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Teratogenic Agents and TheirTeratogenic Agents and TheirEffect on Child HealthEffect on Child Health

ByBy

Prof. Ali ShaltoutProf. Ali Shaltout

Definition of TeratogenDefinition of Teratogen

Any agent that can produce malformation (birth Any agent that can produce malformation (birth

defect), by interfering with normal embryonic defect), by interfering with normal embryonic

developmentdevelopment

Teratogen acts on somatic cells of the developing Teratogen acts on somatic cells of the developing

organismorganism

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Teratogen

Somatic cells

Embryo

Mutagen

Germ cells

Genetic material


Factors Affecting TeratogenicityFactors Affecting Teratogenicity

1.1. Time of exposure:Time of exposure:

– Exposure to the teratogen is usually for short Exposure to the teratogen is usually for short

periodperiod

– Teratogenic exposure must occur a Teratogenic exposure must occur a

considerable time before the developmental considerable time before the developmental

event event

2.2. Dosage:Dosage:

Maternal responseMaternal response

The ability to metabolize the chemicalThe ability to metabolize the chemical

3.3. Heriditary predispositionHeriditary predisposition

4.4. Specificity of teratogensSpecificity of teratogens


IncidenceIncidence

Approximately 6.5% of all birth Approximately 6.5% of all birth

defects are attributed to teratogensdefects are attributed to teratogens


Knowledge of:Knowledge of:

– Which agents are potential teratogens and Which agents are potential teratogens and

their effect on the developing fetus their effect on the developing fetus

Is important:

– Because limiting exposure to teratogens is Because limiting exposure to teratogens is

an effective way to prevent birth defectsan effective way to prevent birth defects

Teratogenic Agents:Teratogenic Agents:

1.1. Durgs and chemicalsDurgs and chemicals

2.2. Maternal infectionsMaternal infections

3.3. Physical agents:Physical agents:

– Ionizing radiation Ionizing radiation

– Prolonged hyperthermiaProlonged hyperthermia

4.4. Maternal diseasesMaternal diseases

Common Teratogenic DrugsCommon Teratogenic Drugs

DrugDrugEffectsEffectsAlcoholAlcoholFetal alcohol syndromeFetal alcohol syndrome

LithiumLithiumEbstein anomaly Ebstein anomaly

PhenytoinPhenytoinCardiac defects, cleft palate, hypoplastic nailsCardiac defects, cleft palate, hypoplastic nails

ChloroquineChloroquineChorioretinitis, deafnessChorioretinitis, deafness

PenicillaminePenicillamineCutis laxa syndromeCutis laxa syndrome

WarfarinWarfarinNasal hypoplasia - Stippled epiphysesNasal hypoplasia - Stippled epiphyses

StreptomycinStreptomycinDeafnessDeafness

Tetracycline Tetracycline Enamel hypoplasiasEnamel hypoplasias

Valproic acid:Valproic acid:Neural tube defectsNeural tube defects

RetinoidsRetinoidsEye & ear defects, HydrocephalusEye & ear defects, Hydrocephalus

ThalidomideThalidomidePhocomeliaPhocomelia

Fetal Alcohol SyndromeFetal Alcohol Syndrome

Growth retardation (prenatal & postnatal) Growth retardation (prenatal & postnatal)

MicrocephalyMicrocephaly

Developmental delayDevelopmental delay

Skeletal and cardiac anamaliesSkeletal and cardiac anamalies

Characteristic facies: (mid face hypoplasia)Characteristic facies: (mid face hypoplasia)

– Short palpebral fissure Short palpebral fissure

– Epicanthic folds Epicanthic folds

– Smooth philtrumSmooth philtrum

– Thin upper lipThin upper lip

– Short, upturned noseShort, upturned nose

–

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Maternal InfectionsMaternal Infections

Several infectious agents can interfere with Several infectious agents can interfere with

embryogenesis and fetal developmentembryogenesis and fetal development

The developing brain, eyes and ears are The developing brain, eyes and ears are

particularly susceptible to damage by infection particularly susceptible to damage by infection


Infectious Teratogenic AgentsInfectious Teratogenic Agents

InfectionInfectionEffectsEffects

VirusesViruses::

CytomegalovirusCytomegalovirusChorioretinitis, deafness, microcephalyChorioretinitis, deafness, microcephaly

Herps simplexHerps simplexMicrocephaly, cataracts, retinitis, cardiac defectsMicrocephaly, cataracts, retinitis, cardiac defects

Varicella zosterVaricella zosterMicrocephaly, chorioretinits, skin defects Microcephaly, chorioretinits, skin defects

Bacteria:Bacteria:

Syphilis Syphilis Hydrocephalus, Osteitis, retinitisHydrocephalus, Osteitis, retinitis

Parasites:Parasites:

ToxoplasmosisToxoplasmosisHydrocephalus, microcephaly, cataracts, Hydrocephalus, microcephaly, cataracts, chorioretinitis, deafness chorioretinitis, deafness

Congenital Rubella SyndromeCongenital Rubella Syndrome

Cardiac: pulmonary artery stenosis (55%)Cardiac: pulmonary artery stenosis (55%)

PDAPDA (43%) (43%)

DeafnessDeafness

Cataracts, Glaucoma, retinopathyCataracts, Glaucoma, retinopathy

Mental retardationMental retardation

IUGR IUGR

Neonatal Purpura, HepatosplenomegalyNeonatal Purpura, Hepatosplenomegaly

Ionizing RadiationIonizing Radiation

Heavy doses of ionizing radiationHeavy doses of ionizing radiation→→ Microcephaly Microcephaly

and occular defectsand occular defects

The most sensitive time of exposure is from 2 to 5 The most sensitive time of exposure is from 2 to 5

weeks after conceptionweeks after conception

Risks of low-dose diagnostic procedures are Risks of low-dose diagnostic procedures are

minimal minimal

Prolonged hyperthermia Prolonged hyperthermia

Prolonged hyperthermia in early pregnancy Prolonged hyperthermia in early pregnancy

– MicrocephalyMicrocephaly

– MicrophthalmiaMicrophthalmia

– EncephaloceleEncephalocele

Excessive use of hot baths and saunas Excessive use of hot baths and saunas

during the first trimester should be avoidedduring the first trimester should be avoided

Maternal diabetes mellitus Maternal diabetes mellitus

Most common malformation in infants of diabetic Most common malformation in infants of diabetic

mother include:mother include:

– Congenital HT DCongenital HT D

– Neural tube defectsNeural tube defects

– Lumbo sacral dysgenesis, HoloprosencephalyLumbo sacral dysgenesis, Holoprosencephaly

– Small left colon syndromeSmall left colon syndrome

– Renal disorders: double ureter, renal vein Renal disorders: double ureter, renal vein

thrombosis, renal agenesisthrombosis, renal agenesis

Maternal phenylketonuria Maternal phenylketonuria

High level of phenylalanine in pregnant woman High level of phenylalanine in pregnant woman

with PKU not on special diet → serious damage to with PKU not on special diet → serious damage to

the fetus:the fetus:

– Mental retardation (100%)Mental retardation (100%)

– Microcephaly Microcephaly

– Congenital heart defectsCongenital heart defects

Congenital rubella syndrome is characterized Congenital rubella syndrome is characterized by all of the following by all of the following exceptexcept: :

1.1. Growth retardationGrowth retardation

2.2. DeafnessDeafness

3.3. PDAPDA

4.4. Macrocephaly Macrocephaly

5.5. CataractsCataracts


Are the following statements true or false?Are the following statements true or false?

1.1. There may be individual difference in sensitivity to There may be individual difference in sensitivity to

specific teratogens T Fspecific teratogens T F

2.2. Teratogen acts on germ cells and alter the genetic Teratogen acts on germ cells and alter the genetic

materialmaterial T F T F

3.3. Prolonged hyperthermia in the first trimester may have Prolonged hyperthermia in the first trimester may have

potential teratogenic effectpotential teratogenic effect T F T F

4.4. Maternal IDDM associated with two to three fold Maternal IDDM associated with two to three fold

increase in incidence of congenital malformations in increase in incidence of congenital malformations in

offspring T F offspring T F

Match each of the following teratogenic agents with Match each of the following teratogenic agents with their most common effect on offspringtheir most common effect on offspring

1.1. Valproic acidValproic acid ( ) Ebstein anomaly( ) Ebstein anomaly

2.2. Maternal phenylketonuriaMaternal phenylketonuria ( ) Phocomelia( ) Phocomelia

3.3. ThalidomideThalidomide ( ) Neural tube defects( ) Neural tube defects

4.4. Maternal DMMaternal DM ( ) Small left colon syndrome( ) Small left colon syndrome

5.5. LithiumLithium ( ) Mental retardation( ) Mental retardation


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