WILLIAM’S OBSTETRICS 25th EDITION

Prenatal Diagnosis
 HISTORICAL PERSPECTIVE

1980s & early

1977 1984
1990s

Beginning of MSAFP levels were Serum screening prior to

widespread serum lower in pregnancies sonography
Screening for fetal with trisomies 21 and → amniocentesis for
anencephaly and 18 at 15-21 weeks ventral wall defects,
myelomeningocele gestation esophageal atresia, fetal
teratoma, epidermolysis
bullosa, etc
Trends in the percentage of births to women aged 35 to 44 years.
This age group accounts for half of
births with Down syndrome

Trends in the percentage of births to women aged 35 to 44 years.

 ANEUPLOIDY
Definition: presence of one or
Screening tests: more extra chromosomes, usually
• Traditional or analyte-based resulting in trisomy, or loss of a
• Cell-free DNA-based chromosome-monosomy

Considerations prior to screening: Prevalence: 4 per 1000 births

1. Has the patient elected screening? Accounts for >50% 1st trimester abortions
2. Would the patient prefer prenatal diagnosis? about 20% of 2nd trimester losses & 6-8%
3. Is this a multifetal gestation? percent of stillbirths and early-childhood
4. Does the fetus have a major anomaly? deaths
 ANEUPLOIDY
Screening tests:
1st trimester
• Traditional or analyte-based

Each maternal serum analyte is

measured as a concentration 2nd trimester
(nanograms per milliliter of AFP)

combinations of first- and

second-trimester screens
 ANEUPLOIDY
Screening tests:
1st trimester
• Traditional or analyte-based

Each maternal serum analyte is hCG PAPP-A

measured as a concentration 2nd trimester
(nanograms per milliliter of AFP)
fetal Down
syndrome

combinations of first- and

trisomy 18
second-trimester screens
maximum thickness of the
subcutaneous translucent
sonographic trisomy 13
area between the skin and measurement
soft tissue overlying the
fetal spine at the back of
the neck
nuchal translucency
Sagittal image of a normal, 12-week fetus demonstrating correct caliper placement (+)
for nuchal translucency measurement. The fetal nasal bone and overlying skin are
indicated. The nasal tip and the 3rd and 4th ventricles (asterisk), which are other
landmarks that should be visible in the nasal bone image, are also shown
 ANEUPLOIDY
Screening tests:
1st trimester
• Traditional or analyte-based

2nd trimester
quadruple marker

Down
Neural-Tube Defect
Trisomy
Syndrome
18 Screening
combinations of first- and
second-trimester screens
MSAFP
↓ ↓ MSAFP
hCG ↑ ↓
sonography
unconjugated
estriol,
↓ ↓
amniocentesis
dimeric inhibin ↑ -
 Integrated and Sequential Screening

Integrated screening

hCG NT MSAFP

PAPP-A hCG
unconjugated
estriol
Sequential screening
dimeric inhibin

stepwise contingent
Cell-Free DNA Screening

Introduced in 2011 identiying DNA fragments

can be performed at any time

not gestational-age dependent ater 9 to 10 weeks' gestation

Results are available in 7 to 10 days

Cell-Free DNA Screening
Down Syndrome 99%

Trisomy 18 96%

Cell-free DNA screening is

recommended as a Trisomy 13 91%
screening option in those at
increased risk for fetal
Turner Syndrome 90%
autosomal trisomy
Cell-Free DNA Screening
Following categories:

Woman who will be 35 years or

Known carriage (patient or
older at delivery
partner) of a balanced
robertsonian translocation
involving chromosome 21 or 13

A positive 1st or 2nd trimester

analyte-based screening test

Prior pregnancy with autosomal

Sonogram with a minor trisomy
aneuploidy marker
 Sonographic Screening
Sonography can augment aneuploidy screening by

providing accurate gestational age

assessment

detecting multifetal gestations

identifying major structural

abnormalities and minor
sonographic markers
Sonographic Screening

1st trimester

2nd trimester
 Sonographic Screening

1st trimester

Fetal NT measurement 2nd trimester

Nasal bone

Ductus venosus flow Tricuspid flow

Sonographic Screening
Second-Trimester Markers-"Soft Signs"
Sonographic Screening
CARRIER SCREENING FOR GENETIC DISORDERS

Cystic Fibrosis Thalassemias

Spinal Muscular Atrophy Sickle Hemoglobinopathies

Tay-Sachs Disease
 Prenatal Diagnostic Procedures and
Preimplantation Testing

Amniocentesis Fetal Blood Sampling

Chorionic Villus Sampling Preimplantation Genetic Testing

 Prenatal Diagnostic Procedures

Amniocentesis Chorionic Villus Sampling Fetal Blood Sampling

Prenatal Diagnostic Procedures

A. Amniocentesis
B. The amniocentesis needle is seen in the upper right portion of this sonogram
Prenatal Diagnostic Procedures

A. Transcervical chorionic villus sampling

B. Catheter entering the placenta is marked and labeled
Prenatal Diagnostic Procedures

A. Access to the umbilical vein

B. Sonogram shows an anterior placenta with transplacental
needle passage into the umbilical vein (U).
 Preimplantation Genetic Testing

For couples undergoing in vitro fertilization (IVF), genetic

testing performed on oocytes or embryos before
implantation may provide valuable information regarding
the chromosomal complement and single-gene disorders

Preimplantation Genetic Diagnosis

It performs to determine if an
oocyte or embryo has the defect Blastomere biopsy

Preimplantation Genetic Screening

The term is used for aneuploidy
screening that is performes on oocytes
or embryo before IVF transfers
Thank you