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EMBRYOLOGY TERATOGENESIS LEARNING OBJECTIVE . At the end of lecture student should be able to Define the birth defects Classify the birth defects Enumerate the causes of birth defects Know the genetic factor involve in birth defects Name the environmental causes producing birth defects . TERATOGEN A teratogen is any infectious agent,drug,chemical or radiation that alters fetal morphology or fetal function if the fetus is exposed during a critical stage of development. THE RESISTANT PERIOD Week 1 of development. Is the time when the conceptus demonstrates the ’all or none’ phenomenon THE MAXIMUM SUSCEPTIBILITY PERIOD Week 3 to 8 embryonic period. Is the time during which the embryo is most susceptible to teratogens because all organs morphogenesis occurs at this time. THE LOWER SUSCEPTIBILITY PERIOD Weeks 9 to 38 fetal period. Time during which the fetus has a lower susceptibility to teratogens because all organs systems have already formed. Teratogens expose generally results in a functional derangement of an organ system INFECTIOUS AGENTS May be viral or nonviral. Viral infections may reach the fetus via the amniotic fluid after vaginal infection transplacentally via the bloodstream after maternal viremia,or by direct contact during passage through an infected birth canal Bacteria appears to be non teratogenic. RUBELLA VIRUS Transmitted to the fetus transplacentally. Risk greatest during the first month of pregnancy. Clinical menifestation. Fetal rubella infection results in the classic triad of cardiac defects(patent ductus arteriosus,pulmonary artery stenosis,arterioventricular septal defects),cataract,and low birth weight. The clinical manifestations include intrauterine growth retardation,hepatosplenomegaly,generalized adenopathy,Hemolytic anemia,hepatitis,jaundice,meningoencephalitis,eye involvement,osteitis,and sensorineural defects CYTOMRGALO VIRUS Most common fetal infection. Transmitted to the fetus transplacentally or by the virus ascending from the cervix during recurrence. Transmitted to perinates during passage through the birth canal or through breast milk. Clinical manifestations are Sensorineural deafness,intrauterine growth retardation,microcephaly,chorioretinitis,hepatospleeno megaly,osteitis,discrete cerebral calcification,mental retardation,heart block,bluish purple lesions on yellow jaundice skin. HERPES SIMPLEX Transmitted to the fetus transplacentally occasionally. Most commonly transmitted to the fetus by direct contact during passage through an infected birth canal. At 10 to 11days of age clinical manifestation. Disease localized to skin,eye,mouth. At 15 to 17days of age. CNS involvement. Untreated disease results in an 80% mortality rate and most survivors have neurologic sequele. The only intervention to prevent infection is delivery by cesarean section with in 4 to 6hours of ruture of amniotic membranes. VERICELLA ZOSTER Transmitted to the fetus transplacentally. Clinical manifestations of fetal varicella syndrome include Cicatricial(scarring) skin,digit hypoplasia,limb paresis,limb paralysis,hydrocephalus,mental retardation,microcephaly,seizure,chorio retinitis, and cataract. Treatment of the neonate is by acyclovir. HUMAN IMMUNODEFICIENCY VIRUS HIV is transmitted to the fetus through blood containing HIV or HIV infected lymphoid cells near the time of delivery after 35days of gestation. HIV infection does not appear to cause any congenital malformation but results in chronic mutisystem infections. FUNGAL INFECTIONS BACTERIAL INFECTIONS. VIRAL INFECTIONS. NON VIRAL INFECTIONS TOXOPLASMA GONDI Transmitted to the fetus transplacentaly, if untreated results in miscarriage,perinatal death,chorioretinitis,microceph aly, Hydrocephalus encephalomyelitis with cerebral calcification. Surviving infants are left with major neurological sequele(eg mental retardation,seizure,spasticity,and visual dificits) TREPONEMA PALLIDUM Transmitted transplacentally. Infection acquired at birth through contact with genital lesion in the birth canal. Results in miscarriage,perinatal death,hepatospleenomegally,hepatitis ,joint swelling,vesiculobullous blisters,nasal discharge with rhinitis,maculopapular rash located in extremities,,eye findings( chorioretinitis,glaucoma,cataract and uveitis),anemia,jaundice,focal erosions of the proximal medial tibia,saw tooth appearance of metaphysis of long bones,abnormal teeth,and acute syphilic leptomeningitis that may present as neck stiffness,and chronic meningovascular syphilis(cranial nerve palsy,hydrocephalus,cerebral infarction) TORCH INFECTIONS Are caused by, Toxoplasma. Rubella. Cytomegalovirus. Herpes virus. And other bacterial and viral infections that are grouped together because they cause similar clinical and pathological manifestations. DRUGS THALIDOMIDE Prescribed for pregnanat women for morning sickness. Drug cause limb reduction,ear and nasal abnormalities,cardiac defects,lung defects,pyloris stenosis,gestrointestinal atresia. AMINOPTERIN Used in cancer chemotherapy. Causes small stature,abnormal cranial ossification,ocular hypertelorism,low set ears,cleft palate,myelomeningocele. BUSULFAN Are alkylating agents used in chemotherapy. Cause cleft palate,eye defects,hydronephrosis,renal agenesis,absence of toes,growth retardation. PHENYTOIN Antiepileptic drug. Causes growth retardation,mental retardation,microcephaly,craniofacial defects,nail and digit hypoplasia. TRIAZOLAM AND ESTAZOLAM Are hypnotic drugs. Causes cleft palate. WARFARIN Anticoagulant. Causes stippled epiphysis,mental retardation,microcephaly,seizure,fetal hemorrhage,optic atrophy in fetus. ISOTRETINOIN Used in the treatment of severe acne. Causes CNS abnormalities,external ear abnormalities,eye abnormalities,facial dysmorphia,cleft palate. CLOMIPHENE Nonsteroid ovulatory stimulant used in women. There are reports of birth anomalies. DIETHYLSTILBESTROL Used to prevent spontaneous abortion. Causes hypoplastic uteruspremature labour,and cervical incompetance. ETHISTERONE,NORETHISTERONE,AND MEGESTROL Causes masculinization of genitalia in female embryo,hypospadias in males and cardiovascular anomalies. NORETHINDRONED AND LEVONORGESTROL Are oral contraceptive. Cause an increase of fetal abnormalities. Particularly of VACTERL SYNDROME. Consisting of vertebral,anal,cardiac,tracheoesophageal,renal,and limb malformation. NICOTINE Delivered to the fetus through cigarette smokiong. Causes intrauterine growth retardation,premature delivery,low birth weight,and fetal hypoxia. ALCOHOL Causes fetal alcohol syndrome,which results in mental retardation,microcephaly,limb deformities,craniofacial abnormalities,cardiovascular defects. OTHER DRUGS Tetracycline Streptomycin Phenobarbitol Valproic acid Diazepam. Lithium. Hidrochlorothiazide. CHEMICAL AGENTS Mercury. Lead. Polychlorinated biphenyls(PCBs) Potassium iodide. Bisphenol. Phthalates. Methoxychlor. RECREATIONAL DRUGS Lysergic acid(LSD) has not shown to be teratogenic Marijuana has not shown to be teratogenic. Caffeine has not shown to be teratogenic. Cocaine results in an increased risks of congenital abnormalities,still births,low birth weight,and placental abruption. Heroin has not shown to be teratogenic,it is the drugs that are taken with heroin that produce congenital anomalies.methadone used to replace heroin is not teratogenic but is also associated with severe neonatal withdrawal. IONIZING RADIATION ACUTE HIGH DOSE(over 250rads) of radiation results in microcephaly,mental retardation,growth retardation,and leukemia. AFTER EXPOSURE TO GREATER THAN 25rads classic fetal defects will be observed so that termination of pregnancy should be offered as an option. DIAGNOSTIC RADIATION. Radioactive iodine cocktails for organ visualization should be avoided after 10 week of gestation because fetal thyroid development can be impaired. REFERENCES. KEITH L.MOORE Developing Human 8th Edition chapter-20 pages 457-485.