Birth Defects and Prenatal Diagnosis PDF

(006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 microtia (small ears), pigmented spots, and short...

(006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 microtia (small ears), pigmented spots, and short palpebral fissures, are not themselves detrimental to OUTLINE health but, in some cases, are associated with major I. CAUSES defects. For example, infants with one minor anomaly have a 3% chance of having a major malformation; II. RISK those with two minor anomalies have a 10% chance; III. ENVIRONMENTAL FACTORS and those with three or more minor anomalies have a 20% chance. Therefore, minor anomalies serve as IV. TYPE OF ABNORMALITIES clues for diagnosing more serious underlying defects. A. Malformation In particular, ear anomalies are easily recognizable B. Disruption indicators of other defects and are C. Deformation D. Syndrome E. Association V. PRINCIPLES OF TERATOLOGY VI. PREVENTION VII.PRENATAL DIAGNOSIS A. Ultrasonography B. Maternal Serum Screening C. Non-Invasive VIII.INVASIVE TECHNIQUE A. Amniocentesis B. Chorionic Villus Sampling C. Cordocentesis IX. HIGH RISK PREGNANCIES X. TREATMENT II. RISK BIRTH DEFECTS/ CONGENITAL MALFORMATION and L-R axes period: 3rd week of development CONGENITAL ANOMALIEs (LATERALITY) Embryonic period/ organogenesis: 3rd to 8th week of ✓ Synonymous terms to describe STRUCTURAL, development – PEAK OF VERTEBREX BEHAVIORAL, FUNCTIONAL and METABOLIC disorders DEVELOPMENT, ORGANS are being DEVELOPED present at birth. ✓ MOST COMMON: STRUCTURAL (e.g. phocomelia, cleft Fetal period: 9th week to birth – NEURAL TUBE AND palate.) – can be seen by naked eyes NOTOCHORD DEVELOPMENT. ✓ Major structural anomalies occur approximately 3% of liveborn infants and birth defects are leading causes of mortality, accounting to approximately 25% of infant deaths. III. ENVIRONMENTAL FACTORS ✓ They are 5th leading cause of years potential life lost prior to IV. age 65 and a major contributor to disabilities. ✓ They are non-discriminatory, the frequencies of birth defects are the same for all races. ✓ Terms used to describe the study of these disorders are teratology (Gr. teratos; monster) and dysmorphology I. CAUSES Environmental factors- 15% - Genetic factors- 30% (Hereditary) Multifactorial / Interaction of environment with genetic susceptibility- 55% Minor anomalies occur in approximately 15% of newborns. These structural abnormalities, such as Infectious agents- rubella virus, herpes simplex, PREPARED AND EDITED BY: TRANS GROUP 6  (006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 varicella, syphilis Non- random appearance of 2 or more anomalies Physical agents- x-rays, hyperthermia that occur frequently than by chance alone; cause Chemical agents- thalidomide (POCOMELIA, not determine (VACTERL- vertebral, anal, AMELIA), valproic acid, opioids, alcohol, lead, ace cardiac, tracheoesophageal, renal, limb inhibitors, tretinoin (NEURAL TUBE DEFECTS), association) cigarettes Abnormalities just occur associated. Meaning Hormones- androgens, des there is another cause. Maternal disease- diabetes, obesity Although they do not constitute a diagnosis, associations are important because recognition of It is not the fetus that is directly infected, it is initially one or more of the components promotes the the mother, if the mother is infected with the search for others in the group. environmental factors, it crosses the barrier, and it affects the fetus. It is either death or malformation, especially if the exposure is during the FIRST TRIMESTER (3rd-8th week). BE CAREFUL IN GIVING MEDICINE, HISTORY TAKING IS VERY IMPORTANT, ASK IF SHE HAS THE INTENTION OF GETTING PREGNANT. IV. TYPE OF ABNORMALITIES A. MALFORMATION Occurs during formation of structures; period of organogenesis; all or none rule, complete or partial absence of structure or in alteration of normal configuration It applies the ALL or NONE RULE, either a complete or partial structural malformation e.g. POCOMELIA – absence of extremities Malformations are caused by environmental and/or genetic factors acting independently or in concert. Most malformations have their origin during the third to eighth weeks of gestation Some complex combinations of defects, such as those observed in cases of heterotaxy, may have their origins where the embryonic axes are being specified as early as the second week. B. DISRUPTION Morphological alteration of already formed structures; caused by destructive processes; amniotic bands Extremities Already formed, but there is alteration because of destructive processes like the presence of amniotic bands. Vascular accidents leading to transverse limb defects and defects produced by amniotic bands are examples of destructive factors that produce disruptions. C. DEFORMATION Result from mechanical forces that mold a part of the fetus over a prolonged period; often involve the musculoskeletal (clubfeet); reversible postnatally D. SYNDROME Group of anomalies occurring together that have specific common cause; risk of occurrence is known. Since the cause is known, we already know when this will occur, E.g. DOWN SYNDROME E. ASSOCIATION  (006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 environmental factors, then the chances of having birth defect is higher - The maternal genome is also important with respect to drug metabolism, resistance to infection, and other biochemical and molecular processes that affect the conceptus. 2. Susceptibility to teratogens varies with the developmental stage at time of exposure - The longer that you are expose, the risk is higher - The most sensitive period for inducing birth defects is the third to eighth weeks of gestation, the period of embryogenesis. - Each organ system may have one or more stages of susceptibility. For example, cleft palate can be induced at the blastocyst stage (day 6), during gastrulation (day 14), at the early limb bud stage (fifth week), or when the palatal shelves are forming (seventh week). - Whereas most abnormalities are produced during embryogenesis, defects may also be induced before or after this period; no stage of development is completely safe. 3. Manifestation of abnormal development depends on dose and duration of exposure to teratogens 4. Teratogens act in specific ways on developing cells and tissues - Initiate abnormal embryogenesis (pathogenesis). - Mechanisms may involve inhibition of a specific biochemical or molecular process; pathogenesis may involve cell death, decreased cell proliferation, or other cellular phenomena. 5. Manifestation of abnormal development are death, malformation, retardation, functional V. PRINCIPLES OF TERATOLOGY disorders. 1. Susceptibility to teratogens depends on VI. PREVENTION genotype of conceptus and the interaction with the environment. - If the abnormal gene is present to the 6. Supplementation- salt with iodine, folate, to parents, and the mother is exposed to prevent Neural Tube Defects  (006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 Supplementation of salt with iodine eliminates C. NON-INVASIVE PRENATAL SCREENNG intellectual disability and bone deformities + results require confirmation by invasive technique resulting from cretinism. Folate supplementation lowers the incidence of neural tube defects, such as spina bifida and anencephaly, and also reduces the risk for hyperthermia-induced abnormalities. 7. Avoidance of alcohol during all stages of pregnancy- TERATOGEN 8. Metabolic control prior to conception especially those soon to be mother, and they have DM, high cholesterol – advise control of metabolic diseases. 9. Precaution on use of drugs/ medications to women of childbearing age; consider possibility of pregnancy, potential teratogenicity of the compound – Medicines may cross the placental barrier and affects the fetus. An essential component of all prevention strategies is to initiate interventions prior to conception. Examples of the effectiveness of ultrasound in imaging the embryo and fetus. A. A 6-week embryo. B. Lateral view of the fetal face. C. Hand. D. Feet. VII. PRENATAL DIAGNOSIS 10. GOAL: provide women-at risk information that gives them opportunity to make informed choices about their pregnancy. 11. Give them the information to guide them, do not dictate what should be done to them. It is still their decision on what should be done to them. The perinatologist has several approaches for assessing growth and development of the fetus in Utero, including ultrasound, maternal serum screening, amniocentesis, and chorionic villus sampling (CVS). In combination, these techniques are designed to detect malformations, genetic abnormalities, overall fetal growth, and complications of pregnancy, such as placental or Ultrasounds showing measures used to assess embryonic and fetal growth. uterine abnormalities. The use and development of in Utero A. Crown-rump length in a 10-week, 6-day fetus. B. Head circumference and therapies have heralded a new concept in which the fetus is now biparietal diameter of the skull (20 weeks). C Abdominal circumference (20 a patient. weeks). D. Femur length (20weeks) A. ULTRASONOGRAPHY- noninvasive, uses high- VIII. INVASIVE TECHNIQUE frequency sound waves reflected from tissues to A. AMNIOCENTESIS- needle inserted trans abdominal create images; trans abdominal or transvaginal; fetal age and growth, congenital anomalies, amniotic fluid lay into the amniotic cavity, ultrasound guided; 20-30ml (amount of AF may determine presence of congenital of fluid is withdrawn; not performed before 14 weeks gestation – may induce abortion anomalies), placental position, multiple gestational. -Look for abnormal cells – KARYOTYPING, typically B. MATERNAL SERUM SCREENING- search for done about 20 weeks of older. B. CHORIONIC VENUS SAMPLING (CVS)- insert needle biochemical markers of fetal status; AFP, a- fetoprotein, produced normally by fetal liver at 14 trans abdominal or transvaginally into the placental mass, aspirate 5-30mg villus tissue weeks and leaks to the maternal circulation via placenta; increase in maternal serum during 2nd -Needs to culture first the venous, then examine the trimester, steady decline after 30 weeks gestation. If cells for abnormalities. This takes a longer time compared to amniocentesis. during the 1st-2nd Trimester declines and in the last trimester it increases, AFP results was reversed, you C. CORDOCENTESIS OR PERCUTANEOUS have a hint that the fetus have anomalies. – Subject for UMBILICAL BLOOD SAMPLING -Insert a needle until the umbilical cord, then check for confirmatory test such as the invasive techniques. abnormal cells. ONLY DO THIS IF THERE IS A POSITIVE RESULT  (006) BIRTH DEFECTS AND PRENATAL DIAGNOSIS DR. PEREDO| 11/26/2020 OF THE NONINVASIVE TECHNIQUES. IX. HIGH RISK PREGNANCIES Advanced maternal age 35 year up Previous family history of genetic problem- Down syndrome, neural tube defect Presence of maternal disease- DM Abnormal Ultrasound or serum screening test X. TREATMENT A. FETAL TRANSFUSION In cases of fetal anemia produced by maternal antibodies or other causes, blood transfusions for the fetus can be performed. Ultrasound is used to guide insertion of a needle into the umbilical cord vein, and blood is transfused directly into the fetus. B. FETAL MEDICAL TREATMENT-treatment is usually provided to the mother and reaches the fetal compartment after crossing the placenta -Folate, Iodized salt crosses the placental barrier C. FETAL SURGERY- open, fetoscopic; because of risks, procedures are only performed in centers with well- trained teams, when there are no reasonable alternatives. - RISKY D. STEM CELL TRANSPLANTATION AND GENE THERAPY- under research, hematologic disorders, metabolic disorders REFERENCE Langman’s Medical Embryology 13th edition T.W. Sadler, pages 126 to 140