Transcript Prenatal Diagnosis

Pregnancy Diagnosis
Obstetrics and Gynecology Hospital of
FudanUniversity
Xing Chen, MD.
Email: [email protected]
For a woman with regular menstrual
cycles, a history of one or more missed
periods following a time of sexual activity
without effective contraception strongly
suggests early pregnancy
Associated Symptoms
Fatigue
Nausea/vomiting
Breast tenderness
physical examination
softening and enlargement of the pregnant uterus
congestion and a bluish discoloration of the vagina
(Chadwick sign)
softening of the cervix (Hegar sign)
Increased pigmentation of the skin
appearance of circumlinear striae on the abdominal
wall (striae gravidarum )
Palpation of fetal parts
appreciation of fetal movement and fetal heart
tones
Pregnancy test
human chorionic gonadotropin (hCG): α/β-subunit
produced in the syncytiotrophoblast
Urine
approximately 4 weeks following the first day of the last
menstrual period
All urine pregnancy tests are best performed on early-morning urine
specimens, which contain the highest concentration of hCG
Serum
specific and sensitive
by following serial quantitative hCG levels and comparing them to
the expected rise derived from normative data for proven normal
intrauterine pregnancies
Ultrasound examination
Abdominal ultrasound allowing visualization
of a normal pregnancy gestational sac 5 to 6
weeks after the beginning of the last normal
menstrual period (corresponding to β-hCG
concentrations of 5000 to 6000 mIU/mL)
Transvaginal ultrasound often detects
pregnancy at 3 to 4 weeks of gestation
(corresponding to β-hCG concentrations of
1000 to 2000 mIU/mL)
Detection of fetal heart activity
“fetal heart tones”
Acoustic fetoscope
beyond 18 to 20
weeks of gestational
age
Electronic Doppler devices
approximately 12 weeks
of gestation
Abnormal Pregnancy
Spontaneous abortion
Ectopic pregnancy
Trophoblastic disease
Prenatal Diagnosis
Prenatal diagnosis
is the science of identifying
structural or functional
abnormalities-birth defects-in
the fetus
Etiology of Birth Defects
Malformation
Deformation
Disruption
Other
Malformation
an intrinsic abnormality "programmed" in
development, regardless of whether a
precise genetic etiology is known
spina bifida
Deformation
caused when a genetically normal fetus
develops abnormally because of
mechanical forces imposed by the uterine
environment
normal limb that develops contractures
because of prolonged oligohydramnios
Disruption
which is a more severe change in form or
function that occurs when genetically
normal tissue is modified as the result of a
specific insult
an amnionic band causing a cephalocele
or limb-reduction abnormality
Other
Syndrome: trisomy 18
Sequence: oligohydramnios leading to
pulmonary hypoplasia
Association: VATER (association of
vertebral defects, anal atresia,
tracheoesophageal fistula with esophageal
atresia, and radial dysplasia)
Techniques
Non-invasive
Minimally invasive
Invasive
Non-invasive techniques
Ultrasound
Magnetic Resonance Imaging (MRI)
Minimally Invasive Techniques
Cell free fetal DNA (cffDNA)
Pre-implantation genetic diagnosis (PGD)
Invasive Techniques
Chorionic villus sampling (CVS)
Amniocentesis
Percutaneous umbilical blood sampling
(cordocentesis)
Key Guidelines
All women contemplating any form of prenatal diagnosis
should be adequately counselled about the risks,
benefits and limitations of any test, and provided with
non-directional written information
Screening test for Down's syndrome and ‘20 week’ scan
for structural anomalies
Women at risk of having a baby with congenital heart
disease should be offered an extra fetal echocardiogram
at 21–24 weeks
The middle cerebral artery Doppler peak systolic velocity
can be used as a non-invasive method for diagnosing of
fetal anaemia
Key Guidelines
Serial ultrasound measurements are of
undoubted use in monitoring fetal growth but all
formulae currently used to estimate fetal weight
are inherently flawed and may give errors up to
±14%
MRI is a useful adjunct to ultrasound in prenatal
diagnosis especially in the diagnosis of intracranial, intra-thoracic and gastrointestinal
anomalies
Key Guidelines
Cell free fetal DNA testing has become widely
established for the management of Rhesus
disease and certain sex linked genetic disorders.
With further research it is poised to offer much
greater benefits in the field of minimally invasive
prenatal diagnosis
Pre-implantation genetic diagnosis provides the
opportunity for parents to avoid the distress of
invasive testing and possible termination.
However, the ethical and legal debate is set to
continue for many years
Key Guidelines
CVS should not be performed before 10 weeks
of gestation as it has been associated with limb
reduction abnormalities. It appears to be safer if
it is performed transabdominally rather than
transcervically
Amniocentesis should not be performed at less
than 15 weeks of gestation as before this it is
associated with greater risk of pregnancy loss
and possible talipes in the fetus
Key Guidelines
In experienced hands CVS and
amniocentesis both carry a similar
procedure related risk of miscarriage of
0.5–1%
Percutaneous umbilical blood sampling is
now limited to potentially lifesaving in utero
transfusion procedures for severe fetal
anaemia
Neural-Tube Defects (NTDs)
anencephaly, spina bifida, cephalocele,
and other rare spinal fusion (schisis)
abnormalities
had higher levels of alpha-fetoprotein
(AFP) in maternal serum and amnionic
fluid
Maternal Serum AFP Screening
influence factors: maternal weight, gestational age, diabetes,
multifetal gestation
Evaluation of Maternal Serum AFP Elevation
genetic counseling
diagnostic test
 Specialized Sonography
 amniocentesis
Specialized Sonography
Transverse and sagittal images of the
spine are increasingly used to characterize
the size and location of spinal defects
Amniocentesis
amnionic fluid AFP level
assay for acetylcholinesterase
Down Syndrome
trisomy 18, 21
First/second trimester: Sonography and
maternal serum markers
Second-Trimester Screening
At 15 to 20 weeks
Triple test:
 MSAFP (maternal serum alpha-fetoprotein )
 hCG or freeβ-hCG
 uE3 (unconjugated estriol )
Quadruple (Quad) test:
+ inh (dimeric inhibin alpha)
First-Trimester Screening
between 11 and 14 weeks
maternal serum analyte screening:
 hCG (or free β-hCG)
 pregnancy-associated plasma protein A (PAPP-A)
sonographic: nuchal translucency (NT)
combination of both
Be aware…
gestational age affects the accuracy
less sensitive in younger women
Be aware…
strong association between increasing
nuchal translucency and fetal cardiac
anomalies
nuchal translucency measurement is 3.5
mm or greater with a normal fetal
karyotype, then targeted sonographic
examination, fetal echocardiography, or
both should be considered
Sonographic Screening for Aneuploidy
Major Structural Defects
"Soft Signs"
Diagnostic Techniques
Second-Trimester Amniocentesis
between 15 and 20 weeks
Early Amniocentesis
between 11 and 14 weeks
Chorionic Villus Sampling (CVS)
at 10 to 13 weeks
Fetal Blood Sampling
percutaneous umbilical blood sampling (PUBS) or
cordocentesis
Fetal Tissue Biopsy
Preimplantation Genetic Diagnosis
Fetal Cells in the Maternal Circulation
Fetal Therapy
-to improve the intrauterine environment
blood product transfusion
administration of medication
transplacentally or via the fetal circulation
laser or radiofrequency ablation of
vascular anastomoses
amnioreduction
shunt placement
fetal surgery
Reference
Obstetrics and Gynecology, 6th edition
Williams Obstetrics, 23rd edition
Prenatal diagnosis: Types and techniques.
Early Human Development. 2012 (88) :3–8