Prenatal Testing

What is the goal of prenatal screening tests?

To use non-invasive, low risk, indirect tests to identify women/pregnancies at high enough risk for common birth defects such as aneuploidies or neural tube defects to warrant invasive tests

What are typical prenatal screening tests?

Ultrasound, cell-free DNA (cfDNA) in maternal blood, carrier screening, maternal serum analytes

What are 1st trimester maternal serum analytes tests?

hCG, PAPP-A

What are 2nd trimester maternal serum analytes tests?

hCG, uE3 (unconjugated estriol), Inhibin, AFP

What is Multiple of Median (MoM)?

Ratio between the patient’s results and the median result appropriate for the gestational age of the fetus

What is the indication of need for further testing with MoM?

Values <0.5 or >2.5 MoM

What is an integrated screen maternal serum analyte test?

Uses results from both 1st and 2nd trimester screens

What is sensitivity?

The detection rate; the proportion of individuals with a condition correctly identified as “positive” by a screening test

What is specificity?

The proportion of individuals without a condition who are correctly identified as “negative” by a screening test

What are the indications for prenatal ultrasounds?

Establishing gestational age, number of fetuses, monitoring fetal growth, amniotic fluid volume (oligohydramnios, polyhydramnios), and detecting structural abnormalities

What is nuchal translucency?

Thickness of the echo-free (dark) space; increased NT associated with an increased risk for fetus with trisomy; combined NT measurement and 1st trimester screen can be used if cfDNA is inconclusive

When is cfDNA tested?

>10 weeks gestation

What does cfDNA test for?

Excess chromosome material (trisomy)

What are the limitations of cfDNA testing?

Requires diagnostic test confirmation, false positives, variable PPV, test failure, doesn’t screen for structural anomalies or most single gene and metabolic disorders

Carrier testing can be offered…?

Pre-pregnancy or during pregnancy

What are common carrier screening testing for caucasians?

CF, SMA, and fragile X

What is AFP?

Alpha-fetoprotein

What values of AFP MoM indicate an increased risk of NTD?

>2.0 to 2.5 MoM

What can cause an elevated MSAFP?

Gestational age older than calculated, multiple gestations, NTD, abdominal wall defects, GI defects, cystic hygroma, placental abnormality, renal abnormalities, urinary obstruction, PCKD

What test can be ordered after an elevated AFAFP?

Nervous system-specific acetylcholinesterase

What does a low MSAFP indicate?

Increased risk of trisomy

How are neural tube defects prevented?

Folic acid

When do neural tube defects occur?

3rd to 4th week of fetal embryonic development

What are examples of prenatal diagnostic tests?

Pre-implantation testing, chorionic villus sampling (CVS), Amniocentesis (Amnio), and percutaneous umbilical cord sampling (PUBS)

What are the indications for prenatal diagnostic testing?

Advanced maternal age, family history of chromosomal abnormality, increased risk based on positive screening, increased risk for NTD, history of genetic disorder, maternal medical condition

What is an example of pre-implantation testing?

Blastomere biopsy

What is chorionic villus sampling (CVS)?

Performed between 10-13 weeks gestation, biopsy of developing placenta, can allow for first trimester termination

What are the disadvantages of chorionic villus sampling (CVS)?

AFAFP cannot be assayed at this stage, so NTD testing must be done, risk of mosaicism, maternal cell contamination, spontaneous abortion can occur

What is amniocentesis?

Performed between 10-15 weeks gestation, US done before to confirm, needle collects small sample of amniotic fluid

What can amniocytes be used for?

Chromosomal analysis, DNA assessment, and biochemical testing

What can amniotic fluid be tested for?

Protein detection, enzyme analysis, and metabolic products

What is percutaneous umbilical blood sampling (PUBS)?

Sample of fetal blood collected from umbilical cord, performed between 19-21 weeks, typically done after culture of amniocytes has failed or yielded abnormal results

Why are all newborns screened 48 hours after birth?

To identify pre-symptomatic infants with diseases for which early intervention can prevent or decrease consequences