Prenatal Diagnosis Flashcards
Basic principles behind and techniques deployed during prenatal diagnosis
- Offer screening to the general population for common disorders such as Down Syndrome and Birth Defects.
- Mother’s blood
- Amniotic fluids
- Ultrasound
- Offer screening to at risk groups for clustered disorders such as Cystic Fibrosis and Tay Sachs
- Offer screening to families with known disorders
- Techniques (comprehended as components of screening)
- Clinical history
- Pedigree analysis
- Diagnostic serum test in patient
- Invasive testing of the fetus via amniocentesis or chorionic villous sampling (CVS)
- Options counseling
Prenatal testing @ mother’s blood
- Hb electrophoresis ==> Sickle cell disease
- DNA analysis for single gene disorders ==> Cystic Fibrosis (CF)
- Karyotypes ==> prior infant with aneuploidy
Prenatal testing @ fetal environment
- DNA analysis ==> CF
- Karyotyping ==> Trisomies
- Biochemical markers
Differentiate between targeted and population-based screening for prenatal diagnosis
Screening programs target diseases which are sufficiently frequent, severe, and the amenable to existing diagnostic techniques.
Prenatal diagnostic screening programs can take a population based approach, such as screening for neural tube defects or Down syndrome. They can be directed at specific population subgroups, such as screening for thalassemia.
Alternatively, prenatal diagnosis can be highly targeted, with testing offered to families known to be carriers of certain diseases or genes, such as hemophilia.
Tay Sachs screening program
Molecular DNA testing detects 94 % of heterozygotes, while the analysis of the ratio of hexosaminidase A to total hexosaminidase detects 98 %
In at risk pregnancies, fetal DNA can be evaluated from amniocentesis or CVS samples.
Thalassemias screening program
- An MCV of greater than 80 percent* excludes heterozygosity for α or β-thalassemia.
- With MCV < 80% → If iron deficiency is not found, hemoglobin electrophoresis showing elevated hemoglobin A2 and hemoglobin F will confirm β-thalassemia.
- DNA-based testing is necessary to detect α-globin deletions, which cause α-thalassemia.
Sickle Cell screening program
Sickle cell anemia screening is done by an MCV <80% followed by hemoglobin electrophoresis once iron deficiency is excluded
CF screening program
Cystic fibrosis screening is one of several tests performed on all newborns in Colorado
The CF gene product (protein) cannot be assayed directly so genetic testing is therefore the current standard for prenatal diagnosis
importance of knowing the correct gestational age in the context of prenatal diagnosis.
In the context of Down’s Syndrome, for example, the ‘normal’ levels of analytes DO change during pregnancy; therefore, knowing the gestational age is critical for an accurate interpretation to transpire.
ultrasound findings used to estimate gestational age and fetal weight.
Specific ultrasound criteria are used for estimating gestational age based on ultrasound. Anatomic features must be visualized in particular planes and markers placed precisely for measurements to be accurate.
In the first trimester, the crown rump length is used to estimate age
Estimating fetal weight beyond 12 weeks
Beyond 12 weeks, the biparietal diameter and abdominal circumference are used. Transverse image of the head used for biparietal diameter (double-headed arrow) and head circumference (dashed oval). The image is taken at the level of the cavum septum pellucidum (CSP). The midline echo (arrowhead) is centered.
Evaluation of gestation age/weight in second trimester
Estimating gestational age and fetal weight in the second trimester involves using the abdominal circumference (AC) measurement at the level that the umbilical vein (UV) passes through the liver. Note the symmetric rib (R) images. The stomach (St) and spine (Sp) are also labeled.
Screening programs for Down’s
The current integrated screening program analyzes maternal blood for several compounds: α-fetoprotein (MS-AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), inhibin A, and pregnancy-associated placental protein A (PAPP-A).
The ultrasound portion of the integrated screen includes a measurement of fetal nuchal thickness or translucency. Down’s Syndrome has ↑ fetal nuchal translucency.
Levels in maternal serum meaning in Down’s screening program
The levels of these analytes are reported as multiples of the median values (MoM) for singleton fetuses at the same gestational age. The 95% detection rate for Down syndrome occurs when approximately 5% of patients will have a “positive” screen result. This is defined as a risk equal to or greater than that of a woman who will be 35 years of age on her due date. The integrated screen is also used to calculate the risk of carrying a fetus with trisomies 13 or 18
Maternal serum levels associated w/trisomies
- Trisomy 21
- aFP = Low
- uE3 = Low
- hCG = Increased
- inhibin = Increased
- PAPP-A = Decreased
- Trisomy 18
- aFP = Low
- uE3 = Low
- hCG = low
- inhibin = normal
- PAPP-A = Decreased
- Trisomy 13
- aFP = Normal
- uE3 = Normal
- hCG = normal
- inhibin = Normal
- PAPP-A = Decreased
