What Is Sequential Screening Test: Why It Is Required And How It Works

Q: What Happens If a Down Syndrome Test Is Positive?

A positive screening test result indicates that your kid has a higher-than-average probability of developing the Down syndrome. Your test findings may contain a number indicating the severity of the danger. However, a high risk does not imply that your child will have Down syndrome.

Not everybody has to undergo screening tests. One of such screening test is “sequential screening.” This screening is an added test done for a diagnosis that is optional and suggested by the doctor. It is a test which most of the expectant mothers are not comfortable, but since it is crucial for the mother, we will highlight everything related to this test.

What Is Sequential Screening?

This screening consists of a sequence of tests done in the prenatal stage like ultrasound and blood test for checking the defects in the neural tube and genetic aberrations. This test is done in two steps to assess the probability of the fetus with Down syndrome, anencephaly, Trisomy 18 Spina Bifida, etc.

The sequential screening is done at the antenatal period of gestation by ultrasound and blood tests initially at 11 to 14 weeks gestation and again at 16 to 20 weeks of gestation. If there any abnormality noted at the 3 months test only then generally 4th month testings are done. For all pregnancies 3 month ultrasound and double marker blood tests needs to be done and 4th month ultrasound which is anomaly scan is mandatory (1).

The process of screening assimilates both the findings of the blood tests and the report of the ultrasound from the first trimester. This test is not mandatory and can be opted if one wants. A medical practitioner helps in deciding if the mother should undertake this test. These tests cannot help in diagnosing a specific situation, but help in comprehending any threats which are there.

Some of the screening tests conducted during pregnancy are:

How Does Sequential Screening Test Work?

The screening process is carried out in two steps, the first being the ultrasound and the blood test that is carried out within ten to fourteen weeks, and another stage where a single blood test is performed at fifteen to twenty-one weeks.

1. Sequential Screening Stage One

During stage one, the following tests are conducted.

Ultrasound

NT refers to the accumulation of fluid at the rear portion of the neck of the baby. The ultrasounds also assist in assessing the fluid in the baby’s body. All babies who get diagnosed with trisomy 18, Down syndrome, or other anomalies are disposed to an additional fluid as well as higher NT. During NT scan not only the thickness of the fluid at the back of the fetus’s neck is measured , nasal bone formation and the measurement of the nasal bone is also seen. These are the ultrasound markers for any genetic abnormality (3).

Apart from the NT magnitude, the ultrasound done during the first trimester helps in determining the baby’s development, gender, and gestational age.

Blood testing

The placenta is known to produce proteins at the time of pregnancy, which can be transmitted to the mother’s blood as well. The babies who are diagnosed with any anomalies, Down syndrome, or trisomy 18 will exhibit higher protein levels. The blood tests also help to assess the following threats, as well.

PAPP-A

The lower protein levels increase the chances of threats of trisomy 18 and down syndrome. It is related to other pregnancy threats comprising of high BP ratings, low weight at birth, miscarriage, etc., but all are not necessarily a sign of unhealthful pregnancy.

HCG

The increased levels of HCG are a sign of Down’s syndrome and trisomy 18. Different types of HCG screening are done for detecting protein levels.

2. Sequential Screening Stage Two

Quad screen, as it is also commonly known as comprises the blood test that assists in calculating the Alpha-fetoprotein, dimeric inhibin, and HCG-free estriol. The placenta produces an increased number of proteins that get transmitted to the mother’s blood, and all babies with anomalies show either a too-high or too-low level of proteins.

The typical proteins that can be calculated in stage two of the blood test are as follows:

1) AFP

The liver of the baby produces a protein in the second half of the pregnancy called Alfa Feto Protein. The level of this protein eventually increases as pregnancy advances. However, the level of AFP will be on the higher side in case the baby has any threats of a defect that happens when the spinal cord and the spine do not develop properly.

Thus, increasing the AFP levels in mothers’ blood indicates neural tube defects such as Spina bifida or chromosomal issues such as Down syndrome in the developing baby. Whereas, AFP levels are found significantly reduced if the baby has any risks of Edward’s syndrome.

2) HCG

The placenta produces HCG protein soon after the implantation of the fertilized egg. However, its levels start diminishing during the second trimester. While increased levels are related to Down Syndrome, declining levels are linked with trisomy 18.

3) Unconjugated estriol (UE3)

Both the liver and the placenta produce this protein, and this stays at increased levels all through the pregnancy. Decreased levels in protein indicate the baby has a chance of Edward’s Syndrome.

4) Dimeric inhibin A (DIA)

Placenta produces this protein, and this protein level lies steady between the 15th as well as 18th week. The increased protein levels are connected with Trisomy 21, while the decreased levels are with Edward’s Syndrome.

Accuracy of Sequential Screening Test

The sequential screening test cannot reveal any genetic anomalies. Decisiveness is dependent on the individual’s skills and the test results, as well. This screening, on the other hand, helps to find the following:

90% of the infants with Down syndrome
80% of the newborn with trisomy 18
80% of the newborn baby with Spina bifida

Trisomy 21, also referred to as Down syndrome, is produced by an additional chromosome, and one in about 600-900 babies is born with it. It also causes cardiovascular disease and mental disorders amongst all. The possibility of Down syndrome in a baby multiply with the age of the mother.

The growing baby has an additional chromosome that leads to Trisomy 18. One in 6000-8000 babies is born with it. It can lead to mental retardation, cardiovascular disease, weak growth, etc. Alike Trisomy 21, the possibility of Edward’s syndrome also increases with the age of the mother.

ONTD or Open neural tube defects take place if the spine is not formed appropriately, exposing and damaging the spinal cord. One out of 1,000 infants has the chance to foster these anomalies. The results of this test are an indication to show the baby has genetic anomalies, but other tests are recommended as well.

How Much Time Do the Results Take?

The results of the sequential screening can be expected in a week or less after submitting the samples of blood.

Sequential Screening Test Results

The very first round of the ultrasound assesses the levels of NT. In case they are too high, the doctor will recommend more tests. To evaluate the cell-free fetal DNA (cf DNA), chorionic villus sampling may conduct. In case the NT or the nuchal translucency fluid is not normal, there are more chances of the baby being detected with chromosome-related anomalies.

What to Do If Sequential Screening Shows High Risk or Abnormal Results?

In a case where the sequential screening shows high risks or not typical results, the doctor will most probably refer the mother to a specialist who deals with cases of high risks in pregnancy like a perinatologist, maternal medicine fetal specialist, etc. These specific doctors can thus recommend additional tests or even refer to other counselors who can describe the detailed results, resolve all queries, and make the ideal decision.

Advanced testing options comprise prenatal screening. An ultrasound will be performed. Amniocentesis, as well as a test that helps to assess if the lady has a higher chance of having a baby with trisomy 21, will also be performed (all of them not compulsory though).

What to Do If Sequential Screening Shows Low Risk or Normal Results?

In case the screening results of stage one are on the normal side, the doctor will ask for a revert at 15-22 weeks for screening at stage 2, and the findings at this stage will further help in assessing trisomy 18, down syndrome, and other anomalies.

In case the results are not abnormal and negative, the baby has fewer chances to have genetic defects. The medical practitioner will persist in keeping, and monitoring the baby all through the prenatal checks.

Are Sequential Screening Procedures Standard for All Pregnant Women?

Sequential screening tests are recommended to all expectant women, yet more importantly, to expecting mothers having a high-risk pregnancy. Sequential screening tests are conducted for women who are:

Above 35 years in age
Those who have had congenital disabilities in the family history
Those who underwent radiation treatments
Women who contracted diabetes
Those who had massive exposure to medicines.

Does Sequential Screening Also Work Accurately for Twins?

Twin detection is also done by sequential screening; however, the evaluation is a tricky one, and its accuracy is lower as well. Distinct laboratories have several approaches to this screening. Few medical experts separately evaluate every fetus, while others assess them as a unit as a whole. The doctor can throw more light on details related to the screening.

Thus, sequential screening helps to figure out the risk that the baby has concerning anomalies in chromosomes and offers the next due step. It is even essential, to let a genetic/ medical practitioner analyze the results for better clarity and vision.

FAQs

1. How Long Does Sequential Screening Take?

You may normally anticipate your test results in one week or less from the time the blood sample is collected.

2. What Happens If a Down Syndrome Test Is Positive?

A positive report in ultrasound and double marker test shows that there is high risk of the fetus is having Down’s syndrome. Then amniocentesis is the definitive measure to rule out Down’s syndrome or other genetic abnormality. If amniocentesis report is also positive then the parents are counselled by the doctors for termination of the pregnancy. So, obstetrician is to be consulted any positive report is found the the next plan of action is to sorted by the doctor themselves , it also depends person to person.

3. Which Screening Test Has The Highest Detection Rate For Down Syndrome?

The best test is the Sequential Integrated Screening test. This test uses the results of three separate tests to figure out how likely it is that a fetus will have chromosomal risks like Down’s syndrome.

References –

Detection Rates for Aneuploidy by First-Trimester and Sequential ScreeningDetection Rates for Aneuploidy by First-Trimester and Sequential Screening
https://journals.lww.com/greenjournal/abstract/2015/10000/detection_rates_for_aneuploidy_by_first_trimester.10.aspx
Sequential Pathways of Testing After First-Trimester Screening for Trisomy 21
https://journals.lww.com/greenjournal/citation/2005/02000/sequential_pathways_of_testing_after.46.aspx
Comparison of combined, stepwise sequential, contingent, and integrated screening in 7292 high-risk pregnant women
https://pubmed.ncbi.nlm.nih.gov/21800336/