Environmental agents (teratogens)

An agent which can cause a birth defect by interfering with normal embryonic or fetal development is known

as a teratogen

The potencial effect of any particular teratogen depends on:

dosage and timing when it is administered during the pregnancy

susceptibility of both mother and her unborn baby

Maternal infections

Several infectious agens can interfere with embrygenesis and fetal development. The developing brain, eyes and ears are particularly susceptible to damage by infection

Viruses

CytomegalovirusHerpes simplexRubellaVaricella zoster HIV

Teratogenic effects of the rubella virus

microcephaly

microphtalmia

cardiac defect

psychomotoric retardation

Rubella syndrome

The symptoms of the infections during embryonicand fetal developmentMicrocephalyMental deficiency DeafnessMicrophtalmia ChorioretinitisGrowth deficiency

Early infancytrombocytopenia, anemiahepatosplenomegalyobstructive jaundiceinterstitial pneumonia

Drugs with proven teratogenic effects in human

ACE inhibitors renal dysplasiaAlcohol microcephaly, cardiac defect

typical faciesChloroquine chorioretinitis, deafnessDiethylstillboestrol uterine malformation

vaginal adenocarcinomaLithium cardiac defectRetinoids ear and eye defectPhenytoin cardiac defect, cleft palate

digital hypoplasiaStreptomycin deafness Tetracyclin dental, enamel hypoplasiaThalidomid phocomeliaValproic acid neural tube defectWarfarin nasal hypoplasia, stippled

epiphysis

Teratogenic effects of the folic acid antagonist

mental retardaton

growth deficiency

craniofacial abnormalitieshypoplasia of frontal bonebroad nasal bridgeprominent eyes micrognathia, cleft palate

Aminopterin syndrome

Fetal hydantoin syndrome

mild to moderate growth deficiencymild mental deficiencycraniofacial abnormalities

ocular hypertelorismbroad nasal bridgelow set abnormal earscleft lip and palatehypoplasia of distal phalanges micro - brachycephaly

Fetal hydantoin syndrome

Fetal trimethadione syndrome

prenatal onset growth deficiency brachycephalymild midface hypoplasiacleft lip and palate cardiovascular abnormalities genitourinary abnormalities

Fetal valproate syndrome

Fetal warfarin syndrome

developmental and mental deficiency

hypotonia, seizures, optic atrophy

hypoplastic nose with low nasal bridge

stippled mineralization in epiphyses, vertebrae,nasal cartilage

Fetal warfarin syndrome

Chemicals which have a proven teratogenic effect in humans

Clinical features Organic mercurials microcephaly

developmental delay seizures

Polyhalogenated biphenyls growth retardation exophtalmus“cola collor baby“

Dioxin, xylen caudal regression syndrome

Pesticides, heavy metals mental retardation ? Littleinformation available

The fetal alcohol syndrome Prenatal use of ethanol can result in wide

spectrum of foetal alcohol effects

Clinical findings

growth retardationmental retardation

microcephalylong smooth philtrumshort palpebral fissures

midfacial hypoplasia

Fetalalcohol

syndrome

Physical agens as a teratogen

Ionizing radiation

Heavy doses of ionizing radiation, far in excessof those used in routine diagnostic radiography, can causemicrocephaly and ocular defectsThe most sensitive time of exposure is from 2-5 weeksafter conception. Ioniz. radiation can also have mutagenicand carcinogenic effects. Risks associated with low dosediagnostic procedures are minimal.

Prolonged hyperthermia

Fetal hyperpyretic syndrome

Defects of CNS : defect of neuronal migratonmicrocephally neural tube defectsdevelopmental delayseizures

MicrophtalmiaFacial defects micrognathia

cleft lip and palatae

Fetal hyperpyretic syndrome

Maternal metabolic, genetic and nutritional factors

Maternal phenylketonuria – serious demage to the fetuspsychomotoric delay

Iodine deficiency mental retardation

Diabetes mellitus insulin dependent – threefold increasein incidence of congenital malformation –

cardiac defectscaudal regression syndrome

Maternal epilepsy cleft lip and palateneural tube defects