3. • Teratology (from the Greek teras
(genitive teratos), meaning monster,
and logos meaning study) is the
medical study of teratogenesis,
congenital malformations or grossly
deformed individuals. Monster is a
pejorative term for a grossly
deformed individual. Another term for
this is Dysmorphology, which literally
means "the study of abnormal form".
4. •Dysmorphology: general term for study of or the subject
•of abnormal development of tissue form a brnch of clinical
•genetics.
•Teratology : abranch of science concerned with the production
•,development,anatomy,andclassfication of malformed fetuses.
•Syndrome: The aggregate of signs and symptoms associated with
•any morbid process and constituting together the picture of the
disease.
•Malformation: failure of proper or normal development
•more specifically , a primary defect that results from a localized
•error of morphogenesis.
5. 1-Thalidomide......1957-1961-----[ 15000 cases ]
-Diethylstilbesterol....1940-1970---[ 1000 cases of vaginal
&cervical carcinoma.
-Retinoic Acid......active ingredient of Accutane used for
ttt of severe Acne [1982-1987]----1000 ceses of maleformation,
1000-7000spontaneous abortion,7000 elective abortion,
maleformations in the form of :craniofacial alteration,
cleft palate,thymic aplesia,absent or defective ears,
psychological impairments,low IQ,
Accutane now is considered X category not used during
pregnancy.
-Valproic Acid....released 1967,by 1980---11500 cases of
lumbosacral spina bifida with meningomyelocele,or
meningocele
with midfacial hypolasia,deficient orbital ridge,prominant
forehead,
CHDs,decreased postnatal growth.
6. •Thalidomide
•released in 1957 in west Germany for morning
sickness in pregnant women , 15000
•cases of deformed babies with multiple
anomalies especially
•Phocomelia,in 1961 the drug withdrawn fron the
market.
•isomer of the drug used for muliple myeloma &
leprosy, Behcet's syndrome, AIDS, T B .
7.
8. • In USA Approximately 200,000
children are born each year with
a birth defect. These
malformations may be
anatomical, physiological or
behavioral.
9.
10. »3% of all Newborns have
a major congenital
maleformation. 20 - 25 %
of them died in the
perinatal period due to
this maleformations.
12. • Irreversible congenital
abnormality affecting a
critical period (palate
development) during the
embryonic and early
fetal stages
• May affect pituitary
growth as the palate
and anterior pituitary
are derived from the
same embryonic tissue.
13. Critical Period Defect:
Anencephaly (absence of brain)
•
Failure for the brain to grow
beyond the
rhombencephalon. Neonate
failed to survive.
14. • Understanding how a teratogen
causes its effect is not only
important in preventing congenital
abnormalities but also has the
potential for developing new
therapeutic drugs safe for use with
pregnant women.
15.
16. Birth Defects occur during Critical
Periods in Development
1. Defects during Zygote are aborted;
2. Defects in the remaining prenatal
period are irreversible;
3. Critical Periods: a time of rapid
change in the development of the
organism (i.e., system or structure) and
if interrupted will result in permanent
congenital abnormalities.
17. • Along with this new awareness of the in
utero vulnerability of the developing
mammalian embryo came the
development and refinement of The Six
Principles of Teratology which are still
applied today. These principles were
developed by James G. Wilson and are
as follows:
18. the 6 principiles of teratology
• *genotype of the conceptus and the manner in
which this interacts with environmental factors;
• *Susceptibility to teratogenic agents varies with
the developmental stage at the time of exposure;
• *The final manifestations of abnormal
development are death, malformation, growth
retardation, and functional disorder;
• Susceptibility to teratogenesis depends on the
*The access of adverse environmental influences
to developing tissue depends on the nature of the
influences (agent);
• *Manifestations of deviant development increase
in degree as dosage increases from the no-effect
to the totally lethal level.
19. FDA Classification of Teratogenic Drug Risk
1980
• A No fetal risk shown in controlled human studies
• B No human data available and animal studies show
no fetal risk or Animal studies show a risk but human
studies do not show fetal risk
• C No controlled studies on fetal risk available for
humans or animals or Fetal risk shown in controlled
animal studies but no human data available (Benefit of
drug use must clearly justify potential fetal risk in this
category)
• D Studies show fetal risk in humans (Use of drug may
be acceptable even with risks, such as in ife-
threatening illness or where safer drugs are
ineffective)
• X Risk to fetus clearly outweighs any benefits from
these drugs
20. Factors That Determine the Effects of
Teratogens
• -Dose reaching fetus
• -Point in development when drug
exposure occurs
• -Duration of exposure
• -Environmental factors
• -Susceptibility of the fetus
21. Effects of Teratogens on the Fetus
• Spontaneous abortion
• Defects in development
• Malformations (major or minor)
• Intrauterine growth retardation
• Mental retardation
• Carcinogenesis
• Mutagenesis (causing genetic mutation)
30. Fetal Alcohol Syndrome
Features: Growth retardation, neurodevelopmental abnormalities (fine motor
skills, LD, behavior disorders, and mental retardation in 50%). Facial
dysmorphia during embryonic period (week 4-8), CNS problems during the fetal
period (migration problems, smaller dendrites, few neurons in brain regions)
31. • Aspirin
• Nonsteroidal Antiinflammatory Agent
• CATEGORY: C in low dose (< 150 mg/day)
• CATEGORY: D in standard doses
• All NSAIDs used near term may cause closure of
the ductus arteriosus, and inhibit labor.
Oligohydramnios after prolonged use is a
common complication.
• BREAST FEEDING:The American Academy of
Pediatrics has classified aspirin as a drug "which
should be given to nursing mothers with
caution" [G3]. The WHO Working Group on
Human Lactation classified the salicylates as
unsafe for use by nursing women [G8].
• NEONATAL SIDE EFFECTS:Altered platelet
function.Dose related metabolic acidosis
32. • Carbamazepine (Tegretol ®, Carbatrol ®)
• Anticonvulsant
• CATEGORY:D
• The risk of neural tube defect is 1 to 2 %
when used as monotherapy during first
trimester. and . Syndrome similar to
hydantoin syndrome is also seen.
• BREAST FEEDING:Excreted into human
breast milk. Compatible [G3].
• NEONATAL SIDE EFFECTS:Possible
marrow suppression
35. Colchicine
• Treatment of gout
• CATEGORY:D
• BREAST FEEDING: Compatible [G3].
• NEONATAL SIDE EFFECTS:
36. Radiation
• In addition to being mutanogenic and
carcinogenic, radiation is teratogenic
exposure to radiation during
organogenesis leads to
microcephaly,blindness, skull
defects,spina bifida,etc...
37. • Studies designed to test the teratogenic
potential of environmental agents use
animal model systems (e.g., rat, mouse,
rabbit, dog, and monkey). Early
teratologists exposed pregnant animals
to environmental agents and observed
the fetuses for gross visceral and
skeletal abnormalities. While this is still
part of the teratological evaluation
procedures today, the field of Teratology
is moving to a more molecular level,
seeking the mechanism(s) of action by
which these agents act.
