Indications for prenate cytogenetic diagnosis

Aneuploidy

most common chromosome ab in pregnancy

most affected emb abort early in first trimester

many before clinical signs of pregnancy

most common forms of aneuploidy that can survive to term

down syndrome, edwards, patau, and s ex ch aneuploidies

Down syndrom

+21

Edwards syndrome

+18

Patau syndome

+13

S ex chromosome aneuploidies

45 X, 46 XXY, 46 XXX

Prenatal cytogenetic diag test

percutaneous umbilical blood sampling PUBS

chorionic villus sampling CVS

amniocentesis

Test and risk for miscarriage

CVS 1/100

amniocentesis 1/200-400

PUBS 1-2/100

tests should only be done in high risk pregnancy

Screen tests

are based on method and time

screen test based on method

maternal blood test: triple screen test and quad screen

ultrasound: sonogram

Screen test based on time

First trimester screen and second

Transvaginal scans

probe transducers are used inside vagina to generate sonogram. most often used during early stages of pregnancy

standard ultrasound

traditional ultrasound exam uses transducer over abdomen to view fetus

doppler ultrasound

produces slight changes in frequency of ultrasound

3-d ultrasound

used to develop 3-d images

Obstetric ultrasound scans

safe non invasive accurate cost effective investigation fo fetus

real time scanner using high frequency sound waves 3.5-7.0

sound waves emitted from and reflected back to transducer

ability of sound waves to be reflected back from tissue varies

sound waves generate the image of fetus

when and why ultrasound is used

ultrasound preformed anytime when ab is suspected

in first trimester (7 weeks)

confirm viability, confirm heartbeat, measure crown-rump length, confirm molar or ectopic pregnancy, assess abnormal gestation.

Second trimester ultrasound

diagnose fetal malformation

13-14 weeks DS

18-20 weeks congential malformation

confirm multiple pregnancy, verify dates and growth, identify excessive or reduced levels of amniotic fluid, evaluation of fetal well-being.

3rd trimester ultrasound

identify placental location, confirm intrauterine death, observe fetal movements, identify uterine and pelvic abnormalities assist in other prenatal diagnostic procedures amniocentesis, cvs, pub

Maternal blood screening test

AFP, hCG, uE3, inhibin-A, PAPP-A

Alpha Fetoprotein AFP

plasma protein produced by fetal yolk and fetal liver

similar to albumin chemically and physically

can be detected during pregnancy in both amniotic fluid and mother blood AFAFP and MSAFP

MSAFP

small amount of AFP passes through mothers blood and rises until late pregnancy

AFAFP

fetus has neural tube defect there will be leakage of fetal plasma into amniotic fluid

AFP MSAFP test

done between 15-18 weeks after last menstrual period

first detectable at 12 weeks

MSAFP increases 15% per week to 25 weeks 250 ng/ml

declines 26 weeks

drops rapidly 2 ng/ml at birth

abnormal MSAFP levels

high levels suggest developing baby has neural tube defect

spina bifida or anencephaly

Neural tube

forms from ectoderm and develops into brain and spinal cord

Neural tube defects

if fails to close correctly results in anencephaly or spina bifida

anencephaly it fails to form at skull

spina bifida fails to close at bottom of spine

Low levels of AFP

combine with ab levels of hCG and estriol may indicate baby has +21,+18, or another type of abnormality

Factors that affect MSAFP levels

gestational age, mothers age, weight, ethnicity (african american women higher asian women lower), and multiple fetuses

Human chorionic gonadotropin hCG

produced in placent

first detected by blood test 11 days after conception and 12-14 after urine test

will reach peak at first 8-11 weeks then decline

85% of normal pregnancy hCG will double every 48-72 hours

Low hCG can indicate

miscalculation of pregnancy dating, possible miscarriage, ectopic pregnancy, edward syndome

High hCG levels

Miscalc of pregnancy, molar pregnancy, multiple pregnancy, down syndrome

unconjugate estriol uE3

estrogen produced by fetus and placent.

low levels can indicate DS or ES

inhibit A

protein produced by placenta and ovaries

high can indicate DS

pregnancy associated plasma protein a PAPP-A

low can indicate DS

Advanced maternal age

35 or older at delivery or 31 and older with twins is most common indication for prenatal diagnosis

significant determinant of risk of all trisomies, structural rearrangements, 47, XXY and marker chromosomes

Advanced maternal age is not risk for

45 X triploid tetraploid or 47 XYY

Positive family history

parent carries balanced translocation

previous child or stillborn with ch ab

previous child with neural tube defect hydrocephalus

Abnormal ultrasound scan result

cystic hygroma

heart abnormalities (ventricular septal defect tetralogy of fallot)

hypoplasia or absence of nasal bone

Positive result for first trimester screen

ultrasound can scan for risk of abnorm inclucing +21, +18

maternal blood screen can measure hCG and PAPP-A

ultrasound eval measures nuchal translucency

done between 11-14 weeks of pregnancy

using age and results can help determine risk

in pregnancy where fetus carries defect +21 +18

levels of PAPP=A tend to be decreased and hCG increased

nuchal translucency is larger than normal (space between fetus neck).

detection rate around 90%

Even if positive result

more test are needed

Positive result from 2nd trimester

triple test given hCG, uE3 and aFP in maternal serum

quad test hCG uE3 AFP and inhibin A in maternal serum

usually between 15-20 week of pregnancy

Fetus carrying down syndrome

AFP uE3 low and hCG and inhibin A high

Fetus carry edwards

uE3 and hCG low and AFP variable

baby with open neural tube defect

has opening in its spine head or abdominal wall that allows higher than usual amounts of AFP to pass into mother blood