C.Anandakumar
                                                                                    Director
                           Antenatal Diagnostic Centre and Well Women Clinic
                                                 Camden Medical Centre Singapore
                                 Chairman Ultrasound Subcommittee (AOFOG).

1) Nuchal Translucency (NT Scan)

Nuchal Translucency (NT Scan) is the area just under the skin at the back of the fetal neck, which can be measured at 10-14weeks gestation. It is the black area lying between the subcutaneous fascia and skin. It increases with gestational age, and great care must be taken to measure it correctly to avoid measurement errors. The optimal time to perform an (NT Scan), if High -End Machines with expertise to visualize 90
per cent of internal organs including the heart is available, would be around 13.0-14.0 weeks.If this scan at 13-14weeks is normal, then the risk of Chromosomal abnormalities (Eg.Downs Syndrome), would be decreased by 85 percent. Hence even at 40 year of age if the Nuchal translucency scan together with Genetic scan at 14weeks are both normal the risk of the fetus to be chromosomally abnormal (Downs syndrome) would be less than 0.1 percent. With such low risk, it would not warrant, performing amniocentesis routinely, if a women is above 35years of age, as, the fetal loss rate with amniocentesis in best of hands is around 0.2-0.4percent.High-End machines and the expertise are not available to assess internal organs accurately, then just perform the NT Scan at around 11-12wks.

• Increased NT Thickness (Greater than 2.5mm) is associated with;
  Chromosomal aneuploidy, including trisomies21 (Downs Syndrome), 18,13 and triploidy and Turners syndrome (45XO). Identifies 77- 82 percent of Downs fetuses with a false positive rate of 5-8 percent.
  
  
• Among Karyotypically normal fetuses with thickened NT,
  there is a greater risk for;
  Birth defects, including cardiovascular (ASD, VSD), pulmonary (Diaphragmatic hernia), renal and anterior abdominal wall (Omphalocoele) defects.
  
  
• Genetic Syndromes;
  Arthrogryposis
  Noonan's syndrome
  Smith-Lemli-Opitz syndrome
  Stickler syndrome
  Jarco-Levine syndrome
  Miller-Dieker syndrome
  Amnion distruption sequence
  Skeletal Dysplasia.

Nuchal Translucency and Early Genetic scan at 13.0-14.0 weeks is crucial for the following reasons;

• To Accurately date the pregnancy.
  Even in women who are sure of the first day of the Last Menstrual Period, the gestational age of the fetus can be wrong by 3-4weeks in 15 percent of cases. With ultrasound at this early stage we can accurately age the pregnancy, with an accuracy of plus or minus 5-10days.
  
  
• To diagnose multiple pregnancy and there chorionicity early.
  Approximately 2 percent of natural conceptions and 10 percent of assisted conceptions results in a multiple pregnancy.
  
  
• To diagnose early pregnancy failure.
  This occurs in 3 percent of pregnancies at early stages.
  
  
• Structural Malformations
  This occurs unfortunately in 3-4 percent of pregnancies.40-50 percent of Perinatal mortality and infant mortality is due to congenital malformations and 85-90 percent of these malformations are structural malformations.85-90 percent of these lethal structural malformations can be excluded with confidence between 13.0-14.0 weeks.
  By doing so, the risk of chromosomal (Downs syndrome) abnormalities can also be decreased by 85 percent at this early stage, as majority of them have structural defects.

2) Ultrasound at 22-23weeks.

All women should be subjected to a second scan between 22-23weeks,as all organs of the fetus are formed and can be clearly visualized by ultrasound. The pickup rate of lethal structural malformations at this stage is well above 95 percent in expert's hands, with the ideal ultrasound machines. If the 14 and 22 weeks scans are both normal, the chances of the women loosing that pregnancy in a developed country would a around 4.9 per thousand.

In addition to visualizing the fetus, the uterine blood flow should be assessed with the Doppler waveform analysis and the cervical length and the internal os of the cervix should be measured. If the uterine blood flow and the cervical assessment are both normal, then it is very unlikely for women to have any major complications in pregnancy (Egg; EarlyPreterm labour, Pre-Eclempsia, Growth Restricted fetus).

3) Assessment of Fetal well-being

60 percent of fetal demise prior to birth is due to Chronic Hypoxia (lack of Oxygen); this is always preceded by growth restriction. The ultrasound is the most accurate modality to assess the fetal growth. The single most accurate parameter to measure is the fetal abdominal circumference, which is done once every 3-4wks after 28weeks, in high-risk pregnancies.


Once the fetus, which is not growing well, is identified, its well being is assessed, with ultrasound by performing Liquor, Biophysical Profile and Doppler assessments.

4) Fetal Echocardiography;

40 percent of Perinatal and Infant Mortality is due to major cardiac malformations. Unfortunately only 11 percent of major cardiac malformations are diagnosed prenataly. With the introduction of routine Fetal Echocardiography Cardiac malformations have become the commonest structural malformation diagnosed prior to birth.

The earliest gestation to visualize the fetal heart clearly, is between 13.0-14.0 weeks and 95 percent of the time can be done by performing an abdominal ultrasound with the high-end machines.85 percent of Major cardiac defects can be excluded by 14weeks.The optimal time to perform fetal echocardiography is around 23wks and at this stage over 95 percent of major cardiac defects can be excluded. The most important prerequisite is highly skilled operator.

5) Genetic Scan

This involves in addition to looking at internal organs of the fetus, it also involves looking


                                                


                                              


                                         

                                             

at the surface structures, looking for markers of chromosomal abnormalities (Downs syndrome). Majority of chromosomal abnormalities are reflected on the Eyes, Ears,Nasal Bone, Tongue and the Fingers. The Genetic Scan should be done is between 13-14weeks and repeated at 22- 23weeks.If both scans are normal, then Genetic Amniocentesis is not warranted except in women over the age of 45,as only then the risk of having a Downs syndrome baby inspite of a normal Genetic scan is equal to the risk of Fetal Loss following Amniocenetsis. (Vintzileos etal 1995).

6) Amniocentesis

The procedure has existed from 1929,but for prenatal diagnosis of chromosomal abnormalities (Downs syndrome) it was first used in 1968.Since early 1980 the extraction of the Amniotic fluid around the fetus is done by introducing a needle through the maternal abdomen into the uterus under ultrasound guidance. This is a simple outpatient procedure and takes only around two to three minutes and does not require any local anesthesia. It can be from14weeks up to 22wks. Well-established laboratories can release the results within 10to 12days of the procedure. The common chromosomal aberrations such as Trisomies 21,13,18 and 45XO can be excluded within 24hrs by performing the FISH or PCR Techniques. All chromosomal abnormalities can be excluded with Amniocentesis with a false negative rate of 1 in 400,000 and a false positive rate of 0.06 percent The complication rate (Fetal Loss) is around 0.2-0.4 percent as long the Canadian MRC recommendation for the operator is adhered to, otherwise the fetal loss rate is around 2-3 percent.

7) Chorionic villus Sampling (CVS)

CVS involves the examination of chorionic Villi (Placental Tissue).
The chorionic villus is sampled either via the vagina, or through the maternal abdomen, both under ultrasound guidance. For the abdominal route local anesthesia is used as the needle used is thicker than that used for amniocentesis. The procedure like the Amniocentesis lasts about 2-3minutes.The preliminary result is usually ready by 3days and the final results within 10days.The false negative rate is around 1 in 100,000 and the false positive rate is around 2 percent for karyotyping. The complication rate (Fetal Loss) is highly dependent on the expertise, and in experts hands rate it is 1.2 percent higher than that of Amniocentesis (1.5%). Amniocentesis should be the invasive test of choice for prenatal diagnosis of chromosomal abnormalities (Downs syndrome) rather than CVS, as the complication rates are lower and it is a more reliable test.

As for prenatal diagnosis of Genetic diseases (Eg Thalasaemia, Duchene's Muscular Dystrophy), CVS is superior to Amniocentesis, hence CVS as a procedure should reserve for prenatal diagnosis of Genetic diseases rather than for chromosomal abnormalities.

8) Fetal Blood Sampling

This procedure involves obtaining fetal blood, either from the umbilical cord or directly from one the fetal vessels (Left portal vein). It is also done under ultrasound guidance and requires special skills. The complication rate (Fetal loss is around 1.2 percent. The results are ready within 48hours.

9) Fetal Tissue Biopsy

This procedure is also done under ultrasound guidance for prenatal diagnosis of certain lethal congenital skin conditions.

10) Intrauterine Fetal therapy

With the availability of the ultrasound, certain conditions can be treated successfully, prior to birth inutero (Hydrops Fetalis, Hydronephrosis).

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