First Trimester Screening (FTS)

Screening for the first trimester



In the first trimester screening test (FTS), two types of measurements are used along with maternal age to calculate the risk of Down syndrome, trisomy 18, and trisomy 13.



In the first trimester screening, a pregnant woman is referred to a laboratory for testing from the beginning of week 11 (11W + 0D) to the end of week 13 (13W + 6D) (the best time to test is between 12W + 0D and 13W + 3D).



Because the test is performed in the first trimester of pregnancy and involves biochemical markers and ultrasound at the same time, screening is called the first trimester.



This type of screening solves the problems of separate screening based on biochemical markers (PAPP-A and Free βhCG) and ultrasound (NT) markers, each of which has been done on its own in the past.



Today, the best solution for first trimester screening is to use methods in which biochemical tests are prepared no later than 2 hours after the blood draw, and the patient's risk is determined only by attending the clinic once.



Clinics with such conditions are called OSCAR or One-Stop Clinic for Assessment of Risk.



Why is it time to start screening in the first trimester of the 11th week of pregnancy?



For three reasons:

1) The beginning of the significant difference between Medina (= middle) [3] in normal fetal society and fetuses with Down syndrome is from week 11 and before that the overlap of the fetuses of these two communities is high.



2) In general, in all screening tests, it is advisable to perform the test when there is a diagnostic test that can be used to confirm the positive cases of screening [4].



The diagnostic test available at this stage is CVS [5], but it cannot be performed earlier than week 11 of pregnancy because firstly the probability of miscarriage is higher and secondly there is a significant relationship between performing this test before week 11 and increasing the incidence of some fetal disorders. Transverse organ disorders [6], micronatia [7] (or small jaw) and small tongue [8] have been observed.



3) In NT ultrasound, in addition to measuring this marker, a number of other examinations of fetal organs are performed, which are not reliable before 11 weeks of gestation. These studies include:



Examination of the exophthalmos (umbilical hernia): [9] In almost all fetuses, between 8 and 10 weeks of gestation, there is a hernia in the intestinal tract, which makes it almost impossible to diagnose a umbilical hernia by creating a hyperacogenic mass at the base of the umbilicus.



Examination of the skull (partial or complete absence of the skull) or anencephaly (absence of the brain): To check for these disorders, the process of skeletalization [10] of the skull must be complete. But the process takes place in Week 11, and pre-Week 11 reviews are unreliable.



Examination of the heart: It is possible to examine the four cavities of the heart and large arteries after the 10th week of pregnancy.



Examination of the stomach and bladder: These organs are 50% of cases in 10 weeks, 80% of cases in 11 weeks and 100% of cases in 12 weeks. [4-1]



Why is the end of the first trimester screening at 13W + 6D?



For three reasons:



1- If the fetus has a disorder, the patient will have the opportunity to choose the methods of termination of pregnancy in the first trimester.



2 - The incidence of edema of the back of the neck [11] in fetuses with abnormal chromosomes during the 18th-14th weeks of pregnancy is less than the incidence in the weeks below 14.



3- The success rate of NT measurement under 14 weeks is about 98% - 100, while from 14 weeks onwards, with the fetus in a vertical position, the probability of success in NT measurement and obtaining a suitable image is less than 90%. . [4-1]



Normal translocation: [12] NT is an indicator of the amount of fluid collected under the skin of the fetal neck. In other words, the maximum thickness of the clear area between the skin and the soft tissue covering the cervical vertebrae is called NT.



In 95% of cases, transdermal transplants [13] can be used to measure NT, and transgender transplants should only be used in obese women.



Because NT marker screening has the greatest impact on risk calculation in the first trimester, it is important that this measurement, along with CRL measurement [15], be performed by an experienced oncologist with the same protocol to obtain the correct risk.



To ensure the accuracy of the NT measurement, it is necessary to attach a standard NT photo according to the ultrasound report. The standard NT image should include the following four features:



1- It is prepared in an acceptable CRL range. Acceptable CRL for measuring NT is between 45 and 84 mm.



2 - The image used to measure NT should include a profile view of the fetus, so that the nose blade and tip can be seen and its magnification is such that only the upper part of the chest and head can be seen in the image.



3. The fetus' neck should be in a neutral position when taking a picture. If the fetal head is too bent forward [18], it can cause a false reduction of up to 0.4 mm, and if it is too bent backwards [19], it can cause a false increase in NT measurement to 0.6 mm. .



4- The location of the calipers (markers) to specify the range of NT in the photo should be inside to inside [20].

Note 1:
Regarding the report of the nasal septum (Nasal Bone = NB) and its inclusion in calculating the risk in the first trimester screening tests, it should be noted that in the national method of screening for Down syndrome, as well as in other reputable global centers, this marker Screening markers are not the first trimester, and although many of the software and even software used by the FMF or Fetal Medicine Foundation are intended for this marker, its reporting and its impact on risk calculation depend on having sufficient sonographic skills. A separate document has been published by NB for sonologists.

Note 2: In 5-10% of cases, the umbilical cord wraps around the neck, in which case the NT at the top and bottom of the umbilical cord should be measured and the average of the two should be reported.

Note 3: According to Canada's latest BCPGSP [21] guidelines, the license to perform a NT sono for sonologists must be renewed every year, and one of the criteria for renewing this license is to perform at least a certain number of NT sonos a year.

NT levels increase in chromosomal abnormalities such as Down syndrome and Turner syndrome.

The highest increase in NT is seen in Turner syndrome (45, XO, where usually the paternal X chromosome is not transferred to the fetus and has a prevalence of 1 to 4000) so that the NT value increases to 8 mm more than normal fetal medina, while in trisomies 21, 18 And 13 is the maximum increase in NT to 2.5 mm higher than normal fetal medina.

Normally, NT levels increase with fetal age. According to various studies, the NT study with CRL is about 45 mm, 1.2 mm and with CRL about 84 mm, is 1.2 mm.

In more than 70% of cases of trisomy 13, 18, and 21, and in nearly 85% of cases of Turner syndrome, NT has more than 95 per cent.

Increased NT in other disorders

1- Heart disorders and large artery disorders (out of every 33 fetuses whose NT is between 2.2 and 2.8 mm, one fetus has cardiovascular disorders. When the NT is more than 3.5 mm, this probability increases to 1 to 16). .

2- Diaphragmatic hernia

3- Pulmonary insufficiency

4 - Skeletal dysplasia [22]: As we know, the accumulation of fluid in the back of the neck originates from the lymphatic system and the lymphatic vessels do not have muscle and to move fluid in these vessels requires contraction and expansion of muscles around it and from Because in skeletal dysplasia we have motor poverty (resulting in a lack of contraction and muscle expansion), this disrupts the lymphatic drainage system, resulting in fluid buildup in the lymphatic vessels and fluid buildup in the back of the neck. Which shows itself as an increase in NT.

5- Congenital infections

6. A wide range of genetic syndromes (especially those that reduce fetal motility)

7- Metabolic and hematological disorders (such as anemia)

8- Hypoproteinemia or decrease in the level of protein in the baby's blood

9. Between 4.5 and 5 percent of normal fetuses have high NT without any particular problem.


NT ultrasound is also used in the following cases:

1- Confirms that the fetus is alive.

2- It confirms the gestational age.

3- Diagnoses twin pregnancies.

4- Examines those birth defects that can be diagnosed at this gestational age.

Note 1:
Regarding the report of the nasal septum (Nasal Bone = NB) and its inclusion in calculating the risk in the first trimester screening tests, it should be noted that in the national method of screening for Down syndrome, as well as in other reputable global centers, this marker Screening markers are not the first trimester, and although many of the software and even software used by the FMF or Fetal Medicine Foundation are intended for this marker, its reporting and its impact on risk calculation depend on having sufficient sonographic skills. A separate document has been published by NB for sonologists.

Note 2:
If NB was not seen in the first trimester with high-tech, high-resolution devices, and other ultrasound markers, including NT, were at low risk, the patient's ultrasound was renewed at 15 weeks and the patient was nominated if the nasal bone did not form. Diagnostic tests such as amniocentesis are performed.

Note 3:
According to the national protocol, the two standard NT and CRL images must be attached to the NT ultrasound report. Otherwise, the above Sono is worthless.

Note 4:
Tricuspid reguregitation and blood flow abnormalities on Doppler ultrasound at the ductus venus also increase the risk of trisomy.

Maternal blood test:

In the mother's blood test, the levels of two substances commonly found in the blood of all pregnant women are measured: PAPP-A, and free beta-HCG.

In pregnancies associated with fetal Down syndrome, the amount of these two substances indicates a tendency to deviate from the expected values.


Biochemical markers measured in the first trimester

PAPP-A marker:

It is a pair-derived glycoprotein that increases during pregnancy.

In some chromosomal abnormalities, this substance decreases and this decrease is more in the 10th to 14th weeks of pregnancy.

This marker is a metalloproteidase enzyme that is secreted from placental trophoblastic cells, especially extraspheric trophoblasts.

Its level increases with a relatively steep slope at 11 to 13 weeks.

Pregnant women whose PAPP-A levels are lower than expected during the 11th to 14th weeks of pregnancy are more likely to have Down syndrome.

By breaking down binding proteins to IGF-BP [23] and releasing it, this enzyme stimulates the aggressive role of trophoblasts and thus plays an important role in embryo implantation.

The IGF molecule is involved in regulating the transport of glucose and amino acids from the placenta. Another biological pattern of IGF is that it has a similar function to growth hormone and therefore plays a role in fetal development.

Decreases in this marker without the presence of chromosomal abnormalities can be seen in the following disorders:

- IntraUterine Fetal Death or IUFD
- Preterm Delivery
- Preeclampsia
- Gestational Hypertension
- IntraUterine Growth Restriction or IUGR
- Sudden abortion

Free βhCG hormone:

The free beta subunit is the hormone hCG, which is mainly secreted by placental trophoblast cells.

During the 9th to 11th week, its level reaches its maximum and then decreases.

Free βhCG levels in the mother's blood, such as hCG levels, in pregnant women with Down syndrome tend to increase. Its changes in the blood are similar to those of hCG, which means it decreases rapidly from the tenth week.

In the blood of a pregnant woman, we see 5 different forms of hCG-dependent molecules or hCG-related molecules:

- nonnicked hCG, which represents the active hormone;

There is a peptide bond in the beta chain of hCG to which the steroidogenic or steroidogenic activity of the hCG molecule depends.

- nicked hCG;

- free α-subunit;

- free β-subunit;

- and the nicked free β subunit

In fact, the source of free BhCG ​​production in the mother's blood comes from the following three sources:

1- Paired directly from the trophoblast

2- Dissociation of hCG molecule in the blood and release of its two subunits is created (dissociation of hCG into free α- and free β-subunits).

3. It is caused by the enzymatic activity of macrophages or neutrophils on hCG molecules (macrophage or neutrophil enzymes nicking the hCG molecule).


In cases of unexplained reduction, the level of other markers is normal, although concomitant complications with PAPP-A are less common.

However, in some studies, lowering it to less than MoM <0.4 increases the risk of Low Birth Weight and Miscarriage, and lowering it to less than MoM <0.25 increases the risk of sudden fetal loss before 24 weeks.

Attention :
If there is an empty sac in the ultrasound, it is possible to have a biochemical blood test and no change in the results, but if a second sac containing a vanished twin is seen, it will affect the index for several weeks. Biochemical tests, it is recommended that judgments be made only on the basis of age and ultrasound index, and that laboratory tests not be performed.

Results from first trimester screening

The results of the first trimester screening tell us how likely it is that the pregnancy will be associated with Down syndrome, trisomy 18, or trisomy 13, which is called the risk of infection in the screening report.

Maternal follow-up protocol in screening for the first trimester

According to the results of the Down syndrome screening test in the first trimester, patients fall into six groups:

1- High risk group: If the risk of a pregnant woman is more than 1:50 (ie, the risk of deductible deduction is less than 50 in the declared risk), it should be referred directly for diagnostic tests.

2- Borderline risk group: If the risk of a pregnant woman is between 1:51 and 1: 1100, it is recommended to wait until the second trimester and perform a combined or sequential test or a screening test with strength. The above diagnosis means NIPT (Non Invasive Prenatal Test) or cell free DNA.

3. Low risk screening group: If the result of the first trimester screening is less than the risk of segregation (1: 1100), the screening for Down syndrome will end and the patient will only be examined for neural tube defects or NTDs to measure alpha photoprotein. And the AFP MoM calculation is referred to the lab at 15 to 16 weeks of gestation.

4 - If only abnormal findings in the fetus, the presence of NT above 3 mm (or more than 99 percent of the fetus according to the height of the fetus), should be referred for amniocentesis.

Note: In the national protocol, it is recommended that numbers above 3 mm be nominated for diagnostic tests, regardless of their age. While this number is 3.5 mm according to the British FMF Institute).

5 - Women of any age, if their fetus has an NT above 3.5 mm, should be referred for fetal echocardiography at 20-18 weeks of gestation.

6- According to the recommendation of the latest BCPGSP guide, in addition to the second group, the following groups should also perform complete sequential tests:

- Women over 35 years of age during childbirth (in the previous edition of this guide, the age of this group of women over 36 years was mentioned.)

- Women with twin pregnancies

- Women who have a history of having a baby or fetus with Down syndrome, Edward, or neural tube defects (or parents who are carriers of any type of translocation, dilation, incision, or inversion that increases the risk of having a child with an unbalanced chromosomal development ).


- Women over 35 who have a history of 3 or more miscarriages. (In the new edition of this guide, this group is deleted and placed in the same first group).

- Women who are HIV-positive (because amniocentesis in this group of women potentially increases the potential for HIV transmission from mother to fetus, so it is best to use a screening test to reduce the number of false positive screening tests in this group of women).


- Women who have had IVF or ICSI.


Note: In the new protocols, according to the joint theory of the American Society of Obstetricians and Gynecologists (ACOG) and the Association of Maternal and Fetal Medicine (AMFM), these four end groups should be candidates for the NIPT test.


After screening the first trimester

The results of the first trimester screening tell the doctor whether it is necessary to perform diagnostic tests such as amniocentesis for the pregnant woman. Most women get screening results after screening, which eliminates the need for diagnostic tests, but women who are at high risk for Down syndrome, trisomy 18, and trisomy 13 are more likely to have diagnostic tests. Recommended as amniocentesis.

                             Benefits of first trimester screening

1- Screening more accurately and earlier, which causes peace of mind in many women.

2- With NT ultrasound, it is possible to diagnose some obvious birth defects.


First trimester screening restrictions

1. About 5% (1 in 20 people) of women who have this screening are identified as at high risk. But at the same time, most women at high risk give birth to normal babies.

2 - To perform routine diagnostic tests, you must wait until the second trimester of pregnancy.

3. Screening for fetal neural tube defects is not possible with this test and should be done with a coding marker test in the second trimester of pregnancy.


Attention:
Monocorion twins are monozygotic, but dichorions can be monozygotic or di-zygotic. Therefore, in monocorionic mode, the detection power is higher and the screening software calculates a risk for both embryos. In de Corion, if one of the fetuses is affected, it affects the biochemical indicators of the other fetus, which is why ultrasound factors are more helpful.

Birth disorders

Congenital disorders are disorders that the baby is born with. Examples of birth defects include open neural tube defects, heart disorders, and leukemia. All women, regardless of their age and family history and previous pregnancies, are 2% to 3% more likely to have a child with birth defects.

Ultrasound is performed between 18 and 20 weeks of gestation, which is recommended for all pregnant women, to more accurately examine birth defects and the developmental process of the fetus.