LEC60: Teratology & Birth Defects Flashcards

1
Q

% of infant deaths in north america attributed to birth defects?

A

> 20%

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2
Q

% newborns w/ major structural anomalies

A

3%

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3
Q

% newborns w/ single minor defect

A

14%

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4
Q

% of birth defects detected by age 2

% by age 5

A

6% by age 2

8% by age 5

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5
Q

when are major development defects most common, %

A

in early embryos

10-15%

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6
Q

% of recognized prenancies that end in miscarriage

A

15%

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7
Q

% of spontaneously aborted conceptuses w/ chromosomal abnormalities

A

50-60%

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8
Q

incidence of major anomalies at birth? most to least common

A

10: 1000 brain
8: 1000 heart
4: 1000 kidneys
2: 1000 limbs
6: 1000 others

TOTAL: 30:1000

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9
Q

overall incidence of major anomalies at birth and most common of those?

A

3%

most common: brain, 1% of major anomalies

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10
Q

types of congential anomalies?

A

1) malformation
2) disruption
3) deformation
4) dysplasia

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11
Q

malformation? ex?

A

intrinsically abnormal development process

ie cardiac abrnormality, VSD

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12
Q

disruption? ex?

A

inference w/ an originally normal development process

fetus starts as normal, sthg happens that disrupts development process

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13
Q

deformation? ex?

A

abnormal form resulting from mechanical forces

ie if no fluid around fetus, > clubbed feet, contractures of limbs

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14
Q

dysplasia? ex?

A

abnormal organization of cells into tissues

ie kidneys dysplasia > multiple cysts replace them

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15
Q

patterns of anomalies?

A

1) field defect
2) sequence
3) syndrome
4) association

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16
Q

field defect?

A

disturbance in just 1 single developmental field

ie kidney, heart

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17
Q

sequence?

A

single structural defect/mechanical factor

ie lack of fluid w/ ruptured membranes due to compression

ie potter’s sequence- bilateral renal agenesis

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18
Q

syndrome?

A

multiple abnormalities that’re pathogenetically related

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19
Q

association?

A

non-random occurrence of multiple anomalies in 2+ people

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20
Q

most common cause of human birth defects?

A

unknown etiology (50-60%)

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21
Q

second most common cause of birth defects?

A

multifactorial inheritance (20-25%)

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22
Q

what is multifactorial inheritance?

A

birth defect caused by combination of genes and environment

ie neural tube defects- know partly genetic, but also can reduce incidence in those genetically predisposed for it if give folic acid while pregnant

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23
Q

% of birth anomalies caused by genetic factors?

A

1/3 of all birth defects

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24
Q

when are chromosomal abnormalities common?

A

in early zygotes/embryos

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25
Q

what is numerical chromosomal abnormality?

A

failure of chromosome pair or 2 chromatids to disjoin during mitosis or meiosis; due to disjunction

ie turner syndrome, autosomal trisomies like trisomy 21, sex chromosome trisomies, mosaicism, triploidy

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26
Q

turner syndrome?

A

numerical chromosomal abnormality (45,X)

most common abnormality in spontaneous abortions

1/8000 live births

75% due to missing paternal X chromsome

27
Q

examples of autosomal trisomies?

A

1) trisomy 18- heart defects, clenched fingers
2) trisomy 13- midline defects ie anencephaly

^^ both are incompatible w/ life

3) trisomy 21- 75% embryos spontaneously abort, 20% stillborn

28
Q

examples of sex chromosome trisomies?

A

1) 47, XXX: 15-25% mild MR
2) 47, XXY: Klinefelters, small testes, infertility
3) 47, XYY: normal appearance, tall

29
Q

mosaicism?

A

numerical chromosomal abnormality

2 cell lines w/ 2+ genotypes

30
Q

triploidy?

A

numerical chromosomal abnormality

failure of separation of 2nd polar body

dispermy

20% of all chromosomally abnormal spontaneous abortuses

31
Q

what are structural chromosome abnormalities?

A

chromosomal breakage and abnormal combination-

ie reciprocal translocation, terminal deletion, ring chromosome, duplication, paracentric inversion, isochromosome, robersonian translocation

due to drugs, chemicals, viruses

32
Q

characteristics of anomalies caused by mutant genes

A

7% of congenital anomalies

heritable

33
Q

achondroplasia

A

birth anomaly caused by G to A transition mutation at ntd 1138 of cDNA in FGFR3 gene on chromosome 4p

autosomal dominant- so if parent has it, have 50% chance of passing it on to fetus

if both parents are carriers, not compatible w/ life

34
Q

what is a teratogen, what % of anomalies acct for, how do they occur?

A

any agent- drug, virus, alochol- that causes a congenital anomaly

causes 7-10% of anomalies

mechanisms often unclear

ie thalidomide

35
Q

basic principles in teratogenesis? aka factors that determine/impact teratogenic influence?

*HY*

A

*HY*

1) timing of exposure - if occurs during critical period of particular organ system development, will cause effect
2) dosage of drug or chemical- severity of abnormality:[teratogen]
3) genotype (genetic constitution) of embryo- diff species or indivs may respond diff to same substance

36
Q

when and what is critical pd of human development?

A

1st 2 weeks after conception - when egg is fertilized, implanting, membranes developing

“all or nothing” time - exposure causes either fetal/embryonic death or has no effect

37
Q

when is susceptibility to teratogens greatest?

A

during organogenesis, 3-8 weeks! when organs are developing

38
Q

what occurs re: birth anomalies, during fetal pd?

A

8-38 weeks

no major anomalies but can have physiologic changes, minor morphological abnormalities & functional disturbances

ie exposure to alcohol- won’t cause structural defect in brain, but will cause physiological disturbance

39
Q

are all developing organs equally susceptible to teratogens at all times?

A

no- pds of high and less sensitivity occur during embryonic and fetal periods

most likely to have abnormality occur if exposure is during a highly sensitive period for a given organ or other aspect of developing embryo

40
Q

do teratogens just effect 1 organ?

A

no, they can affect >1 organ

41
Q

high doses of radiation affects?

A

CNS and eye

42
Q

rubella as teratogen affects?

A

eye defects, deafness, cardiac anomalies

43
Q

thalidomide impact across pregnancy?

A

early: meromelia-absence of limbs
later: hypoplasia of limbs

after critical pd: no affect on limbs

44
Q

does dose matter re: teratogens?

A

yes- dose-response relatoinship whereby the greater the exposure, the more severe the phenotypic effect

45
Q

how do we know about safe doses of drugs for preg women?

A

animal research- dose used is usu at much higher levels than that used in humans

46
Q

what is phenytoin?

A

drug that causes fetal hydantoin syndrome in 5-10% of exposed embryos - because only those embryos w/ GENETIC PREDISPOSITION to developing syndrome will have abnormalities

dose also important

47
Q

fetal hydantoin syndrome

A

caused by phenytoin exposure among embryos genetically susceptible to defective development

wide-spaced eyes, long philtrim, epincanthal folds, gigital hypoplasia, neurodevelopmental problems

48
Q

what are criteria for calling something a teratogen? proof of teratogenicity?

A

1) frequency fo anomaly increased above background risk

OR

2) malformed infants have history of maternal exposure more often than normal infants

49
Q

are case reports sufficient data to prove teratogenicity?

A

no, unless agent and anomaly are exceedingly rare

50
Q

% of congenital anomalies caused by drugs/chemicals

A

< 2%! so actually pretty rare for drug to be teratogen

51
Q

is caffeine a teratogen?

A

no

although over 300 mg/day may cause low birth-weight, miscarriage if early on

52
Q

is alcohol a teratogen?

if so, incidence of teratogenic effects?

what are effects?

when does alc have greatest effect on fetus?

A

yes

dose-dependent response to alc

1-2/1000 live births

fetal alc effects (FAE) = behavioral and learning difficulties

susceptible pd spans major pt of gestation

53
Q

coumadin re: fetus

A

anticoagulant

known teratogen - can cause bleeding in fetus

antagonist of vitamin k; can cause IUGR, zeisures, nasal hypoplasia, stippled epiphysis, CNS defects (dandy-walker malformation)

54
Q

oral acne med teratogen?

A

retinoic acid - vitamin A

severe ear defects, cardiac and CNS defects, craniofacial, thymic aplasia, cleft palate, neuropsychological impairment, & spontaneous abortion

critical pd- 3rd-5th wk

55
Q

environment chemicals that can cause birth defects?

A

1) lead:

spontaneous abortions, IUGR, anoalies, functional deficits

2) polychlorinated biphenyls (PCBs):

IUGR, skin discoloration, contaminated waters

56
Q

when can hyperthermia cause defect? what happens?

A

early exposure to hot tub or sauna is assoc w/ increaesd risk for neural tube defects

57
Q

infectious agents as teratogens? what do they cause?

A

micro-organisms can cross placenta, enter fetal blood stream- cause

spontaneous abortion, stillbirth, congenital anomalies, neonatal sequelae

get prenatal dx

rubella, CMV, herpes simplex, varicella, toxoplasmosis, syphylis are eg

58
Q

is radiation teratogen? effect?

A

yes- high-levels of ionizing radiation cause cell death, chromosomal injury, anomalies, mental retardation

severity lreated to dose, dose rate, stage of embryologic development

greatest risk for severe mental retardation- 10-18 weeks GA

5 rads or less is safe! diagnostic levels of radiation aren’t teratogenic

59
Q

are elctromagnetic fields teratogenic?

A

ie electric blankets, computers?

NO

60
Q

is ultrasound teratogenic?

A

NO

61
Q

is diabetes teratogenic?

A

if poorly controlled, 2-3 fold increase in congenital anomalies if mom’s diabetes is poorly controlled

can cause neural tube defects, cardiac defects, sacral agenesis, limb macrosomia, stillbirths

62
Q

what are mechanical factors that might cause clubfoot, congenital hip dislocation?

A

oligohydramnios

uterine anomalies

fibroids

early amniocentesis

63
Q

what does it mean to be anomaly caused by multifactorial inheritance? what usu results?

A

combo of genetic & environmental factors

usu single major anomaly results- cleft lip, NTD, pyloric stenosis

risk of recurrence is based on frequency in general pop & categories of relatives- higher risk w/ closer-degree relative

64
Q

which of following is true re: teratogens, birth defects?

1) teratogens don’t have any effect after pd of organogenesis
2) teratogens can cause severe abnormalities during implantation
3) teratogens should show dose-response effect
4) chromosomal abnormalities are leading cause of birth defects

A

1) false bc can have minor functiona, physiologic effects
2) false- all or nothing response during implantation- either death of embryo or no effect at all

3) teratogens should show dose-response effect- true!

4) false- leading cause is unknown!