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Clinical Science > Teratogenesis > Flashcards

Teratogenesis Flashcards

1
Q

What is teratogenesis?

A

the process by which congenital malformations are produced in an embryo or fetus

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2
Q

What are the five principles of teratogenesis?

A

-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

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3
Q

Approximately 31% of fertilizations end in what?

A

spontaneous abortions

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4
Q

About 3% of infants are born with what?

A

structural anomalies

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5
Q

What is the critical fetal period for teratogenesis and why?

A

3-16 weeks due to impairment of organogenesis

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6
Q

What are the potential adverse effect(s) of fetotoxic exposure at pre-implantation stage?

A

spontaneous abortions

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7
Q

What are the potential adverse effect(s) of fetotoxic exposure at the embryonic (2-8 weeks) stage?

A

-spontaneous abortions
-structural malformations

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8
Q

What are the potential adverse effect(s) of fetotoxic exposure at the fetal (8-40 weeks) stage?

A

-central nervous system function
-growth restriction
-neurobehavioral effects
-fetal demise

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9
Q

When do most birth defects occur and why is this an issue?

A

occur prior to 8 weeks which is usually before the first prenatal appointment

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10
Q

What should you do whenever you are prescribing medications to a patient who is of child-bearing age?

A

ensure you know the pregnancy status by asking when their last menstrual period was and if they could be pregnant

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11
Q

What is the description of category A medications?

A

well-controlled studies in humans show no risk to the fetus

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12
Q

What is the description of category B medications?

A

no well-controlled studies have been conducted in humans; animal studies show no risk to the fetus

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13
Q

What is the description of category C medications?

A

no well-controlled studies have been conducted in humans; animal studies have demonstrated an adverse effect on the fetus

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14
Q

What is the description of category D medications?

A

evidence of human risk to the fetus exists; however, benefits may outweigh risks in certain situations

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15
Q

What is the description of category X medications?

A

controlled studies in animals or humans demonstrate fetal abnormalities; the risk in pregnant women clearly outweighs any possible benefit

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16
Q

Drugs in the mother’s blood can pass through what structure to get to the fetus?

A

the umbilical cord

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17
Q

What was a medication marketed in the 1950s for nausea in pregnancy and was widely used in Europe, Australia, and Japan?

A

thalidomide

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18
Q

Why was approval of the use of thalidomide in the US withheld?

A

Dr. Frances Kelsey was concerned over the safety and side effects of thalidomide such as peripheral neuropathy

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19
Q

What is peripheral neuropathy?

A

weakness, numbness, and pain in your extremities

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20
Q

What did the tragedy of thalidomide lead to?

A

the development of testing of pharmaceuticals for adverse effects on fetal development

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21
Q

What are these deformities associated with?
-amelia
-meromelia
-phocomelia

A

thalidomine use

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22
Q

What is amelia?

A

complete absence of a limb or limbs

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23
Q

What is meromelia?

A

partial absence of a limb

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24
Q

What is phocomelia?

A

form of meromelia where there is an absence of long bones with hands and feet attached to trunk with small rudimentary bones

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25
Q

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

A

thalidomide use

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26
Q

What is thalidomide still used for today?

A

treatment of:
-leprosy
-HIV
-multiple myeloma

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27
Q

What act was created due to the outcomes of the thalidomide tragedy?

A

Kefauver-Harris Drug Amendments Act

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28
Q

Prior to the Kefauver-Harris Drug Amendments Act, medications could be sold for how long after application filed with the FDA?

A

60 days

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29
Q

What did the Kefauver-Harris Drug Amendments Act enforce after the thalidomide tragedy?

A

-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

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30
Q

What is diethystilbestrol (DES)?

A

a potent estrogen used to prevent spontaneous abortion and premature labor (used between 1940 and 1971)

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31
Q

By 1953, where there any beneficial effects of DES?

A

No, but it was still used and came in many forms/combinations with other hormones

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32
Q

An estimated 2-10 million _____ and _____ were exposed to DES during the first decade of its use

A

women and their fetuses

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33
Q

What were the effects of DES for women who took DES, “DES mothers”?

A

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)

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34
Q

What were the effects of DES for females exposed to DES in utero, “DES daughters”?

A

-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

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35
Q

What were the effects of DES for males exposed to DES in utero, “DES sons”?

A

-increased risk for cysts of epididymis, microphallus, undescended testicle or testicular hypoplasia, decreased sperm count
-no decrease in fertility
-no increase in cancer risk

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36
Q

What is another term for undescended testicle?

A

cryptorchidism

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37
Q

What is testicular hypoplasia?

A

one testicle is significantly smaller than the other

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38
Q

Excessive amounts of what vitamin has been associated with teratogenicity?

A

Vitamin A

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39
Q

What teratogenic medication are these deformities associated with?
-cleft lip
-cleft palate
-hydrocephalus (water in ventricles of brain)
-cardiac deformities

A

vitamin A

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40
Q

What teratogenic medication is a vitamin A isomer (13-cis-retinoic acid)?

A

isotretinoin (Accutane)

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41
Q

What is isotretinoin (Accutane) used in?

A

treatment of cystic acne

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42
Q

What are the adverse effects of using isotretinoin (Accutane) while pregnant?

A

-increased risk of spontaneous abortion
-20-30% of exposed neonates have evidence of abnormalities such as thalidomide-like malformations and malformation in multiple organs

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43
Q

What program was started to reduce prenatal exposure to isotretinoin (Accutane)?

A

iPLEDGE

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44
Q

Isotretinoin prescribers must be what?

A

-registered with the iPLEDGE program
-demonstrate awareness of its potential effects

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45
Q

When a female patient of child-bearing age is using isotretinoin, what must she do?

A

-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

46
Q

Which teratogenic medications are commonly used in treatment of hypertension?

A

-angiotensin converting enzyme inhibitors (ACES)
-angiotensin receptor blockers (ARBS)

47
Q

What are the 1st trimester fetal risks of taking ACES and ARBS?

A

risks are unclear but possibly cardiovascular and central nervous system abnormalities

48
Q

What are these fetal effects associated with:
-growth retardation
-renal dysfunction
-fetal demise
-oligohydramnios

A

the use of ACES and ARBS in the 2nd and 3rd trimester of pregnance

49
Q

What is oligohydramnios?

A

decreased amniotic fluid

50
Q

Treatment of hypertension often begins with what as the initial medication?

A

ACE inhibitor

51
Q

ACE inhibitor medication names end in what?

A

-pril

52
Q

What are some common side effects of ACE inhibitors that lead to switching to a different type of medicatin?

A

dry and hacking cough

53
Q

What is used as a substitute for ACE inhibitors? (still a teratogenic medication)

A

ARBs

54
Q

ARB medications end in what?

A

-artan

55
Q

What teratogenic medications are used to treat depression, anxiety, and OCD?

A

Selective Serotonin Reuptake Inhibitors (SSRI)

56
Q

What category of medication do SSRIs fall into?

A

Category C

57
Q

The use of what medication while pregnant may result in transient newborn respiratory disease?

A

SSRIs

58
Q

What are the two SSRIs that have worse effects than the others?

A

Paroxetine (Paxil) and Fluoxetine (Prozac)

59
Q

What medication(s) cangenerally lead to an increased risk of several cardiac defects and craniosynostosis?

A

Paroxetine (Paxil) and Fluoxetine (Prozac)

60
Q

What is craniosynostosis?

A

the fusion of parts of the baby’s skull in utero resulting in the head being misshapen

61
Q

What medication are these effects associated with if taken while pregnant:
-anencephaly
-atrial septal defects
-other cardiac structural abnormalities
-gastroschisis
-omphalocele

A

Paroxetine (Paxil)

62
Q

What is anencephaly?

A

small formed brain

63
Q

What happens in gastroschisis and omphalocele?

A

intestines are born outside of the body

64
Q

What teratogenic medications are used for the treatment of seizure disorders and bipolar disorder?

A

anticonvulsants

65
Q

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

A

the use of anticonvulsants while pregnant

66
Q

What teratogenic medications are taken by women during pregnancy to relieve pain?

A

NSAIDS

67
Q

What are some examples of teratogenic NSAIDS?

A

-aleve
-ibuprofen
-advil
-naproxen
-ketoprofen
-celecoxib

68
Q

The use of what medication during the first trimester increases the risks of having a baby with cardiac ventricular septal defects (VSD)?

A

NSAIDS

69
Q

What medication taken during the third trimester of pregnancy increases the risks of pulmonary hypertension in newborns?

A

NSAIDS

70
Q

What have some studies shown related to NSAID use during pregnancy that other studies have not?

A

increased rate of spontaneous abortion

71
Q

What teratogenic medication is used as an anticoagulant in patients who have had deep vein thrombosis?

A

Warfarin (Coumadin)

72
Q

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)

A

Warfarin

73
Q

What happens in nasal hypoplasia?

A

baby is born with a small nose with depressed bridge

74
Q

What happened in stippled epiphyses?

A

ossification of the long bones that can cause elongated or deformed shaft

75
Q

What teratogenic medication is used in treatment of generalized anxiety and has a very high potential for abuse quickly after starting?

A

Benzodiazepines

76
Q

What is termed “a bottle of wine in a pill” and has an almost immediate effect?

A

Benzodiazepines

77
Q

What do Benzodiazepine medication names end in?

A

“lam” or “pam”
example: alprazolam, diazepam

78
Q

What medication are these possible fetal outcomes associated with?
-noenatal withrawal
-cyanosis (blue baby)
-hypotonia (low muscle tone)

A

Benzodiazepines

79
Q

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?

A

Acetaminophen (Tylenol)

80
Q

What outcomes are associated with the use of Acetaminophen during pregnancy?

A

-abnormal neurodevelopment, particular ADHD
-increased risk for developing autism

81
Q

The fetus only eliminated alcohol at a rate of what percent that of the mother?

A

3-4%

82
Q

The teratogenic effects of alcohol use depend on what?

A

-quantity of alcohol used
-pattern of drinking behavior

83
Q

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?

A

being at 2 drinks/day
more evident at 4 drinks/day

84
Q

Most fetal alcohol syndrome occurs in mothers who have what?

A

alcohol use disorder (typically >8-10+ drinks/day)

85
Q

What are these facial characteristics associated with?
-small eye openings
-smooth philtrum
-thin upper lip

A

fetal alcohol syndrome (FAS)

86
Q

What are these characteristics associated with?
-“railroad track ears”
-decreased elbow pronation/subination
-incomplete expenstion of digits
-defects in palmar crease: “hockey stick crease”

A

FAS

87
Q

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

A

FAS

88
Q

What happens in ptosis?

A

eyelid drooping

89
Q

What happens in strabismus

A

one eye does not align correctly

90
Q

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

A

Tobacco

91
Q

What happens in placenta previa?

A

blockage of the cervix so the baby will not drop

92
Q

What does nicotine-induced vasospasms cause when used during pregnancy?

A

impaired fetal oxygen delivery

93
Q

Placental changed caused by tobacco use in pregnant females result in what?

A

reduction of gas exchange

94
Q

Carbon monoxide exposure does what when tobacco is used during pregnancy?

A

diminishes oxygenation of tissues

95
Q

What can tobacco use result in when used during pregnancy?

A

-low birth weight
-preterm delivery and preterm death
-34% of SIDS cases related to cigarette use

96
Q

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

A

smoking

97
Q

What is associated with marijuana use during pregnancy?

A

-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

98
Q

Maternal effects of cocaine use are likely related to what?

A

vasoconstriction and hypertension

99
Q

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

A

cocaine use

100
Q

What are these “in-utero” effects caused by?
-spontaneous abortion
-fetal demise
-IUGR: intrauterine growth retardation

A

cocaine use

101
Q

Cocaine use while pregnant increases the risk of what?

A

premature birth

102
Q

What are the neurobehavioral issues in babies that usually occur 48-72 hours after birth?

A

-high-pitched crying and excess suck reflex
-irritability/jittery/tremors
-can have episodes of either apnea or tachypnea

103
Q

What are the long term effects in the children where cocaine was used during pregnancy?

A

-may be linked to long-term behavioral issues with aggression and attention span
-possible confounded by other factors such as poverty and environment

104
Q

What are some of the names of different opioids?

A

-heroin
-codeine
-fentanyl
-opium
-methadone
-oxycodone
-meperidine
-hydrocodone
-hydromorphone
-buprenorphine

105
Q

Out of all the opioids, which is most rapid acting and most likely to produce dependence?

A

Heroin

106
Q

Codeine use during pregnancy increases the risk of what?

A

fetal congenital heart defects

107
Q

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

A

heroin

108
Q

What is meconium?

A

while baby is in utero, it has a bowel movement which can cause aspiration of own feces and infections can develop

109
Q

What are these “at birth” effects associated with?
-irritability and behavioral issues
-low birth weight
-feeding difficulties
-vomiting and loose stools
-seizures

A

the use of opioids

110
Q

When opioids are used during pregnancy, the babies are born _____

A

addicted

111
Q

When babies are born addicted to opioids, what is the course of action?

A

The baby is given morphine and is slowly weaned off

112
Q

What are the effects associated with?
-small for gestational age (SGA) or low birth weight
-preterm delivery
-lethargy at birth
-neurotoxicity, cardiac toxicity, hepatotoxicity

A

methamphetamine use in pregnancy

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