Screening in the First Trimester. Screening for Down Syndrome.
Screening in the first trimester, screening for Down Syndrome, combined screening test or early biochemical screening are all synonyms but it is best to talk about screening in the first trimester. Now I’m going to explain why. We need to understand what this screening is and what its objectives are.
Combined screening test is performed to detect trisomy 21 (Down Syndrome), trisomy 13 (Patau Syndrome), and trisomy 18 (Edwards Syndrome).
Screening (from English screening: sifting, selection) is a systematic, research method in the field of medicine, the purpose of which is to make a preliminary selection through a general classification in a pre-selected area of study (samples or individuals). Pre-selection or stratification of the sample serves to gather objects that carry certain attributes and later undergo a special study. from Wikipedia, the free encyclopedia.
In the UK (I can comment to some extent on the healthcare system in this European country in particular because of my experience there as a duty doctor in private hospitals, an obstetrician in state hospitals and specializing in fetal medicine there, I have not worked and studied in other countries and I would not allow myself to comment), the majority of the first ultrasound examinations of pregnant women take place between 11 and 14 weeks of pregnancy. To clarify, pregnancy lasts 280 days, 10 lunar months (by 28 days) or 40 weeks of pregnancy (WOGP) from the first day of the last menstrual period. In Western literature, pregnancy is counted in weeks, so I will describe it divided in weeks. It is precisely because of the fact that the first examination is in this period and it has several purposes.
Before we start with the ultrasound, we need to collect data about the pregnancy and the woman, the so-called history. We ask about your age, LMP (first day of the last menstrual period), the way of conception - spontaneous/natural or in vitro, problems during pregnancy, alcohol, cigarettes and drugs consumption, past and current diseases, previous surgeries, previous pregnancies, a problem during previous pregnancies, family illness, etc. All of this gives us information about your health and possible risks for your current pregnancy, which enables us to develop a follow-up plan.
I’m sure most of you are aware that a blood sample is taken. We assess the level of free bHCG and PAPP-A. The relationship between the pregnancy hormone (free bHCG) and the pregnancy protein (PAPP-A) is a marker for chromosomal diseases that are important for calculating the risk for the three most common trisomes - Down Syndrome (trisomy 21), Patau Syndrome (trisomy 13) and Edwards Syndome (trisomy 18). They also have significance for the detection of triploids, predictive markers for preeclampsia and IUGR (fetal retardation).
The first goal of screening in the first trimester is to establish an intrauterine pregnancy with a viable embryo or fetus after 12 WOP, through hearbeat ultrasound, fetal movements, Doppler ultrasound confirming cardiac activity and the establishment of singleton or multiple pregnancy. If there are two or more fetuses, one should determine whether they have a common placenta or individual placenta, as well as general or separate amniotic sacs. The next step is to measure the size of the fetus, i.e CRL (crown-rump length), which determines the exact duration of pregnancy and determines EDD (estimated date of delivery) if the pregnancy has occurred spontaneously. We believe that during this period of pregnancy, all fetuses are of the same length and by accurately measuring them, according to very strict criteria, we may determine the due date with great precision. Pregnancies that occurred after in vitro fertilization with the transfer of a fresh embryo, the due date is determined by the in vitro protocol. This is because in spontaneous pregnancy, even in case of very precise menstruation, it is not always known when ovulation and fertilization have exactly occurred. The old method of determining the due date according to Naegele’s formula (LMP - 3 months, + 7 days) is old and gives significant deviations. With a fresh transfer, the day and the fertilization time is clear, so this is the most accurate way to know the exact due date. Transfering frozen embryo is again determined by the in vitro protocol, but the CRL method can also be used. The importance of determining the exact term is not just a whim on the part of doctors but is essential to track the growth of the fetus. Deviations from normal height parameters may indicate inaccuracies in determining the due date, but may be an indicator of many diseases.
Combined screening test aims to detect the most common chromosomal illnesses by calculating the risk based on your age, some factors from your anamnesis, blood tests, and ultrasound markers. Ultrasonic markers include nuchal translucency (fluid behind the fetus’ neck), nasal bone, ductus venosus (blood vessel in the liver of the fetus), tricuspid blood flow (right heart blood flow) and heart rate. All of these markers have strict criteria for their identification and any deviation from these criteria leads to false results.
The next step is to examine the anatomy of the fetus. Between 11 and 14 WOP the embryo has a length of 45 to 84 mm and of course this makes this part of the testings not very easy and has it’s limitations, but an experienced specialist can detect or reject a lot of pathology. You may not believe it, but a high-resolution ultrasound and an examination by a fetal medicine specialist can reject at this stage 83% of the major heart abnormalities. I would like to add that these are complex (large) cardiac anomalies. Keep in mind that up to 30% of all cardiac abnormalities are detected by fetal medicine specialists in the United Kingdom, and up to 50% of them in utero in the large specialist cardiac centers.
Organogenesis (organ formation) is largely completed at this stage, but there are still structures that are still being formed, such as the brain, and we track their development at this stage. Even with such small fetal dimensions, we can visualize the head, brain, eyes, hard palate, heart, spine, stomach, kidney, bladder, limbs, placenta and amniotic fluid, as well as discover or reject anomalies in all these structures.
After the examination, you should have the results. It is important to understand that a combined screening test is not a diagnostic method but a screening method. I.e. we will give you as a result about the possibility your baby be born with Down, Patau, or Edwards syndromes. Combined screening test, which is performed by a certified fetal medicine specialist, (you can check if your doctor is certified by FMF London on the following website https://fetalmedicine.org ) can detect between 90-95% of the fetuses affected by Down Syndrome. For several years, there has been a new screening method for detecting Down, Patau, Edwards syndromes and some DNA anomalies by isolating fetus DNA from the mother’s blood. The method is 99.2% reliable, safe and easy to implement. Of course, I personally would advise you to consult with a fetal medicine specialist before doing this test and after you get the results for several reasons. Keep in mind that this blood test detects isolated counts of syndromes, and there are many other conditions which can not be detected. Interpreting the result of the free cell DNA test should be based on combined screening test by a specialist who has the knowledge about it.
Biochemical screening is based on blood sampling and the study of hormone (free bHCG) and protein (PAPP-A) only produced during pregnancy. There is no scientific data on this method for its accuracy. When biochemical screening is combined with other factors, it attains certain meaning. It has been found that using only maternal age (MB) can detect up to 30% of the fetuses with Down syndrome; combining MB + biochemical serum (free bHCG, estradiol, Inhibin A, alpha-feto protein) between 15 and 18 weeks of pregnancy (WOP) increases the detection to 50-70%; MB + nuchal translucency (the fluid behind the fetus’ neck in 11-14 WOP) increases to 70-80%; MB + nuchal translucency** + biochemical serum (free bHCG and PAPP-A) in 11-14 WOP increases detection to 85-90%; MB + nuchal translucency** + nasal bone** of the fetus in 11-14 WOP increases detection to 90% and MB + nuchal translucency** + nasal bone** + biochemical serum (free bHCG and PAPP-A) of the fetus in 11-14 WOP increases the detection to 95%. The latter method is called combined screening test. As with any screening, here I have false positive results at 5%. This means that of all women who are being screened, 5% of them will get positive results without their fetuses being affected.
* The text is borrowed from ‘The 11–13+6 weeks scan’ Prof. Kypros Nicolaides
** ultrasonic markers for detection of chromosomal abnormalities – nuchal translucency, nasal bone, tricuspid regurgitation, blood flow in ductus venosus, heart rate
If, for any reason, a combined screening test between the 11th and 14th WOP is missed, a later biochemical screening may be performed. Between the 15th and the 18th week of pregnancy, blood sampling for biochemical serum testing (free bHCG, estradiol, Inhibin A, alpha-feto protein) as well as an ultrasound scan to establish the pregnancy due date can be performed. The credibility of the method is up to 50-70% with a high percentage of false positive results.
Methods for detecting 100% chromosomal and DNA abnormalities are chorionic villus sampling and amniocentesis. These are invasive procedures that involve the risk of miscarriage or premature birth, depending on how long they are performed. Once again, the discussion of the risk of abortion as a result of these examinations is coming back to the agenda. For the moment, we can say that the risk is 1% or 1 in 100 manipulations. A risk of 0.2% or 1 in 500 is mentioned, but many factors such as specialist experience, the risk of abnormalities in the fetus, etc. should not be forgotten.
Yet you are pregnant, enjoy your pregnancy! Take care of yourself and pay attention to you and your loved ones. I’ll open a bracket again and warn you about weight gain during pregnancy - according to the latest research, women who put on too much weight raise the risk of preeclampsia. For this, eat mindfully, move and remember that pregnancy is a physiological process, not a disease.