Endo/Repro - Genetics - Prenatal Diagnosis; Intrauterine Infection; Pregnancy & Teratogens Flashcards
What is α-fetoprotein?
Is it normally found in amniotic fluid?
Fetal albumin;
no
What is a notable situation in which α-fetoprotein leaks into the amniotic fluid?
Are there others?
Neural tube defects;
yes
What is indicated by an increase in α-fetoprotein in a pregnant woman’s serum?
Potential fetal neural tube defect (or other defect)
How much folic acid should a woman be ingesting daily before and after conceiving?
How long before fertilization? How long after?
400 μg;
1 month before — through the first trimester (at least)
At how many menstrual weeks does the neural tube close?
6
A healthy woman presents at clinic indicating that she and her husband are trying to get pregnant. They have one son, who was born with a neural tube defect.
What do you recommend?
What is the risk of large doses of the substance you recommend?
Counseling + larger doses of folic acid (2-4 mg)
masking B12 deficiencies
What are the substances checked in a quad screen?
Maternal serum metabolites:
α-fetoprotein, estriols, β-HCG, inhibin A
When is a quadruple screen useful?
2nd Trimester
Values are predictive at 15-to-20 weeks of gestation
(accurate gestational age is essential)
True/False.
The quad screening is only useful in the third trimester.
False.
The quad screening is meant to be given in the second trimester.
Interpret the following quadruple screen results:
α-fetoprotein — decreased
estriols — decreased
β-HCG — increased
inhibin A — increased
Down syndrome
Interpret the following quadruple screen results:
α-fetoprotein — decreased
estriols — decreased
β-HCG — decreased
inhibin A — unchanged
Trisomy 18 (Edward’s syndrome)
Are all 4 maternal serum metabolites in a quadruple screen necessary for diagnosing neural tube defects?
No;
just α-fetoprotein (increased)
List the expected quadruple screen results for a woman carrying a fetus with Down syndrome (trisomy 21).
α-fetoprotein — decreased
Estriols — decreased
β-HCG — increased
Inhibin A — increased
List the expected quadruple screen results for a woman carrying a fetus with Edward’s syndrome (trisomy 18).
α-fetoprotein — decreased
Estriols — decreased
β-HCG — decreased
Inhibin A — unchanged
List the expected quadruple screen results for a woman carrying a fetus with neural tube defect.
α-fetoprotein — increased
Estriols — n/a
β-HCG — n/a
Inhibin A — n/a
True/False.
A quadruple screen measures fetal serum levels of the following four metabolites:
α-fetoprotein, estriols, β-HCG, inhibin A
False.
A quadruple screen measures maternal serum levels of the following four metabolites:
α-fetoprotein, estriols, β-HCG, inhibin A
Are false positives common in a quadruple screen?
What is the sensitivity for trisomy 21 and trisomy 18?
Not very (~4%);
~75%
(90% for neural tube defects)
List a few techniques via which fetal samples can be obtained for genetic analysis.
Amniocentesis
Chorionic villus sampling
Fetal blood sampling
When can amniocentesis be done for genetic analysis?
Are there any contraindications?
After 15 weeks gestation;
anhydramnios, certain infections
When is chorionic villus sampling performed (if necessary)?
Are there any contraindications?
Between weeks 10 - 13 of gestation;
cervical infections
When can fetal blood sampling be performed?
After 20 weeks
When is it best to perform a fetal ultrasound checking for abnormalities?
Weeks 18 - 20
Combined use of the triple screen and detailed ultrasound detects about __% of Down syndrome.
75
What are some potential indications for a ‘genetic ultrasound’ during pregnancy?
- Advanced maternal age
- Abnormal maternal metabolite screening
- Family history of specific disorder
- Teratogen exposure
(among others)
When is the ‘first screening’ of pregnancy?
What three portions does it entail?
Does it check for neural tube defects?
Mid-to-late 1st trimester;
(1) nuchal translucency measurement, (2) free β-HCG, (3) pregnancy-associated plasma protein;
no (only maternal α-fetoprotein in the 2nd trimester)
If the first screening of pregnancy shows abnormalities, what happens next?
A sequential (integrated) screening in the 2nd trimester;
may include chorionic villus sampling + a quad screen
What is ‘cell free fetal DNA’?
A newer screening test involving analysis of fetal chromosomal fragments in maternal blood
(99% sensitive for trisomy 21 and 18);
done after 10 weeks gestation
What are some fetal conditions that might show an increased nuchal translucency?
Trisomy 13, 18, and 21;
Turner’s syndrome;
complex congenital heart disease;
other genetic disorders
What are the main 5 infectious diseases that are teratogenic to fetal development?
TTORCH
Treponema pallidum
Toxoplasmosis
Rubella
CMV
Herpes
What is the clinical presentation of a fetus carried to term by a women infected with Zika virus?
Microcephaly,
intracranial abnormalities,
brain calcifications
What type of virus is the Zika virus?
A flavivirus
What is the incidence of toxoplasmosis infection among pregnant women?
0.5%
True/False.
On toxoplasmosis: most congenitally infected newborns are asymptomatic at birth.
True.
What is the more common presentation for a newborn that was infected with toxoplasma gondii in the uterus?
Chorioretinitis
List some of the various effects of toxoplasma gondii on a fetus in the 1st trimester.
Microcephaly, chorioretinitis, SGA, brain calcifications;
hepatosplenomegaly, rash, lymphadenopathy, jaundice;
fever, pneumonia
True/False.
Maternal infection with toxoplasma gondii in the 3rd trimester is associated with increased spontaneous abortion.
False.
Maternal infection with toxoplasma gondii in the 1st trimester is associated with increased spontaneous abortion.
What infectious agent causes syphilis?
Treponema pallidum
While most are asymptomatic, what are some of the main clinical S/Sy that may be seen in a newborn infected with syphilis while in-utero?
Chorioretinitis,
deformed nails,
alopecia,
maculopapular rash that may progress to desquamation or bullae
(also, hepatosplenomegaly, jaundice, lymphadenopathy, fever)
True/False.
A fetus is susceptible to treponema pallidum infection at any stage of gestation.
What is the fetal risk if the mother has primary or secondary siphilis?
True;
50%
Describe the effects of congenital rubella infection on the eyes, heart, ears, and head.
Eyes: cataracts, glaucoma, microphthalmia, salt and pepper retinopathy
Heart: peripheral pulmonic stenosis, patent ductus arteriosus, VSD, myocarditis
Head: microcephaly, encephalitis, mental retardation
Ears: deafness
Describe the pathology of congenital rubella infection in infected fetuses.
Focal areas of tissue necrosis and cell death (i.e. aplasia or hypoplasia).
It is thought that vascular endothelial cells become infected and presumably damage tissue through embolization and altered perfusion. Affected organs have been noted to contain decreased absolute cell number and altered cell growth patterns.
What percentage of women of childbearing age have no immunity to rubella?
10%
Primary CMV infection occurs in what percentage of pregnant women? And fetuses?
1 - 2%
1 - 2%
What are the effects of CMV infections in the 1 - 2% of fetuses infected?
90% asymptomatiic;
of the 10%, most have hearing loss and mental retardation
What is the severe form of CMV-related effects on fetal development?
Microphthalmia, microcephaly, hydrocephalus, chorioretinitis, hernia, hearing loss, mental retardation, brain calicifications
What are the main effects of congenital herpes infection?
Growth retardation, microcephaly
(15% skin lesions only
- 15% CNS only (lethargy, anorexia, vomiting)*
- 70% disseminated (jaundice, purpura, RDS, shock))*
True/False.
90% of fetal herpes is due to HSV-II.
True/False.
90% of fetal herpes is due to HSV-I.
An infant delivered to a mother infected with HSV-I has a 50% chance of being infected. When would the infection occur?
During delivery
(infected birth canal)
Which of the following can cause intrauterine fetal infection?
Varicella
Hepatitis B
Toxoplasmosa gondii
Parvovirus B19
Measles
CMV
Treponema pallidum
HPV
Influenza virus
Mumps
Rhinovirus
Rubella
Enterovirus
Herpes
HIV
All of them
Name some of the factors to consider when evaluating the risk and effects of a teratogen on fetal development.
- Timing (embryonic stage?)
- Duration
- Dose
- Teratogenicity
- Access to embryo
A newborn presents with low birth weight and growth retardation.
What teratogenic substance may have been ingested by the mother?
Nicotene
What are the two main effects of nicotene on fetal development?
Retarded fetal growth –> leading to low birthweight
What are the main S/Sy of a newborn affected by fetal alcohol syndrome in terms of CNS characteristics?
CNS: mild mental retardation, microcephaly, poor coordination, hypotonia, irritability, hyperactivity
What are the main S/Sy of a newborn affected by fetal alcohol syndrome in terms of growth characteristics?
Growth deficiency: prenatal and postnatal deficiency
What are the main S/Sy of a newborn affected by fetal alcohol syndrome in terms of facial characteristics?
Facial characteristics: short palpebral fissures, short upturned nose, hypoplastic philtrum, smooth, thinned upper vermilion, hypoplastic maxilla, retrognathia, micrognathia
List some of the most commonly abused recreational drugs that are also teratogenic.
Alcohol
Nicotene
Cocaine
Heroin
Marijuana
Methadone
What ratings are used to categorize the teratogenic risk for prescription drugs?
A, B, C, D, X
What is the teratogenic risk of a prescription drug in the ‘A’ risk category?
Controlled studies in women failed to demonstrate a risk to the fetus.
What is the teratogenic risk of a prescription drug in the ‘B’ risk category?
Animal studies have not shown a risk to the fetus, but well controlled studies in pregnant women are not available
What is the teratogenic risk of a prescription drug in the ‘C’ risk category?
Either animal studies have revealed an adverse affect on the fetus, or there are no well-controlled studies in women; or studies in animals and humans are not available. (use benefit outweighs risk concept)
What is the teratogenic risk of a prescription drug in the ‘D’ risk category?
There is positive evidence of human fetal risk, but benefits in some situations may outweigh risks
What is the teratogenic risk of a prescription drug in the ‘X’ risk category?
Animal or human studies have demonstrated fetal risk and the risk outweighs any possible benefit in pregnancy. These drugs are contraindicated in pregnancy.
Animal or human studies have demonstrated fetal risk from a prescription medication, and the risk outweighs any possible benefit in pregnancy.
What is the risk category for this drug?
X
(absolutley contraindicated)
Can methotrexate or aminopterin be used during pregnancy?
Only methotrexate after the 1st trimester
Which crosses the placenta (and is teratogenic), heparin or warfarin?
Warfarin
What teratogen is associated with severe phocomelia?
Thalidomide
What is the main cause of vaginal clear cell adenocarcinoma?
In-utero diethystilbestrol (DES) exposure
What did diethystilbestrol (DES) used to be used to accomplish?
Why is it no longer used?
To prevent pregnancy loss;
- It didn’t work
- It causes vaginal clear cell adenocarcinoma
Female fetuses with what enzymatic abnormality produce an excess of androgens?
21-hydroxylase deficiency
