Teratogensis

 Teratogensis

Teratology

Teratology is the study of abnormal development in embryos and the causes of congenital malformations or birth defects.

· These anatomical or structural abnormalities are present at birth although they may not be diagnosed until later in life. They may be visible on the surface of the body or internal to the viscera.

· Congenital malformations account for approximately 20% of deaths in the perinatal period.

· Approximately 3% of new-born infants will have major malformations and another 3% will have malformations detected later in life.

 Teratogen 

                Any chemical(drug), infection, physical condition or deficiency that , on fetal exposure, can alter fetal morphology or subsequent function.

Causes

· Causes of congenital anomalies Multifactorial or unknown (70%)

· Genetic (20%)

· Environmental(10%)

· Intrauterine infection (2%)

· Maternal metabolic disorders (2%)

· Drugs & chemicals  (5%)

· Ionizing radiation  (1%).

Effects of teratogens

 Immediate  death and abortion.

 At birth  malformation functional defects.

 Delayed : carcinogenesis mutagenesis

Teratogenic agents Maternal medical disorders

1. Diabetes mellitus

Infants of insulin-dependent diabetic mothers have up to 22 % incidence

of cardiac , renal, gastrointestinal, CNS & skeletal malformation.

 Most of the malformations occur between the third & sixth week post conception & are increased if there is hyperglycaemia during that stage of gestation.

2.Epilepsy

3.Phenylketonuria

          Infants have an increased

incidence of mental retardation, microcephaly,& low birth weight.

4.Virilising tumours 

    It produce pseudo hermaphroditic

changes in female fetus.

5.Infections Syphilis

       The incidence of congenital infection is inversely proportional to the duration of maternal infection & degree of spirochetemia. In utero infection may result in : PTL or miscarriage S.B. Neonatal death in up to 50 % of affected infants.

 Congenital infection can manifest as : hepatosplenomegaly, joint swelling, skin rash, anemia, jaundice, snuffles, metaphyseal dystrophy & periostitis.

Toxoplasmosis :

                Active primary infection during pre‰ـ‬infection.‬‬‬‬‬‬‬

 Rubella virus (German measles)

The congenital rubella syndrome includes: CNS, CV, ocular, ear defects & IUGR. Cytomegalovirus:

       The risk of severe complications is much higher for infants of mothers who had a primary infection in pregnancy compared to those who had recurrent infection.

 Herpes simplex virus type 2

 Fetal infection during the first trimester

results in miscarriage .

In few cases ,fetal anomalies occur. 6.Hyper thermia Sustained maternal temperature > 38 C between 4 & 14 weeks

gestation , rather than spiking fevers , is teratogenic.

Risks of teratogenicity 

           The mutagenic effects are very

small Risk of leukaemia for children exposed to X - ray pelvimetry increases from 1 in 3000 to 1 in 2000.

After the tenth week of gestation , the fetal thyroid can be retarded in addition to any adverse effects of radiation . Iodine-containing cough preparation , antiseptic solutions or X ray adjuncts should be avoided throughout pregnancy.

 Radiation Exposure in Pregnancy                  Cumulative dose of 5 rad considered safe No increase in risk of pregnancy loss CNS abnormalities Risk during 10-17 weeks gestation  10 rad  increased risk for mental retardation, microcephaly  Should delay non-urgent radiographs > 17weeks  

Malignancies.

 Very small increase in malignancies, mostly leukaemia 2 rad, malignancy risk increases from 3.6/10,000 (baseline population) to 5/10,000 Gene mutations Very small increase in incidence of gene mutations 50-100 rad needed to double baseline mutation rate.

Chemicals Effects

         Abortion from embryo toxicity, IUGR Organic mercury: neurological damage, blindness, deafness Polychlorinated biphenyls: IUGR, pigmented gums & nails, skull calcification. Herbicides: congenital malformation.