1

Teratogenesis & twins

Dr. Lubna Nazli

2

Objectives

• Congenital malformations

• Causes & types

• Twins: causes and types.

3

Teratology

• Teratology– Science that studies the causes of abnormal

development– Birth defects is the number one cause of

infant mortality

4

Congenital Malformations• Causes

– Genetic/chromosomal– Environmental

• Incidence– 2-3% of newborn (4-6% by age 5)– In 40-60% of all birth defects cause is unknown

• Genetic/chromosomal– 10%-15%

• Environmental– 10%

• Multifactorial (genetic & environmental)– 20%-25%

5

Types of Anomalies• Malformations

– Occur during formation of structures• Complete or partial absence• Alterations of its normal configuration

• Disruptions– Morphological alterations of structures after

formation• Due to destructive processes

– Vascular accidents bowel atresias

6

• Deformations– Due to mechanical forces that mould a part of

fetus over a prolonged period of time• Clubfeet due to compression in the amniotic cavity• Often involve the musculoskeletal system & may

be reversible postnatally

• Syndromes– Group of anomalies occuring together with a

specific common etiology• Diagnosis made & risk of recurrence is known

7

Environmental factors

• Infectious agents

• Radiation

• Chemical Agents

• Hormones

• Maternal Disease

• Nutritional Deficiencies

• Hypoxia

8

Infectious Agents• Rubella (German Measles)• Cytomegalovirus• Varicella (chickenpox)• HIV/AIDS• Herpes Simplex Virus

9

Radiation• Teratogenic effect of ionizing radiation well

established– Microcephaly– Skull defects– Spina bifida– Blindness cleft palate– Extremity defects

• Direct effects on fetus or indirect effects on germ cells

• May effect succeeding generations• Avoid X-raying pregnant women

10

Chemical agents/Drugs

• Thalidomide– Found to cause amelia & meromelia

• Total or partial absence of the extremities

• Anticonvulsants (to treat epilepsy)• Antianxiety drugs (minor tranquilizers)• Antipsychotic drugs (major tranquilizers)• Antihypertensive agents• Aspirin

– Potentially harmful in large doses

Wednesday, April 19, 2023

11

Unilateral phocomelia upper limb(Thalidomide toxicity)

12

Alcohol• Relationship between alcohol consumption

& congenital abnormalities• Fetal alcohol syndrome

13

Cigarette Smoking

• Has not been linked to major birth defects– Smoking does contribute to intrauterine

growth retardation & premature delivery– Some evidence that is causes behavioral

disturbances

14

Hormones• Androgenic Agents

– Synthetic progestins were used frequently to prevent abortion

» Masculinization of female genitalia

• Oral Contraceptives– Low teratogenic potential, discontinue if

pregnancy suspected

15

Maternal Disease• Disturbances in CHO metabolism (diabetic

mothers)– High incidence of stillbirth, neonatal deaths– Abnormally large infants– Congenital malformations– Oral hypoglycemic agents maybe

teratogenic

16

Environmental Chemicals

• Mercury– Fish, seed corn sprayed with mercury

containing fungicide• Multiple neurological symptoms

• Lead abortions– Growth retardation– Neurological disorders

17

Prevention of birth defects

• Good prenatal care

• Iodine supplementation eliminates mental retardation & bone deformities– Prevent cretinism

• Folate/Folic Acid supplementation incidence of neural tube defects

• Avoidance of alcohol & other drugs during all stages of pregnancy incidence of birth defects

18

Principles of teratology

• Susceptibility varies with developmental stage at time of exposure– Most sensitive period for inducing birth defect is weeks 3-

8 of gestation

• Manifestations of abnormal development depend on dose & duration of exposure

• Teratogens act in specific ways on developing cells & tissues to initiate abnormal embryogenesis

• Manifestations of abnormal development death, malformation, growth retardation, functional disorders

19

Chromosomal & Genetic Factors

• Numerical Abnormalities– Trisomy 21 (Down syndrome)– Trisomy 18– Trisomy 13– Klinefelter Syndrome– Turner Syndrome– Triple X Syndrome

• Structural Abnormalities

• Mutant Genes

20

Twinning

Types of twins

• Monozygotic or maternal twins

• Dizygotic or Fraternal twins

• Conjoined or Siamese twins

21

Human twins are classified into two major groups:

• Monozygotic (one-egg, or identical) twins and Dizygotic (two-egg, or fraternal) twins.

• Fraternal twins are the result of two separate fertilization events, whereas identical twins are formed from a single embryo whose cells somehow dissociated from one another.

• Identical twins may be produced by the separation of early blastomeres, or even by the separation of the inner cell mass into two regions within the same blastocyst

22

Identical twins formationmonozygotic twins

23

Conjoined Twins

• are identical twins who develop with a single placenta from a single fertilized ovum.

• are always of the same sex. • are more often females than males, at a ratio of

3:1. • occur as often as once in every 40,000 births

but only once in every 200,000 live births. • are more likely to occur in India or Africa than in

China or the United States.

24

Types of Conjoined Twins

• Craniopagus: Cranial union only, about 2% of all conjoined twins.

• Pygopagus: Posterior union of the rump, about 19% of all conjoined twins.

• Thoracopagus: Anterior union of the upper half of the trunk. The most common form of conjoined twins (about 35%), it always involves sharing the heart.

• Cephalopagus: Anterior union of the upper half of the body with two faces on opposite sides of a conjoined head. Extremely rare. The heart is sometimes involved. A combination of types 3 and 4 is called cephalothoracopagus.

25

• Parapagus:(sometimes called diprosopus): lateral union of the lower half, extending variable distances upward, about 5% of all conjoined twins. Heart sometimes involved.

• Ischopagus: Anterior union of the lower half of the body, about 6% of all conjoined twins. Heart not involved.

• Omphalopagus: Anterior union of the midtrunk, about 30% of conjoined twins.

26

27

Craniopagus

28