prenatal diagnosis jy

8/6/2019 Prenatal Diagnosis Jy

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PRENATAL DIAGNOSIS

By Dr. JY Ho (Manipal)


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REFERENCES

Hacker & Moore. Essentials of Obstetrics & Gynaecology

5th Edition, 2010.

Royal College of Obstetrics & Gynaecology (RCOG)

Guidelines.

Medscape. Prenatal Diagnosis : Congenital

Malformations and Genetic Disorders, 2011.

http://www.who.int/whosis/mort/profiles/mort_wpro_mys_

malaysia.pdf. WHO Mortality Country Fact Sheet 2006.

American College of Obstetricians and Gynecologists(ACOG). Screening for fetal chromosomal abnormalities.

Washington (DC): American College of Obstetricians and

Gynecologists (ACOG); 2007 Jan. 11 p. (ACOG practice

bulletin; no. 77).


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INTRODUCTION

Congenital anomalies account for 20-25% of

perinatal deaths worldwide.

In Malaysia, congenital anomalies account for13% of neonatal deaths (WHO Mortality Country

Fact Sheet 2006)

Prenatal diagnosis employs various non-invasiveand invasive techniques to determine the health

or any abnormality in an unborn fetus


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BENEFITS OF PRENATAL

DIAGNOSIS

Determines outcomes of pregnancy

Helpful for couples to decide whether tocontinue pregnancy

Indicates possible complications that canarise at birth process

Helpful for managing remaining weeks of

pregnancy

Prepares the couples for the birth of a child

with an abnormality

Helpful for the improvement of the outcomesof pregnancy using fetal treatment


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PREREQUISITES OF PRENATAL

DIAGNOSIS

Pregnant woman > 35years

A previous child or family history of birth defects,

chromosomal anomaly or genetic disorder

A previous child with mental retardation Multiple fetal losses

Abnormal serum marker screening results

Consanguinity

Maternal conditions predisposing to fetalabnormality

Teratogenic exposure

Suspected abnormal ultrasound findings

A parent who is a known carrier of genetic disorder


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TECHNIQUES

NON-INVASIVE

INVASIVE


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NON-INVASIVE TECHNIQUES

Fetal visualization Ultrasound

Fetal echocardiography

MRI

Radiographs

Screening for neural tube defects (NTDs)

Maternal serum -fetoprotein (MSAFP)

Screening for fetal Down syndrome

MSAFP, maternal unconjugated estriol, maternal

serum -hCG, serum inhibin A


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Separation of fetal cells from mothers

blood

Assessment of fetal-specific DNA

methylation ratio


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ULTRASOUND TVS/TAS

Harmless to both fetus and mother

Developing embryo can be visualized at 6 wks gestation

TVS :

- accurate dating, fetal location & number, nuchal

translucency

- cervical length in mid-trimester (identify risk of preterm

delivery

- placental location in 2nd or 3rd trimester


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TAS :

- 16-20weeks structural abnormalities

- 3rd trimester fetal growth (fetal biometry), amniotic

fluid index

- biophysical profile (risk of fetal death within a week

following BPP score of >8 is less than 1%)

Doppler : umbilical & fetal middle cerebral artery

Guide invasive sampling

amniocentesis, chorionic villus sampling, cordocentesis, fetal

biopsies


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FETAL ECHOCARDIOGRAPHY

Can be performed at 15 weeks gestation & beyond

Can identify major structural cardiac defects and

rhythm disturbances with duplex or colour flow

doppler

Recommended when cardiac defects are suspected:

y Identification of extracardiac malformations on routine

ultrasound

y Family history of congenital heart disease

y Suspected genetic disease or fetal chromosome

abnormality associated with heart defects

y Exposure to potentially teratogenic agents


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SCREENING TESTS

MSAFP Triple Test -hCG +

PAPP-A

Nuchal

Translucency

Time (Wks) 15-18 15-18 10-14 11-14

Observation MSAFP&UE3

-hCG

-hCG PAPP-A

Nuchal thickness 3mm

Anomaly to

Detect

Open

NTD

Downs syn Downs syn Downs syn

Test

Sensitivity

Rate

65% 60% 65% 70%

False

PositiveRate

3-5% 5% 5% 5-6%

Inhibin A serum level in Downs syndrome

MSAFP : maternal serum -fetoprotein UE3 : maternal unconjugated estriol

-hCG : maternal -human chorionic gonadotropin

PAPP-A :pregnancy-associated plasma protein A


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SEPARATION OF FETAL CELLS FROM

MOTHERS BLOOD

Fetal blood cells make access to maternal

circulation through placental villi

Can be collected at 18 weeks gestation

Can be analyzed for the diagnosis of genetic

disorders using molecular genetic techniques by

isolating DNA and amplifying it by PCR

Successfully used in the diagnosis of cystic

fibrosis, sickle cell anemia and thalassemia in

fetus


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INVASIVE TECHNIQUES

Fetal visualization

- Embryoscopy

- Fetoscopy

Fetal tissue sampling

- Amniocentesis

- Chorionic villous sampling (CVS)

- Cordocentesis (Percutaneous Umbilical BloodSampling-PUBS)

Preimplantation genetic diagnosis (PGD)


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Cytogenetic investigations

Detection of chromosomal aberrations

Fluorescent in situ hybridization

Molecular genetic techniques

Linkage analysis using microsatellite markers Restriction fragment length polymorphisms

(RFLPs)

Single nucleotide polymorphisms (SNPs)

DNA chip

Dynamic allele-specific hybridization (DASH)


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EMBRYOSCOPY

Performed in the 1st

trimester

A rigid endoscope is inserted via the cervix in

the space between amnion and chorion, understerile conditions & USG guidance to

visualize the embryo for diagnosis ofcongenital malformations


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FETOSCOPY

Performed in the 2nd

trimester

A fine caliber endoscope is inserted into the

amniotic cavity through a small maternal

abdominal incision, under USG guidance

Visualize fetus for structural abnormalities

Also used for fetal blood and tissue sampling

3-5% risk of miscarriage


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AMNIOCENTESIS

Performed between 14-20 weeks

22-gauge needle is passed through motherslower abdomen into clear pocket of amniotic

fluid under USG guidance

10-20ml of amniotic fluid obtained

0.5-1.0% fetal loss and maternal Rh

isoimmunization (anti-D Ig given to Rh vemothers)

Amniotic cells require 1-2 weeks culture forchromosomal analysis


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Genetic diagnosis

- diagnose chromosomal anomalies (trisomy21)

- DNA amplification by PCR allow molecularanalysis of genetic disorders (cystic fibrosis,

sickle cell disease)

Biochemical testing- Amniotic fluid -fetoprotein (AFAFP)

- in fetal dorsal / ventral wall defect (NTD,

gastrochisis)

Diagnosis of perinatal infections

- by culture / PCR (CMV,VZV,Parvovirus B19,

toxoplasmosis)


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3rd trimester fetal lung maturity

- phosphatidylgycerol, lecithin-

sphingomyelin ratio

Therapeutic amniocentesis

- polyhydramnios & twin-twin transfusion

syndrome


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CHORIONIC VILLOUS SAMPLING

Performed between 10-12 weeks gestation

Transcervically or transabdominally

A catheter is passed through the cervix or

abdominal wall into uterus under USG guidanceA sample of chorionic villi surrounding the sac is

obtained

Chromosome analysis can be carried out within 3

days

Information obtained is the same as in

Amniocentesis


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ADVANTAGES AND DISADVANTAGES OF

CVS OVER AMNIOCENTESIS

Advantages Disadvantages

Quicker results

Abnormalities can bedetected early

More acceptable decisions

about termination of

pregnancy can be taken(abortion much safer)

Higher risk of miscarriage

(2-3%)

Risk of fetal limb defects

Higher rate of maternal cell

contamination and confined

placental mosaicism leads todiagnostic ambiguity


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CORDOCENTESIS (PUBS)

Features Information obtained

Performed after 16 weeks

A 25 gauge needle is

inserted into the umbilical

cord under USG guidance

Fetal blood is collected from

umbilical vein for

chromosome analysis and

genetic diagnosis

Same as in Amniocentesis

(but more rapid using fetal

leukocyte culture result

available in 3 days)

Fetal anaemia (superseded

by doppler of fetal MCA)

Risk :Fetal loss rate 1%

Chorioamnionitis

Cord hematoma

Thrombosis of umbilical

vessels


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Features Advantages

a technique used to identify

genetic defects in embryos

created through IVF before

pregnancy

for selective transfer and

implantation of pregnancies

into the uterus that are not

affected by a specific genetic

disorder

more acceptable to those

couples who oppose abortions

preventing heritable geneticdisease, thereby eliminating

the dilemma of pregnancy

termination following

unfavorable prenatal diagnosis

Preimplantation Genetic Diagnosis (PGD)


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1ST TRIMESTER SCREENING

Maternal age Fetal nuchal translucency (NT) thickness

Maternal serum -hCG

Pregnancy-associated plasma protein-A (PAPP-A)

Visualization of nasal bone by USG

* Combination of the above :

Increase Down syndrome detection rate to 93%

Women found to have increased risk of aneuploidyshould be offered genetic counselling and option of

CVS / amniocentesis

Hacker & Moore. Essentials of Obstetrics & Gynaecology 5th Edition, 2010.


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2ND TRIMESTER SCREENING

Triple screening tests

- MSAFP

- Maternal unconjugated estriol

- Maternal serum -hCG

Anomaly scanAmniocentesis

- AFAFP

- Acetylcholinesterase (present only in open NTD)

* MSAFP detect 80-85% of all open NTDs

* Triple screen detect 70% of Down syndrome

* Triple screen + Serum Inhibin A detect 81% of Down syndrome

Hacker & Moore. Essentials of Obstetrics & Gynaecology 5

th

Edition, 2010


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