LEC60: Teratology & Birth Defects Flashcards Preview

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Flashcards in LEC60: Teratology & Birth Defects Deck (64):
1

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

> 20%

2

% newborns w/ major structural anomalies

3%

3

% newborns w/ single minor defect

14%

4

% of birth defects detected by age 2

% by age 5

6% by age 2

8% by age 5

5

when are major development defects most common, %

in early embryos 

10-15%

6

% of recognized prenancies that end in miscarriage

15%

7

% of spontaneously aborted conceptuses w/ chromosomal abnormalities

50-60%

8

incidence of major anomalies at birth? most to least common

10:1000 brain

8:1000 heart

4:1000 kidneys

2:1000 limbs

6:1000 others 

TOTAL: 30:1000

9

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

3% 

most common: brain, 1% of major anomalies

10

types of congential anomalies?

1) malformation

2) disruption

3) deformation

4) dysplasia

11

malformation? ex?

intrinsically abnormal development process 

ie cardiac abrnormality, VSD

12

disruption? ex?

inference w/ an originally normal development process 

fetus starts as normal, sthg happens that disrupts development process

13

deformation? ex?

abnormal form resulting from mechanical forces 

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

14

dysplasia? ex?

abnormal organization of cells into tissues 

ie kidneys dysplasia > multiple cysts replace them

15

patterns of anomalies? 

1) field defect

2) sequence

3) syndrome

4) association

16

field defect?

disturbance in just 1 single developmental field 

ie kidney, heart

17

sequence? 

single structural defect/mechanical factor 

 

ie lack of fluid w/ ruptured membranes due to compression

ie potter's sequence- bilateral renal agenesis 

18

syndrome?

multiple abnormalities that're pathogenetically related 

19

association?

non-random occurrence of multiple anomalies in 2+ people

20

most common cause of human birth defects?

unknown etiology (50-60%)

21

second most common cause of birth defects?

multifactorial inheritance (20-25%)

22

what is multifactorial inheritance?

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 

23

% of birth anomalies caused by genetic factors?

1/3 of all birth defects

24

when are chromosomal abnormalities common?

in early zygotes/embryos

25

what is numerical chromosomal abnormality?

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

26

turner syndrome?

numerical chromosomal abnormality (45,X)

most common abnormality in spontaneous abortions 

1/8000 live births 

75% due to missing paternal X chromsome

27

examples of autosomal trisomies?

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

examples of sex chromosome trisomies?

1) 47, XXX: 15-25% mild MR 

2) 47, XXY: Klinefelters, small testes, infertility 

3) 47, XYY: normal appearance, tall

29

mosaicism?

numerical chromosomal abnormality

2 cell lines w/ 2+ genotypes 

30

triploidy?

numerical chromosomal abnormality 

failure of separation of 2nd polar body

dispermy

20% of all chromosomally abnormal spontaneous abortuses

31

what are structural chromosome abnormalities?

chromosomal breakage and abnormal combination- 

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

 

due to drugs, chemicals, viruses

32

characteristics of anomalies caused by mutant genes

7% of congenital anomalies 

heritable

 

33

achondroplasia

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

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

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

causes 7-10% of anomalies 

mechanisms often unclear

ie thalidomide

35

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

*HY*

*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

when and what is critical pd of human development?

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

when is susceptibility to teratogens greatest?

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

38

what occurs re: birth anomalies, during fetal pd?

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

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

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

do teratogens just effect 1 organ?

no, they can affect >1 organ

41

high doses of radiation affects?

CNS and eye

42

rubella as teratogen affects?

eye defects, deafness, cardiac anomalies

43

thalidomide impact across pregnancy?

early: meromelia-absence of limbs 

later: hypoplasia of limbs 

after critical pd: no affect on limbs

44

does dose matter re: teratogens?

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

45

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

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

46

what is phenytoin?

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

fetal hydantoin syndrome

caused by phenytoin exposure among embryos genetically susceptible to defective development 

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

48

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

1) frequency fo anomaly increased above background risk 

OR

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

 

49

are case reports sufficient data to prove teratogenicity?

no, unless agent and anomaly are exceedingly rare

50

% of congenital anomalies caused by drugs/chemicals

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

51

is caffeine a teratogen?

no

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

52

is alcohol a teratogen?

if so, incidence of teratogenic effects?

what are effects? 

when does alc have greatest effect on fetus?

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

coumadin re: fetus

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

oral acne med teratogen?

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

environment chemicals that can cause birth defects? 

1) lead:

spontaneous abortions, IUGR, anoalies, functional deficits

2) polychlorinated biphenyls (PCBs):

IUGR, skin discoloration, contaminated waters 

56

when can hyperthermia cause defect? what happens?

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

57

infectious agents as teratogens? what do they cause?

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

is radiation teratogen? effect?

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

are elctromagnetic fields teratogenic?

ie electric blankets, computers? 

NO

60

is ultrasound teratogenic? 

NO

61

is diabetes teratogenic?

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

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

oligohydramnios

uterine anomalies

fibroids

early amniocentesis

63

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

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

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

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!