Wednesday, July 14, 2010

Fetal Development and Drug Effects

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Early in the embryonic period (conception to 56 days), during the preimplantation and presomite stage (0 to
14 days), exposure to a teratogenic agent usually produces an “all or none” effect on the ovum. The ovum either dies from a lethal dose of a teratogenic drug or it regenerates completely after exposure to a sub- lethal dose. During organogenesis, insult with the same teratogen may produce major morphologic changes.

Causes of malformation

These are classified into …

• Genetic defects: monogenic origin and chromosomal abnormalities (25%) e.g. Down syndrome.

• Interaction between hereditary tendencies and non-genetic environ- mental factors (20% of all defects) e.g. congenital hip dislocation
• Environmental factors: e.g. maternal infections, chemicals and drugs (10% of all defects). Only 2 viruses and a protozoan have been proven to induce malformation. Bacteria tend to release toxins that cause extensive tissue damage and fetal death rather than structural anomalies. The viruses are rubella (cataract, heart disease and deafness) and cytomegalovirus (CMV) infection (deafness, mental retardation, microcephaly, chorioretinitis, seizures, blindness and optic atrophy). The protozoan Toxoplasma gondii (hepatosplenomegaly, jaundice, rash, chorioretinitis, cerebral calcifications and hydrocephalus or microcephalus.
• Maternal infections account for 2% and maternal diseases e.g. diabetes and hyperthermia account for 1-2%.
• Unknown causes: account for 60-65% of cases.

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