Day 15, Lecture 1: (Sept. 13): Prenatal Development Defects: Genetic and Other Causes of Fetal Abnormalities Flashcards Preview

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Flashcards in Day 15, Lecture 1: (Sept. 13): Prenatal Development Defects: Genetic and Other Causes of Fetal Abnormalities Deck (33)
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1
Q

% of major structural anomalies of liveborn infants

A

2-3%

2
Q

Define Birth Defects

A
  • Congential malformations
    • Structural, behavioral, functional, and metabolic disorders present at birth
3
Q

Brith defects prenatal identification

A
  • U/S sensitivity varies depending on
    • type of anomly
    • population screened (obesity is a limitation)
    • Site of ultrasound (tertiary center vs. community-based facility)
  • Contemporary number is 80% of major anomalies in a tertiary MFM practice
4
Q

__% of newborns are born with minor anomalies

A

15%

5
Q

Some minor anomalies are associated with major anomalies. Give the relative risk for one, two, and three minor anomalies

A
  • one minor
    • 3% risk major
  • two minor
    • 10% risk major
  • Three minor
    • 20% risk major
6
Q

____ is the study of congenital anomalies

A

Dysmorphology

7
Q

Teratogens

A
  • increase frequency of adverse fatal effect
  • Dose-Response relationship
  • Period of greatest sensitivity typically organogenesis
  • Often a genetically more susceptible group
  • Exogenous teratogens:
    • Coumadin (Warfarin)
    • Alcohol
    • Dilantin
    • Accutane
    • Thalomid
  • Endogenous Teratogens:
    • Elevated blood glucose
    • Elevated Phenylalanine
8
Q

What is the familial recurrence in Multifactorial inheritance

A

about 2-5%

9
Q

What is the most common fetal aneuploidy after first trimester

A

Down Syndrome

10
Q

What is the typical IQ for Down Syndrome patients

A

<70; MR can range from mild to severe

11
Q

Chance of cardiac defects in Down syndrome patients

A

>50%

12
Q

___% of Down Syndrome patients survive to 1 y/o; and over ___% survive to 50 y/o

A
  • 85-90% survive to 1 y/o
  • 50% survive to 50 y/o
13
Q

Types of Prenatal Tests

A
  • screening tests
    • identify high-risk patients
      • results should be thought of as “low-risk” vs. “high-risk” not “negative” vs. “postive”
  • Diagnostic tests
    • Identify abnormality
      • results “normal” or “negative vs. “abnormal” or “postive”
14
Q

___ is the major fetal colloid in the first half of pregnancy.

A

Alpha-Fetoprotein (AFP)

15
Q

Causes of elevated maternal serum AFP (MSAFP)?

A
  • Spina Bifida
  • Gastroschisis
16
Q

Aneuploidy Screening second trimester

A
  • initial screening test for aneuploidy was maternal age (high-risk>or equal to 35 y/o)
  • Lower MSAFP values associated with fetal aneuploidy (primarily T21)
  • Initial Strategies used maternal age combined with fixed cut-offs (e.g. <0.5 MoM)
  • Now use likelihood ratio (LR) determined from Gaussian distributions
    • you take affected relative probablity at that level divided by relative probability of unaffected at that AFP level.
    • then you multiple this ratio with the RR of the persons age
  • using a 1:270 second trimester Down syndrome cut-off (equal to risk at 35 y/o), MSAFP allowed identification of an additional 20% of affected prgnancies
  • Triple Screen
    • similar LRs, hCG, and UE3 added to MSAFP
  • Quadruple screen
    • Similar LRs, hCG, UE3, and Inhibin-A added to MSAFP
    • test for T21 and T18
  • Low-risk (negative) screen not a guarantee of normalcy
  • Most patients with a high-risk (positive) screen have normal fetus
  • Those with positive screens will be offered additional testing
    • e.g.
      • Genetic amniocentesis
17
Q

What is the quadruple screen?

A
  • MSAFP, LRs, hCG, UE3, and Inhibin-A
  • can test for T21 and T18
  • can be done at 14-22 weeks Gestational age
  • Results affected by GA and must be adjusted based on maternal weight, diabetic or not, and race
  • For twin pregnancies
    • a “pseudo-risk” will be calculated
    • detection rates lower in twins and essentially worthless in higher-order multiples
18
Q
A
19
Q

First Trimester screening for aneuploidy

A
  • Nuchal Translucency (NT)
    • NT measurement between 11 and 13 weeks GA associated with aneuploidy
    • Aneuploidy risk increases as a continuous function of the NT
  • Age plus NT plus serum markers
    • Pregancy-associated plasma protein-A (PAPP-A)
    • hCG
  • Sensitivity for T21 of 80-85% at a 5% false positive rate
20
Q

Newest Aneuploidy Screening tests

A
  • Cell-free fetal DNA (cffDNA)
    • About 10% of the DNA framents in a pregnant woman’s serum is fetal in origin
    • Isolated using various methods (different companies’ tests)
    • Though a screening test, detection rates very high
    • In high-risk groups (35 y/o or older, u/s anomaly, prior infant with aneuploidy)
      • T21 and T18 99%
      • T13 about 90%
      • Sex chr abnl 95-99%
      • other chr microdeletions/duplications 90-98%
      • If normal 99.5%
  • Performance is not as good in low-risk patients (concept of prevalence affecting PPV and NPV)
21
Q

cffDNA is not as good in low-risk patients as it is in high -risk patients because prevalence effects PPV and NPV

A
22
Q

Ultrasound as a Diagnostic Test

A
  • Used for
    • Confirming/determining gestational age
    • Determining number of fetus(es)
    • confirming live fetus(es)
    • Looking for structural malformations (e.g. detect 95-98%) of ONTD)
    • Aiding in performance of diagnostic and therapeutic fetal procedures
23
Q

Ultrasound as a Screening Test

A
  • Increased risk of aneuploidy/other genetic abnormalities if structural anomalies (AV canal detect-fetus has T21 until proven otherwise)
  • Also, increased risk of aneuploidy if ultrasound “markers”
24
Q

Ultrasound Aneuploidy Markers

A
  • Echogenic intracardiac focus
  • Echogenic bowel
  • Thickened nuchal fold
  • Pyelectasis
  • Short femur/humerus
  • Absent nasal bone
25
Q

why and why not to do prenatal screening

A
  • Why to screen
    • More information about the pregnancy
      • Reassurance
      • Planning
      • Decision-making, continue?
      • Utility of information is patient-specific
  • Why not screen for more
    • Expanded carrier screening panels on the market-can screen for > 90 conditions
    • Pre- and post-test counseling recommended; resources not available
    • Range of symptoms, severity, treatment availability, life expectancy
    • not cost-efective
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