Prenatal Diagnosis

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Prenatal Diagnosis

• Learning outcomes
• At the end of this lecture you should be able to
• Discuss the indications or reasons for undergoing
  prenatal diagnosis.
• Describe the main types of prenatal diagnosis
  test and what they demonstrate.
• Discuss the meaning of the test results in terms
  of human disorders.

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WHY?
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Goals of PreND

• Informed choice for at risk parents
• Reassurance, reduce anxiety for high-risk
• groups
• To allow high risk families to initiate
• pregnancy
• Appropriate management of pregnancy,
• delivery and postnatal care. Psychological
• preparation.
• Prenatal treatment of affected fetus

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Invasive vs. non-invasive methods
Non-invasive PreND Methods Presenting no
significant risk to the health of mother or
baby. Maternal serum alpha-fetoprotein Maternal
serum screen Ultrasonogrpahy Isolation of
foetal cells from maternal blood
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Maternal Serum Screening Between 15 - 22 weeks For
Alpha fetoprotein (AFP) - yolk sac, GI tract and
liver of foetus Human chorionic gonadotrophin
(hCG) - syncytiotrophoblast (the outer layer of
the chorionic villi, bathes directly in maternal
blood, hCG secreted directly to maternal
blood) Unconjugated estriol - foetal adrenal
gland and liver. PREDICTS RISK OF SPECIFIC
FOETAL ABNORMALITIES
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High levels of AFP in maternal blood are
associated with Neural Tube Defects.
anencephaly
Neural tube closes between 3 and 4 weeks of
development.
www.uoguelph.ca/zoology/devobio/miller
400 micrograms of folic acid every day lowers the
risk of NTDs by 50 to 70!
encephalocele
medgen.genetics.utah.edu/photographs/diseases
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Triple Test Interpretation of Results
NTD anencephaly, spina bifada and
encephalocele.
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Results are not diagnostic, only predict
increased risk.
False positive and false negative results
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Isolation of foetal cells from maternal blood
Foetal cells are found in the maternal
circulation as well as cell-free DNA. 900-3,000
cells reported from 6 ml blood sample. Often
degenerating Low number and degenerating state
- not a reliable clinical method. Not a
frequently used detection method.
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Ultrasonography
High resolution, real-time scanning for foetal
assessment and detection of morphological
abnormalities.
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2 Dimensional Ultrasound

• Very high frequency sound waves
• Emitted from a transducer in contact with
• abdomen or with specially designed
  transvaginal probe
• Beams scan the fetus and are refelcted back
  onto
• the same transducer.
• The reflected information is recomposed into
  
• picture on monitor screen.

Abdominal transducer
Used in very early pregnancy
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4D
3D
(Dynamic 3D)
Special probes and software used to accumulate
and render a 3D image.
http//www.medison.co.kr/korean/ig/ig_01e.asp
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Main use of ultrasonography

• Diagnosis and confirmation of pregnancy.
• Viability of foetus, especially when vaginal
  bleeding present.
• Determination of gestational age and assessment
  of foetal size.
• Diagnosis of foetal malformations.
• Multiple pregnancies.
• Hydramnios (excessive) and oligohydramnios
  (decreased)
• amniotic fluid.
• 7. Assessement of the foetus, eg. positioning,
  movements, breathing, heartbeat, intrauterine
  death .

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Ultrasound scans are believed to be very safe and
are therefore widely used as a routine method for
monitoring pregnancy. The pattern and frequency
of use varies depending on financial resources
and local policy. Three routine and frequent
points in pregnancy for UltraSound use 1. Early
(7-12 weeks) Confirm, exclude ectopic prenancy,
date. 2. 18-20 weeks Screen for
congenital malformations, exclude multiple
pregnancies and verify dates and growth. 3.
Around 35 weeks Foetal and placental position
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• Use of ultrasound scanning
• for identifying foetal abnormalities
• Visualisation method for implementation of
  invasive techniques such as amniocentesis and
  chorionic villae sampling.
• (Pre)-Screening method for soft markers for
  chromosomal abnormalities.
• Absence of fetal nasal bone
• Nuchal translucency
• 3. At risk families for single gene defects or
  multi-factorial genetic disease, where
  biochemical tests do not exist.
• 4. Determination of foetal sex from 15 weeks,
  pre-screen to determine need for invasive tests.
• 
  Workshop topic!

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The appearance of skin edema is very graphic
with a shaggy lion's mane that begins at the top
of the head and extends a variable level down the
back and around the sides. The texture is lumpy
in those cases due to failure (or delay) of the
lymphatic channels to develop in skin with the
resultant accumulation of large pockets of fluid
within and beneath the skin. This finding is
associated with a range of chromosome problems
including but not limited to Down's Syndrome.
http//www.amnionet.com/contents.htm
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Maternal Serum Screening
Ultrasound
Predictive NOT Diagnostic
Routine Population Screen
Targeted Investigation At Risk
Does the risk justify use of invasive methods?
Invasive Methods
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Indications for Invasive Prenatal Diagnosis
i.e. when the risk of a severely affected child
may out weigh inherent risk from the screening
method.
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• Routine ultrasound suggests abnormality.
• Advanced maternal age - known increase risk
  of Trisomy 21
• Trisomy 18.
• Previous affected child with chromosomal
  abnormality.
• Structural chromosome abnormality in either
  parent.
• Family history of genetic disorder where DNA
  or biochemical test is available.
• Family history of an X linked disorder (with
  no specific
• prenatal test).
• Family history of neural tube defect.

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Invasive methods i.e. invade the body Are
associated with RISK to foetus
Invasive PreND Methods Amniocentesis (0.5-1.0
incr. risk of pregnancy loss) Chorionic
villus sampling Cordocentesis - direct
sampling of foetal blood from cord
Preimplantation genetic diagnosis - IVF
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Amniocentesis is the most commonly used invasive
prenatal diagnostic test. Samples of amniotic
fluid are removed during an ultrasound scan _at_
15-16 weeks. Cells from the foetus are isolated
from the fluid and used for DNA analysis,
biochemical screening and/or karyotyping. Fluid
also analysed eg. AFP.
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Transcervical or Transabdominal CVS 10-12 weeks
Risk of miscarriage about 1
Chorionic Villi Sampling also known as Chorionic
villus biopsy or CVS is a procedure for sampling
the chorion, one of the membranes that form
around the embryo in early stages of pregnancy,
before the placenta forms.
www.loveyrusso.com/ cvs.htm