Week 3 teratogens

Question 1

What congenital abnormalities does thalidomide cause?

Answer 1

Phocomelia (extremely shortened limbs, feet and hands arise close to the trunk); defects of the eyes, ears, heart, genitals, kidneys, digestive tract, and nervous system

Question 2

At what stage of development is the fetus most at risk for thalidomide-induced abnormalities?

Answer 2

3-8 weeks (first trimester)

Question 3

What congenital abnormalities does methotrexate cause?

Answer 3

Abnormalities in multiple organ systems

Question 4

At what stage of development is the fetus most at risk for methotrexate-induced abnormalities?

Answer 4

First trimester (38% of cases)

Question 5

What congenital abnormalities do ACE inhibitors cause?

Answer 5

Decreased renal blood flow; leads to renal failure, hypotension, anuria, skull hypoplasia

Question 6

At what stage of development is the fetus most at risk for ACE inhibitor-induced abnormalities?

Answer 6

Second or third trimester

Question 7

What is the estimated morbidity of ACE inhibitor-induced abnormalities?

Answer 7

Approximately 10-20%

Question 8

What congenital abnormalities does lithium cause?

Answer 8

Ebstein’s anomaly (inferiorly displaced tricuspid valve), increased risk for any cardiac malformation, moderately increased risk for all congenital anomalies

Question 9

What congenital abnormalities does isotretinoin cause?

Answer 9

CNS, cardiac, ear, thymic, brachial arch abnormalities; potential increased risk for SAB

Question 10

By how much do anticonvulsants increase the risk for anomalies?

Answer 10

Up to 3x background risk, about 10%

Question 11

What congenital abnormalities does phenytoin cause?

Answer 11

Fetal dilantin syndrome - nail hypoplasia

Question 12

What congenital abnormalities do valproic acid and carbamazepine cause?

Answer 12

Neural tube defects

Question 13

What are the signs and symptoms of fetal alcohol spectrum disorder?

Answer 13

Global growth deficiency, microcephaly, learning disabilities, mild/moderate intellectual disabilities, ADHD impulsivity, poor memory, conduct disorder, facial dysmorphology (“train tracking” of ears, flattened face, small upper lip); small increased risk for birth defects

Question 14

What affect does prenatal ethanol exposure have on gene expression?

Answer 14

Changes in intracellular calcium; alters numerous signaling pathways, some specific targets include SHH, Fgf-8, Pax6

Question 15

What congenital abnormalities does cocaine cause?

Answer 15

Pregnancy loss, abruption, intrauterine growth retardation (IUGR), microcephaly

Question 16

What congenital abnormalities does tobacco cause?

Answer 16

Poor fetal growth, behavioral problems, IQ deficit, some congenital anomalies (evidence is all over the place)

Question 17

What maternal infections are known to cause birth defects?

Answer 17

TORCHZ - toxoplasmosis, “other” (varicella, syphilis), rubella, cytomegalovirus, herpes, zika

Question 18

What are the common clinical manifestations of TORCH infections?

Answer 18

Intrauterine growth restriction (IUGR), prematurity, hypo-/hyperthermia, apnea, tachypnea, problems in multiple systems

Question 19

What are the clinical features of congenital rubella syndrome?

Answer 19

IUGR, microcephaly, cataracts, sensorineural hearing loss, chorioretinitis, meningoencephalitis, intellectual disability

Question 20

What is the incidence of congenital rubella syndrome?

Answer 20

85% risk if mother has first trimester infection

Question 21

What are the clinical features of congenital cytomegalovirus infection?

Answer 21

Sensorineural hearing loss, chorioretinitis, microcephaly, intellectual disability

Question 22

What is the incidence of congenital cytomegalovirus infection?

Answer 22

1% of newborns in US, only 10% symptomatic, 5-17% of asymptomatic newborns will develop hearing loss

Question 23

What are the clinical features of zika?

Answer 23

Severe neurological complications (microcephaly, inflammation and apoptosis of nerve cells), malformation of the eyes and ears

Question 24

What congenital anomalies are associated with maternal type 1 diabetes?

Answer 24

Cardiac defects, sacral agenesis, neural tube defects, pregnancy loss

Question 25

What congenital anomalies are associated with gestational diabetes?

Answer 25

Fetal macrosomnia (large), hypoglycemia after birth due to high insulin levels during development, polycythemia, hypertrophic cardiomyopathy, microcolon; most spontaneously resolve

Question 26

What is the incidence of birth defects in infants born from mothers with type 1 diabetes?

Answer 26

Approximately 10% (IDDM in first trimester)

Question 27

What congenital anomalies are associated with infants born from mothers with phenylketonuria?

Answer 27

Microcephaly, intellectual disability, cardiac defects, pregnancy loss; dose response to increasing Phe levels

Question 28

What congenital anomalies are associated with prenatal lead and methylmercury exposure?

Answer 28

Neurological/CNS impairment