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46 Cards in this Set
- Front
- Back
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Define:
a) Teratogen b) Hadegen c) Trophogen |
a) any agent (virus, chemical, etc.) that acts during embryonic or fetal development to produce a permanent alteration of form or function
b) an agent that interferes with an organ c) an agent that alters growth |
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List criteria a potential teratogen must fulfil (5)
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1) defect completely characterized
2) Agent crosses placenta 3) Exposure occurs during a critical developmental period 4) Biologically plausible association 4) Epidemiological findings must be consistent 5) Causes defects in non-human animals |
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a) In considering teratology, what is the 'implantation period' defined as?
b) Insults in this period usually result in? |
a) 0-2wks GA
b) Death of zygote |
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a) When is the 'embyropathic period' in teratology?
b) Insult during this period usually results in what? |
a) 2-8wks GA
b) major structural malformation |
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a) When is the 'fetopathic' period in teratology?
b) Insult during this period usually results in what? c) Give an example of a fetopathic insult |
a) 8wks-term
b) damage to developmental process, can also be structural damage c) EtoH and development of FAS |
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Most major malformation occur during this gestational age range
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2-10 weeks
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What structures are most sensitive to damage/teratogenicity beyond 10 weeks?
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CNS
Ear Eyes Teeth External genitalia |
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Disruption of folic acid metabolic pathways can lead to what congenital defects?
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Neural tube
Cardiac Cleft lip/palate Renal abnormalities ? Down syndrome |
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List features of fetal hydantoin syndrome
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Craniofacial
long upper lip thin vermillion border midface hypoplasia upturned nose Growth impairment Developmental delay Widely spaced nipples hypoplasia of distal phalanges |
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List 10 known/accepted teratogens
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Alcohol
Valproic acid ACEi/ARB Tetracyclines Statins Warfarin Methotrexate Cyclophosphamide Phenytoin Androgens Misoprostol Lithium DES Thalidomide Methimazole Tretinoin Ribavirin |
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What 5 major organs/organ systems can be affected by alcohol in utero?
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Cardiac
Renal Skeletal Eyes Ears |
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For FAS (fetal alcohol syndrome), list 3 facial dysmorphic features.
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small palpebral fissures
thin vermilion border smooth philtrum |
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Approximately what percentage of infants are affected by fetal alcohol spectrum disorder in the US?
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1%
Alcohol is one of the most common causes of non-genetic mental retardation |
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Antiepileptic drug therapy (AED) in general increases the fetal risk of major malformations by:
a) 2-fold b) 3-fold c) 4-fold |
a) 2-fold (2-3% to 4-6%)
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In general, major malformations affect what structures/systems (5)?
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Cardiac
Renal Neural tube Lip/Palate Skeletal (these are similar to those affected by interference of folic acid pathways |
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List AEDs that are teratogens
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Valproate
Phenytoin Phenobarbital Carbamazipine Topirimate |
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Which AED when combined in polytherapy seems to carry the highest risk for malformation?
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Valproic acid
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What is the risk of major malformation with valproic acid:
a) monotherapy b) polytherapy |
a) 1-2% (Williams) - 9% (UTD)
b) 10% |
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a) Besides malformations and structural defects, what others concerning effects are felt to be associated with fetal in utero exposure to AEDs?
b) Which AED seems to have the highest risk of this? |
a) Neuro-cognitive development
b) Valproic Acid |
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How do AEDs result in malformations?
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Unknown (UTD), theories include:
Interference with folic acid metabolic pathways Deficient epoxide hydralase (incr free radicals when exposed to AEDs) Phenobarbital - lowers folate levels (Williams) |
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What has use of ACE inhibitors been associated with?
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embryopathy and fetopathy
specifically: 1T: 8% major malformation: cardiac and CNS 2T-3T: affected renin-angiotensin, result in olig/anuria and ischemia of renal tubules and dysgenesis. cause hypotension and hypoperfusion. oligo can result in lung hypoplasia and limb contractures. |
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Are ACEi considered safe for breastfeeding? Which ones?
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Enalapril
Captopril |
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Is there good evidence fluconazole leads to malformations?
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From case studies, but large cohort studies have not shown this. Seems to be dose-dependent, low-dose (e.g. 150mg once) is ok.
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What deleterious effects on pregnancy have been described with maternal NSAID use?
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per Williams OB - not considered teratogens...
Prenatal/1T may impair conception/implantation/fertility 3T: oliohydramnios premature closure of ductus arteriosus doppler changes umbilical artery (reversible) IVH, NEC, BPD the last three associations are weaker. |
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Are antimalarials contraindicated in pregnancy? (e.g. hydroxychloroquine, quinine)
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No. Good safety data exist. Plaquinel can be used for rheumatic disease/lupus with good fetal tolerance.
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What are potential maternal and fetal adverse effects of amnioglycosides (e.g. gentamicin)?
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Ototoxicity
Nephrotoxicity Attempt to avoid by using divided doses. E.g. in pregnancy use 3 daily-divided doses instead of 1 dose protocol. |
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LIst 3 antibiotics that can displace bilirubin and result in neonatal jaundice?
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Septra (sulfonamides)
Nitrofurantoin Ceftriaxone |
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Are tetracyclines generally contraindicated in pregnancy?
Why? According to Williams OB, what is one potential acceptable use? |
Yes
staining of teeth deposition in long bones treatment of maternal syphilis if PCN desensitization cannot be accomplished. |
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What category is cyclophosphamide?
What malformations can result from maternal cyclophosphamide exposure in the first trimester? |
X
miscarriage missing/hypoplastic digits single coronary artery, imperforate anus, microcephaly |
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What category is methotrexate?
What malformations have been described following its use in pregnancy women? |
X
FGR, failure of calvarial ossification, carniosynostosis, hypoplastic supraorbital ridges, small posteriorly rotated ears, micrognathia, and severe limb abnormalities. The critical period for their development is 8 to 10 menstrual weeks. |
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For fetuses exposed to tamoxifen in utero (e.g. treatment of maternal breast Ca) how long should they be followed for the development of abnormalities/cancer?
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20 years (Williams OB)
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What category is ribavirin?
What animal data is there? |
X
Based on animal studies showing skeletal malformations, eye, GI tract malformations. |
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a) What is the problem with danazol if used accidentally through the first trimester?
a) What should be ensured when prescribing a women danazol? |
a) High incidence of virilization of female fetus
b) Reliable contraception |
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What medication that appears safe in pregnancy can cause 'gray baby syndrome' in exposed premature neonates?
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Chloramphenicol
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What malformation has been reported to occur with increased incidence in women taking SSRI, particularly paroxetine (Paxil)?
What is the specific nature of this defect? What is the absolute risk increase? relative risk increase? What two neonatal side effects can maternal use of SSRIs have? |
Cardiac
ASD, VSD 1% (RR 2.0 - from 1% to 2%) Neonatal withdrawal syndrome self-limiting, mild, 2days Persistent pulmonary hypertension in the Newborn more severe, can be lethal, about 1% of exposed infants |
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What rare adverse outcome has been reported for neonates of women taking SSRIs in pregnancy?
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Serotonin-like syndrome.
Hyperpyrexia, seizures, weight loss. |
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What drug is considered one of the most potent teratogens in common use?
What is the drug commonly used for? |
Isotretinoin - an isomer of retinoic acid/vitamin A
Cystic acne |
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What can first trimester exposure to isotretinoin cause?
What is the characteristic finding? |
miscarriage
25-fold increased risk of fetal malformation Microtia, Anotia (undeveloped/absent pinna (ear) |
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How long prior to conception should isotretinoin be discontinued?
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half-life 12h, probably safest to wait a month.
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How long has etretinate been found at detectable levels in human serum.
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3yrs after discontinuing the medication.
(half life 120d) |
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Is isotretinoin cream/gel safe?
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Yes - minimal absorption.
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a) If exposed to thalidomide during the critical time window - 35-50 days menstrual age (7-9wks), what percentage of fetuses will have major malformations?
b) What structures are mainly affected? c) What is phocomelia? |
a) 20%
b) Limbs (usually upper), bowel, cardiac, ears. c) Total absense of a bone or limb segment |
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How does thalidomide exert its teratogenic action?
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Intercalates into DNA at GC-rich sequences, inhibits their transcription.
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Of the following classes of illicit drugs, which are known teratogens and what do they cause?
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Amphetamines - not teratogens
Cocaine - IUFD, skull defects, aplasia cutis, renal & cardiac anomalies, porencephaly, ileal atresia, infarcts, neurocognitive delay Heroin - not teratogenic, + withdrawal symptoms Marijuana - not teratogenic, +/- LBW PCP - not teratogenic, + withdrawal symptoms LSD - not teratogenic Tobacco - FGR, ?gastroschisis |
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a) What is DES?
b) What was it used for? c) When did it come off the market in North America? |
a) Diethylstilbestrol - a non-steroidal synthetic estrogen
b) adverse pregnancy outcomes, menopausal symptoms c) 1971 (early 70's) |
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Women exposed to DES in utero are at increased risk of what medical/health complications?
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1) Cervicovaginal clear cell adenocarcinoma (CCA)
2) Congenital anomalies and epithelial changes of the reproductive tract (adenosis, hooded cervix) 3) Subfertility (mild) 4) Adverse pregnancy outcomes (SA, IUFD, PTB, GHTN) 4) Earlier age at menopause (1yr on average) 5) Breast cancer (RR 2) 6) Cervical intraepithelial neoplasia |
