Embryology and Tetralogy

Question 1

1) What causes reversible hearing loss in the fetus?
a) ASA
b) Streptomycin
c) Cysplatinum

Answer 1

B. Streptomycin. Aminoglycosides have been associated with congenital deafness in newborn

Question 2

2) What enzyme is seen with Dilantin exposure?

Answer 2

) Epoxide hydrolase. Several drugs (carbamazepine, phenobarbital, phenytoin) are metabolized in microsomes and produce epoxides. Epoxides can cause oxidative stress and result in fetal malformations, particularly because fetal ability to process epoxides is immature. The enzyme used to detoxify epoxides is epoxide hydrolase.

Question 3

3) What drug stays around in the maternal system the longest?
a) Etretnoate
b) Coumadin

Answer 3

A. Etritinate. Etrinate is a retinoic acid and causes malformations similar to isoretinoic acid (Accutane). The main difference between etrinate & Accutane is that etrinate is lipophilic and has a half-life of 120 days and can be detected in serum for 3 years after use. Women are advised not to get pregnant for at least 2 years after use. Another notable drug with a long half-life is leflunomide, which is used to treat RA.

Question 4

4) What drug is commonly associated with microotia?

Answer 4

The classic drug associated with microtia (or any abnormal ear development) is isoretinoin. Any retinoic acid can be associaed with microtia. Other drugs that cause microtia/anotia: mycophenolate (used for immunosuppression in transplant recipients), thalidomide.

Question 5

5) The use of valproic acid carries what risk of NTD?
a) 1-2%
b) 3-5%
c) 15-20%
d) 50%

Answer 5

A. 1-2%. Most of the anti-epileptics confer a risk of 1-2% of NTD, with increasing risk with polypharmacy.

Question 6

14) Why is it a bad plan to give I131 in pregnancy?

Answer 6

131I concentrates in fetal thyroid beginning at 10-12 weeks and therefore may obliterate fetal thyroid if given after this time.

Question 7

15) What is the chorionicity/amnionicity if embryo divides between day 8 and 13?
a) di/di
b) mono/di
c) mono/mono
d) conjoined

Answer 7

C. Monoamniotic. If twinning occurs <3 days, it precedes the formation of the chorion & therefore each twin develops its own chorion = dichorionic pregnancy. From days 3-8, the chorion has already formed but not the amnion. Thefore, twinning results in monochorionic, diamniotic pregnancy. Twinning from 8-13 days results in monoamniotic monochorionic pregnancy. Cleavage from 13-15 days results in conjoined twins. Twinning cannot occur after 15 days.

Question 8

17) Drugs in the highest concentration in breast milk are more likely to be:
a) protein bound
b) ionized
c) lipid soluble

Answer 8

Lipid soluble. To minimize infant exposure, select drugs with shorter half-life, poorer oral absorption, & lower lipid solubility.

Question 9

18) Elevated fasting levels of which of the following is associated with NTD:

Answer 9

Homocystine. This is a folic acid metabolism question.

Question 10

20) Which of the following agents can potentially cause renal anomalies along with oligohydramnios?
a) Verapamil
b) Captopril
c) Ritodrine

Answer 10

B=captopril. All ACE inhibitors & potentially ARBs interrupt the fetal renin-angiotensin system. This can cause renal artery spasm, alter development of the kidneys, lead to oligohydramnios and Potter’s sequence.

Question 11

21) Which of the following agents least causes a cardiac defect?
a) Rubella
b) OCPs
c) CMW
d) Toxoplasmosis

Answer 11

OCPs. The estrogens & progestins have not been demonstrated to be teratogenic, although they may be listed as category D because they have no benefits in pregnancy. Congenital rubella syndrome is associated with fetal heart defects, particularly if infected <12 wks.

Question 12

21) Which of the following agents least causes a cardiac defect?
a) Rubella
b) OCPs
c) CMW
d) Toxoplasmosis

Answer 12

OCPs. The estrogens & progestins have not been demonstrated to be teratogenic, although they may be listed as category D because they have no benefits in pregnancy. Congenital rubella syndrome is associated with fetal heart defects, particularly if infected <12 wks.

Question 13

22) Which of the following causes the highest risk of fetal spina bifida?
a) Valproic acid
b) Previous spina bifida

Answer 13

B=previous spina bifida = recurrence risk of 1.5%, with 2 previous affected pregnancies=7%. Risk with valproic acid is 1-2%?

Question 14

22) Which of the following causes the highest risk of fetal spina bifida?
a) Valproic acid
b) Previous spina bifida

Answer 14

B=previous spina bifida = recurrence risk of 1.5%, with 2 previous affected pregnancies=7%. Risk with valproic acid is 1-2%?

Question 15

23) Which of the following (in excess) can potentially cause genitourinary, bone, and CNS anomalies?
a) Vitamin A
b) Vitamin B6
c) Vitamin C
d) Vitamin E

Answer 15

A=vitamin A. Retinoids are associated with fetal anomalies – isotretinoin is one of most teratogenic substances. Vitamin A is not teratogenic within recommended daily amount set by FDA but in very large doses can cause anomalies seen with retinoic acid – microtia, cleft palate, heart defects.

Question 16

24) Which of the following can potentially cause microtia?
a) Hydantoin
b) Alcohol
c) Trimethidone
d) Thalidomide

Answer 16

E=Thalidomide. An environmental/drug exposure is not identified in most cases of microtia. Thalidomide also causes limb reduction defects. Other drugs associated with microtia are: isotretinoic acid, mycophenolate.

Question 17

26) Which of the following radiographic imaging causes radiation exposure greater than 1 rad?
a) CT pelvimetry
b) Barium enema
c) Plain abdominal film
d) Chest x-ray

Answer 17

) B=barium enema. Another study associated with radiation exposure >1 rad is IVP

Question 18

27) Which enzyme is theoretically deficient in fetuses who manifest birth defects from anti-epileptic drugs?

Answer 18

epoxide dehydrogenase

Question 19

27) Which enzyme is theoretically deficient in fetuses who manifest birth defects from anti-epileptic drugs?

Answer 19

epoxide dehydrogenase

Question 20

29) Fetal alcohol syndrome & associated defects

Answer 20

IUGR, facial anomalies (small palpebral fissure, absent philtrum, epicanthic folds, flattened nasal bridge, short nose, thin upper lip), low set ears, retarded midface development, CNS-microcephaly, MR, ADHD

Question 21

Oral contraceptives & the only major congenital malformation associated with its use

Answer 21

VATERL, norethindrone masculinize female fetus in 1% of exposures –from somebody else’s answers – None of my reading supports this.

Question 22

31) CMV embryopathy

Answer 22

Most common cause of intrauterine infection (0.5-2.5% of all births), 5-10% infected have neurologic sequelae, sequelae due to inflammation. Reinfection can occur due to antigenic and genetic disparity among CMV strains. May become latent & be reactivated. Mainly transplacental transmission although 30-50% acquisition rate if positive genital CMV infection at time of birth. Congenital infection in utero are most concerning, may be primary or recurrent. Primary infection more dangerous to fetus. 2.5% of fetus infected → 90% asymptomatic → 5-10% late sequelae , 10% symptomatic→90% neurologic sequelae.
Symptoms at birth: premature, low birth weight, microcephaly, chorioretinitis, hepatosplenomegaly, jaundice, thrombocytopenic purpura
Survivors of above have: microcephaly, intracranial calcifications, severe MR, chorioretinitis
Late sequelae if asymptomatic: sensorineural hearing loss, subnormal intelligence, behavioral problems
Perinatal transmission: no serious complications unless <1200g
Poorer prognosis: primary maternal infection (not recurrent) in 1st or 2nd trimester
Diagnosis: serologic infection not predictive of fetal infection, paired specimen IgM. Isolation of virus does not differentiate primary from recurrent infection. No change in antibody levels with recurrent infection. Look for periventricular calcifications. Virus isolation more sensitive & direct than serology.

Question 23

31) CMV embryopathy

Answer 23

Most common cause of intrauterine infection (0.5-2.5% of all births), 5-10% infected have neurologic sequelae, sequelae due to inflammation. Reinfection can occur due to antigenic and genetic disparity among CMV strains. May become latent & be reactivated. Mainly transplacental transmission although 30-50% acquisition rate if positive genital CMV infection at time of birth. Congenital infection in utero are most concerning, may be primary or recurrent. Primary infection more dangerous to fetus. 2.5% of fetus infected → 90% asymptomatic → 5-10% late sequelae , 10% symptomatic→90% neurologic sequelae.
Symptoms at birth: premature, low birth weight, microcephaly, chorioretinitis, hepatosplenomegaly, jaundice, thrombocytopenic purpura
Survivors of above have: microcephaly, intracranial calcifications, severe MR, chorioretinitis
Late sequelae if asymptomatic: sensorineural hearing loss, subnormal intelligence, behavioral problems
Perinatal transmission: no serious complications unless <1200g
Poorer prognosis: primary maternal infection (not recurrent) in 1st or 2nd trimester
Diagnosis: serologic infection not predictive of fetal infection, paired specimen IgM. Isolation of virus does not differentiate primary from recurrent infection. No change in antibody levels with recurrent infection. Look for periventricular calcifications. Virus isolation more sensitive & direct than serology.

Question 24

32) Toxo embryopathy

Answer 24

Life stages of toxo: trophozoite, cyst, oocyst – oocyst found only in cat. Humans infected from oocysts in cat feces & cysts in undercooked meat. Oocysts in cat feces infective for 4-5 days.
Acute maternal infection in 0.2-1.0%. Acute congenital toxo in 0.01-0.1%.Primary toxo in pregnancy: 1/3 chance of fetal infection, if no treatment then 1/3 clinically detectable illness & 2/3 subclinical disease (late CNS sequelae possible). Rate of infection in fetus higher if maternal infection in 3rd trimester (2/3) but severity of fetal infection greatest if maternal infection in 1st trimester.
Rarely, mother has focal necrotizing retinochoroiditis.
Fetal/newborn clinical disease: intracerebral calcifications, chorioretinitis, hydrocephalus.
Diagnosis: 4-fold rise in IgG titer, titer peaks in 1-2 months, low titers persist for years. IgM appear in a week and persist for a year. Negative results virtually rule out infection. Culture fetal blood, culture amniotic fluid, IgM to toxo in fetal blood. PCR of amniotic fluid >4wks after maternal infection.
US findings: ventriculomegaly, increased placental thickness, intracranial density, hepatic density, ascities
Treatment: Spiramycin, pyrimethamine, sulfonamide, folic acid