Teratogenic Agents And Their

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

Somatic cells

Embryo

Mutagen

Germ cells

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 :Viruses Cytomegalovirus

Effects Chorioretinitis, deafness, microcephaly

Herps simplex

Microcephaly, cataracts, retinitis, cardiac defects

Varicella zoster

Microcephaly, chorioretinits, skin defects

Bacteria: Syphilis Parasites: Toxoplasmosis

Hydrocephalus, Osteitis, retinitis 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 minimal

are

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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