Teratogenic Agents and Their

Effect on Child Health

By

Prof. Ali Shaltout

 Definition of Teratogen

 Any agent that can produce malformation (birth

defect), by interfering with normal embryonic
development

 Teratogen acts on somatic cells of the developing

organism

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 Teratogen Mutagen

Somatic cells Germ cells

Embryo Genetic material

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 Factors Affecting Teratogenicity

1. Time of exposure:
– Exposure to the teratogen is usually for short
period
– Teratogenic exposure must occur a
considerable time before the developmental
event
n Dosage:
 Maternal response
 The ability to metabolize the chemical

2. Heriditary predisposition
3. Specificity of teratogens

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 Incidence

 Approximately 6.5% of all birth

defects are attributed to teratogens

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 Knowledge of:
– Which agents are potential teratogens and
their effect on the developing fetus
 Is important:
– Because limiting exposure to teratogens is
an effective way to prevent birth defects
 Teratogenic Agents:
1. Durgs and chemicals
2. Maternal infections
3. Physical agents:
– Ionizing radiation
– Prolonged hyperthermia
4. Maternal diseases
 Common Teratogenic Drugs

Drug Effects
Alcohol Fetal alcohol syndrome

Lithium Ebstein anomaly

Phenytoin Cardiac defects, cleft palate, hypoplastic nails

Chloroquine Chorioretinitis, deafness
Penicillamine Cutis laxa syndrome
Warfarin Nasal hypoplasia - Stippled epiphyses

Streptomycin Deafness
Tetracycline Enamel hypoplasias
Valproic acid: Neural tube defects
Retinoids Eye & ear defects, Hydrocephalus

Thalidomide Phocomelia
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 Fetal Alcohol Syndrome
 Growth retardation (prenatal & postnatal)
 Microcephaly
 Developmental delay
 Skeletal and cardiac anamalies
 Characteristic facies: (mid face hypoplasia)
– Short palpebral fissure
– Epicanthic folds
– Smooth philtrum
– Thin upper lip
– Short, upturned nose
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 Maternal Infections

 Several infectious agents can interfere with

embryogenesis and fetal development

 The developing brain, eyes and ears are

particularly susceptible to damage by infection

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 Infectious Teratogenic Agents
Infection Effects
:Viruses
Cytomegalovirus Chorioretinitis, deafness, microcephaly

Herps simplex Microcephaly, cataracts, retinitis, cardiac defects

Varicella zoster Microcephaly, chorioretinits, skin defects

Bacteria:
Syphilis Hydrocephalus, Osteitis, retinitis
Parasites:
Toxoplasmosis Hydrocephalus, microcephaly, cataracts,
chorioretinitis, deafness
 Congenital Rubella Syndrome

 Cardiac: pulmonary artery stenosis (55%)

PDA (43%)
 Deafness
 Cataracts, Glaucoma, retinopathy
 Mental retardation
 IUGR
 Neonatal Purpura, Hepatosplenomegaly
 Ionizing Radiation

 Heavy doses of ionizing radiation→ Microcephaly

and occular defects
 The most sensitive time of exposure is from 2 to 5
weeks after conception
 Risks of low-dose diagnostic procedures are
minimal
 Prolonged hyperthermia

 Prolonged hyperthermia in early pregnancy

– Microcephaly
– Microphthalmia
– Encephalocele
 Excessive use of hot baths and saunas
during the first trimester should be avoided
 Maternal diabetes mellitus

 Most common malformation in infants of diabetic

mother include:
– Congenital HT D
– Neural tube defects
– Lumbo sacral dysgenesis, Holoprosencephaly
– Small left colon syndrome
– Renal disorders: double ureter, renal vein
thrombosis, renal agenesis
 Maternal phenylketonuria

 High level of phenylalanine in pregnant woman

with PKU not on special diet → serious damage to
the fetus:
– Mental retardation (100%)
– Microcephaly
– Congenital heart defects
Congenital rubella syndrome is characterized
by all of the following except:

1. Growth retardation
2. Deafness
3. PDA
4. Macrocephaly
5. Cataracts

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Are the following statements true or false?

1. There may be individual difference in sensitivity to

specific teratogens T F
2. Teratogen acts on germ cells and alter the genetic
material T F
3. Prolonged hyperthermia in the first trimester may have
potential teratogenic effect T F
4. Maternal IDDM associated with two to three fold
increase in incidence of congenital malformations in
offspring T F
 Match each of the following teratogenic agents with
their most common effect on offspring

1. Valproic acid ( ) Ebstein anomaly

2. Maternal phenylketonuria ( ) Phocomelia
3. Thalidomide ( ) Neural tube defects
4. Maternal DM ( ) Small left colon syndrome
5. Lithium ( ) Mental retardation

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