Birth Defects and Prenatal Diognosis. Assoc. Prof. E. Elif Güzel, MD

Birth Defects and Prenatal Diognosis Assoc. Prof. E. Elif Güzel, MD

Birth Defects Structural, behavioral, functional, metabolic disorders present at birth Leading cause of infant mortality (%25) Importance of placental membrane

Teratology Science that studies the causes and mechanisms of the abnormal development Major structural anomalies occur in %3 of new borns. Minor anomalies occur in app. %15 of new borns. small ears, pigmented spots no serious medical significance serve as clues for associated major defects

Causes of Birth Defects %40-45 unknown Genetic factors, such as chromosome abnormalities and mutant genes (%28) Environmental factors (%3-4) Multifactorial inheritance (%20-25) Twinning %0.5-1

Malformations Types of Abnormalities occur during formation of organogenesis. may result in complete or partial absence of a structure or in alterations of its normal configuration

Disruptions result in morphological alterations of already formed structures caused by destructive processes e.g, defects produced by amniotic bands

Deformations result from mechanical forces applied on a part of the fetus over a period. e.g, clubfeet, are caused by compression in the amniotic cavity. Deformations often involve the musculoskeletal system and may be reversible postnatally.

A syndrome: group of anomalies occuring together that have a specific common cause. Association: nonrandom appearance of two or more anomalies that occur together, but the cause is not known. Down Syndrome (trisomi 21) Single, transverse line on the hand Characteristic eye-nose appearance Incurving of 5 th digit

Principles of Teratology Teratogens: factors that cause birth defects Teratogenicity of an agent depends on; Genotype of the embryo Maternal genome (drug metabolism, resistance to infection) Developmental stage at the time of exposure Dose and duration of exposure

Teratogens don t induce any birth defects during the first 2 weeks, but may cause death of the embryo The most sensitive period is the 3 rd -8 th weeks of gestation No stage of development is completely safe

Viruses Infectious Agents Rubella Cataracts, heart defects, hearing loss

Cytomegalovirus Microcephaly, blindness, mental deficiency, fetal death some infants may be asymptomatic at birth but later develop symptoms Herpes simplex virus Microphthalmia, microcephaly, retinal dysplasia Varicella virus Scarring of the skin, limb hypoplasia, eye and brain damage Other viruses Coxsakie B; spontaneous abortion Measles, mumups; fetal death or transmitted to the fetus hepatitis B; transmitted to the fetus Hepatitis A, C, E; rarely transmitted from placenta

Toxoplasmosis Toxoplasma gondii Poorly cooked meat; feces of domestic animals can carry the parasite Characteristic features are cerebral calcifications desructive changes in eyes Infants may appear normal at birth, but develop abnormalities later.

Physical agents Radiation High levels of ionizing radiation Causes any type of birth defect depending upon the dose and stage of development Chromosome injury Hyperthermia Neurulation is affected Neural tube defects

Pharmaceutical Drugs Thalidomide immunomodulatory and sedative agent extremity defects Anticonvulsants Diphenylhydantoin; Fetal hydantoin syndrome

Antipsychotic agents Lithium; Heart malformations Antidepressant drugs SSRIs; Heart malformations Anticoagulants Warfarin Skeletal abnormalities Heparin Does not appear to be teratogenic

Antibiotics Tetracyclins Deposited in the active calsification sites Tooth and bone defects Streptomycin Deafness Penicillin Appears to be harmless

Chemical Agents Alcohol Fetal alcohol syndrome Structural defects (maxillary hypoplasia, short nose, thin upper limb) growth deficiency, intellectual disability, heart defects Cigarette smoking Intrauterine growth retardation Premature delivery

Isotretinoin (accutane), analogue of vitamin A Prescribed for the treatment of cystic acne Highly teratogenic Vitamin A itself may be teratogenic at high doses!

Heavy Metals Mercury containing fungicides; Neurological symptoms Lead Abundantly present in the environment Increased abortions, growth retardation

Maternal Disease Diabetes Stillbirths, neonatal deaths, abnormally large infants, congenital malformations Insulin is not teratogenic Obesity Neural tube defects Heart defects

Nutritional Deficiencies Iodine deficiency Impaired medical and physical growth Poor maternal nutrition prior to or during pregnancy Low birth weight and birth defects Severe starvation during pregnancy Schizophrenia

Male-Mediated Teratogenesis Exposures to chemicals Ethylnitrosourea and radiation Mutations in male germ cells Mercury, lead, solvents, alcohol, cigarette smoking Spontaneous abortion, low birth weight, birth defects Advanced paternal age Structural birth defects, Down syndrome

Prevention of Birth Defects Supplementation of salt with iodine Metabolic control of diabetes Folate supplementation Avoidance of alcohol Precautions must initiate prior to conception!

Factors Influencing Fetal Growth Maternal vascular disease Intrauterine infections Cigarette smoking Alcohol Maternal malnutrition Placental problems Genetic factors

Ultrasonography Prenatal Diognosis Uses high-frequency sound waves Safe and commonly used Reveals; Fetal age and growth Presence or absence of congenital anomalies Amount of amniotic fluid Placental position and umbilical blood flow Multiple gestations

Maternal Serum Screening α-fetoprotein (AFP) levels produced from fetal liver increases in case of some abnormalities, e.g neural tube defects decreases in case of Down syndrome

Amniocentesis A needle is inserted transabdominally into the amniotic cavity. App. 20 ml of fluid is withdrawn Performed between 15-18 weeks AFP levels Genetic analysis of the fetal cells

Chorionic Villus Sampling A needle is inserted transabdominally or transvaginally into the placental mass and app. 5-30 mg of villus tissue is aspirated Genetic analysis Performed between 10-12 weeks

Indications for Invasive Procedures Advanced maternal age Family history of a genetic problem Previous birth of a trisomic child (e.g, Down syndrome) Presence of a maternal disease (e.g, diabetes) Abnormal USG or serum screening test

References 1. The Developing Human: Clinically Oriented Embryology by Keith L. Moore, T. V. N. Persaud and Mark G. Torchia (2013). 9 th ed. Elsevier Saunders, Philadelphia. ISBN: 978-0-8089-2444-9 2. Langman s Medical Embryology by T.W. Sadler (2012). 12 th ed. Lippincott Williams & Wilkins, Philadelphia. ISBN: 978-1-4511-4461-1