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Endocrine And Reproductive System Class > Teratogenesis > Flashcards

Teratogenesis Flashcards

1
Q

What are birth defects?

A

Structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth or later in life

  • Clinically significant birth defects
  • Malformation
  • Disruption
  • Deformation
  • Dysplasia
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2
Q

Birth defects are…

A

Multifactorial diseases

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3
Q

What is a teratogen?

A

Teratogen: An agent which produces a permanent structural or functional alteration in an organism exposed during embryonic or fetal life

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4
Q

What is teratogenesis?

A

Teratogenesis: The process by which birth defects are produced

Principles:
➢ Dose of teratogen
➢ Genotype
➢ Time of action of the agent:
increased teratogenicity at critical period of development
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5
Q

What are physically and medically important teratogens?

A
  • Physical:
  • Ionizingradiation
  • Maternal diseases as teratogens:
  • Uncontrolled Diabetes
  • Drugs/medication:
  • Thalidomide
  • Valproic acid
  • Phenytoin
  • Warfarin
  • Tetracycline
  • Isotretinoin
  • Alcohol
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6
Q

What illicit substances are teratogens?

A
  • Cocaine

* Marijuana

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7
Q

What chemical is a clinically important teratogen?

A

Methylmercurry

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8
Q

What infections are clinically important teratogens?

A
  • Infections:
  • Toxoplasma Gondii ( Toxoplasmosis)
  • Other (Syphilis, varicella-zoster, parvovirus B19)
  • Rubella virus ( German measles) • Cytomegalovirus ( CMV)
  • Herpes simplex virus
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9
Q

What is congenital toxoplasmosis?

A

Caused by protozoan toxoplasma gondii an intracellular parasite

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10
Q

What is the prognosis of congenital toxoplasmosis ?

A

Severity related to gestational age and time of infection

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11
Q

How is congenital toxoplasmosis managed?

A
  • Antenatal screening

- Treatment during pregnancy reduces the risk of transmission

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12
Q

What are the symptoms of congenital toxoplasmosis?

A

At birth most children are asymptomatic but may develop symptoms later.

Classic signs: Chorioretinitis, hydrocephalus, intracranial calcifications, convulsions.

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13
Q

What is congenital syphilis?

A

Syphilis is caused by the bacteria Treponema pallidum
• Transmission:
• Sexuallytransmitted
• Transplacental→ may occur at any stage of pregnancy

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14
Q

What are the clinical manifestations of congenital syphilis?

A

Clinicalmanifestations:

  • Stillbirths(hydropsfetalis),
  • Congenital syphilis: deafness, hydrocephalus, intellectual disability, craniofacial anomalies
  • Early or late presentation of symptoms
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15
Q

How is congenital syphilis managed?

A

Management
• Prevention:antenatalserologicalscreening
• Treatment with penicillin

• Incidence increasing due to association with HIV infection

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16
Q

What are signs of congenital syphilis?

A

Saddle nose

Saber shins

Hutchinson teeth

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17
Q

What is Congenital Cytonegalovirus (CMV)?

A
  • One of the most common viral infections in the fetus.
  • Induces abortions if the mother is infected during the early development
  • 90% children are asymptomatic at birth
  • Up to 10-15% develop symptoms later, notably sensorineural hearing loss
  • Other defects : microcephaly, hydrocephalus, microphthalmia, intellectual disability
18
Q

What is the significance of Herpes Simplex in pregnancy?

A
  • Virus that causes cold sores and genital warts
  • Abortions in early pregnancy
  • In late pregnancy premature birth and malformations can occur
  • Fetal infections most frequently occur during delivery
  • Mucocutaneous: Eye, mouth and skin eruptions within 48 hours
  • CNS: microcephaly, chorioretinitis and mental deficiency
  • Disseminated
19
Q

How is Herpes Simplex in pregnancy managed?

A

Early diagnosis in mother

Antiviral therapy

20
Q

What is congenital Rubella Syndrome?

A

• “German measles “ Rubella virus infection

Features:
• Cataract and retinopathy
• Cardiopathies: PDA, pulmonary artery stenosis
• CNS : microcephaly and mental deficiency
• Deafness
• Skin lesions
• Prophylaxis with vaccine (MMR)

21
Q

What drugs are teratogens?

A
  • Thalidomide
  • Retinoic acid and its derivatives
  • Tetracycline
  • Anticonvulsants: Lithium, phenytoin
  • Alcohol
22
Q

What is the importance of Thalidomide in limb development?

A
  • Thalidomide inhibits Fibroblast growth factors FGFs from the apical ectodermal ridge (AER) of the limbs which leads to the proximal limb tissue not developing, while the distal limb tissue continues to differentiate.
  • Inhibits angiogenesis
23
Q

What is Amelia?

A

Amelia
• Complete absence of limbs
• Suppression of limb bud development in the 4th week
• Thalidomide induced Amelia is more frequent in the lower limb

24
Q

What is Maromelia?

A

Meromelia ( Phocomelia)
• Partial absence of limbs
• Disturbance of limb development
during 5th week

25
Q

What is the role of tetracyclines in pregnancy?

A

When used during tooth development (second half of pregnancy) tetracyclines may cause permanent yellow-gray-brown discoloration of the teeth and enamel hypoplasia. The use of tetracycline during pregnancy is generally not recommended, especially during the last half of pregnancy.

26
Q

What is the importance of isotretinoin (retinoids acid) in pregnancy?

A
  • Used for treatment of severe acne
  • Severely teratogenic even at low doses.
  • Critical period of exposure – 3rd to 5th week
  • High doses of vitamin A during pregnancy can produce the same effects.
Defects:
• spontaneous abortion
• neuropsychological impairment
• premature birth
• neonatal death

Prevention p: mandatory contraception

27
Q

What is phenytoin (Dilantin)?

A

Affects 5-10% of the embryos based on their genotype

28
Q

What is valproic acid?

A

Valproic acid
Drug used in treatment of epilepsy, bipolar disorder and migraines

Associated defects:
– Spina bifida, ASD, VSD, Cleft palate, Hypospadias, Polydactyly, Craniosynostosis.
– Fetal valproate syndrome ( rare)
– Increased risk of autism

29
Q

What is Fetal Hydantoin syndrome?

A

Fetalhydantoinsyndrome.
• Mental deficiency, IUGR, ptosis hernias, depressed nasal bridge, microcephaly, epicanthal folds and hypoplasia of nails and distal phalanges

30
Q

What are the anti convulsive drugs?

A

Phenytoin(Dilantoin)

Valproic acid

Warfarin

Organic mercury

31
Q

What is the importance of Warfarin ?

A

Warfarin (anticoagulant) inhibits vitamin K epoxide reductase and can cross the placental barrier.

• The critical period 6-12 weeks,

• Hypoplasia of the nasal cartilages, stippled (dotted) epiphysis
CNS defects and fetal hemorrhage

• Later trimesters: microcephaly, optic atrophy and some mental disorders.

32
Q

What is organic mercury?

A

Organic mercury occurs when bacteria interact mercury present in the sediments in water bodies

  • accumulates in the tissue of aquatic animals like fish(swordfish, shark, kingfish)
  • Neurotoxic in high concentrations causing loss of nerve cells, decreased brain size and problems with neuronal migration.
  • Symptoms : spasticity, seizures mental retardation
  • Congenital Minamata disease
33
Q

What recreational drugs are used as teratogens?

A
  • Alcohol
  • Tobacco
  • Cocaine
34
Q

What are the consequences of alcohol during pregnancy?

A

Alcohol crosses the placenta and remains within the amniotic fluid

  • Risk of birth defects is directly related to the amount and frequency of consumption
  • Disrupts DNA and protein synthesis, inhibits cell migration, disrupts metabolic pathways and the transfer of nutrients across the placenta

• Spontaneous abortion, preterm delivery and still births
Fetal Alcohol Syndrome (FAS)

35
Q

What is fetal alcohol syndrome?

A
  • Growth deficiency
  • Low IQ (average = 63)
  • Mild to moderate microcephaly
  • Facial defects: Short nose, smooth philtrum, thin upper lip
  • Heart murmur
  • Small distal phalanges
36
Q

What factors influence cigarette smoking in pregnancy?

A
  • Epigeneticchanges:DNAmethylation
  • Nicotine:vasoconstrictor;decreased uterine blood flow
  • CO: impaired oxygen delivery fetus

These are all linked to chronic fetal hypoxia

37
Q

What are the defects of cigarette smoking in pregnancy?

A 
Defects:
• Low birth weight (Women who stop smoking before pregnancy or 2-3 months into pregnancy, reduce their risk of having a low birth weight baby to that of non smoking women! )
• Intra uterine growth retardation (IUGR)
• Preterm labor and premature delivery
• Placentaldefects
• Suddeninfantdeathsyndrome(SIDS)
• Conotruncaldefects
• Some orofacial ( cleft lip and palate)
38
Q

What is cocaine?

A

Readily crosses the placenta and causes severe vasoconstriction in the fetus

  • Can lead to low birth weight
  • Probable neurobehavioral disorders
  • These babies tend to be easily stimulated and difficult to soothe
39
Q

What is cannabis?

A

Use of cannabis during pregnancy was not associated with increased risk of perinatal mortality or morbidity

  • Confounding factors ? Other drugs, alcohol ….
  • Cannabis use throughout pregnancy may be associated with lower birth weight
40
Q

What is maternal diabetes?

A

Uncontrolled maternal diabetes mellitus alters the expression of developmental genes and is associated with the following defects:
•Macrosomia (large baby)
•Impaired growth
•Pulmonary disease ( in neonatal period)
• CNS
• Heart: VSD’s, transposition of the great arteries, ASD’S and Coarctation of the aorta
• Skeletal
•Metabolic disorders( hypoglycemia, hypocalcemia)

Endocrine And Reproductive System Class (36 decks)

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