Prenatal Diagnosis Flashcards
What is the definition of screening?
The identification, among apparently healthy individuals, of those who are sufficiently at risk of a specific disorder to justify a subsequent diagnostic test or procedure
What three criteria are needed for a screening test?
- Should identify women who are at increased risk, prior to having definitive diagnostic test
- Should be offered to all pregnant women who are considered to be only at population risk
- Should be beneficial to those who receive it
At what point should all mothers have amniocentesis?
When the risk of all diagnosable chromosomal abnormalities exceeds the reported risk of miscarriage, commonly around 35 years maternal age.
What is used for first trimester chromosomal abnormality screening? What would be found in abnormal?
PaPP-A - Pregnancy-associated plasma protein A - decreased in all chromosomal abnormalities
hCG - human chorionic gonadotropin - DECREASED in all chromosomal abnormalities, but INCREASED in Down’s syndrome
Nuchal translucency - thickness behind fetus’ neck - increased in all chromosomal abnormalities
What are the two tests for second trimester chromosomal abnormality screening?
- Triple test (MSAFP, hCG, estriol)
2. Quad test (MSAFP, hCG, estriol, inhibin)
What is MSAFP and when is it increased vs decreased?
Maternal Serum Alpha Feto Protein
Increased in Neural Tube Defects
Decreased in Down Syndrome
What are typical quad test findings for a Down syndrome baby?
MSAFP - low
hCG - high
estriol - low (fetal-placenta unit not well intact)
inhibin - high (produced in placenta)
What are the ultrasound findings for a baby with Down syndrome?
- Nuchal translucency is increased (skin of neck separation from underlying tissue)
- Nasal bone - reduced in length or absent
- AV cardiac defect
- Duodenal atresia - DOUBLE BUBBLE sign
What is the correct series of screening / diagnostic tests for Down syndrome?
- Run first trimester screening for PaPP-a, NT, hCG.
- If results indicate Down’s syndrome -> immediate diagnostic testing. If results are negative, proceed to second trimester screening (quad test)
- If second trimester screening is positive -> diagnostic testing
Make sure to test fetus if first semester screen was positive even if second semester was negative.
If MSAFP is high, which is amniocentesis checking for?
High acetylcholinesterase, which indicates a neural tube defect.
What does folic acid reduce the risk for?
Both orofacial clefting and neural tube defects
What are potential ultrasound findings for trisomy 18 (Edward)?
- Omphalocele - intestines not returning to body properly
- Rocker bottom feet
- Clenched hands
- Polyhydramnios
- Cystic hygroma
- CNS defects or neural tube defect
What are potential ultrasound findings for trisomy 13?
- Omphalocele as well
- Echogenic kidneys
- Polydactyly
- Cleft lip / palate
- Holoprosencephaly or microcephaly
What are potential ultrasound findings for Turner syndrome?
- Cystic hygroma
- Cardiac defects - coarctation of the aorta
- Horseshoe kidneys
- Hydrops - accumulation of fluid
How does ffDNA work? Is this considered diagnostic or screening?
Free fatal DNA - derived primarily from syncytiotrophoblasts in the placenta, fetal DNA appears as early as 5-7 weeks and is 5-25% of circulating DNA in mother’s serum. Next generation sequencing makes detect of chromosomal abnormalities 99% of the time and requires only a blood draw.
Considered a SCREENING test. Need to confirm definitively with appropriate diagnostic procedure
What is chorionic villous sampling, what are its two routes, and its major advantage? Disadvantage?
Sample the chorionic villous either transcervically or transabdominally.
Advantage: available early in pregnancy
Disadvantage: Quite difficult to do, and there may be some placental mosacism which makes it wrong
What is the biggest fetal risk of CVS?
Increased risk for hemangioma
What are the advantages and disadvantages of amniocentesis?
Advantage: easiest to perform, highly reliable cytogenetic results
Disadvantage: Results are not available til later (16-18 weeks), fetal trauma and Rh- blood types are at risk.
Why is early amniocentesis (10-13 weeks) no longer done?
Higher rate of fetal loss, since the 20 mL of amniotic fluid needed is a larger proportion of the amniotic fluid at that time
What is PUBS, and what are the advantages and disadvantages?
Percutaneous umbilical blood sampling
Advantage: Full fetal karyotyping + hamtology and serology, can assess CVS mosacism
Disadvantage: Must be done later in gestation, hardest to do, higher fetal loss
What is the bane of prenatal diagnosis?
Mosaicism
What is pseudomosaicism vs constitutional vs confined placental mosacisim?
Pseudomosaicism: Mutation arose during cell culture
Constitutional: Recognized in amniocentesis only, a true mosaicism of the embryo
Confined placental: Mosaicism of placenta only, encountered via chorionic villous sampling
What two things are at higher risk when mosaicism is present?
- Uniparental disomy
2. Fetal growth restriction
What are some uncommon teratogens?
- Phenytoin - epileptic drug
- Retinoic acid - vitamin A
- Tetracycline
- Lithium - bipolar
- Carbamazepine - epileptic, bipolar
What are some infectious teratogens?
TORCH
Toxoplasmosis
Rubella
Cytomegalovirus
Also: Varicella
Are pre-gestational diabetes associated with chromosomal abnormalities? What is it associated with?
No, but is at increased risk for major malformations, including:
Cardia anomalies
Neural tube defects
Renal anomalies
Most specific: Caudal regression syndrome
What is caudal regression syndrome?
Most specific major anomaly detected with pregestational diabetes (not gestational)
Sacral agenesis / abnormal fetal development of lower spine
What maternal hemoglobin A1c level is the threshold for congenital malformation increased risk?
<7%. Massive risk increase at >10%
What does maternal obesity put the baby at risk for?
NTD, orofacial clefts, cardiac malformations, anorectal atresia, hydrocephaly
When is preimplantation genetic testing used?
For IVF - remove 1-2 cells of trophoectoderm on blastomere
What is preimplantation genetic screening vs diagnosis?
It is only considered diagnosis if the parents are known to carry a mutation or balanced chromosomal rearrangement
When is gender selection used in IVF?
If there are X-linked mutations the baby is at risk of inheriting
What is the mechanism by which maternal diabetes increases congenital malformations?
Hyperglycemia-induced oxidative stress
What is the increased risk for congenital malformations with assisted reproductive technologies? Why?
30%!!!!
ART may interfere with epigenetic mechanisms, like imprinting of genes
What disease has the greatest relative risk of occurring with assisted reproductive technologies?
Beckwith-Wiedemann Syndrome - imprinting error on chromosome 11 - sixfold increase in relative risk. An overgrowth syndrome often associated with paternal uniparental disomy
