L7: Teratogenicity Flashcards
Def of Teratogen
- Any agent that can produce malformation (birth defect), by interfering with normal embryonic & fetal development.
- Teratogen acts on somatic cells of the developing organism โ produce birth defect.
Teratogen acts on somatic cells of the developing organism โ produce birth defect.
..
Def of Teratogenicity
Capability of producing fetal malformation.
Def of Teratology
Science studies cause, mechanism & pattern of abnormal development
Difference Between Teratogen & Mutagen
Incidence of Teratogenicity
- An estimated 303.000 newborns die within 28 days of birth every year worldwide due to congenital anomalies.
- Approximately 10% of all birth defects are attributed to teratogens.
Principles of Clinical Teratology
Exposure to teratogen in
- Pre-implantation
Exposure to teratogen in
- Implantation to time of organogenesis
Exposure to teratogen in
- Fetal โ> neonatal Stage
Factors affecting Teratogenicity
- Time of exposure
- Dosage
- Hereditary predisposition
- Specificity of teratogens
Factors affecting Teratogenicity
- Time of Exposure
Factors affecting Teratogenicity
- Dosage
Depend on:
- Maternal response
- The ability to metabolize the chemical (such as delayed clearance).
MOA of Teratogens
Importance of preventive medicine
- 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.
Types of Teratogenic Agents
Drugs & Chemical Teratogens
- Alcohol
Drugs & Chemical Teratogens
- Lithium
Ebstein anomaly
Drugs & Chemical Teratogens
- Toluene
- Microcephaly, Psychomotor retardation.
- Caudal regression sequence.
Drugs & Chemical Teratogens
- Tobacco
- Dose related IUGR
- Fetal loss.
- Prematurity
- Neonatal death
Drugs & Chemical Teratogens
- Lead
- Anemia
- Abortion
- Neurological disorders
- Mental retardation
Drugs & Chemical Teratogens
- CO
- Still birth
- Spontaneous Abortion
- Prematurity
- Growth retardation
Drugs & Chemical Teratogens
- Mercury
- Minamata syndrome (Multiple neurological symptoms)
Drugs & Chemical Teratogens
- Pesticides
Incraesed risk of fetal death
Drugs & Chemical Teratogens
- Chloroquine
Deafness, Chorioretinitis
Drugs & Chemical Teratogens
- Pencillamine
Cutis laxa syndrome
Drugs & Chemical Teratogens
- Warfarin
- Nasal hypoplasia
- Stippled epiphysis
- Hypoplasia of terminal and proximal phalanx of index finger
Drugs & Chemical Teratogens
- Streptomycin
Deafness (10 - 15% sensori-neural hearing loss)
Drugs & Chemical Teratogens
- Tetracycline
- Enamel hypoplasia (Increased caries)
- Permanent teeth discoloration
- Diminished growth of long bones (weakened fetal bones)
Drugs & Chemical Teratogens
- Trimethoprim
Drugs & Chemical Teratogens
- Anticonvulsants
The least teratogenic anticonvulsant is โฆโฆ.
phenobarbitone
Drugs & Chemical Teratogens
- Phenytoin
Drugs & Chemical Teratogens
- Valproic Acid
Drugs & Chemical Teratogens
- Fetal valproic Syndrome
Drugs & Chemical Teratogens
- Diazepam
- 1st trimester exposure: increased risk for cleft lip and palate.
Drugs & Chemical Teratogens
- Carbamazpine (Tegretol)
Phenotype similar to FHS
Drugs & Chemical Teratogens
- Cocaine
Drugs & Chemical Teratogens
- Thalidomide
Drugs & Chemical Teratogens
- ACEI
Drugs & Chemical Teratogens
- Vit A
Drugs & Chemical Teratogens
- hormones
Drugs & Chemical Teratogens
- OCP
Drugs & Chemical Teratogens
- Androgenic Agents
Drugs & Chemical Teratogens
- Aspirin
In the 1st trimester โ-> cleft palate.
Drugs & Chemical Teratogens
- Chemotherapy
All Chemotherapy โ> Multiple congenital anomalies
Drugs & Chemical Teratogens
- Metronidazole
- If it used in first trimester, it may cause fetal malformations. โ> but using it in second and third trimester is acceptable
Drugs & Chemical Teratogens
- Corticosteroids
1% risk for cleft palate or adrenal atrophy.
Drugs & Chemical Teratogens
- Retinoids
- Eye and ear defects โ> Hydrocephalus
Classification Based on Teratogenie Potential
Classification Based on Teratogenie Potential
- Category A
Classification Based on Teratogenie Potential
- Category B
Classification Based on Teratogenie Potential
- Category C
Classification Based on Teratogenie Potential
- Category D
Classification Based on Teratogenie Potential
- Category X
Teratogenic Maternal Infections
- CMV
- HSV
- VZV
- Rubella
- HIV
- Syphilis
- Toxoplasma
- TB
Teratogenic Maternal Infections
- CMV
Teratogenic Maternal Infections
- HSV
Teratogenic Maternal Infections
- VZV
Teratogenic Maternal Infections
- Rubella
Teratogenic Maternal Infections
- HIV/AIDS
Teratogenic Maternal Infections
- Syphilis
Teratogenic Maternal Infections
- Toxoplasma
Teratogenic Maternal Infections
- TB
Weight loss - lymphadenopathy - refusal to suckle - hepatosplenomegaly
Teratogenic Physical Agents
- Ionizing Radiation
- Maternal Hyperthermia
Teratogenic Physical Agents
- Ionizing Radiations
Teratogenic Effects of Ionizing Radiation
Teratogenic Effects of Ionizing Radiation
- Most Sensitive Time
from 2nd to 5th week.
Teratogenic Effects of Ionizing Radiation
- Safe Time
- Beyond 20w: the fetus id completely developed and become more resistant to the effect of radiation
Teratogenic Effects of Maternal Hyperthermia
Teratogenic Maternal Diseases
- DM
- Hyperthyroidism
- Hypothyroidism
- SLE
- PKU
- Malnutrition
Teratogenic Maternal Diseases
- DM
Teratogenic DM effects
- Which Type?
DM Type I is More
Teratogenic DM effects
- Neural
- Neural tube defect: anencephaly, spina bifida
- Hydrocephalus, holoprosencephaly
Teratogenic DM effects
- Heart
CHD: TGA (8%), hypertrophic cardiomyopathy
Teratogenic DM effects
- Renal
Renal disorders: Agenesis, double ureter, renal vein thrombosis
Teratogenic DM effects
- Others
Teratogenic Hyperthyroid effects
Teratogenic Hypothyroid effects
Increased risk for loss of pregnancy
Teratogenic SLE effects
- Early Loss of pregnancy
- Complete Heart Block
- Lupus Rash
Teratogenic PKU effects
Teratogenic effects
- Vit A Deficiency
Anophthalmia
Teratogenic effects
- FA Deficiency
Teratogenic effects
- Vit D Deficiency
Bone & teeth malformation
Teratogenic effects
- Ca Deficiency
Bone Malformtions
Teratogenic effects
- K deficiency
Preterm Labor
Teratogenic effects
- Fe Deficiency
Anemia
Notes on thyroid Disorders & teratogenicity
Father Role in Teratogenicity