TERATOGENS Teratology – the study of birth defects and their etiology Teratos (Greek) – monster Any agent that acts during the embryonic or fetal stage Structural or functional abnormalities (malformation) in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy Birth defects are known to occur in 3-5% of all newborns Direct damage to fetus, abnormal development Ectoderm – forms exoskeleton o Hair o Nails o Skin Mesoderm – develops into organs o Circulatory o Lungs (epithelial o Skeletal o muscular Endoderm – forms the inner lining of organs o Digestive o Liver o Pancreas o Lungs (inner layers) TYPES OF TERATOGENS Natural o Poisonous plants like skunk cabbage veratrum, ionizing radiation Pharmaceutical o Thalidomide, tetracycline, streptomycin, valproic acid, warfarin, diethylstilbestrol, retinoic acid, penicillin Industrial o Lead methyl, mercury, cadmium, arsenic Microbial o Treponema palladium (syphilis), coxsackie virus, herpes simplex, rubella (German measles), cytomegalovirus (CMV) Metabolic conditions in the mother o Diabetes, autoimmune disease (including Rh incompatibility), phenylketonuria, dietary deficiencies, malnutrition Physical agents Metabolic conditions Infections Drugs Chemicals TORCH Toxoplasmosis Other disease (syphillis) Rubella Cytomegalovirus Herpes simplex TORCH SCREEN – an immunologic survey that determine whether these infections exist in either the pregnant women or the newborn TOXOPLASMOSIS Protozoan infection Spread commonly through handling cat stool in soil or cat litter Almost no symptoms except for body malaise and posterior lymphadenopathy May cause CNS damage, hydrocephalus, microcephaly, intracerebral calcification, retinal deformities TOXOPLASMOSIS: PRENATAL DIAGNOSIS Placental thickening with a "frosted glass" appearance Cerebral ventricular dilation is usually symmetrical and bilateral and leads to hydrocephalus Hyper-echogenic fetal bowel Hepato-splenomegaly and hepatic densities, pleural, pericardial effusions, and ascites If diagnosis is established, serum analysis during pregnancy Sulfonamides is prescribed Pyrimethamine-antiprotozoal agent RUBELLA Cause mild rash and mild systemic illness but can bring devastating effects to the fetus, which includes Deafness Mental and motor challenges Cataracts Cardiac defects (PDS, pulmonary stenosis) Retarded IUG Thrombocytopenic purpura Dental and facial clefts RUBELLA: MODE OF TRANSMISSION Rubella virus is transmitted through person-toperson contact or droplets shed from the respiratory secretions of infected people. Infection can be communicated seven days before and 4 days after the appearance of the rash Rash appears 2-3 weeks following exposure and persist for three days If a woman is infected with rubella during pregnancy, the virus can cross the placenta and infect the fetus RUBELLA: DIAGNOSIS Rubella titer (1st prenatal visit) Greater than 1:8 – immunity to rubella Less than 1:8 – susceptible to viral invasion Initially extremely high – recent infection has occurred RUBELLA: MANAGEMENT A woman who is not immunized before pregnancy cannot be immunized during pregnancy. After immunization, women is advised not to get pregnant for at least 3 months. All women with low rubella titer's should be immunized to protect against rubella in future pregnancies. CYTOMEGALOVIRUS Member of herpes virus Transmitted through droplet infection from person to person Infant may be born: o Neurologically (hydrocephalus, microcephaly) o Eye damage (optic atrophy, chorioretinitis) o Deafness o Chronic liver disease o Blueberry muffin lesions CYTOMEGALOVIRUS: DIAGNOSIS Isolation of CMV antibodies in serum CYTOMEGALOVIRUS: PRENATAL USG Oligo-hydramnios Polyhydramnios IUGR Fetal ascites, hyperchogenic bowel Microcephaly, ventriculomegaly Intracranial calcification Hepatomegaly CYTOMEGALOVIRUS: PREVENTION Through hand washing before eating Avoid crowds of young children NO TREATMENT FOR THE INFECTION EXIST HERPES SIMPLEX VIRUS Virus spread into the bloodstream (viremia) and crosses to the fetus Infection takes place in the 1st tri-spontaneous miscarriage, severe congenital anomalies 2nd or 3rd tri-premature birth, IUGR For women with history of genital herpes and existing genital lesions, CS birth is often advised to reduce the risk of neonatal infection Intravenous or oral Acyclovir (Zovirax) may be administered to women during pregnancy SYPHILIS Treponema pallidum Extremely damage the fetus after 16th to 18th week of intrauterine life Transmitted via sexual contact SYPHILIS: DIAGNOSIS Serologic screening (vdl or plasma reagin) on the 1st prenatal visit SYPHILIS: CLINICAL MANIFESTATION Fetal: o Stillbirth o Neonatal death o Hydrops fetalis Intrauterine death in 25% Perinatal mortality in 25-30% Early congenital (typically 1st 5 weeks) o Cutaneous lesions (palms/soles) o HSM o Jaundice o Anemia o Snuffles o Periostitis and metaphysical dystrophy o Funisitis (umbilical cord vasculitis) Late congenital: o Frontal bossing o Short maxilla o High palatal arch o Hutchinson teeth o 8th nerve deafness o Saddle nose o Perioral fissures Can be prevented with appropriate treatment SYPHILIS: TREATEMENT Penicillin G – DOC for all syphilis infection Maternal treatment during pregnancy very effective (overall 98% success) Treat newborn if o Mother was treated <4 weeks before delivery o Maternal titers do not show adequate response (less than 4-fold decline) TERATOGENIC DRUGS (DO NOT TAKE IN FIRST TRIMESTER OF PREGNANCY) ANALGESIC o Gastroschisis o Decrease prostaglandin decrease uterine contraction delayed onset of labor & prolonged period of pregnancy o During delivery severe bleeding because aspirin decrease platelet aggregation ANTICONVULSANT o Fetal hydantoin syndrome Cranio-facial malformation Cleft lip palate Broad nasal bridge Abnormal ears Congenital heart disease Limb malformation Mental and growth retardation ANTICOAGULANT o Fetal warfarin syndrome Nasal hypoplasia (bones appears small) Bone stippling Mental retardation o Respiratory distress syndrome o Fetal and maternal hemorrhage ANTIDEPRESSANT ANTITHYROID VITAMIN A o Retinoic acid embryopathy It is a congenital condition caused by the exposure of the developing fetus to teratogenic substances called retinoid. Retinoic acid is a man-made retinoid derivative of Vitamin A used to treat cystic acne and cancer. o Carnie-facial dimorphism o Cleft palate (facial malformation) o Thymic aplasia (missing of organ) o o o Neural tube defect (birth defect of brain) Dental discoloration in children Maternal hepatoxicity (drug that cause injury to liver) with large parenteral doses) ANTIBIOTIC o Chloramphenicol Hypotension Cyanosis Prevented by using the drug at recommended doses and monitoring blood levels METAL TOXIC SEDATIVE/HYPNOTICS AMINOGLYCOSIDES o Gentamycin, streptomycin, sulfamethoxazole, trimethoprim o Neonatal hemolysis o Methemoglobinemia DO NOT TAKE DURING PREGNANCY NICOTINE AND COCAINE o Both nicotine and cocaine are known to be addictive o Developing fetuses become addicted too o Both drugs constrict blood vessels o This decreases oxygen delivery to the fetus o Low birthweight babies, because they didn’t get enough oxygen to grow o Newborns going through withdrawals from drugs o Most cannot adjust their own body temperatures o Neural tube defect Problem with the formation of the brain and/or spinal cord Spina bifida Myelomeningocele ALCOHOL o Addictive and legal drug o Beer, wine, liquor – all affect the fetus the same o Just as alcohol damages adult brains, it also damages fetal brains o Development of facial features change o Majority of damage with alcohol is due to consumption during second trimester o Physical and behavioral deficits can result THALIDOMIDE o Thalidomide was first marketed in 1957 in West Germany. o o o o o o o The German drug company developed and sold the drug. Primarily prescribed as a sedative or hypnotic, thalidomide also claimed to cure "anxiety, insomnia, gastritis, and tension". Afterwards, it was used against nausea and to ease morning sickness in pregnant women. Soon, Thalidomide became an over the counter drug in Germany. Shortly after the drug was sold in Germany, between 5,000 and 7,000 infants were born with Phocomelia (malformation of the limbs). Only 40% of these children survived. Throughout the world, about 10,000 cases were reported. Only 50% of the 10,000 survived. Their effects included deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness. Teratogens such as thalidomide, alcohol, vascular compromise by amniotic bands or other causes, and maternal diabetes have been reported to cause this severe limb deficiency. Amelia is a rare condition with an incidence range from 0.053 to 0.095 in 10,000 live births. PREGNANCY AND RADIATION EXPOSURE Ionizing radiation is the kind of electromagnetic radiation produced by x-ray machines, radioactive isotopes, and radiation therapy machines. There is potential for the embryo or fetus to be exposed during the diagnostic or therapeutic procedures for women who are pregnant. Most diagnostic procedures expose the embryo to less than 50 mSv. This level of radiation exposure will not increase reproductive risks (either birth defects or miscarriage). According to published information, the reported radiation dose to increase the incidence of birth defects or miscarriage is above 200 mSv. TERATOGENIC DRUGS (major non-antibiotics) CAPTAIN Corticosteroids Androgens Progestin & phenytoin Thalidomide Aspirin Indomethacin MALDIVES Methotrexate Alcohol & ace Lindane Danazol Iodine radioactive and Isotretinoin Valproate Efavirenz Sulphonamide TERATOWA Thalidomide Epileptic medications (valproic acid, phenytoin) Retinoid (Vitamin A) ACE Inhibitors, ARBS Third element (Lithium) Oral contraceptives, hormones Warfarin alcohol