 Let us go straight to the topic. Any woman who is pregnant is at risk of having a fetus with aneuploidy. And this risk is called as a background risk or a priori risk. And according to the age, we have tables which tell at a particular age, what is the risk for a woman to have a child with a fetus affected with trisomy 21. Now the question is, can we detect and diagnose genetic abnormalities most of the times? The answer would be yes, but with a combination of multiple parameters, especially three methods for detecting aneuploidy. One is by the use of serum biochemistry, other by use of sonography, and the third by use of DNA testing. When we talk about serum biochemistry, we have the double marker test in the first trimester, triple quadruple and pentascreening in the second trimester. So in the first trimester, sonography plays an important role in giving us certain clues telling that this fetus could be at risk for aneuploidy or other genetic abnormalities. We will quickly go through the markers of the first trimester, aneuploidy. This is normal nuclear translucency, and this is increased nuclear translucency. This is normal nasal bone demonstration, and this is a unnausified nasal bone in the first trimester and in the second trimester. This is a normal tricuspid waveform with E and A waves without regurgitation, and this is a large pan systolic waveform from a tricuspid valve with regurgitation. This is a normal ductus venous waveform with a forward flow during the atrial contraction, that is the A wave is always forward, and this is an abnormal ductus venous showing a reversed A wave or an A wave reversal, which is a marker for aneuploidy. So these are the common four aneuploidy markers, which give us an indication that this fetus could be at a higher risk for aneuploidy. So a combination of the maternal age and any one of these markers or multiple markers, along with the maternal serum, beta-HCG and PAPA will give us a risk for aneuploidy. In the first trimester, we have to use certain softwares for arriving at the risk, and these softwares will ask you for the patient details, the maternal age, maternal weight, maternal height, background conditions of the mother, like diabetes, SLE, lukers, etc. Also details about previous gestations, and the input page for the present details would have the CRL, the details about the nucleotranslucency, the thickness, the nasal bone presence or absence, the tricuspid valve regurgitation, doctor's venous regurgitation, the uterine dopplers and their PIs, and using a combination of the maternal age, maternal race, maternal weight, height, the CRL, the nucleotranslucency, and also if we have the blood sample of the patient by a combination of beta-HCG, PAPA, mumps, we can arrive at a risk in the end of the first trimester. So at the end of the first trimester, the maternal a priori risk is converted into a combination of ultrasound findings and the maternal serum markers, which is called as the combined risk or the first trimester risk. So at the end of the first trimester, we will have to assign a risk for the mother. So when the risk for the fetus comes as less than 1 in 1000, we call it as low risk and no more testing is required. We can proceed to an 18-week stifa scan. When the risk comes as a high risk, which is more than 1 in 250, then we need to counsel for a Corian Willis sampling or we need to ask for a 16-week anomaly scan for a stifa scan followed by an amniocentesis. When the patient has a risk between 1 in 250 to 1 in 1000, then this is called as intermediate risk. In cases of intermediate risk, we have to advise for a 16-week genetic sonogram or an NIPT and then take a call at the 17th week, whether to go for an invasive testing or not. So this is how a risk is assigned at the end of first trimester. So the maternal age-related risk is converted to a first trimester risk at the end of first trimester. We move on to the second trimester, where we have the chance to do a triple marker test or a quadruple marker test and then we have the ultrasound which can be called as a genetic sonogram or a tifa scan. So when we do our tifa scan or genetic sonogram, we have certain findings which are called as soft markers or fetal aneuploidy. So these are usually seen between the 18 and 22 weeks. These are not abnormalities but indicate an underlying aneuploidy or a non-chromosomal abnormality. So we will quickly look at the second trimester aneuploidy markers. The first marker is the nasal bone which can be absent and which will be called as an unossified nasal bone. The second would be an enlargement of the cerebral lateral ventricle which would be called as ventricleomegaly when it exceeds 10 millimeters in the axial plane in a medialateral direction. Third is the nucle fold which is a measurement of the nucle fold thickness in the axial plane. Fourth is an aberrant right subclavian artery which arises as a last branch from the iota and moves towards the right shoulder close to the spine in the posterior mediastina. Then we have the echogenic bowel which is an increased echogenicity of the bowel which is equal to or more than the bone. And then we have pelvic tessia which is an increase in the anterior posterior dimension of the renal pelvis measuring more than 4 millimeters. Then we have echogenic intracardiac foci which are echogenic nodular structures on the papillary muscles of either or one cardiac ventricle. Then we have single umbilical artery which shows a two vessel cord. And we have coroid plexuses which are cystic structures in the coroid plexus. And we have enlarged cisterna magna where it measures more than 10 millimeters. A lot of analysis has been done on these second trimester markers and one of the best compilation of all these analysis is by Agatha Cleos where which is an article which says meta-analysis of second trimester markers. So this second trimester markers from almost 15 to 20 studies of these markers have been collated. And then the findings for the increased findings for echogenic focus, ventricleomegaly, increased nucleophore, etc. All the markers have been collated and they have arrived at detection rates, false positive rate, likelihood ratio, positive likelihood ratio, negative likelihood ratio and likelihood ratio when there is an isolated marker. I would spend a minute more here for us to understand what this means. In the second trimester the aneuploidy markers are unosified nasal bone, aberrant rights of cleven artery, ventricleomegaly, increased nucleophore, echogenic bowel, pelvic tecia, echogenic intracardiac focus, short humerus, short femur. So each of these markers indicate the presence of aneuploidy by themselves or by combination. And each of these markers according to their strengths of, according to their strengths of identifying aneuploidy have a positive likelihood ratio and a negative likelihood ratio. And when these markers are isolated then we have a single likelihood ratio. Now likelihood ratios talks about the strengths of these markers and their ability to identify aneuploidy. And if you see that the likelihood ratios are arranged in their descending order with the nasal bone having 6.5 as the highest, ARSA, ventricleomegaly and increased nucleophore having approximately 3.8, echogenic bowel having 1.6 and pelvic tecia, echogenic focus, short humerus, short femur having 1. So these are arranged in their descending order and you can see we can group them into four groups. The first group is unosified nasal bone with 6.5 as a likelihood ratio. The second group which has ARSA, ventricleomegaly and increased NF, all of them in the upper part of the body having likelihood ratio of half of 6.5 approximately which is 3.8. The third group is echogenic bowel which has a likelihood ratio of half of it 1.6. And the last group with all the four markers with the likelihood ratio one. So the numbers to be remembered are 6.5, 3.8, 1.6, 1.0, approximately half of each. So this is how we need to group these likelihood ratios into four groups and remember the numbers. Now, let us see how we can do risk assessment so that we can do genetic counseling. When the patient comes, she comes with an age risk. Then we convert the age risk using a first trimester scan and give a scan risk. Then we send them for a double marker test and combine the first trimester scan report and arrive at a first trimester risk. At the end of first trimester risk, we have a first trimester risk. Then if we do a triple marker or quadruple marker and a TFA scan or genetic sonogram in the second trimester, we can arrive at a sequential risk. So using these results, we can come to a final risk after our genetic sonogram at the 18th week. So we can see that the performance increases as we add on the test and by using a sequential scan, we can detect 95 percent of aneuploidis.