prenatal diagnosis Flashcards
Examples of Prenatal Treatment:
- In congenital adrenal hyperpasia (CAH),
- Severe combbined immunodefficiencv disease
was the first
Indications of Prenatal Diagnosis:
? The pregnant woman is 35 years or older at the time of pregnancy.
¿She or her parents have had a previous child with a chromosomal abnormality.
¿She has a history of recurrent abortions, or her husband’s previous wife suffered from several miscarriages.
- strong family history is present.
*The couple is known to be carriers of a chromosomal translocation.
@Pregnant woman is affected with type (1 DM,)epilepsy or myotonic dystrophy.
She was exposed to viral infections, such as rubella or cytomegalovirus.
? The mother is exposed to excessive medication or to environmental hazards.
@History of of Down syndrome or some other chromosomal abnormalities are present in her or her family.
2 A history of single gene disorder is present in her or her family.
@ Her male relatives have Duchenne muscular dystrophy or severe hemophilia.
She is suspected of having some other harmful gene on X her chromosomes.
The fetus is diagnosed in utero to have some hereditary error of metabolism.
& The fetus is detected to be at increased risk for a
NTD
Noninvasive Techniques:
A. Fetal visualization:
• Ultrasound.
• Fetal echocardiography.
o MRI (magnetic resonance imaging).
• Radiography.
B. Maternal serum biochemistry tests. bloo
A. Separation of fetal cells from mother’s blood & examination.
Invasive Techniques:
A. Fetal tissue sampling:
• Amniocentesis.
• Chorionic villus sampling (CVS).
• Cordocentesis: Percutaneous umbilica
blood sampling (PUBS).
• Percutaneous skin biopsy.
• Other organ biopsies, including muscle and
liver bionsv.
B. Fetal visualization:
Embryoscopy
Fetoscopy
C. Cytogenetic investigations:
• Detection of chromosomal abnormalities.
• Fluorescent in situ hybridization (FISH).
D. Molecular genetic techniques:
O Linkage analysis using microsatellite markers.
• Restriction fragment length polymorphisms (RFLPs)
•Single nucleotide polymorphisms (SNPs):
• DNA chip.
• Dynamic allele-specific hybridization (DASH).
Neural Tube Defects (NTDs)
Due to
Deficiency folic acid
A family history of NTDs exists, or a child with NTDs is already present the family.
Maternal exposure to drugs that are associated with NTDs, such as valproic acid.
The mother has type 1 DM
Ultrasound findings indicated NTDs around wk.?
@ Ultrasound findings indicated NTDs around wk12
of pregnancy or later during the anomaly scan that is carried out at around wks. 18-20.
• AFPis produced by the
yolk sac & later by the liver.
? The foetal liver begins to produce AFP from the
6 weeks
The highest concentration of AFP in foetal serum occurs in the………………, then it falls progressively until term.
Amniotic fluid AFP increases steadily during early pregnancy reaching maximum levels at ………week.
& then declines.
• In NTD, MSAFP continues to rise & peaks in the ………/trimester.
• MSAFP test has the greatest sensitivity between …………weeks of gestation
The highest concentration of AFP in foetal serum occurs in the mid-trimester, then it falls progressively until term.
Amniotic fluid AFP increases steadily during early pregnancy reaching maximum levels at 13-14 week. & then declines.
• In NTD, MSAFP continues to rise & peaks in the third/trimester.
• MSAFP test has the greatest sensitivity between 16-18 weeks
of gestation
when 80% of NTD-affected pregnancies can be identified. It also can be
performed between 15-22 weeks’ gestation.
False Results of MSAFP
False negative results of MSAFP:
closed
(NTDS
False positive results of MSAFP: MSAFP levels increases with:
• Twins,
• MSAFP increases with gestational age.
• Abdominal wall defect.
o Gestational diabetes.
o In association with intrauterine growth retardation.
• Renal anomalies.
Diagnosis of NTDs:
combination of the MSAFP and US
NTDs can be differentiated from other fetal defects, such as abdominal wall defects, by acetyl-cholinesterase test carried out on amniotic fluid, that is obtained by amniocentes
If the levels of acetyl-cholinesterase and amniotic fluid AFP increased, it is suspected as a case of a NTD.
…………: Changes in chromosome
number by the addition of a whole or a part of a chromosome.
Aneuploidy
Abnormalities In Maternal Serum Analytes With DS:
Down Syndrome:
Increased serum levels of:
1. Total hCG.
2. Free BhCG.
3. Inhibin
Decreased levels of:
4.MSAFP.
5.Unconjugated estriol (uE3).
6.Pregnancy-associated plasma protein
(PAPP-A).
Inhibin is a hormone produced by the
gonads, pituitary gland
placenta
Inhibin A
Used in prenatal diagnosis at a gestational age
16-18 weeks.
Inhibin A is also used as a marker for
ovarian cancer.
Low MSAFP level indicates :
oDown syndrome.
•Other chromosomal aneuploidy.
•Failing pregnancies.
Estriol level in maternal serum depends upon:
- Viable fetus,
- A properly functioning placenta,
- Maternal well-being.
• In the
………. trimester, the level of
indication for the well-being of the fetus.
estriol (uE3) gives an
third
……….. produce enough ß-hCG,
trophoblasts
Serum hCG secretion in normal pregnancy. Note the rapid early increase ( doubling every …….
48 hrs. through days 70)
Down Syndrome:
Screening may be performed in
1st trimester.
Risks are calculated using a combination of:
- Maternal age.
- Analytes: maternal serum
free B- hCG & PAPP-A
US for measuring foetal
nuchal translucency thickness
increased in trisomy 21 pregnancies.
which is
Nuchal Translucency Test:
• It’s a measurement of the size of the translucent space behind the neck of the fetus using ultrasound ………. weeks of pregnancy, reflecting the amount of fluid that has accumulated under the skin of the fetus.
at 10-14 weeks of pregnancy
How Can You Confirm the Diagnosis?
o Karyotyping.
OFISH Technique.
Cystic Fibrosis (CF):
lethal ……..genetic disease
autosomal recessive
mutations of cystic fibrosis gene are found in
several nunared mutations or cystc morosis gene are lound In lames with the condition, but about 70% of mutations involve deletion of a single codon (so called ( AF508) on Chromosome 7 which is a deletion
of phenyl alanine at position 508.
• Fetal blood cells pass to maternal blood through the
• These cells can be collected safely
from
• placental villi]
12-18 weeks
• Fetal blood cells can be separated & DNA is isolated & amplified by PCR
& used in the diagnosis of:
o Cystic fibrosis.
o Sickle cell anemia.
o Thalassemia.
Amniocentesis:
14-20 wks.
- CVS: a
10-12 wks. of
-Cordocentesis; Percutaneous Umbilical
lood Sampling (PUBS):
Performed after
wks.
16
Fetal liver biopsy
17-20 wks.) for:
Skin Biopsy:
1 17-20
Fetal muscle biopsy
- At 18 wks. for diagnosis of Becker-Duchenne muscular dystrophy.
measurement of MSAFP & either total hCG or free B-hCG. Programs achieve detection rates of about 60% for a false-positive rate of about 5%.
Addition of measuring …………..&……….improves the sensitivity &humber of false positives.
serum uE3& Inhibin-A
