures, such as amniocentesis or chorionic villus sampling.

2. Limitations in certain cases:

   • Additionally, NIPT may have limitations in certain cases, such as pregnancies with multiples (twins or more) or in cases of maternal mosaicism. 

FTS vs NIPT

Who is indicated for FTS?

1. Maternal age: 

   • FTS is often recommended for women of advanced maternal age (typically 35 years or older at the time of delivery). The risk of chromosomal abnormalities, including Down syndrome, increases with maternal age.

2. Previous pregnancy with chromosomal abnormality: 

   • Individuals who have had a previous pregnancy with a chromosomal abnormality may be advised to undergo FTS for subsequent pregnancies.

3. Family history:

   • Individuals with a family history of chromosomal abnormalities may be recommended to undergo FTS.

4. Abnormal ultrasound findings:

   • If an ultrasound examination detects abnormalities, FTS may be recommended to assess the risk of chromosomal abnormalities.

5. Concerns or anxiety: 

   • Some individuals may choose FTS due to personal concerns or anxiety regarding the risk of chromosomal abnormalities.

Who is indicated for NIPT?

1. High-risk pregnancies: 

   • NIPT is often recommended for pregnancies considered to be at higher risk of chromosomal abnormalities, such as advanced maternal age, based on the higher sensitivity and specificity of NIPT.

2. Positive First Trimester Screening (FTS): 

   • If FTS results indicate an increased risk of chromosomal abnormalities, NIPT may be recommended for further confirmation.

3. Previous pregnancy with chromosomal abnormality: 

   • Individuals with a history of a previous pregnancy with a chromosomal abnormality may opt for NIPT for early and accurate screening.

4. Parental carrier of balanced translocation: 

   • In cases where one of the parents is known to be a carrier of a balanced translocation involving chromosome 21, NIPT may be recommended.

5. Twin pregnancies: 

   • NIPT can be used in twin pregnancies to assess the risk of chromosomal abnormalities.

References

1. Norwitz ER, Levy B. Noninvasive prenatal testing: the future is now. Rev Obstet Gynecol. 2013;6(2):48-62. PMID: 24466384; PMCID: PMC3893900.

2. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/first-trimester-screening-nuchal-translucency-and-nipt