[ppt]prenatal tani - wordpress.com · web viewinvasiveproceduresused in prenatal diagnosis:...
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Goal of screening is to detect or define risk for disease in an
asymptomatic low risk population.
SCREENING TESTS DURING PREGNANCY
An ideal perinatal genetic screening test should:
Identify common or important fetal disorders
Be cost-effective and easy to perform
Have a high detection rate and a low false-positive rate
Be reliable and reproducible
Screen for disorders for which a diagnostic test exists
Be positive early enough in gestation to permit safe and legal options for
pregnancy termination if desired
SCREENING TESTS DURING PREGNANCY
Complete blood count
Blood typing
Fasting glucose level
Antibody screening
Pap smear
Urine analysis
Urine culture
Rubella
Hepatitis B and C
HIV
BASIC TESTS DURING PREGNANCY
Incidence of Major congenital abnormalities: 2 to 3 percent of
pregnancies.
Screening tests
Diagnostic tests
SCREENING of FETAL ANOMALIES
Screening for neural tube defects (NTD)
Screening for aneuploidies
Screening for fetal structural anomalies
SCREENING of FETAL ANOMALIES
Neural tube defects (NTDs) are the second most common class of
birth defect after cardiac anomalies
Reported frequency : ~ 0.9 per 1000 births.
SCREENING FOR NTDs
Maternal Serum Alpha-Fetoprotein (MSAFP) Screening
AFP is a glycoprotein synthesized by the fetal yolk sac and later by the fetal
gastrointestinal tract and liver.
It is the major serum protein in the embryo and fetus and is thus analogous to
albumin.
Defects in fetal integument, such as neural-tube and ventral wall defects,
permit AFP to leak into the amnionic fluid, resulting in dramatically increased
maternal serum AFP levels.
SCREENING FOR NTDs
Maternal Serum Alpha-Fetoprotein (MSAFP) Screening
Screening is generally performed from 15 through 20 weeks.
AFP is measured in nanograms per milliliter and reported as
multiples of the median (MoM) of the unaffected population.
Cut-off value: 2.0 or 2.5 MoM.
SCREENING FOR NTDs
1. Maternal weight—The AFP concentration is adjusted for the maternal volume
of distribution.
2. Gestational age—The maternal serum concentration increases by
approximately 15 percent per week during the second trimester.
3. Race/ethnicity—African American women have at least 10-percent higher
serum AFP concentrations but are at lower risk for fetal NTDs.4. Diabetes—Serum levels may be 10 to 20 percent lower in women with insulin-
treated diabetes.5. Multifetal gestation—Higher screening threshold values are used in twin
pregnancies.
FACTORS INFLUENCING AFP LEVELS
99 percent of fetuses with open spina bifida had one or more of
these findings
1. Frontal nothcing (Lemon sign)
2.Small biparietal diameter,
3.Ventriculomegaly
4.Obliteration of cysterna magna,
5. Banana sign
SONOGRAPHIC FINDINGS
It has been replaced in most centers by targeted sonography.
If the amnionic fluid AFP level was elevated, an assay for
acetylcholinesterase was performed, and if positive, was considered
diagnostic of an NTD.
Acetylcholinesterase leaks directly from exposed neural tissue into
the amnionic fluid.
AMNIOCENTESIS
All women who present for prenatal care before 20 weeks should be
offered screening
ANEUPLOIDY SCREENING
Types of screening:
1. Maternal age screening is a poor screening test, because approximately 70
percent of Down syndrome pregnancies are in women younger than 35 years.
2. First-trimester screening at 11 to 14 weeks’ gestation, using the fetal nuchal
translucency measurement together with serum analytes,
3. The addition of other serum analytes to second-trimester screening
4. Combinations of first- and second-trimester
5. Maternal serum cell-free fetal DNA testing for trisomy 21, 18, and 13
ANEUPLOIDY SCREENING
At 11 to 14 weeks’ gestation: Fetal nuchal translucency
measurement together with serum analytes, has achieved Down
syndrome detection
• Nasal bone
FIRST TRIMESTER ANEUPLOIDY SCREENING
The most commonly used screening protocol combines the NT
measurement with serum hCG and PAPP-A (Pregnancy Associated
Protein-A).
Detection rates: 79 to 87 percent
False-positive rate: 5 percent
FIRST TRIMESTER ANEUPLOIDY SCREENING
Triple test: Between 16-20 weeks gestation
AFP hCG Unconjugated estriol:
Quadri test: AFP, hCG, estriol and 4. inhibin are measured.
Cut-off value : 1:200
Amniocentesis and cytogenetic analysis is recommended
SECOND TRIMESTER ANEUPLOIDY SCREENING
Using massively parallel sequencing or chromosome selective
sequencing to isolate cell-free fetal DNA from maternal plasma, fetal
Down syndrome and other autosomal trisomies may be detected as
early as 10 weeks’ gestation.
Detection rates for trisomies 21, 18, and 13: ~ 98%
False-positive rate: 0.5% or less.
CELL FREE FETAL DNA SCREENING
This technology has recently become clinically available as a
screening test,
It is not considered a replacement diagnostic test.
Pretest counseling is recommended.
If an abnormal result is identified, genetic counseling and invasive
prenatal diagnostic testing should be offered to confirm the results.
CELL FREE FETAL DNA SCREENING
Test may be offered to the following groups: (ACOG 2012)
1. Women 35 years or older at delivery
2. Those with sonographic findings indicating increased risk for fetal aneuploidy
3. Those with a prior pregnancy complicated by trisomy 21, 18, or 13
4. Patient or partner carries a balanced Robertsonian translocation indicating increased risk
for fetal trisomy 21 or 13
5. Those with an abnormal first-, second-, or combined first and second-trimester screening
test result for aneuploidy.
6. The College does not recommend offering the test to women with low-risk pregnancies or
multifetal gestations
CELL FREE FETAL DNA SCREENING
1. Structural anomalies (Hard markers)
2. Aneuploidy markers (Soft markers)
3. Other findings
SONOGRAPHIC SCREENING
Cardiac defects,
Central nervous system,
Facial anomalies,
Cystic hygroma,
Diaphragmatic hernia
Gastrointestinal,
Genitourinary anomalies
Nonimmun hydrops
Limb anomalies
STRUCTURAL ANOMALIES
Ventriculomegaly (>10 mm):
İsolated hydrocephaly: 3%
Hydrocephaly+ spina bifida: 8%
Isolated spina bifida: 33%
Dandy Walker Malformation
Aneuoploidy risk ↑
Holoprosencephaly• Risk of trisomy 13: 50-75%
CENTRAL NERVOUS SYSTEM
Holoprosencephaly
Cleft lip and palate:
• Aneuploidy ↑ (tri.13 , 18)
• Medyan cleft lip and palate: 82%
FACIAL ANOMALIES
Soft markers are normal variants rather than fetal abnormalities,
In the absence of aneuploidy they do not significantly affect
prognosis.
SOFT MARKERS
• Nuchal skinfold thickening
• Echogenic intracardiac focus
• Renal pelvis dilation
• Echogenic bowel
• Short femur and humerus
• Nasal bone absence or
hypoplasia
• Single umbilical artery
• Choroid plexus cyst
• Clinodactily
• Echogenic bowel
SOFT MARKERS
• Nuchal skinfold thickening
• A measurement ≥ 6 mm is considered abnormal
Nasal bone absence
• In approximately two thirds of fetuses with Down
syndrome, the nasal bone is not visible at the 11-
to 14-week examination
SOFT MARKERS
• Echogenic fetal bowel
• it increases the risk for Down syndrome approximately sixfold
Choroid plexus cyst:
Echogenic intracardiac focus
SOFT MARKERS
Invasive procedures used in prenatal diagnosis:
Amniocentesis,
Chorionic villus sampling, and
Fetal blood sampling
Preimplantation genetic diagnosis permits similar diagnoses to be
made in oocytes or embryos before implantation.
PRENATAL DIAGNOSTIC TESTS
Is the most common invasive procedure used to diagnose fetal
aneuploidy and other genetic conditions.
It is generally performed between 15 and 20 weeks’ gestation.
The time needed for karyotyping is 7 to 10 days.
AMNIOCENTESIS
Complications
Fetal loss rate following midtrimester amniocentesis : In sigletons: 1
per 300 to 500 . In twins: 1.8%
Amnionic fluid leakage in 1 to 2 percent and
Chorioamnionitis in less than 0.1 percent
Needle injuries to the fetus are rare.
AMNIOCENTESIS
If performed between 11 and 14 weeks, amniocentesis is termed
“early.”
Sac puncture may be more challenging due to lack of membrane
fusion to the uterine wall.
Higher rates of procedure-related complications than other fetal
procedures.
ACOG recommends against the use of early amniocentesis.
EARLY AMNIOCENTESIS
CVS is generally performed between 10 and 13 weeks’ gestation.
The primary advantage of villus biopsy is that results are available
earlier in pregnancy, allowing safer pregnancy termination, if
desired.
• A full karyotype is available in 7 to 10 days.
CHORIONIC VILLUS SAMPLING (CVS)
Complications:
Fetal loss rate is comparable to that with amniocentesis (2 percent)
Limb reduction defects and oromandibular limb hypogenesis:
When performed at ≥ 10 weeks’ gestation, the incidence of limb
defects does not exceed the background rate.
Vaginal spotting is not uncommon.• Chromosomal mosaicism is identified in up to 2 percent of
specimens. Amniocentesis should be offered,
CHORIONIC VILLUS SAMPLING (CVS)
This procedure is also called cordocentesis or percutaneous
umbilical blood sampling (PUBS).
Fetal blood karyotyping can be accomplished within 24 to 48 hours.
Fetal loss rate is approximately 1.4 percent
FETAL BLOOD SAMPLING
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.
There are two separate categories of testing
1. Preimplantation genetic diagnosis (PGD)
2. Preimplantation genetic screening (PGS)
PREIMPLANTATION GENETIC TESTING
There are three techniques:
1. Polar body analysis: Sampling of first and
second polar bodies should not affect fetal
development
2. Blastomere biopsy: is done at the 6- to 8-cell
(cleavage) stage when an embryo is 3 days old
3. Trophectoderm biopsy: involves removal of 5
to 7 cells from a 5- to 6-day blastocyst
PREIMPLANTATION GENETIC TESTING
PREIMPLANTATION GENETIC DIAGNOSIS (PGD)• When either or both members of a couple are known carriers of a
specific genetic disease or a balanced chromosomal rearrangement,
preimplantation genetic diagnosis (PGD) may be performed to
determine if an oocyte or embryo has the defect.
• Only embryos without the abnormality would be implanted.
PREIMPLANTATION GENETIC DIAGNOSIS (PGD) It is used to diagnose:
single-gene disorders such as cystic fibrosis, β-thalassemia, and
hemophilia;
to determine gender in X-linked diseases;
to identify mutations such as BRCA-1 that do not cause disease but
confer significantly increased risk;
PREIMPLANTATION GENETIC SCREENING (PGS) This term is used for aneuploidy screening that is performed on
oocytes or embryos before IVF transfer. Such screening is used with
couples who are not known to have or carry a genetic abnormality.
Most commonly, FISH is used to identify the copy number of selected
chromosomes, and it is performed on a single blastomere
1. Single step approach (75 g 2 saat OGTT)
2. Two-step approach
– First step: 50 g 1 hours glucose screening
– Second step: 100 g 3 hours Oral Glucose Tolerence Test (OGTT)
GESTATIONAL DİABETES SCREENING
ACOG recommend a two-step approach to screen and diagnose
gestational diabetes
Screening should be performed between 24 and 28 weeks’ gestation
• 50-g screening test is followed by a diagnostic 100-g, 3-hour oral
glucose tolerance test (OGTT)
GESTATIONAL DİABETES SCREENING
First step: 50-g oral glucose challenge test. If plasma glucose level >140mg/dl Second step: 100-g, 3-hour oral glucose tolerance test (OGTT) Two or more of the venous plasma glucose concentrations listed
must be met or exceeded for a positive diagnosis.
GESTATIONAL DIABETES SCREENING
Measurement of cervical length by transvaginal ultrasonography:
Benefit of routin screening is not clear.
Fetal fibronectin: Benefit of routin screening is not clear.
Periodontal disease: increase the risk of preterm labor
independently. Treatment decrease the risk.
Bacterial vaginosis: is an independent risk factor of preterm labor.
SCREENING FOR PRETERM LABOR
There is no effectiv preventive measure.
Uterine artery Doppler:
Early diastolic notch • Etkili bir önlem yok• • Serum markers: are nonspecific.
SCREENING FOR PREECLAMPSIA
Group B streptococcus screening: prevent neonatal sepsis
effectively
HIV screening: ACOG recommends routin screening and treatment.
Treatment decrease perinatal transmission
Rubella, Hepatitis B, varicella screening : Immunisation is offered
according to immunoglobulin titer. After vaccination, contraception
is recommendedfor 3 months.
SCREENING FOR INFECTIOUS DISEASES
1. Williams Obstetrics 24.th edition-Cunningham et al. The McGraw-Hill
Companies-2014
2. Gabbe: Obstetrics: Normal and Problem Pregnancies, 6th ed., 2013
3. Current Obstetrics & Gyneacology , McGrawHill, LANGE, 12 th edition 2015
4. Moore KL, The Developing Human, Tenth Edition, Copyright © 2016 By
Elsevier, Inc.
5. Creasy And Resnik’s Maternal-fetal Medicine, Seventh Edition, Elsevier
Saunders, 2014
REFERENCES