Screening for Fetal Chromosomal Abnormalities

Pairs well with the 2021 Russian River Pinot Noir Davis Family Vineyards 

Five Pearls

1. Cell-free DNA screening has the best sensitivity and specificity of all screening methods. But before you order it, it's best to get a prenatal ultrasound

2. Best non-cell-free screening modality is the sequential integrated serum screen (1st-tri serum + NT ultrasound + 2nd-tri serum)

3. Formal anatomy survey should be offered at 18 - 22 wga; can identify soft markers for T21 and T18

4. Prenatal genetic screening should be offered to all pregnant women regardless of risk profile

5. Anything that doesn't add up, it's best to just refer to a genetics counselor or even your friendly MFM for clarification.

The (very) Basics of DNA and Reproduction

* apart from RBCs and cornified cells of your skin, hair, and nails, every one of your body's cells has a nucleus

* gametes (sperm or ova) are haploid, meaning their nuclei contain 23 chromosome

* somatic cells are diploid, meaning their nuclei contain 23 pairs of chromosomes (46 chromosomes total)

* when a sperm meets an ovum, magic happens!

* the sperm fertilizes the egg to create a zygote: the 23 chromosomes of the sperm combine with the 23 chromosomes of the ovum

* for the next 24 hrs, the zygote undergoes rapid, mitotic division ("cleavage"); after about 100 cells have been formed, it's called a blastula

* the total mass of the original zygote has not changed, it has merely divided, and each individual cell is called a blastomere

* the blastula consists of a spherical layer of cells called the blastoderm surrounding a yolk-filled cavity called a blastocoel.

* in mammals, the blastoderm arranges itself into an inner and outer layer of cells, the embryoblast and trophoblast, respectively. The former will go on to form the fetus, the latter the placenta.

Illustration credited to Libretexts.org (click image for source)

* the embryoblast undergoes gastrulation, where it rearranges itself into three germ layers: endoderm, mesoderm, and ectoderm, and the fetus gradually develops from here

* any chromosomal defect - whether parts missing, extra copies, or missing copies - can lead to abnormalities in the development of the fetus

Illustration credited to Libretexts.org (click image for source)

Epidemiology of chromosomal abnormalities

* chromosomal abnormalities are found in 1-in-150 pregnancies

* they are more common in the 1st trimester (aneuploidies are the most common reason for early pregnancy loss)

* incidence of aneuploidies increases proportionately with maternal age and presence of a paternal chromosomal abnormality or translocation

* Trisomy 21 (Down syndrome) is the most common chromosomal aneuploidy among live infants (1-in-700 live births)

* although risk of aneup