prenatal diagnosis Flashcards
basic principles of prenatal screening
- Screen the General Population for Common Disorders - Down syndrome, birth defects. 2. Offer Screening to at Risk Groups for Clustered Disorders- Cystic fibrosis, Tay Sachs. 3. Offer Screening to Families with Known Disorders
Indications for Ultrasound
Fetal presentation, Suspected multiple gestation, Establish EDD, Suspected fetal death, Suspected oligohydraminos, Abnormal AFP , fetal anatomy, placenta location
Fetal presentation, Suspected multiple gestation, Establish EDD, Suspected fetal death, Suspected oligohydraminos, Abnormal AFP , fetal anatomy, placenta location
How is gestational age estimated in first trimester
Crown-rump length on US- can only be used early because later on the fetus extends and flexes its spine
How is gestational age estimated in 2-3 trimester
Biparietal diameter, abdominal circumference, femur length on US
screening for trisomies and neural tube defects
Check maternal serum for alpha-feto protein, unconjugated estriol, HcG and inhibin A. On US look for nuchal translucency
list the non-invasive vs invasive testing methods
non invasive: maternal serum for analytes (ie. AFP), karyotype, fetal cells. Also ultrasound. Invasive: amniocentesis or chorionic villus sampling, both have small risk to fetus.
indications for invasive diagnostic methods
Advanced maternal age (defined as > 35 years old at due date), Positive aneuploidy screening test (biochemical and/or ultrasound), Abnormal ultrasound findings: anatomic, IUGR, amniotic fluid volume, Known parental chromosome rearrangements, Previous affected child
Where is alpha feto protein made
fetal yolk sac and liver
What is alpha feto protein
major blood protein of fetus- like albumin. It is not present in maternal blood normally, so any AFP is from the fetus.
Causes of high and low alpha feto protein
high: neural tube defects (the defect causes release of more AFP into the amniotic fluid), omphalocele (abd defect), gastroschisis (abd defect). Low: downs syndrome
list conditions which Ashkenazi Jews are at increased risk for
AR conditions- Tay Sachs, Canavan disease, Gaucher disease, Nieman-Pick disease, Bloom syndrome, Fanconi anemia C, and mucolipidosis
What is Tay Sachs
AR lysosomal storage disorder caused by a deficiency in hexosaminidase A. Gangliosides accumulate in the body, and their presence in the CNS leads to blindness, severe neurologic disease, and death, usually by the age of 6
Diagnosis of fetal Tay Sachs
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 samples obtained via amniocentesis or CVS
Diagnosis of hemoglobinopathies
Thalassemias: MCV <80% followed by hemoglobin electrophoresis once iron deficiency is excluded
Cystic fibrosis diagnosis
Prenatally or newborn. Prenatal testing of CF gene . 75% have delta F508 deletion. Panels are available to test for less common mutations, but not all mutations are known so some may be missed. Start by testing mom, then offer partner testig if mom is positive. If both are affected, CVS or amniocentesis is offered.
Screening for down sydrome
analyzes maternal blood: low AFP, increased hCG, low estriol, increased inhibin A, decreased PAPP-A. Levels of analytes are reported as multiples of the median values for fetuses of same gestational age. The ultrasound imaging component of the integrated screen includes a measurement of fetal nuchal thickness or translucency, due to increased fluid around neck.
screening for trisomy 18
Maternal serum: low AFP, low unconjugated estriol, low hCG, decreased PAPP-A. Inhibin A not used. Nuchal translucency on US
screening for trisomy 13
decreased PAPP-A in maternal serum
screening for neural tube defect
maternal serum: increased AFP. Amniocentesis: increased AFP and acetylcholinesterase
Circulating Cell Free Fetal DNA & Intact Fetal Cells
small amounts of cell free DNA from the fetus can be detected in maternal blood- currently being used to look at chromosomes 13, 18, 21, X and Y. Massively parallel sequencing compares the levels of cell free chromosomes compared to a normal range.
amniocentesis
needle used to collect amniotic fluid and fetal cells. Can be done btw 14-20 weeks, using US guidance
Chorionic Villus Sampling
A catheter is passed into the placenta under ultrasound guidance. Trophoblast cells from the chorionic villi are obtained. CVS can be safely performed from 9.5 -12.5 weeks gestation. Does not detect neural tube defects
Percutaeous umbilical cord blood sampling
involves introducing a needle into the umbilical cord near its site of insertion into the placenta and extracting fetal blood. Highly invasive, the complication rate is 1 to 2%, and is largely dependent on the associated fetal status. This is usually reserved for assessing fetal anemia and diagnosing fetal infections in severely compromised fetuses.
pre-implantation genetic diagnosis during IVF
polar body biopsy, blastomere biopsy or aspiration from the six- to eight-cell embryo at 2 to 3 days, and trophectoderm biopsy from the 5- to 6-day blastocyst. Blastomere biopsy on day 3 is the most common technique
