Dr Ogunwale A.

N
UFM UNIT
 OUTLINE
Introduction
Objective of prenatal diagnosis
Indications for prenatal diagnosis
Techniques of Prenatal diagnosis
Brief Discussions
Current trends
Beyond Prenatal diagnosis
Conclusion
• 30 years ago, fetal medicine did not exist; the
fetus, concealed in the uterus, was a
passenger, not a patient.

• During the last three decades, owing to the

development of cardiotocography, ultrasound
and Doppler imaging, sampling techniques,
biochemistry, genetics and molecular biology,
considerable knowledge has been
accumulated, allowing a more precise
definition of fetal physiology, anomalies and
diseases.
The fetus has thus
become a patient, that
we can diagnose,
monitor and treat.
AIM
The purpose of prenatal
diagnosis is not simply to
detect abnormalities in fetal life
and allow termination. Rather,
it...
• Provides a range of informed choices to the
couples at risk of having a child with
abnormality
• Provides reassurance and reduce anxiety,
especially among high-risk groups
• Allows couples at high risk to know that the
presence or absence of the disorder could be
confirmed by testing
• Allow the couples the option of appropriate
management (psychological,
pregnancy/delivery, postnatal)
• To enable prenatal treatment of the affected
foetus
Indications for prenatal diagnosis:
advanced maternal age (esp >35)
previous child with a chromosomal abnormality
family history of a chromosome abnormality
family history of single gene disorder e.g sickle cell
trait
family history of a neural tube defect
family history of other congenital structural
abnormalities
abnormalities identified in pregnancy
other high risk factors (consanguinity, poor obst,
history, maternal illnesses
Techniques of prenatal diagnosis
A number of well-studied techniques
are used for prenatal diagnosis. For
many of these techniques, the
accuracy, reliability, and safety of the
procedures are positively correlated
with operator experience.
Non Invasive techniques
Ultrasonography
Fetal Echocardiography
Fetal MRI
Fetal Radiography
Minimally Invasive
Maternal serum
markers:AFP,hCG,uE3,Inhibin A etc
(Essentially screening tests)
Isolation of fetal cells from maternal
circulation
Techniques of prenatal diagnosis
Invasive testing techniques:
Amniocentesis
Chorionic villus sampling
Cordocentesis
Fetal tissue sampling
Fetal skin biopsy
Other organ biopsies, including
muscle and liver biopsy
others
Fetoscopy
Embryoscopy
Preimplatation genetic diagnosis
Preimplantation biopsy of blastocysts obtained
during in vitro fertilization
Cytogenetic investigations
Detection of chromosomal aberrations
Fluorescent in situ hybridization
Polymerase chain reaction
Molecular genetic techniques
Linkage analysis using microsatellite
markers
Restriction fragment length
polymorphisms (RFLPs)
Single nucleotide polymorphisms (SNPs)
DNA chip
Dynamic allele-specific
hybridization(DASH)
Non invasive tests
Ultrasonography
Diagnosis of fetal malformations eg
hydrocephalus, anencephaly, myelomeningocoe,
achondroplasia and other dwarfism, spina bifida,
exomphalos, Gastroschisis, duodenal atresia and fetal
hydrops. With more recent equipment, conditions
such as cleft lips/ palate and congenital cardiac
abnormalities are more readily diagnosed and at an
earlier gestational age.
First trimester ultrasonic 'soft' markers for
chromosomal abnormalities such as the
absence of fetal nasal bone, an increased
fetal nuchal translucency (the area at the
back of the neck) are now in common use
to enable detection of Down syndrome
fetuses.
Fetal Echocardiography
Performed transvaginally or transabdominally
Can be performed from 15 weeks
Identification of an extracardiac malformation on
routine ultrasound
Suspected chromosome abnormality associated with
heart defects
Exposure to potentially teratogenic agents etc
Family history of congenital heart defects
Fetal MRI
Effective in diagnosing soft tissue anomalies
Has been used in the diagnosis of Polymicrogyria
Fetal Radiography
fetal skeleton can be visualized by radiography from
10 weeks'.
used for the diagnosis of inherited skeletal dysplasias,
esp osteochondrodysplasia, in the second and third
trimesters.
Because of the dangers of radiography to the fetus,
this technique rarely is used.
Minimally invasive techniques:
BIOCHEMICAL TESTING TECHNIQUES
Essentially screening techniques
Used in the screening for fetuses with Chromosomal
abnormalities
Different maternal serum markers are used in 1st and
2nd trimesters
Bhcg, PAPP-A, are used to screen for chromosomal
defects in tandem with
Ultrasonography for nuchal transluscency and
Maternal age
In the 2nd trimester:
Serum Alpha fetoprotein
Bhcg, uE3, Inhibin A
QUAD test
Penta test
These have further been organised into testing
modalities:
Full integrated screening tests .87% DS
The Serum Integrated Screening Test (1 st and 2nd
trimester tests without NT).85% DS
The sequential screen (Women with high
calculated risks in first trimester are allowed to
have CVS. Others will go on to have the QUAD
test 86% DS

* DS- Sensitivity to Down Syndrome Detection

TRIPLE TEST
AFP UE3 HCG

Down’s Dec. Dec. Inc.

syn.
Trisomy Dec. Dec. Dec.
18
SB, Inc n/a n/a
Omph
gastrosch
Invasive methods of prenatal diagnosis
Amniocentesis
Aspiration of 10-20 ml of amniotic fluid
through the abdominal wall under ultrasound
guidance around the 16th weeks of gestation.
In about 14 days there will be enough cells for
chromosome analysis for biochemical or DNA
studies .Sometimes a longer time is needed to
grow more cells.

Couples should be informed of the risk of

abortions (0,5-1%)
CHORIONIC VILLUS SAMPLING
Enables diagnosis in first trimester (10-14 weeks
of gest.) under ultrasound guidance by trans-
cervical or trans-abdominal aspiration of
chorionic villi

These are fetal cells derived from the outer

layer of the developing trophoblast.

Allows for diagnosis in first trimester. In

addition the villi also provides a rich source of
DNA

Disadvantage is in higher risk of abortion (2-

3%) and limb abnormalities.
FETAL BLOOD SAMPLING
POSSIBLE FROM 18 WKS

• US-GUIDED PUNCTURE OF:

1. UMBILICAL VEIN IN THE CORD( cordocentesis) PUBS
• PLACENTAL INSERTION
• UMBILICAL INSERTION
• FREE LOOP
2. INTRA-HEPATIC PORTION OF THE UMBILICAL VEIN
3. CARDIAC CHAMBERS
Blood taken for chromosomal analysis, genetic
diagnosis, hematological disorders
Cordocentesis
Fetoscopy
Visualisation of foetus by means of endoscope
(its use has limited by modern USS & FBS
techniques
It can be undertaken to diagnose a subtle
structural abnormalities pointing to a serious
diagnosis
Can also be used to obtain fetal samples for
some diagnosis as inherited skin disorders
(epidermolysis bullosa) and some metabolic
disorders in which enzymes are only in specific
organs
Fetoscopy
 CURRENT TRENDS
1.Preimplantation genetic testing screening
A technique used to identify genetic defects in embryos
created through in vitro fertilization (IVF) before
pregnancy.
. Preimplantation genetic diagnosis (PGD) refers
specifically to when one or both genetic parents has a
known genetic abnormality and testing is performed
on an embryo to determine if it also carries a genetic
abnormality.
• In contrast, preimplantation genetic screening (PGS)
refers to techniques where embryos from presumed
chromosomally normal genetic parents are screened
for aneuploidy.
• PGD was developed in the United Kingdom in the
mid 1980s as an alternative to current prenatal
diagnoses. Initially, PGD revolved around
determination of gender as an indirect means of
avoiding an X-linked disorder.
2.Detection of fetal cellular materials in
maternal blood
-The detection of fetal nucleated cells in
maternal blood.
 Isolation of fetal trophoblastic cellular
elements shed into the uterine cavity and
the endocervical canal.
 The analysis of fetal free genetic material
present in maternal plasma.
These new methods have extended the
frontiers of prenatal diagnosis, making
Diagnosis of RhD status,fetal sex
determination, iagnosis autosomal
dominant conditions easier without
resorting to invasive techniques such as
CVS.
 Beyond Prenatal Diagnosis

(1) Do we institute timely medical or

surgical treatment of the condition before
or after birth,
(2) Informed consent and medico-legal
implications ... ‘‘wrongful births’’
 (3)False positives and false negatives
(4).Ethical issues: ‘designer babies’, pre-
implantation genetics
Considering the possibility of false positive
results
Societal pressures .Pro and anti abortion
Absence of equipments to perform in utero
procedures
Need for extensive counselling and multi
disciplinary approach
Conclusion
Prenatal diagnosis is a double edged sword.
It confers an almost unimaginable power
on us-physicians-, and the society. It also
comes with a great cost in ethical and
medico-legal terms.There are difficult
questions ahead, and It will be interesting
to see how we as obstetricians practicing in
an evolving society like ours will negotiate
the inevitably tortuous path ahead.
YOU HAVE BEEN
A WONDERFUL
AUDIENCE.