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ABGC > Teratology > Flashcards

Teratology Flashcards

1
Q

incidence of birth defects

A
  • 3-5% overall risk

- 1% (~1 in 100) babies born with CHDs

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2
Q

percentage of birth defects due to teratogens

A

5-10%

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3
Q

miscarrying pregnancies

A

approximately 20% of all recognized pregnancies

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4
Q

risk perception with medication exposure

A
  • 50-90% of all women exposed to meds in pregnancy, but most of these are not teratogenic
  • women and providers tend to estimate their risk for teratogenic effects to be about 25%
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5
Q

teratogen

A

any medication, chemical, infectious disease or environmental agent that might interfere with normal fetal development and may result in miscarriage, birth defects or adverse pregnancy outcomes

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6
Q

possible teratogenic effects

A
  • SAB
  • pregnancy complications
  • IUGR
  • patterns of major, minor malformations
  • metabolic dysfunction
  • cognitive dysfunction
  • altered social behavior
  • malignancy
  • complications in the neonatal period
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7
Q

thalidomide

A
  • drug used as a sedative

- resulted in 20-50% of exposed pregnancies having sever limb defects

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8
Q

thalidomide critical period

A

between 30-50 days post-LMP

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9
Q

principles of teratology

A
  • developmental timing
  • dose
  • genetic susceptibility
  • pattern of malformation
  • tissue access
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10
Q

developmental timing

A

most important factor in determining the risk for a birth defect to affect the pregnancy

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11
Q

heart formation

A

ends at about 6w post-conception, 8w post-LMP

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12
Q

limb formation

A

complete by the end of the first tri

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13
Q

brain formation

A

any teratogen that can affect cognition or behavior can cause issues at any point in the pregnancy

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14
Q

warfarin embryopathy

A
  • nasal hypoplasia that can cause respiratory distress in the newborn period
  • stippled epiphyses-calcifications of joints that don’t typically cause physical disability
  • limb hypoplasia
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15
Q

warfarin critical period

A

6-9w post-conception, 8-11w post-LMP

-need moms to switch to alternate anti-thrombotic

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16
Q

ACE inhibitor/ARB embryopathy

A
  • renal tubular dysplasia
  • IUGR
  • hypocalvaria with large anterior fontanelle
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17
Q

ACE inhibitor/ARB critical period

A

2nd and 3rd trimester of pregnancy

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18
Q

effects of renal tubular dysplasia

A
  • oligohydramnios
  • Potter sequence
  • pulmonary hypoplasia
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19
Q

ACE inhibitor mechanism of activity

A
  • reduce intrauterine blood flow, causing placental perfusion and severe fetal hypotension
  • block fetal angiotensin-converting enzyme in fetus disrupting fetal hemodynamics
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20
Q

Potter sequence

A
  • renal problems lead to oligo
  • this can lead to other abnormalities, including club foot, pulmonary hypoplasia, sometimes eye and cardiac anomalies
  • facies: low-set abnormal ears, epicentral folds, micrognathia, flattened nose/profile
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21
Q

SSRI effects in the first trimester

A

-smaller studies showed no increased risk for birth defects
-larger studies found a range of implications, including
+craniosynostosis
+anencephaly
+omphalocele
+2 fold CHD risk (1 in 200)

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22
Q

SSRI effects throughout pregnancy

A
  • can result in mild short-lived neonatal adaptation syndrome-like a less severe version of withdrawal
  • potential effects on gross motor and language development
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23
Q

SSRI effects after 20w of pregnancy

A

variable opinions on increased risk for pulmonary HTN of the newborn
+would lead to the need for a NICU stay
+risk in the past has been thought to be only about 1%

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24
Q

discontinuation of SSRI effects

A

untreated depression is likely to lead to recurrence in the first trimester

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25
Q

nausea and vomiting in pregnancy

A
  • common-occurs in ~80% of women between weeks 6-12

- 1% will progress to life-threatening hyperemesis gravidarum

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26
Q

hyperemesis gravidarum treatment

A

-traditionally includes antihistamines, phenothiazines, and antiemetics
+ondansetron (antiemetic) has recently been seen with a two-fold CHD risk
-Diclegis is now the only FDA approved N&V medication

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27
Q

dose

A

-teratogens tend to exhibit a dose-response relationship
+can be greater in animals than humans
-greater exposure generally leads to a greater effect
+a threshold below which no effect can be seen is sometimes present

28
Q

methylmercury

A

-high levels of mercury can lead to neurological problems in women and children-severe CNS and motor effects
+asymptomatic levels are about 8bbp in skin, 2ppm in hair
+affected kids with 5-110ppm in hair
-per FDA, women recommended to eat fish during pregnancy, but avoid those high in mercury

29
Q

radiation

A

-pattern of malformations: ID, microcephaly, seizures, minor eye malformations, GR, possible increased risk for carcinogenesis
-no increased risk below 5 rads
+most diagnostic tests do not go above this, only possible with abdominal CTs
+often times affected kids were exposed to 20-25 rads

30
Q

fluconazole

A

-antifungal medications
-mostly non-associated with no birth defects
+however some women treated with it in large doses of Valley fever had babies with severe craniofacial, cardiac and limb anomalies
+requires large oral or IV dosage
+possible risk for Antley-Bixler phenocopy

31
Q

common anti-convulsants

A
  • pheytoin
  • valproate
  • trimethadione
  • barbiturates
  • carbamazepines
  • anticonvulsant embryopathy usually refers to these older medications
32
Q

anticonvulsant use

A
  • drug cocktails/polytherapy worse

- increasing use of drugs for other maternal conditions-ex: bipolar

33
Q

anticonvulsant embryopathy

A
  • dysmorphic features-hypertelorism, broad depressed nasal bridge, short-upturned nose, cupid’s bow lip, nail hypoplasia
  • major malformation risk-myelomeningocele, oral clefting, CHDs (aorta, PDA), limb anomalies
  • neurobehavioral: DD, dose dependent increased risk for diminished IQ, ASD
34
Q

anticonvulsant risk values

A

-highest risks for valproic acid, phenobarbital, carbamazepine, trimethadione
+6-15% risk of major malformations
-possible reduced risk in newer meds
-DD risk independent of additional anomalies
-higher polydrug therapy risk
-best outcomes if optimal lower risk therapy identified prior to conception

35
Q

tissue access

A

teratogen present in maternal circulation in high enough amounts to cross the placenta

36
Q

Organogenesis

A

Days 18-60 of gestation

-NTD develops between days 23-30

37
Q

Maternal diabetes risks

A
  • miscarriage, stillbirth, preterm birth
  • macrosomia (>10lbs)
  • cardiac defects
  • NTDs and caudal regression
  • polyhydramnios
  • other birth defects
  • maternal HTN and preeclampsia
  • hypoglycemia “knocks out” important cells
38
Q

MDM counseling and recommendations

A

-lower risks in controlled and gestational diabetes
+need to consider co-morbidities like HBP
-recommend folic acid beginning preconception
-level II/anatomy scan b/t 18-20w
-msAFP or AFAFP b/t 16-20w
-fetal echo b/t 20-22w

39
Q

FDA teratogen classification

A
  • A, B, C, D alphabetically least to most concerning
  • X is contraindicated, except if benefit to mom significantly outweighs risk
  • N is not yet classified
  • lettering will be removed because of the medical mismanagement associated with the system
40
Q

retinoic acid embryopathy

A

-ID can be seen in absence of additional anomalies (30-60%)
-can lead to CNS, CV (aortic arch anomalies), ear and thymus anomalies in 20-30% of exposed fetuses
+related to disruption of neural crest cell migration/function

41
Q

retin-A/tretinoin

A

topically absorbed, and although effects likely less severe or non-existent suggested to be avoided during pregnancy

42
Q

genetic susceptibility

A

-teratogenicity related to maternal and fetal DNA and metabolizing enzymes
+cytochrome p450 (CYP)
+only 30% of babies affected by teratogens
-future research may work towards personalized medicine

43
Q

smoking in pregnancy risks

A
  • infertility
  • ectopic pregnancy
  • miscarriage
  • preterm birth
  • IUGR (dose dependent)
  • placental abruption & placenta previa
  • SIDS
  • orofacial clefts
44
Q

fetal orofacial clefts and cigarettes

A

-association in some studies but not in others
-thought to be related to polymorphisms in TGF-alpha
+moms more likely to have a child with problems if they are in contact with teratogen and have the particular allele

45
Q

codeine and breastfeeding

A
  • rare association of use and newborn respiratory failure

- moms were ultra-rapid metabolizers of morphine

46
Q

CMV incidence

A

-primary infection occurs in 1-4% of all pregnancies
-most infected newborns are unaffected (85-95%)
+primary maternal infection only results in congenital infection in 30-40% of cases
+secondary infection thought to be related to a different strain of the virus

47
Q

CMV pattern

A

in 10-14% of infected pregnancies the following may occur to varying degrees

  • IUGR
  • cerebral calcifications, ID
  • ocular abnormalities, deafness
  • hepatosplenomegaly
  • petichiae
  • most common adverse outcome is hearing loss
48
Q

vaccines in pregnancy

A

some can be given in pregnancy, though recommended to be up to date prior to conception

49
Q

viral and parasitic infections in pregnancy

A

generally can lead to damaging effect in the CNS and hematopoietic systems

50
Q

alcohol in pregnancy

A

no known safe level, but effects only thought to be seen in addicted mothers

51
Q

FASD implications

A

-IUGR and postnatal GR
-CNS effects-brain malformations, seizures
-CHD, renal anomalies, skeletal implications
+ID, DD
+behavioral problems-irritability, ADHD, ASD
-facial dysmorphism
+ptosis, SHORT palpebral fissures, micropthalmia
+smooth philtrum
+thin upper vermillion

52
Q

benzodiazepines

A
  • used mostly to treat anxiety
  • some associations with oral clefting in animal models and older studies
  • use in the end of pregnancy has a higher risk for neonatal adaptation syndrome
53
Q

Zika virus

A

neurotropic flavivirus in the same class as dengue, West Nile, Chikungunya, Yellow Fever, Japanese Encephalitis

54
Q

Zika symptoms

A

-usually incubates 3-14d
-80% infected asymptomatic or with mild symptoms
+can get conjunctivitis, fever, joint pain, rash
+muscle pain & headache can also happen
+possible increased risk for Guillan-Barre related to autoimmune disease reaction
-infection and damage to placenta can lead to congenital infection

55
Q

congenital Zika risks

A

*highest risks in 1st tri exposures
-microcephaly
+~13% of vertical transmission cases, often not seen until 3rd tri
-brain calcifications
-other brain anomalies (ventriculomegaly, abnormal gyral patterning, cerebellar hypoplasia & cerebellar vermis or brainstem hypoplasia, hypo plastic corpus callosum)
-IUGR
-eye anomalies & hearing loss
-arthrogryposis & club foot
-neuromotor anomalies and seizures

56
Q

Zika testing

A

-PCR of serum & urine of RNA
+serum remains positive usually up to 7 days
+urine has delayed positive (3-14d)
-consider asymptomatic travelers may have incubation period
-IgM
+subject to cross-reactivity can be tested 4d-12w post symptom
-PRNT
+infects serum with live virus when IgM positive and measure dilution
+subject to cross-reactivity
-amniotic fluid PCR
+no longer recommended to rule out because a negative result doesn’t exclude risk

57
Q

fetal kidney development

A

not complete until 16w

-amniotic fluid may not accurately represent fetal cell makeup until this point

58
Q

congenital rubella syndrome

A
  • caused by infection exposure in 1st and early 2nd tri, though effects can be seen into 3rd tri
  • earlier exposures increase risk for SAB, SNHL, ID, cataracts, CHD, “blueberry muffin” phenotype due to platelet destruction and blood pooling under skin
  • later exposure increases risk for ID, microcephaly, ASD, diabetes and autoimmune disease
59
Q

fetal valproate syndrome

A
  • includes fetal hydantoin syndrome as subtype (kids more dysmorphic); drug cocktails worse
  • higher intake correlated with higher risk
  • 20 fold ONTD and cardiac anomaly risk increase
  • CL+or-P, GU, skeletal anomalies, DD, autism, and endocrine disorders may also occur
60
Q

toxo

A

brain and eye anomalies

61
Q

HSV

A

increased risk for SAB, blindness, deafness, cerebral palsy, ID

62
Q

syphilis

A

increased risk SAB, deafness, ID

63
Q

Lithium exposure

A

increased risk for CHD (Ebstein anomaly) in fetuses of exposed mothers

64
Q

warfarin embryopathy

A
  • SGA
  • extremity hypoplasia
  • optic atrophy, CHD
65
Q

maternal HTN

A

increased risk LBW, preterm labor, still birth and maternal mortality

66
Q

maternal autoimmune disease

A
  • ex: Lupus

- can lead to IUGR, fetal heart block

ABGC (34 decks)

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