Teratogenesis Flashcards
What is teratogenesis?
the process by which congenital malformations are produced in an embryo or fetus
What are the five principles of teratogenesis?
-Susceptibility to teratogens is variable
-susceptibility is specific for stage of development of embryo or fetus
-the mechanism of teratogenesisis specific for each teratogen
-teratogenesis is dose-dependent
-teratogens produce death, growth, retardation, malformation, or functional impairment
Approximately 31% of fertilizations end in what?
spontaneous abortions
About 3% of infants are born with what?
structural anomalies
What is the critical fetal period for teratogenesis and why?
3-16 weeks due to impairment of organogenesis
What are the potential adverse effect(s) of fetotoxic exposure at pre-implantation stage?
spontaneous abortions
What are the potential adverse effect(s) of fetotoxic exposure at the embryonic (2-8 weeks) stage?
-spontaneous abortions
-structural malformations
What are the potential adverse effect(s) of fetotoxic exposure at the fetal (8-40 weeks) stage?
-central nervous system function
-growth restriction
-neurobehavioral effects
-fetal demise
When do most birth defects occur and why is this an issue?
occur prior to 8 weeks which is usually before the first prenatal appointment
What should you do whenever you are prescribing medications to a patient who is of child-bearing age?
ensure you know the pregnancy status by asking when their last menstrual period was and if they could be pregnant
What is the description of category A medications?
well-controlled studies in humans show no risk to the fetus
What is the description of category B medications?
no well-controlled studies have been conducted in humans; animal studies show no risk to the fetus
What is the description of category C medications?
no well-controlled studies have been conducted in humans; animal studies have demonstrated an adverse effect on the fetus
What is the description of category D medications?
evidence of human risk to the fetus exists; however, benefits may outweigh risks in certain situations
What is the description of category X medications?
controlled studies in animals or humans demonstrate fetal abnormalities; the risk in pregnant women clearly outweighs any possible benefit
Drugs in the mother’s blood can pass through what structure to get to the fetus?
the umbilical cord
What was a medication marketed in the 1950s for nausea in pregnancy and was widely used in Europe, Australia, and Japan?
thalidomide
Why was approval of the use of thalidomide in the US withheld?
Dr. Frances Kelsey was concerned over the safety and side effects of thalidomide such as peripheral neuropathy
What is peripheral neuropathy?
weakness, numbness, and pain in your extremities
What did the tragedy of thalidomide lead to?
the development of testing of pharmaceuticals for adverse effects on fetal development
What are these deformities associated with?
-amelia
-meromelia
-phocomelia
thalidomine use
What is amelia?
complete absence of a limb or limbs
What is meromelia?
partial absence of a limb
What is phocomelia?
form of meromelia where there is an absence of long bones with hands and feet attached to trunk with small rudimentary bones
What are other deformities associated with?
ENT system:
-malformations of inner and outer ear
-hearing loss
-visual impairment
-cleft palate
Other:
-intellectual disability and autism
-congenital heart disease
-urogenital and gastrointestinal defects
thalidomide use
What is thalidomide still used for today?
treatment of:
-leprosy
-HIV
-multiple myeloma
What act was created due to the outcomes of the thalidomide tragedy?
Kefauver-Harris Drug Amendments Act
Prior to the Kefauver-Harris Drug Amendments Act, medications could be sold for how long after application filed with the FDA?
60 days
What did the Kefauver-Harris Drug Amendments Act enforce after the thalidomide tragedy?
-FDA requires manufacturers prove safety and efficacy prior to approval
-FDA is given 180 days to review new medications
-Adverse events must be recorded
-Process of drug approval can now take 8-10 years
What is diethystilbestrol (DES)?
a potent estrogen used to prevent spontaneous abortion and premature labor (used between 1940 and 1971)
By 1953, where there any beneficial effects of DES?
No, but it was still used and came in many forms/combinations with other hormones
An estimated 2-10 million _____ and _____ were exposed to DES during the first decade of its use
women and their fetuses
What were the effects of DES for women who took DES, “DES mothers”?
modest increase in the relative risk of breast cancer only (counseling on potential small increase in risk, breast self-examination and regular mammograms encouraged to these patients)
What were the effects of DES for females exposed to DES in utero, “DES daughters”?
-early onset and increased risk of vaginal cancer
-increased risk of cervical cancer
-structural defects in cervix, uterus, and fallopian tubes
-infertility or poor pregnancy outcomes
What were the effects of DES for males exposed to DES in utero, “DES sons”?
-increased risk for cysts of epididymis, microphallus, undescended testicle or testicular hypoplasia, decreased sperm count
-no decrease in fertility
-no increase in cancer risk
What is another term for undescended testicle?
cryptorchidism
What is testicular hypoplasia?
one testicle is significantly smaller than the other
Excessive amounts of what vitamin has been associated with teratogenicity?
Vitamin A
What teratogenic medication are these deformities associated with?
-cleft lip
-cleft palate
-hydrocephalus (water in ventricles of brain)
-cardiac deformities
vitamin A
What teratogenic medication is a vitamin A isomer (13-cis-retinoic acid)?
isotretinoin (Accutane)
What is isotretinoin (Accutane) used in?
treatment of cystic acne
What are the adverse effects of using isotretinoin (Accutane) while pregnant?
-increased risk of spontaneous abortion
-20-30% of exposed neonates have evidence of abnormalities such as thalidomide-like malformations and malformation in multiple organs
What program was started to reduce prenatal exposure to isotretinoin (Accutane)?
iPLEDGE
Isotretinoin prescribers must be what?
-registered with the iPLEDGE program
-demonstrate awareness of its potential effects
When a female patient of child-bearing age is using isotretinoin, what must she do?
-start 2 forms of birth control 1 month prior to starting, during, and 1 month after use
-must have 2 negative pregnancy tests before prescription
-pregnancy testing monthly on therapy
-pregnancy testing on month after cessation of medication
Which teratogenic medications are commonly used in treatment of hypertension?
-angiotensin converting enzyme inhibitors (ACES)
-angiotensin receptor blockers (ARBS)
What are the 1st trimester fetal risks of taking ACES and ARBS?
risks are unclear but possibly cardiovascular and central nervous system abnormalities
What are these fetal effects associated with:
-growth retardation
-renal dysfunction
-fetal demise
-oligohydramnios
the use of ACES and ARBS in the 2nd and 3rd trimester of pregnance
What is oligohydramnios?
decreased amniotic fluid
Treatment of hypertension often begins with what as the initial medication?
ACE inhibitor
ACE inhibitor medication names end in what?
-pril
What are some common side effects of ACE inhibitors that lead to switching to a different type of medicatin?
dry and hacking cough
What is used as a substitute for ACE inhibitors? (still a teratogenic medication)
ARBs
ARB medications end in what?
-artan
What teratogenic medications are used to treat depression, anxiety, and OCD?
Selective Serotonin Reuptake Inhibitors (SSRI)
What category of medication do SSRIs fall into?
Category C
The use of what medication while pregnant may result in transient newborn respiratory disease?
SSRIs
What are the two SSRIs that have worse effects than the others?
Paroxetine (Paxil) and Fluoxetine (Prozac)
What medication(s) cangenerally lead to an increased risk of several cardiac defects and craniosynostosis?
Paroxetine (Paxil) and Fluoxetine (Prozac)
What is craniosynostosis?
the fusion of parts of the baby’s skull in utero resulting in the head being misshapen
What medication are these effects associated with if taken while pregnant:
-anencephaly
-atrial septal defects
-other cardiac structural abnormalities
-gastroschisis
-omphalocele
Paroxetine (Paxil)
What is anencephaly?
small formed brain
What happens in gastroschisis and omphalocele?
intestines are born outside of the body
What teratogenic medications are used for the treatment of seizure disorders and bipolar disorder?
anticonvulsants
What are these general abnormalities usually associated with?
-cleft palate/cleft clip
-spina bifida (lower spine doesn’t close)
-atrial septal defects (low cardiac output)
-developmental delay
-limb abnormalities
the use of anticonvulsants while pregnant
What teratogenic medications are taken by women during pregnancy to relieve pain?
NSAIDS
What are some examples of teratogenic NSAIDS?
-aleve
-ibuprofen
-advil
-naproxen
-ketoprofen
-celecoxib
The use of what medication during the first trimester increases the risks of having a baby with cardiac ventricular septal defects (VSD)?
NSAIDS
What medication taken during the third trimester of pregnancy increases the risks of pulmonary hypertension in newborns?
NSAIDS
What have some studies shown related to NSAID use during pregnancy that other studies have not?
increased rate of spontaneous abortion
What teratogenic medication is used as an anticoagulant in patients who have had deep vein thrombosis?
Warfarin (Coumadin)
These abnormalities are associated with use of what medication during the first trimester of pregnancy?
Skeletal abnormalities:
-nasal hypoplasia
-long bone developement abnormalities (stippled epiphyses)
Warfarin
What happens in nasal hypoplasia?
baby is born with a small nose with depressed bridge
What happened in stippled epiphyses?
ossification of the long bones that can cause elongated or deformed shaft
What teratogenic medication is used in treatment of generalized anxiety and has a very high potential for abuse quickly after starting?
Benzodiazepines
What is termed “a bottle of wine in a pill” and has an almost immediate effect?
Benzodiazepines
What do Benzodiazepine medication names end in?
“lam” or “pam”
example: alprazolam, diazepam
What medication are these possible fetal outcomes associated with?
-noenatal withrawal
-cyanosis (blue baby)
-hypotonia (low muscle tone)
Benzodiazepines
What teratogenic medication was deemed safe for use in pregnancy until recently; can be combined with codeine for severe pain in pregnancy; and it used frequently for back or muscle pain in pregnancy?
Acetaminophen (Tylenol)
What outcomes are associated with the use of Acetaminophen during pregnancy?
-abnormal neurodevelopment, particular ADHD
-increased risk for developing autism
The fetus only eliminated alcohol at a rate of what percent that of the mother?
3-4%
The teratogenic effects of alcohol use depend on what?
-quantity of alcohol used
-pattern of drinking behavior
The smallest effects of alcohol use such as low birth weight begin at how many drinks a day and become more evident at how many drinks a day?
being at 2 drinks/day
more evident at 4 drinks/day
Most fetal alcohol syndrome occurs in mothers who have what?
alcohol use disorder (typically >8-10+ drinks/day)
What are these facial characteristics associated with?
-small eye openings
-smooth philtrum
-thin upper lip
fetal alcohol syndrome (FAS)
What are these characteristics associated with?
-“railroad track ears”
-decreased elbow pronation/subination
-incomplete expenstion of digits
-defects in palmar crease: “hockey stick crease”
FAS
What are these deformities associated with?
-growth retardation prenatally or postnatally
-atrial/ventricular septal defects
-multiple skeletal abnormalities (scoliosis)
-renal dysplasia/aplasia (horseshoe kidney)
-vision and ocular abnormalities (ptosis of lids, stabismus)
-hearing loss
FAS
What happens in ptosis?
eyelid drooping
What happens in strabismus
one eye does not align correctly
The use of what during pregnancy puts the mother at an increased risk:
-placenta previa
-preterm premature rupture of membranes (PPROM)
-increased risk of placental abruption
Tobacco
What happens in placenta previa?
blockage of the cervix so the baby will not drop
What does nicotine-induced vasospasms cause when used during pregnancy?
impaired fetal oxygen delivery
Placental changed caused by tobacco use in pregnant females result in what?
reduction of gas exchange
Carbon monoxide exposure does what when tobacco is used during pregnancy?
diminishes oxygenation of tissues
What can tobacco use result in when used during pregnancy?
-low birth weight
-preterm delivery and preterm death
-34% of SIDS cases related to cigarette use
What may contribute to or increase the risk of these physicality’s with certain genotypes when used during pregnancy?
ENT:
-cleft lip/cleft palate
GI tract:
-gastroschisis
-anal atresia (hole doesn’t develop)
Other defects of:
-digits and limbs
-heart
-kidneys
smoking
What is associated with marijuana use during pregnancy?
-no apparent effect on birth weight or gestational age
-no association with prematurity or congenital abnormalities
-no effect on overall IQ, but some increase difficulty with problem-solving skills, learning and memory deficits
-heavy marijuana use seems to increase memory and learning issues
-studies conflict and may be confounded by other socioeconomical factors, which can also hinder child development
Maternal effects of cocaine use are likely related to what?
vasoconstriction and hypertension
What are these maternal effects with pregnancy associated with?
Cardiac:
-myocardial infarction
-arrythmias
-aortic rupture
Neurologic:
-CVA (stroke)
-seizure
GI/GYN:
-bowel ischemia
-placental abruption
cocaine use
What are these “in-utero” effects caused by?
-spontaneous abortion
-fetal demise
-IUGR: intrauterine growth retardation
cocaine use
Cocaine use while pregnant increases the risk of what?
premature birth
What are the neurobehavioral issues in babies that usually occur 48-72 hours after birth?
-high-pitched crying and excess suck reflex
-irritability/jittery/tremors
-can have episodes of either apnea or tachypnea
What are the long term effects in the children where cocaine was used during pregnancy?
-may be linked to long-term behavioral issues with aggression and attention span
-possible confounded by other factors such as poverty and environment
What are some of the names of different opioids?
-heroin
-codeine
-fentanyl
-opium
-methadone
-oxycodone
-meperidine
-hydrocodone
-hydromorphone
-buprenorphine
Out of all the opioids, which is most rapid acting and most likely to produce dependence?
Heroin
Codeine use during pregnancy increases the risk of what?
fetal congenital heart defects
What drug chronically used during pregnancy can increase the risk of these issues?
-fetal growth restriction and death
-abruptio placenta
-preterm labor
-intrauterine passage of meconium
heroin
What is meconium?
while baby is in utero, it has a bowel movement which can cause aspiration of own feces and infections can develop
What are these “at birth” effects associated with?
-irritability and behavioral issues
-low birth weight
-feeding difficulties
-vomiting and loose stools
-seizures
the use of opioids
When opioids are used during pregnancy, the babies are born _____
addicted
When babies are born addicted to opioids, what is the course of action?
The baby is given morphine and is slowly weaned off
What are the effects associated with?
-small for gestational age (SGA) or low birth weight
-preterm delivery
-lethargy at birth
-neurotoxicity, cardiac toxicity, hepatotoxicity
methamphetamine use in pregnancy
