Ultrasound Guided ‘Invasive Prenatal Diagnostic Techniques’ Simplified Raju R Sahetya
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IntroductionCHAPTER 1

Many clinical and historical factors can lead to the indications for prenatal diagnosis. Regardless of the specific indication, invasive prenatal testing should be performed with detailed genetic counseling before the procedure. Such counseling is needed to obtain critical information from the patient to assess properly the fetal risk; to review personal and family histories that may have an impact on this risk; to describe the risks, benefits, and limitations of the procedure(s) to be offered; and provide empathetic support to women who are considering such testing.
Genetic counseling should be provided in a nondirective fashion, thus providing women with the necessary information (written and verbal) to arrive at prenatal diagnostic decisions but without coercing the woman, either overtly or covertly, into making a particular decision.
Antenatal screening identifies those pregnancies at ‘high-risk’ of fetal abnormalities, such as aneuploidy, malformation, intrauterine infections, fetal anemia, but the diagnosis can only be confirmed or ruled out by direct examination of fetal tissue or blood.
Until recently, fetal cells could only be obtained by an invasive procedure: Amniocentesis, Chorionic villous sampling or Cordocentesis. While fetal cells can now be extracted from the maternal circulation and analyzed for specific indications, this technique is not widely available and its clinical use remains limited.
This book Ultrasound Guided ‘Invasive Prenatal Diagnostic Techniques’ Simplified will focus on training the reader in invasive prenatal diagnostic techniques.
All pregnant women should be made aware that both diagnostic and screening tests are available for detection of aneuploidy in pregnancy. The majority of women will choose to have screening 2tests, as this carries no innate risk to her and the pregnancy. She will not wish to discuss diagnostic testing.
For some, the consequences of having a child affected by aneuploidy are of such enormity, that no screening test will give sufficient reassurance. If such concerns are expressed, the mother must have ample opportunity to discuss the full range of diagnostic tests that are available. It is for the women to decide which risk is most acceptable.
The women at increased risk of aneuploidy in pregnancy must be made aware of the risks they are at, and all about the invasive diagnostic techniques. They can then balance the risk of a problem in the pregnancy against the risk of a procedure and make an informed decision on whether or not to proceed with invasive diagnostic technique.
Women who deserve to undergo invasive prenatal diagnostic techniques are those:
  1. Women who are at screen ‘high-risk’
  2. Women or their families with ‘specific chromosome abnormality’
  3. Ultrasound ‘defect in fetus identified’.
Women Who are at Screen ‘High-Risk’
A proportion of pregnancies screened for aneuploidy will be classed as ‘high-risk’. These need ample opportunity to discuss their individual risk calculation and the diagnostic tests appropriate for their gestational age to rule out of confirm the aneuploidy.
Women or their Families with ‘Specific Chromosome Abnormality’
Women or their partners, who carry a balanced chromosome inversion or translocation and are themselves unaffected, are at increased risk of chromosomal abnormities in pregnancy. The fetal medicine team should assess these couples to ensure that the correct risk is calculated, the possible outcomes are understood and the correct diagnostic test is offered to them.
Ultrasound ‘Defect in Fetus Identified’
Structural abnormalities in a fetus, such as duodenal atresia, congenital diaphragmatic hernia, cardiac abnormalities, cystic hygroma, holoprosencephaly (HPE), are strongly associated with 3specific chromosome abnormalities. The risks of aneuploidy will vary, depending on the abnormality identified.
The entire above mentioned patient, high risk for chromosomal abnormality, should undergo invasive prenatal diagnostic technique to visualize chromosomes and to reach an accurate diagnosis (Figs. 1.1A and B).
In India ‘Invasive Prenatal Diagnostic Techniques’ can be conducted at a center that is registered under the Pre-Conception and Prenatal Diagnostic Techniques (PCPNDT) Act 1994, as Ultrasound and Genetic Clinic. The person performing the procedures should be a registered medical practitioner and should be trained and experienced operator.
Women should be given an outline of all the procedures available, the timing of each test and the pregnancy risks associated with each technique, to make an informed decision about prenatal invasive testing. Ideally, these discussions should be supplemented with explanatory booklets that outline the pertinent points and salient statistics. Informed, written consent should be obtained before any testing is performed.
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Figs. 1.1A and B: Seeing chromosomes for diagnosis.
Here is what the International Society for Prenatal Diagnosis (ISPD) recognizes as the optimal prenatal testing protocol for Down syndrome (Fig. 1.2):
  1. Nuchal translucency (NT) test at 11–13 weeks combined with serum markers.
    [ISPD states that 12 weeks is the optimal time for NT testing. ISPD further recognizes that NT is a useful indicator beyond just testing for Down syndrome, e.g. cardiac defects—and says it should be made available separate-and-apart from screening and diagnostic testing for Down syndrome].
  2. Offer first trimester (1T) ultrasound (UT) for other soft markers if provider has been validated to perform such testing, e.g. absence of fetal nose bone, tricuspid regurgitation.
  3. Contingent test: if Step 1 returns borderline risks, then have Step 2 at a specialist center.
  4. Quad test if patient first presents at or after 14 weeks. Though Quad test can be done between 14 and 21 weeks, ISPD recognizes that 15–19 weeks is optimal for also open neural tube screening.
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    Fig. 1.2: ISPD optimal prenatal testing protocol for Down syndrome.
  5. 5Combine options Step 1 and Step 4 in stepwise or contingent testing provided all screening test data is included in final risk assessment. Only make available integrated screening when chorionic villous sampling (CVS) is not available.
    [Stepwise/contingent is where Step 1 results are reported and then an offer is made to conduct second trimester (2T) quad testing where the results will then be combined; integrated is where Step 1 is performed but results are not reported until 2T test results are returned. Because Integrated has the highest detection rate, American Congress of Obstetricians and Gynaecologists (ACOG) recommends that ‘ideally’ it should be offered, but it has been criticized on the basis of disrespecting a mother's right to know because it does not report Step 1 results].
  6. Contingent 2T UT to modify risks for Steps 1, 4, or 5 results; i.e. like Step 3, if Steps 1, 4, or 5 return borderline risks, have a second trimester ‘anomaly scan’ performed at 18–23 weeks at a validated center.
    [ISPD further notes that 2T UT, on its own, is ‘not a very effective screening test’].
  7. Noninvasive Prenatal Screening (NIPS) for high risk women.
    [‘High risk’ is a result from Steps 1 to 6, or based on maternal age, UT abnormality suggestive of Down syndrome, family history with Down syndrome/aneuploidy, history of previous pregnancy with Down syndrome/aneuploidy].
Step 7 of the ISPD statement is consistent with the previously released guidelines from ACOG and National Society of Genetic Counsellors (NSGC), i.e. NIPS should be offered only to high-risk patients. ISPD makes clear that maternal age alone is insufficient to assess fetal Down syndrome risk other than advanced maternal age being an indicator of high risk for purposes of offering NIPS. Like every other professional guideline, ISPD states that NIPS is not a replacement for amniocentesis or CVS, and only amnio or CVS can provide a definitive diagnosis of Down syndrome.