Prenatal Genetic Screening

congenital malformations

anatomical/structural abnormalities present at birth, cause 20% of perinatal deaths

causes of congenital malformations

genetic factors, environmental factors, multifactorial inheritance

teratogens

substance capable of causing abnormal structure in an embryo

sensitive period concept

certain structures are more sensitive to teratogens at certain times, a noxious event cannot influence development if development is completed

categories of teratogens

physical agents, chemical agents, maternal factors

physical teratogen examples

radiation, high heat (hyperthermia) over 38.9 Cme

mechanical teratogen examples

uterine abnormalities, oligohydramnios, amniotic bands

how often are congenital malformations caused by drugs/chemicals?

not often

chemical teratogen examples

alcohol, antithyroid drugs, coumadin, daunorubicin, DES

some effects of fetal alcohol syndrome

growth restriction, mental development issues, congenital heart defects, joint anomalies

what are some maternal factors that can negatively affect the fetus?

DM, sickle cell anemia, advanced age, hx of children w/ chromosomal disorders, exposure to teratogens

what congenital malformations can antithyroid drugs cause?

polydactyly & goiter

chromosomal abnormalities

genetic defects that can be diagnosed and identified microscopically

what are the typical effects of chromosomal abnormalities?

mental development issues, high mortality rates, multiple anatomic abnormalities

what are the different genetic anomalies that can result in genetic disease?

-abnormal # of chromosomes

-abnormal structure of chromosomes

-defects on 1 gene

karyotype

the complete chromosomes of a cell

photomicrograph

photo of the isolated karyotype

euploid

normal set of 23 pairs of chromosomes

aneuploid

too many or too few chromosomes

trisomy

an extra chromosome

triploidy

an extra set of chromosomes

genotype

genetic makeup of an individual

phenotype

physical expression of a genetic makeup

autosomal dominant

one parent is affected by the trait, its evident in every generation, probability of passing it is 50%

autosomal recessive

both parents are unaffected by the trait, trait may not be evident every generation, recurrence risk for offspring after presentation of the trait is 25%

genetic screening

performed between 11.5-13.5 wks, 2 parts: nuchal translucency & maternal blood test, detects 85% of chromosomal disorders

what is the advantage of including nasal bone measurements in genetic screens?

it increases detection of trisomy 18 or 21

what is the next step if abnormal results are found during a genetic screen?

chorionic villus sampling is offered

nuchal translucency screening

measures the fluid at the back of the fetal neck, taken between 11.5-13.5 wks, calculates risk of trisomy 18 or 21, measurement is taken inner to innera

abnormal nuchal translucency findings

NT > 3mm, if abnormal measurement is found w/ a normal karyotype its assoc w/ heart defects

normal or abnormal?

abnormal

PAPP-A & beta hCG screening

produced by trophoblastic tissue, low levels indicate abnormal implantation, placental placement, or risk of trisomy 21

non-invasive prenatal testing NIPT

serum screening test that indicates if theres an increased risk of trisomy 18, 21 or 13, performed after 10 wks, offered to pts w/ 1 fetus and risk factors for aneuploidy

chorionic villus sampling CVS

performed between 9-12 wks transcervically or transab, trophoblastic cells are taken for culture and karyotyped, diagnosis can be made earlier than amniocentesis

why was this CVS performed transabdominally?

because of the position of the placenta. transabdominally allowed the best access with least interference to the fetus

quad/triple screen

aka multiple-marker screening, screening for biochemical markers for fetal abnormalities, includes: MSAFP, hCG, unconjugated estriol uE3, inhibin-A

what conditions can the quad screen diagnose?

open neural tube defects, trisomy 21 & 18

alpha fetoprotein AFP

glycoprotein produced in the fetal liver that crosses the placental into the maternal serum

what are elevated levels of AFP associated with?

incorrect dates, multiple gestations, open neural tube defects, abdominal wall defects, hemorrhaging, placental chorioangioma, maternal HCC

what are decreased levels of AFP associated with?

incorrect dates, chromosome abnormalities, fetal demise

in trisomy 18 what will the lab values look like?

decreased MSAFP, hCG, uE3

in trisomy 21 what will the lab values look like?

decreased MSAFP & uE3, elevated hCG & inhibin-A

amniocentesis

evaluates the amniotic fluid level of AFP & acetylcholinesterase levels for chromosomal karyotyping, usually performed at 16 wks

what genetic screenings can be performed during the 1st trimester?

nuchal translucency, NIPT/cell-free DNA testing, beta hCG, PAPP-A, CVS