Topic 11b: prenatal screening Flashcards
what are the goals of a prenatal disgnosis consultation?
- To assess the chance for a fetus to have a genetic condition or congenital anomaly
- To provide the parents with information about the condition, its etiology, prognosis, and management (e.g. termination of pregnancy)
- To provide psychological support if TOP is elected, and/or coordinate multidisciplinary pre- and postnatal care if pregnancy continued
what are some indications for referral of prenatal diagnosis?
- Abnormal (positive) results of maternal serum screening for trisomy 21, 18, 13
- abnormal findings on the ultrasound (e.g. club foot, heart defect)
- Previous child with a chromosome abnormality
- Parental chromosome abnormality
- Family history of other genetic disorder or malformation
- Teratogen exposure (e.g. alcohol, drugs, infection)
- Infertility, multiple miscarriages
what used to be the criteria to undergo prenatal screening/diagnosis? why?
to have a pregnancy over the age of 35 (since the risk of numerical chromosomal abnormalities increases with maternal age)
the chance of having an embryo with chromosomal abnormalities ________ as the pregnancy progresses.
decreases, more cases of fetal demise so of those that do survive has greater chance to be healthy
what is the goal of prenatal screening programs?
Designed to provide a woman with a more precise chance than that based upon maternal age alone, that she is carrying a fetus with one or more specific health conditions (e.g. trisomy 21, 13, 18 or congenital malformation)
what are the key charcateristics of prenatal screening programs? and what do we want ideally?
- sensitivity: % affected fetuses that have positive screen result (i.e. detection rate(
- Positive predictive value: % screen positive cases that are actually affected
- False positive rate: % screen positive cases that are actually unaffected
we want to maximize sensitivoty and minimize FP
what are the options for prenatal screening?
- maternal serum screening
- noninvastive prenatal screening
what is maternal serum screening?
This is when we look at concentrations of certain fetalplacental products present in maternal circulation at 16 weeks of preganancy (AFP, uE3, hCG)
How do AFP, uE3, and hCG change when there is increased risk of trisomy?
AFP and uE3 decreases
hCG increases
in the 1980s, when was maternal serum screening done and what was its sensitivity and FPR?
done in the 2nd trimester (16 weeks) and had a 70% sensitivity with ~5% FPR
what factors affect serum screening performance?
- gestational dating (Inaccurate dating can cause false positives)
- maternal weight (dilution effect)
- Insulin-dependent diabetes mellitus (some markers are lower)
- smoking (affects risk calculations)
- assisted reporduction (IVF pregnancies higher risk of false positive screening)
maternal serum screening can be used for detect of which condition?
Increased maternal AFP associated with open neural tube defects (NTD) – Can detect ~85% of cases of NTD
but now ultrasound better
in 1990, how did maternal serum screening evolve/change?
- now, 1st trimester screening (11-13 weeks)
- can also integrate Nuchal translucency thickness (NT) via ultrasound
- new serum markers: Pregnancy-associated plasma protein A (PAPP-A) and β-hCG
now sensitivity of 79-90% with 5% FPR
first line in Quebec
what is nuchal translucency and how does it change with down’s syndrome?
the thickness of the space behind the baby’s neck
having a space is normal (normal that fluid is there) but an increase in thickness may indicate increase risk of down’s syndrome
in 2000, how did maternal serum screening evolve?
now integrated screening: measure NT, PAPP-A in 1st trimester and AFP, uE3, hCG, inhibin-A in 2nd trimester
this has a 94% detection rate and 5% FPR but not first line since results delivered later in pregnancy
what is noninvasive prenatal screening? how does it compare to maternal serum screening?
- meausure circulating cell-free fetal (i.e. placental) DNA.
- this can be done starting from 10 weeks gestation and has a 99% detection rate with < 2% FPR
- this is also non-invasive and better than maternal serum screening but also very expensive so not publically funded/not first-line
in quebec, who is eligible for Quebec-funded NIPT?
- Previous pregnancy with T21, T13, T18
- Maternal age ≥ 40y at EDD
- Twin pregnancy (As of April 2023) – sreening less effective in twins
- Genetics consult
what screening can be done in the 2nd trimester?
serum screening (AFP, uE3, hCG) and ultrasound screening (can find subtle anomolies such as cleft palate, congenital heart defect, club foot)
what are the cirrent guidelines regarding prnatal screening/tests?
- Screening recommended as first step, no matter what age
- Offer invasive prenatal diagnosis if screening results are positive
what is the purpose of screening?
- Can identify pregnant patients from general population (not just advanced maternal age) who are at increased risk, offer diagnostic test
- Can identify patients who are at decreased risk, avoid invasive test
what are prenatal dignosis techniques?
- Chorionic villus sampling (CVS)
- Amniocentesis
what is Chorionic villus sampling (CVS)? when is it usually done?
take a small sample of the placenta and analyze the cells (either go through vaginally or through the abdomen; this is done at 11-14 weeks
what are the risks/issues of Chorionic villus sampling (CVS)?
1% chance of miscarriage and in the analysis itself there may be technical issues (mosaicism – fetal and placental cells may be different, maternal cell contamination in 1-2% of cases)
what sort of results can we get with chorionic villus sampling?
- 3-5 days for QFPCR (tests for trisomies 13, 18, 21 and sex chromosome aneuploidy)
- 2-3 weeks for chromosomal microarray
- can also do single gene tests to check for specific diseases if there is family history
what is amniocentesis? when is it done?
take a sample of the amniotic fluid and is done after 15 weeks
what are risks/issues with amniocenesis?
1/200 chance of miscarriage (very low) and no technical issues (no contamination and cells come from fetus not placenta)
what sort of resulst can we get with anmiocenesis?
- 3-5 days for QFPCR (tests for trisomies 13, 18, 21 and sex chromosome aneuploidy)
- 2-3 weeks for chromosomal microarray
- can also do single gene tests to check for specific diseases if there is family history
which is better CVS or amniocenesis?
depends:
CVS is done earlier (so can get results quicker) but there is more risk (and follow-up amnio may be needed)
amnio is done later but there is lower risk fo miscarriage
what sort of thing do we have to think sbout during a prenatal diagnosis consultation?
- Consultation: discuss a list of possible problems
- We would never describe a child only as a list of medical problems
- Role of parental adaptation
- Role of society helping to support families with disabilities
