Teratogens Flashcards
Infection can be required through:
venereal transmission, respiratory spread, contact with infected blood products, cat litter or uncooked meat
Venereal transmission can cause:
syphilis gonorrhea, herpes virus, CMV, HIV
therefore can be in vagina and passed to baby during birth (may consider a C-section is infection is diagnosed and active)
Respiratory spread can cause:
rubella, varicella, coxsackie
contact with infected blood products can cause:
HIV, hepatitis, malaria
cat litter or uncooked meat can cause:
toxoplasmosis
classic teratogenic time period during pregnancy
weeks 7-10 from last menstrual period (most women don’t know they are pregnant yet)
prenatal infection can cause:
- embryonic death and reabsorption (extremely early infections);
- spontaneous abortion (SAB) and stillbirth (after pregnancy is recognized);
- prematurity, IUGR, low birth weight (usually infection in 3rd trimester);
the majority of children exposed to infection are:
normal infants!
general signs of infection post-delivery:
purpura (red rash), jaundice, hepatosplenomegaly, pneumonitis (inflammation of lungs), meningoencephalitis (inflammation of brain)
IgG antibody
antibody associated with lifelong immunity, forms 3-4 weeks after IgM
IgM antibody
initial antibody formed following viral infection - goes away after 6 months
CMV symptoms
- Mom is typically ASYMTPOMATIC
- high risk of intellectual disability/developmental delay
- pneumonia
- hepatosplenomegaly
- jaundice
- thrombocytopenia
- microcephaly
- deafness
- blindness (optic nerve atrophy)
- brain calcifications
Individuals at higher risk for CMV:
health care workers
Treatment for CMV
NONE
CMV ultrasound findings
hepatic calcifications, fetal ascites
Congenital Rubella Syndrome features
- ocular concerns: cataracts, glaucoma (10-30%)
- CNS: deafness (60-70%), intellectual disability, microcephaly (10-25%)
- cardiac: PDA (10-20%)
- low birth weight
- prematurity
- blueberry muffin purpura
Toxoplasmosis maternal symptoms
flu-like illness or mono, but most are asymptomatic. 1/3 chance of fetal infection if mom has it
Individuals at higher risk for Toxo
exposure to raw or undercooked mutton or lamb, direct contact with cat shit
Some factors that affect tetratogenicity:
developmental phase, genotype, dose effect
How to evaluate whether an agent is a teratogen:
phenotypic effect, animal model, dose-response relationship, plausible biological explanation (present during critical periods of development)
categories of teratogens
deficiency/excess of endogenous agents, medications, industrial chemicals, environmental contaminants, physical agents (trauma, hyperthermia, radiation), infections, maternal disease
Medications that are classic known teratogens
Warfarin, Streptomycin, Valproid Acid (and basically every other seizure medication), ACE inhibitors, Lithium
Maternal diseases that have teratogenic effects
Insulin dependent diabetes, hypo/hyperthyroidism, PKU, hypertension, autoimmune disorders
Most common psychosocial reaction to teratogens
guilt
Thalidomide
- can treat leprosy, multiple myeloma, hyperemesis & pregnancy related nausea
- can cause limb reduction defects, ear anomalies
Diethylstilbestrol (DES)
- was used from 1940 and 1971 to prevent miscarriage, premature labor, and related complications of pregnancy (didn’t work)
- can cause vaginal adenosis/adenocarcinoma, cervical erosion and ridges
Warfarin
- blood thinner to treat clotting d/o
- can cause nasal hypoplasia, stippled epiphyses, CS defects
Hydantoin
- can treat epilepsy
- can cause dysmorphic facial features, hypoplastic nails, growth and developmental delay
Aminopterin and methotrexate
- chemotherapy
- pregnancy loss, hydrocephalus, low birth weight, dysmorphic facial features
Streptomycin
- can treat TB
- can cause hearing loss
Tetracycline
- can treat acne and skin infections
- can cause stained teeth, enamel hypoplasia
Valproic acid
- can treat seizures and bipolar disorder
- can cause neural tube defects, dysmorphic facial features
Isotretinoin
- can treat severe acne
- can cause pregnancy loss, hydrocephalus, other CNS defects, small or absent thymus, microtia/anotia, conotruncal heart defects
Antithyroid drugs
- can cause hypothyroidism, goiter
Penicillamine
- medication is immunosuppression to treat rheumatoid arthritis, Wilson’s disease, cystinuria
- can cause cutis laxa
ACE Inhibitors
- can treat hypertension, congestive heart failure
- can cause renal dysgenesis, oligohydramnios sequence, skull ossification defects
- in contrast to most teratogens, critical period is second & third trimester
Carbamazepine (Tegretol anticonvulsant)
- can treat epileptic seizures and nerve pain
- can cause neural tube defects
Cocaine
- can cause pregnancy loss, placental abruption, growth retardation, microcephaly
Lithium
- can treat bipolar disorder
- can cause Ebstein anomaly
Methylmercury
- primarily occurs through the consumption of contaminated food such as fish
- can cause cerebral atrophy, spasticity, mental retardation
Lead
- can cause pregnancy loss, CNS damage
Polychlorobiphenyls (PCBs - ingested)
- exposure through food
- can cause low birth weight, skin discoloration
Cigarette smoking during pregnancy
can cause pregnancy loss, low birth weight
Hyperthermia during pregnancy
can cause neural tube defects
Chronic alcoholism during pregnancy
- classic triad of FAS involves a pattern of growth deficiency, CNS involvement and facial dysmorphology.
Therapeutic Radiation during pregnancy
can cause growth and developmental delay, microcephaly
Maternal Insulin Dependent Diabetes Mellitus
can cause congenital heart defects, caudal
deficiency, neural tube defects,
limb defects, holoprosencephaly, pregnancy loss
Maternal Hypo/Hyperthyroidism
can cause goiter, growth and developmental
retardation
Maternal Phenylketonuria
can cause pregnancy loss, microcephaly, mental retardation, facial dysmorphism, congenital heart defects
Maternal Hypertension
can cause intrauterine growth retardation
Maternal autoimmune disorders
can cause congenital heart block, pregnancy
loss
Potential teratogenic effects
- spontaneous abortion
- growth retardation
- microcephaly
- patterns of major and minor malformations
- metabolic dysfunction
- cognitive dysfunction or mental deficiency
- altered social behavior
- malignancy
Recreational drugs with known teratogenic effects
- alcohol
- cigarette smoke
- cocaine
- toluene
Methadone
- can treat pain & drug addiction
- can cause developmental problems, behavioral problems, adverse effects on fetal growth, increased risk of stillbirth, premature birth, decreased fetal movements, neonatal withdrawal
Buprenorphine/Subutex
- can treat pain & drug addiction
- DOES NOT significantly increase risk for birth defects
- 60% neonatal withdrawal
Naloxone/Suboxone
- can treat pain & drug addiction
- no human data but animal data is reassuring
- neonatal withdrawal is possible
Naltrexone
- can help prevent relapses into drug & alcohol abuse
- limited human data, but does not significantly increase risk for birth defects
- theoretical risk for behavioral abnormalities
Toluene
- aromatic hydrocarbon found in some spray paints, glues and lacquers
- inhaled to cause acute intoxication
- can cause microcephaly, intellectual disability, growth deficiency, craniofacial abnormalities similar to fetal alcohol syndrome
Isotrentinoin (Accutane)
- can treat severe acne
- can cause CNS anomalies, ear anomalies, cardiac defects, thymus anomalies, intellectual disability
Etretinate
- can treat psoriasis
- stored in the body for long time (years)
- can cause same as isotrentinoin: CNS anomalies, ear anomalies, cardiac defects, thymus anomalies, intellectual disability
Trentinoin (Retin A)
- can treat acne, wrinkles
- theoretical risk b/c of relation to isotrentinoid, but likely to be low risk
- generally administered topically
Dietary Vitamin A
- can cause CNS defects, urinary tract defects, face, palate, heart, ear deformities
Beta carotene
- provitamin A compound provided by vegetables
- NOT teratogenic
- found in prenatal supplements
Diagnostic X-ray during pregnancy
NOT believed to be teratogenic (<5 rads & serious risk to fetus occurs when absorbed dose is 10 rads or more)
Lead exposure during pregnancy
- NO increased risk for structural malformations
- Inconsistent data re: IUGR
- greatest concern for neurobehavioral development
Theoretical effects of paternal exposure to teratogens
- DNA mutations in sperm (ex: radiation)
- Alterations to fertility
- Presence of agent in sperm directly affects fetal development
- NO PATERNAL EXPOSURE HAS EVER ACTUALLY BEEN SHOWN TO BE TERATOGENIC
Phenytoin
- can treat seizures (anti-convulsant)
- can cause IUGR, microcephaly, hypoplastic nails and distal phalanges
