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Flashcards in Teratogens Deck (28):
1

Infection may be acquired through:

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

2

Infections acquired through venereal transmission (that are teratogens)

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

3

Infections acquired through respiratory spread (that are teratogens)

- rubella
- varicella
- coxsackie
- parvovirus

4

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

- HIV
- hepatitis
- malaria

5

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

- toxoplasmosis

6

Classic teratogenic gestational period

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

7

Timing of infection affects severity

- 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

8

General signs of infection after delivery

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

9

Women should ideally have preconception screening for:

- 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)

10

Types of antibodies measured

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

11

Fetal interpretation of infection (IgG & IgA transplancental movement)

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

12

Cytomegalovirus (CMV)

- 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

13

Herpes (DNA Virus)

- 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

14

Varicella Zoster (DNA Virus)

- 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)

15

Human Parvovirus B19

- 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

16

Diagnosis of fetal infection

- 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

17

Rubella

- 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

18

Toxoplasmosis

- 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)

19

Syphilis

- 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

20

Human Immunodeficiency Virus (HIV)

- 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)

21

Evaluating whether an agent is a teratogen

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

22

Ways which a teratogen can produce an effect

- cell death
- cell to cell interactions
- cell migration
- mechanical disruption

23

Categories of teratogens

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

24

Medications that are teratogens

- 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

25

Industrial chemicals that are teratogens

- Methylmercury
- Lead
- Polychlorobiphenyls (PCBs - ingested)

26

Environmental chemicals that are teratogens

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

27

Physical agents that are teratogens

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

28

Maternal diseases that can act as teratogens

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