Teratogens

Question 1

Infection may be acquired through:

Answer 1

• venereal transmission
• respiratory spread
• contact with infected blood products
• cat litter or uncooked meat

Question 2

Infections acquired through venereal transmission (that are teratogens)

Answer 2

• syphilis
• gonorrhea
• herpes virus
• cytomegalovirus (CMV)
• HIV

Question 3

Infections acquired through respiratory spread (that are teratogens)

Answer 3

• rubella
• varicella
• coxsackie
• parvovirus

Question 4

Infections acquired through contact with infected blood products (that are teratogens)

Answer 4

• HIV
• hepatitis
• malaria

Question 5

Infections acquired through cat litter or uncooked meat (that are teratogens)

Answer 5

• toxoplasmosis

Question 6

Classic teratogenic gestational period

Answer 6

• days 31-71 (7-10 weeks from LMP)
• During organogenesis (organs are forming)
• Most women do not yet know that they are pregnant!

Question 7

Timing of infection affects severity

Answer 7

• extremely early infections (before pregnancy is recognized) lead to embryonic death and resorption
• spontaneous abortion and stillbirth (SAB) infection in recognized pregnancy
• prematurity 24-37 weeks after LMP (usually infection in 3rd trimester) - IUGR and low birth weight
• congenital disease - at delivery or later on

Question 8

General signs of infection after delivery

Answer 8

• purpura (red rash)
• jaundice (yellow-ish)
• hepatosplemomegaly (enlarged liver & spleen)
• pneumonitis (inflammation of lungs)
• meningoencephalitis (inflammation of brain)

Question 9

Women should ideally have preconception screening for:

Answer 9

• rubella (immunization should be done, some batches of rubella vaccine were no good)
• toxoplasmosis (if you have a cat or eat rare meat)
• cytomegalovirus (if you are a healthcare worker…CMV is excreted in urine)

Question 10

Types of antibodies measured

Answer 10

• IgG (antibody associated with lifelong immunity, starts 3-4 weeks after IgM)
• IgM (initial antibody formed following viral infection, goes away after 6 months)

Question 11

Fetal interpretation of infection (IgG & IgA transplancental movement)

Answer 11

Since IgG is a small molecule it can pass transplacentally to fetus – therefore +IgG in cord blood can be maternal

IgM is too large to pass transplacentally – therefore, if the cord blood is +IgM for a specific illness, the fetus has been infected

Question 12

Cytomegalovirus (CMV)

Answer 12

• High risk of intellectual disability/dev delay
• IUGR
• pneumonia
• hepatosplenomegaly
• thrombocytopenia
• microcephaly
• deafness
• optic nerve atrophy
• brain calcifications
• Ultrasound: echogenic bowel, fetal ascites, hepatic calcifications
• Rarely diagnosed during pregnancy because asymptomatic (10% of women have mono-like symptoms)
• Virus most commonly isolated in urine
• No treatment available for affected mother and child
• Can be sexually transmitted and therefore can be in vagina and passed to baby

Question 13

Herpes (DNA Virus)

Answer 13

• no obvious malformations
• risk for CNS malformations
• no curative treatment
• primary maternal infection causes the greatest risk in early pregnancy and near term
• infection does not confer immunity
• there are 2 types of herpes: type 2 (genital form) causes the problem
• Virus in vagina and passed to baby is a problem, therefore do C-section when active infection

Question 14

Varicella Zoster (DNA Virus)

Answer 14

• chicken pox
• 10-21 day incubation period, most contagious before breaking out
• Can be transmitted transplacentally at any time during pregnancy (even before blister – most infectious)
• 3% risk obvious abnormalities: scarring of skin, limb hypoplasia, microcephaly, cataracts, blindness, neonatal chicken pox,
• possible CHD (would need perfect exposure timing)

Question 15

Human Parvovirus B19

Answer 15

• Classic rash – ‘slapped cheek’ and fever
• In adults it can cause acute polyarthalgia syndrome of hands, wrists, knees
• 10% risk of death any gestational age, but worst at 10-20 weeks
• Causes severe anemia – CHF – death (breaks down bone marrow)
• No risk for congenital anomaly even if exposure during 1st trimester
• IgM will be + in 90% of cases by 3rd day after symptoms appear

Question 16

Diagnosis of fetal infection

Answer 16

• High MSAFP may be seen 4-6 weeks before sonar abnormality noted (breaking down fetal RBC)
• Hydrops on sonar – congestive heart failure
• PUBS – fetal IgM with low fetal RBC count
• Only treatment available – fetal transfusion in utero – buying time until recovery from infection

Question 17

Rubella

Answer 17

• German measles
• Mild maternal illness - fever, rash, cervical lymph node inflammation
• Fetus infected transplacentally – congenital rubella syndrome
• 10-20% mortality in 1st year of life in fetus is infected
• Malformations seen in infected children similar to CMV, blueberry muffin sign (bruises from low platelets)
• cataracts, glaucoma, intellectual disability, deafness, microcephaly, cardiac PDA, low birth weight
• risk of long-range diabetes secondary to pancreatic infection

Question 18

Toxoplasmosis

Answer 18

• Sources of toxo are: Raw or undercooked meat (especially mutton or lamb), direct contact with cat feces
• most mom’s are asymptomatic, possible flu or mono symptoms
• of fetuses infected, 1/3 clinically detectable infection: intracerebral calcification (isolated nodules), retinal inflammation (can destroy the optic nerve), hydrocephaly
• of fetuses infected, 2/3 have clinical disease – DD, neurological problems
• medication for affected mom’s when baby hasn’t shown signs yet: Spiramycin (reduces disease process but cannot correct damage already done)

Question 19

Syphilis

Answer 19

• sexual contact is the only mode of transmission
• not associated with major malformations
• Has affinity for skin, mucous membranes, liver, CNS, bones – 2nd and 3rd trimester
• Penicillin G –drug of choice

Question 20

Human Immunodeficiency Virus (HIV)

Answer 20

• retrovirus
• maternal acquisition through sexual contact, shared needles, contaminated blood transfusion
• Perinatal HIV transmission may occur in utero, during delivery, and through breast feeding
• Treatment/Prevention in pregnancy (Zidovudine ZDV)

Question 21

Evaluating whether an agent is a teratogen

Answer 21

• phenotypic effect
• animal model
• dose-response relationship
• plausible biological explanation (present during critical periods of development)

Question 22

Ways which a teratogen can produce an effect

Answer 22

• cell death
• cell to cell interactions
• cell migration
• mechanical disruption

Question 23

Categories of teratogens

Answer 23

• Deficiency/excess of endogenous agents
• Medications
• Industrial chemicals
• Environmental contaminants
• Physical agents (trauma, hyperthermia, radiation)
• Infections (CMV, toxo, parvo, etc)
• Maternal disease

Question 24

Medications that are teratogens

Answer 24

• Thalidomide
• Diethylstilbestrol (DES)
• Warfarin
• Hydantoin
• Trimethadione (anticonvulsant no longer available in US)
• Aminopterin and Methotrexate
• Streptomycin - causes hearing loss
• Tetracycline
• Valproic acid
• Isotretinoin
• Antithyroid drugs
• Penicillamine (immunosuppression to treat rheumatoid arthritis) - causes cutis laxa
• ACE Inhibitors
• Carbamazepine (Tegretol anticonvulsant) - causes NTDs
• Cocaine
• Lithium - causes Ebstein’s anomaly

Question 25

Industrial chemicals that are teratogens

Answer 25

- Methylmercury - Lead - Polychlorobiphenyls (PCBs - ingested)

Question 26

Environmental chemicals that are teratogens

Answer 26

- cigarette smoking - causes IUGR - hyperthermia - causes NTDs - chronic alcoholism - causes dysmorphism, growth probs, microcephaly - therapeutic radiation - causes growth and developmental retardation, microcephaly

Question 27

Physical agents that are teratogens

Answer 27

- trauma - hyperthermia - radiation - ionizing radiation, x-ray exposure

Question 28

Maternal diseases that can act as teratogens

Answer 28

- insulin dependent diabetes mellitus - hypo/hyperthyroidism - phenylketonuria (PKU) - hypertension - autoimmune disorders