Teratogens Flashcards

1
Q

congenital defects

A
  • Refers to all inborn abnormalities, morphological or biochemical at birth
  • Measurable effect on physical, intellectual, and social wellbeing
  • ~50-80 % of conceptuses lost before implantation
  • > 50% miscarriages due to chromosomal structural abnormalities
  • ~2% of all pregnancies terminate in stillbirths
  • Congenital defects found in 6% of all liveborn infants examined during the first year of life
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2
Q

causes of congenital defects

A

Environmental factors
o Infectious Agents
o Chemical & Pharmacological
o Radiation

Genetic defects
o Chromosomal
o Monogenic

Idiopathic

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3
Q

congenital anomalies - birth defects

A
Most common birth defects are: 
o heart defects
o cleft lip/cleft palate
o down syndrome
o spina bifida
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4
Q

teratogens - environmental factors

A

Teratogen – any agent that can harm an embryo or fetus
- Effects depend on:
o Critical period of development (structures forming)
o Dosage and duration of exposure of drug/chemical
o Father’s exposure may affect embryo
o Genotype of mother and embryo
o Same defect can get caused by different teratogens
o One teratogen can cause different defects
o Long-term effects depend on postnatal environment
o Some effects not apparent until later in life

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5
Q

critical periods of prenatal development

A
Each organ or structure has a critical period when it is most sensitive to damage from teratogens. 
heart: wk 2.5-5.5
lower limb: wk 3.5-5.5
ear: wk 3.5-8.5
CNS: wk 3-16
eyes: wk 4.5-8.5
arms: wk4-6
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6
Q

rubella (infectious agent)

A
  • Infectious viral disease caused by Rubella virus
  • Causes mild infection in adults, but severe effects in fetuses
  • Congenital rubella syndrome. –> miscarriage or birth defects including heart defects , deafness, brain damage, eye problems, cardiac abnormalities, mental retardation
  • Most dangerous during 1st trimester (40-60% chance of affected fetus)
  • No woman should try to conceive unless they have had rubella or have been immunized!
  • Women planning a pregnancy –> blood test, to check sufficient antibody titers against rubella present
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7
Q

toxoplasmosis (infectious agent)

A
  • A zoonotic intracellular parasitic infection caused by Toxoplasma gondii (a protozoan)
  • Carried by many mammals: rabbits, dogs with, but final host = cats
  • Caused by eating undercooked/contaminated meat (avoid cold cured meats including salami, parma ham, chorizo and pepperoni), handling cat feces
  • Can cross the placenta -> can affect the brain (e.g. hydrocephalus, mental retardation) and impaired vision & blindness) during first trimester
  • Induces miscarriage later in pregnancy
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8
Q

zika virus (infectious agent)

A
  • Zika virus flavivirus
  • Outbreaks recorded in Africa, the Americas, Asia and the Pacific
  • Transmitted through the bite of an infected aedes arthropods (mosquitoes)
  • Symptoms generally mild and include fever, rash, conjunctivitis, muscle and joint pain , malaise or headache
    Congenital zika syndrome
  • Zika virus can be transmitted from mother to fetus during pregnancy

Congenital Zika syndrome: Infection during pregnancy -> can cause infants to be born with microcephaly and other congenital malformations

  • Zika infections in pregnant women also have been linked to miscarriages and stillbirth
  • In CT scans of infants -> calcifications in brain tissue
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9
Q

listeria and salmonella (infectious agent)

A

Listeria:

  • Listeria bacteria -> infection called listeriosis
  • Pregnant women advised not to eat any uncooked mould-ripened soft cheese (brie, camembert), raw seafood (oysters, sashimi, sushi), smoked ready-to-eat seafood and cooked ready-to-eat prawns
  • Listeria infection during pregnancy can cause miscarriage, stillbirth or severe illness in newborns

Salmonella:

  • Salmonella bacteria -> can cause gastroenteritis or food poisoning
  • Avoid foods that contain raw and undercooked eggs (poached,
  • homemade mayonnaise), or reheated chicken
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10
Q

thalidomide (Chemical and Pharmacological Teratogens)

A
  • 1950-1960: To prevent nausea and vomiting = morning sickness
  • Tested on animals and was deemed “safe”
  • Can cause severed birth defects if taken during first 2 months of pregnancy
  • Phocomelia: fetus with hands and feet without arms or legs
  • Ectromelia: total absence of limbs
  • Malformation of eyes, ears, noses, hearts, thumbs
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11
Q

alcohol (Chemical and Pharmacological Teratogens)

A
  • Compromises functioning of the placenta
  • Can easily cross placenta –> adversely affects fetal development
  • Chronic alcohol abuse can result in fetal alcohol syndrome (30-45%)

Fetal alcohol syndrome (FAS)
- Microcephaly, malformation of heart, limbs, joints and face, hyperactivity, seizures, tremor, lower IQ, major adjustment problems, slow physical growth, poor motor skills, attention difficulties, verbal learning difficulties

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12
Q

cigarette smoking (Chemical and Pharmacological Teratogens)

A
  • Cleft lip
  • Abnormal lung functioning
  • Miscarriage
  • Low-birth-weight
  • Ectopic pregnancy –> implantation in fallopian tube
  • Sudden Infant Death Syndrome
  • Higher concentration of nicotine in foetus
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13
Q

radiation

A
  • Radiation – death, mental retardation
  • Severity differs depending on stage of pregnancy and absorbed dose
  • Most significant during organogenesis
  • 25 % of surviving children born at the time of atomic bomb explosion over Hiroshima & Nagasaki had CNS abnormalities (microcephaly & mental retardation)
  • Relative risk of leukaemia and cancer may be as high as 1.4 –> Avoid X-rays during pregnancy
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14
Q

alterations in chromosome structure

A
Only very few compatible with live birth 
-  Often associated with cancer
o Deletions
o Duplications
o Translocations
o Inversions
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15
Q

deletions

A
  • Cri du chat (cry of the cat):
  • Deletion of a small portion of chromosome 5
  • Children have severe mental impairment, a small head with unusual facial features, and a cry that sounds like a distressed cat
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16
Q

duplications

A
  • Fragile X Syndrome:
  • Affects 1:1500 males, 1:2500 females
  • Often associated with intellectual disability
  • Expansion of the CGG trinucleotide repeat affecting the Fragile X mental retardation 1 (FMR1) gene on the X chromosome
  • Most people 29 repeats , Fragile X > 700 repeats due to duplications –> failure in correct protein expression required for normal neural development
17
Q

translocations

A
  • Fragment of a chromosome is moved (“trans-located”) from one chromosome to another
  • Balance of genes is still normal i.e. no genetic material has been gained or lost
  • Transcription of genes can be altered
  • Can cause cancer if placed in front of promotor of growth regulating gene
18
Q

Acute Myeloid Leukemia (AML)

A
  • Translocation t(15/17)
  • Affects ~ 4:100,000 Australians
  • Leukemias starting in the myeloid cell line
  • Rapid growth of poorly differentiated white blood cells. –> accumulate in the bone marrow
  • Often inadequate production of red blood cells and platelets -> anaemia, easy bleeding & bruising
  • Immature –> unable to function properly to prevent or fight infection
19
Q

inversions

A
  • Chromosome breaks in 2 places –> broken piece flips then re-inserts back to front
  • Does not involve loss or gain of chromosomal material
  • Protein expression might be affected
  • Inversion on chromosome 9 is most common but does not cause disease
  • In Hemophilia A, 40% of mutations due to Inversions
20
Q

what is a teratogen

A

agent that induces or increase incidence of a congenital malformation

21
Q

what is a congenital malformation

A

Inborn abnormality, morphological or biochemical at birth

Malformations that effect noate at birth

22
Q

most common 4 malformations in a baby

A
  1. Heart defects
  2. Cleft lip/cleft palate
  3. Down syndrome
  4. Spinda bifida
23
Q

Why is the embryo/fetus most vulnerable to teratogens up to the third month?

A

major structural abnormalities coincide embryonic period – during organogenesis so why most vulnerable, after that period – more physiological changes

24
Q

categories of environmental factors that cause congenital malformations

A

Infectious agents, chemical and pharmacological, radiation, malnutrition (less environmental)

25
Q

what does idiopathic mean

A

relating to or denoting any disease or condition for which the cause/origin is unknown

26
Q

3 infectious agents that cause congenital malformations

A

Rubella virus –> rubella
Toxoplasma gondii –> toxoplasmosis
Zika virus flavivirus –> zika virus

27
Q

thalidomide causes

A

Phocomelia: foetus with hands and feet without arms or legs
Ectromelia: total absence of limbs
Malformation of eyes, ears, noses, hearts, thumbs