Faculty of

Medicine
Medical Education-
Damietta
University

Level 1
Semester 1
Module 1B
 Prenatal Diagnosis
By

Almandouh Hussein Bosilah, MD

Assistant prof. of obs/Gyna
 Instructor information
• Contact: ……………..Department.
• Official email: almandohhussen@yahoo.com
• Mobile : 01024253388
• Academic hours:
➢……………day: 00:00-00:00 AM
➢…………...day: 00:00-00:00 AM
 Learning Outcomes
By the end of the lecture, the students will be able to:
1- define teratogens and their effects

2- discuss methods to prevent or decrease the risk of genetic defects

3- identify disease that could be screened and how to screen

4- outline indications for prenatal screening

5- define genetic counselling utility and approach

 Lecture Content
• Definitions
• Case scenario and clinical correlation
• Benefits of prenatal diagnosis
• Indications of prenatal diagnosis
• Methods of prenatal diagnosis
• Invasive
• Non-invasive
 Case scenario and clinical correlation

❖Mrs. Z is 38 years old, married for 12 years and has 3 children the
youngest is 10 years old and discovered to be trisomy 21 ( Down
syndrome ),

❖Now she has unplanned pregnant in the first trimester 8weeks.

She asked for medical advice and how to deal with her pregnancy?
 Definitions

• Prenatal diagnosis is a way to find out if the pregnancy has a

particular inherited or genetic condition.

• It means " Diagnosis before birth

• " Teratogens: a physical , chemical ,infectious agents or maternal ,

paternal conditions that can cause a structural or functional defects in
the developing embryo
 Definitions

• Prenatal screening focuses on finding problems among a large

population with affordable and non-invasive methods.

• Prenatal diagnosis focuses on pursuing additional detailed

information once a particular problem has been found, and can
sometimes be more invasive.
 • Examples of teratogen
• Effect of teratology
• Physical agents radiation
1-All or none • Maternal diseases DM ,
phenylketonuria, SLE
2-Embryonic phase
• Infectious agent : rubella, toxoplasmosis,
3-The fetal phase
herpes

• Drugs and chemicals (A, B, C, D, X),

Chromosomal & Genetic Disorders
• Numerical
• Structural
• Single gene defect
• Ex . Fragile x mental retardation

• Duchene muscle atrophy

• Spinal muscle atrophy gene

 Types Of Fetal Anomalies

• Structural abnormalities

• Chromosomal abnormalities

• Fetal disease ( infection , anemia )

 How To Decrease Or Prevent
Risks?
• Identification of high risk cases

• Avoid exposure to teratogen in vulnerable periods of pregnancy

• Screening for structural and chromosomal defects in pregnancy

• Preimplantation genetic screening and diagnosis

• Education of families with known genetic disorders regarding risks ( eg Duchene,

hemophilia, thalassemia )
 Prerequisites Of Screening
• Relevance – the condition screened for must be relevant and important
• Effect on management – alternative management options must be available
• Sensitivity – the test must have a high detection rate for the condition
• Specificity – the test must exclude the vast majority who do not have the
condition
• Affordability – the test should be cheap enough to be cost effective
• Equity – the test should be available
 Indications
• Maternal age > 35 years

• Exposure to teratogen in pregnancy

• Family history chromosomal abnormality or genetic disorder

• Bad obstetric history ( losses )

• Abnormal maternal serum screening test

• Ultrasound anomaly
 Genetic Counselling
• The National Society of Genetic Counselors (NSGC) defines
genetic counseling as the understanding and adaptation to the
medical, psychological and familial implications of genetic
contributions to disease

• Genetic counselor is an expert with a Master of Science degree

in genetic counseling, works as members of a health care team

• Genetic counselors are present at high risk or specialty prenatal

clinics that offer prenatal diagnosis, pediatric care centers, and
adult genetic centers.
• Genetic counselors provide information and support to families who
have members with birth defects or genetic disorders, and to
families who may be at risk for a variety of inherited conditions.
They identify families at risk, investigate the problems present in
the family, interpret information.
• Genetic counseling can occur before conception

• The goals of genetic counseling are to increase understanding

of genetic diseases, discuss disease management options, and
explain the risks and benefits of testing.[8]

• Counseling sessions focus on giving vital, unbiased information and

non-directive assistance in the patient's decision-making process.
 Benefits of prenatal diagnosis
• helps determine the outcome of a pregnancy
• identifies possible complications that can arise during pregnancy and birth
• Leads to further genetic evaluations for conditions discovered during
pregnancy
• can be helpful in improving the outcome of the pregnancy, by using fetal
treatment or by planning delivery in a tertiary care center.
• Screening helps couples determine whether to continue pregnancy ti rO
a evah ot meht eraperp pleh nacchild with abnormality.
 Indications of Prenatal diagnosis:
• Advanced maternal age
• Previous baby a htiw genetic abnormality
• Recurrent miscarriages
• Family history of genetic abnormality
,such as single gene disorder , neural tube defect or other gebetic
structural abnormalities
• Maternalsesaesid cinorhc , MD ) srotcaf ksiR )
•Consanguinity
• The American College of Obstetricians and Gynaecologists
(ACOG) has recommended that serum screening, cell-free DNA screening,
and diagnostic tests, such as chorionic villus sampling (CVS)
and amniocentesis, be discussed with and offered to all women early in
pregnancy, regardless of their age.

• According to The Royal College of Obstetricians and

Gynecologists ( RCOG) , it may be possible to define pregnancy
complication risk in the first trimester by combining biochemical and
biophysical markers with obstetric history. This could allow antenatal care
to be personalized, with patient and complication-specific content.
 Invasive Diagnostic Test
• Chorionic villous sampling
• Amniocentesis
• Cordocentesis
• fetoscopy
 Amniocentesis:
A procedure in which amniotic fluid is removed from the uterus for
testing or treatment.
 Benefits of Amniocentesis :
• Genetic Testing : such as Down Syndrome (Trisomy 21)
• Fetal Lung Testing : fetal lung maturity test by sampling amniotic fluid (
usually between 32 to 39 weeks) to determine whether the fetal lungs
are mature for birth.
• Diagnosis of Fetal Infections.
• Detection of Severity of Anemia in babies who have Rh Sensitization
• Treatment of Polyhydramnios : by draining excess amniotic fluid from
uterus.
• Paternity Testing : by collecting DNA from Fetus and comparing it to
DNA from the potential father.
 Risks of Amniocentesis :
• Leaking amniotic fluid : from vagina, rare, usually stops within 1
week.
• Miscarriage : in 2nd trimesteric amniocentesis.
• Needle Injury : to the baby , rare.
• Rh Sensitization : rare , by entering of Rh+ve fetal blood cells into
maternal circulation. Maternal immunity forms antibodies against
fetal RBCs.
( In Rh-ve Mothers , Rh immunoglobulin injection should be given after
amniocentesis )
• Infection : rare.
• Infection Transmission to fetus
 Cordocentesis :

• Percutaneous umbilical blood sampling.

• Usually done after week 18 of pregnancy.
• Use of cordocentesis is becoming rare,
because diagnostic procedures such as
amniocentesis
and chorionic villus sampling, which pose
a lower risk of fetal death, can be used
instead for prenatal diagnosis of disease.
• Cordocentesis is most often done to test for
anemia in the baby
 Chorionic Villus Sampling (CVS)
• A sample of chorionic villi is removed from the placenta for
testing. The sample can be taken through the cervix
(transcervical) or the abdominal wall (transabdominal).
• Can be done as early as 10 weeks pregnancy. Usually
between 11 and 14 weeks pregnancy .
• Benefits of CVS :
- Genetic Testing
• Disadvantage :
( CVS can't detect certain birth defects, such as neural tube defects.
If neural tube defects are a concern, an ultrasound or genetic
amniocentesis might be recommended instead)
• Risks of CVS :
- Miscarriage
- Rh Sensitization
- Infection
 Fetal Tissue Biobsy

• US guided fetal tissue sampling using maternal transabdominal trocar.

• Usually done between 17 to 20 weeks Pregnancy.
▪︎ Benefits :
-detect hereditary conditions of the fetus that
can not be identified through more conventional methods such as
amniocentesis or chorionic villus sampling of
the placenta. e.g skin biobsy for
Diagnosis of epidermal dysplasias.
▪︎ Risks :
- Spontaneous miscarriage & Preterm delivery
- Infection & Hemorrhage
 Coelocentesis

• Sampling of coelomic space

between amniotic membrane
and uterine cavity .
• Usually done before 10 weeks
pregnancy.
▪︎ Benefit :
Fetal Loss < Amniocentesis
 Non-Invasive Methods
Fetal Ultrasonography
• An imaging technique that uses sound waves to produce
images of a fetus in the uterus.
• Usually done during the first trimester to confirm the pregnancy.
* If the Pregnancy continues uncomplicated :
- The next ultrasound is typically offered during the second
trimester, when anatomic details are visible.
* If a problem is suspected :
- A follow-up ultrasound or additional imaging tests, such as
an MRI, might be recommended.
 Types of Fetal US :
• Transvaginal US ( TVS)
• Transabdominal US :
- 2D Ultrasound ➔ help monitoring baby growth and development.
- Specialized sonographic evaluation ➔ when a fetal abnormality
is known or suspected.
- 3D ultrasound ➔ help diagnose facial abnormalities & Neural
tube defects.
- Doppler ultrasound ➔ provide details about fetal blood flow.
- Fetal echocardiography ➔ This exam provides a detailed picture
of a baby's heart. It might be used to confirm or rule out a
congenital heart defect.
 Fetal Doppler US

Fetal Echocardiography
Structural Anomalies Down syndrome
• Nuchal translucency
• Nasal bone
• Soft markers
 Benefits of Fetal Ultrasonography
• Confirm the pregnancy and its location : detect whether the
pregnancy is intrauterine or extrauterine (ectopic pregnancy).
• Determine fetal gestational age : CRL in 1st trimester & Femur
length , Biparietal diameter (BPD) , Head and Abdominal
Circumferences in 2nd and 3rd trimesters.
• Confirm the number of babies. : singleton or multiple pregnancy.
• Evaluate Fetal growth : check for IUGR & Macrosomia
• Study the placenta and amniotic fluid levels : check for placental
abnormalities & oligo and polyhydramnios.
- Identify birth defects
- Investigate fetomaternal complications : e.g bleeding
- Perform other prenatal tests : guide needle placement in Amniocentesis &
Chorionic Villus Sampling.
- Identify fetal sex
- Determine fetal lie, position and presentation before delivery

N.B :
US should be used only for valid medical reasons
( Not only for fetal sex identification or keeping videos and photos )

• Risks :
US is generally SAFE
 Magnetic Resonance Imaging (MRI)
▪︎ Benefits :
• MRI is an adjunct to good prenatal ultrasound scan (US).
- It provides significant additional information that improves
diagnostic accuracy in evaluation of the fetal brain, spine, neck,
chest, abdomen, and urinary tract.
- MRI provides important anatomic information that helps in
planning delivery and surgical procedures.
▪︎ Risks :
MRI is generally SAFE.
• Fetal MRI of Central Nervous System
* Cell free fetal DNA in maternal plasma 8 ws
* Double test 10 – 13 ws+6ds
* Triple test 14 – 18 ws
* Quadriple test 14 – 18 ws
 Cell-free Fetal DNA

• Cell free Fetal DNA is obtained by Venipuncture of the mother.

• Usually done after at least 10 weeks pregnancy.
▪︎ Benefits :
- Available to all pregnant women .
- It can be used to screen for certain chromosomal disorders, including:
Down syndrome (trisomy 21)
Trisomy 18
Trisomy 13
- It can also be used to screen for fetal sex.
- Some prenatal cell-free DNA screening tests might also screen for the increased chance of:
Trisomy 16
Trisomy 22
Triploidy
Sex chromosome aneuploidy
Certain disorders caused by a chromosomal deletion (microdeletion syndrome)
 ▪ Risks :
Cell-free fetal DNA is generally SAFE.
( It may cause Anxiety , but it can be used to avoid other invasive prenatal
diagnosis methods such as Amniocentesis and CVS )
• Double test , free β HCG, PAPPA

• Triple , βHCG, α fetoprotein, estriol

• Quadriple, BHCG, α fetoprotein, estriol,

inhibin
 Triple Test
• It is a test that measures the amounts of three substances in a
pregnant woman's blood:
- Alpha-fetoprotein (AFP) ➔ produced by Fetus.
- Human chorionic gonadotropin (hCG)
- Estriol (uE3).
- When a test for the hormone inhibin A is added, it's called a “Quad
screening”
• Usually done in 2nd Trimester
( Between 15 and 18 weeks pregnancy , but may be done up to week
22 )
▪ Benefits :
- Helps in the Diagnosis of :
• Neural Tube Defect
• Down’s Syndrome
• Trisomy 18
▪︎ Risks :
Triple or Quad screening
Is generally SAFE.
Summary
 Questions 1

• objective : discuss methods to prevent or decrease the risk of genetic defects

• Recall ( level 1 )

• 1- Recognize the material which is not appropriate for antenatal diagnosis of genetic
disorders :
• A- fetal blood
• B- amniotic fluid
• C- chorionic villi
• D- maternal urine

Answer: D
 Questions 2

• Objective : identify disease that could be screened and how to screen.

• Level 3

• Select the disease ( s ) that could be screened prenatally

• A- maternal diabetes
• B- Down syndrome
• C- renal disorders with pregnancy
• D- heart disease

• Answer : a & b
 Questions 3

• Recall level1
• Select the invasive test which is not widely used for Karyotyping of the
fetus:
a- amniocentesis
b-cordocentesis
c- fetal skin biopsy
d- chorionic villous sampling

• Answer: C
Skin biopsy for diagnosis of skin diseases
 Case scenario and clinical correlation

❖Mrs. Z is 38 years old, married for 12 years and has 3 children the
youngest is 10 years old and discovered to be trisomy 21 ( Down
syndrome ),

❖Now she has unplanned pregnant in the first trimester 8weeks.

She asked for medical advice and how to deal with her pregnancy?
 Discussion & Feedback
2-5 minutes
 References

• Obstetrics by ten teachers : Prenatal diagnosis