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임신 중 방사선(X-ray) 노출이 태아에 어떤 영향을 미칠까?
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임신 중 방사선(X-ray) 노출이 태아에 어떤 영향을 미칠까?

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  • 1. Radiation in pregnancy CHA의대 강남차병원 산부인과 조연경
  • 2. Definition (1)• Roentgen (R): units of exposure• Rad, Gray (Gy): absorbency into human tissue – 100rad = 1Gy (gray) = 1 J/kg• Rem, Sivert (Sv): biological effectiveness of absorbed radiation – 100rem = 1Sv
  • 3. Definition (2)• Relative biological effectiveness(RBE) – correction factor for predicting the biological effect of absorbed radiation – 1 rem = 1 rad/RBE or 1 Sv = 1Gy/RBE In radiation in soft tissue, RBE is about 1  rad & rem (or Gy & Sv): used interchahgeably
  • 4. Effects of radiation (1Gy) prenatal exposure in rodentsExposure group Preimplantation Embyo Fetus Spontaneous ++ ± - Abortion Congenital - + - Malformation Intrauterine - + +growth restriction Mental - + + retardation (Schull WJ & Otake. 1999)
  • 5. Effects of radiation exposureGestational age Weeks after Fetal dose Observed effects conceptionPreimplantation 0-2 0.05-0.1Gy Animal data:prenatal deathmajor 1-8 0.2-0.25 Gy sensitive stage for growth restrictionorganogenesis 2-15 Small head size < 8weeks :intellectual deficit (-) Most sensitive time for induction of childhood cancerRapid neuron 8-15 > 0.1 Gy Small head size, seizure, IQ point ↓development and (↓25/0.1 Gy)migrationAfter 15- term >0.1 Gy Increased frequency of childhood cancerorganogenesis andrapid neurondevelopment > 0.5 Gy Severe mental retardation (16-25 weeks) (Schull WJ & Otake. 1999)
  • 6. Ionizing radiation & malformationMalformation Estimated threshold dose Gestational age at greatest riskMicrocephaly > 20Gy 8-15 weeksmental retardation 0.06-0.31Gy (8-15 weeks) 0.25-0.28 Gy (16-25 weeks) 8-15 weeks > 0.5Gy (8-15 weeks)Reduction of IQ 0.1 Gy 8-15 weeksOther malformation > 0.2 Gy 3-11 weeks
  • 7. Radiation and mental retardation• 8-15 weeks, : Risk of impaired CNS development > 5 times than 16~25 weeks• < 8 weeks, or > 25 weeks - No increased risk of mental retardation
  • 8. Cancer incidence (1950-1984) & A-bomb radiation exposure DS86 maternal uterine dose (Gy) 0 0.01-0.29 0.30-0.59 > 0.6Mean dose (Gy) 0.000 0.087 0.416 1.372No. at risk 710 682 129 109Person –years 21770 21659 4095 3287Cancer cases 5 7 3 3Adjusted 22.4 32.5 77.8 97.0rate/100,000Estimated RR 1.00 1.24 2.18 4.78 [1.01-2.10] [1.06-6.32] [1.19-7.93]
  • 9. Risks of leukemia in various groupsGroup Approximate risk Increased risk over occurrence control populationSiblings of leukemic 1/720 4 ~ 10 yearschildrenGestational exposure 1/2000 1.5U.S white children 1/2800 1< 15 y.o. (Brent RL, Teratology, 1986)
  • 10. Estimated conceptus doses from radiographic and fluoroscopic examinations examinations Typical conceptus dose (mGy)Cervical spine < 0.001Extremities <0.001Chest 0.002T-spine 0.003Abdomen 21cm patient thickness 1 33cm patient thickness 3L-spine 1Limited IVP 6Small bowel study 7Barium enema 7 (McCollough CH 2007)
  • 11. Estimated conceptus doses from single CT & Nuclear medicine examExaminations Typical conceptus doses (mGy)Extra-abdominal Head CT 0 Chest CT 0.2Abdominal Abdomen, routine 4 Abdomen/pelvis, routine 25 Early 1st trimester End of 1 st trimesterBone scan 5 4Whole body PET scan 15 10Thyroid scan 0.2 0.1 (Pavlidis NA, 2002)
  • 12. Probability of birth with no malformation and no childhood cancerDoses to conceptus No malformation No childhood No malformation (mGy) (%) cancer(%) and childhood cancer (%) 0 96.00 99.93 95.93 0.5 95.999 99.926 95.928 1.0 95.998 99.921 95.922 2.5 95.995 99.908 95.91 5.0 95.99 99.89 95.88 10.0 95.98 99.84 95.83 50.0 95.90 99.51 95.43 100.0 95.80 99.07 94.91 (Wagner LK 2002)
  • 13. Spontaneous risk vs additional risk Type of risk Spontaneous risk Additional risk (0Gy exposure) from 0.05Gy Spontaneous abortion 150,000/106 pregnancies 0 Major ongenital 30,000/106 pregnancies 0 malformationSevere mental retardation 5,000/106 pregnancies 0childhood leukemia/year 40,000/106 <?1-3/106year pregnancies/year prematurity 40,000/106 pregnancies 0 growth restriction 30,000/106 pregnancies 0 stillbirth 20-2,000/106 pregnancies 0 infertility 7% of couples 0
  • 14. Cancer in pregnancy Tumot type incidence Breast cancer 1: 3,000-10,000 Cervical cancer 1.2 : 10,000 Hodgkin’s disease 1: 1,000-6,000Malignant melanoma 2.6: 1,000 leukemia 1: 75,000-100,000
  • 15. Ultrasonography• Medical ultrasound: 1-20 MHz• No independently confirmed significant biological effects in mammals in low megahertz frequency range and < 100 mW/cm2 (American Institute of Ultrasound in Medicine, 1982)• Largely replaced X-ray as the 1’ method of fetal Imaging during pregnancy
  • 16. Repeated Dx doses of x-ray/US :prenatal effect Exposure Body weight Body length Head length Brain weight groups Control 1.25 ±0.010 25.62±0.094 8.10 ±0.042 0.086 ±0.001 X+U 1.22 ±0.012 25.38 ±0.012 8.08 ±0.041 0.085 ±0.001 U+X 1.20 ± 0.011* 25.12 ±0.201 8.07 ±0.046 0.086 ±0.001 X+X 1.22±0.015 25.34±0.188 8.09±0.040 0.086±0.001 U+U 1.19±0.013* 25.03±0.205* 7.97±0.045 0.083±0.001(18-day mouse fetuses after repeated exposures to diagnostic doses of X-ray/USduring organogenesis) (Hande MP, 1995)
  • 17. Repeated Dx doses of x-ray/US :postnatal effect Exposure groups Postnatal mortality Sex ratio % brain weight- body weight ratio Control 11.81 0.98 1.57±0.17 X+U 16.45 1.03 1.55 ±0.19 U+X 18.67 0.88 1.56±0.19 X+X 16.00 1.05 1.55±0.18 U+U 20.00* 0.94 1.45±0.18 (18-day mouse fetuses after repeated exposures to diagnostic doses of X-ray/US during organogenesis) (Hande MP, 1995)
  • 18. Continuing a pregnancy after exposureGestational age Fetal absorbed dose Control < 5 rad 5-15 rad > 15 rad < 2 wk recommended recommended recommended 2-8 wk recommended 8-15 wk recommended 15 wk-term recommended recommended recommended (Wagner LK, 1995)
  • 19. Magnetic Resonance Imaging• Magnet: alter the energy state of hydrogen protons• Mice  eye malformation (Tyndall DA, 1991)• Embryo is not sensitive to the magnetic field (more studies are needed)• But, Prudent to exclude pregnant women from MRI during the 1st trimester
  • 20. Nuclear medicine• Tc 99m – brain, bone, renal, cardiovascular – < 0.5 rad• Ventilation-perfusion scan – TechTc99m, 127Xe, 133Xe – < 50 mrad• Radioactive iodine – Readily cross the placenta – Adverse effect on fetal thyroid (esp. after 10-12weeks) – Contraindicated during pregnancy – If a diagnostic scan is essential, 123I or Tecnetium Tc99m
  • 21. Contrast agent• In CT, derivatives of iodine – In animals, not teratogenic/Neonatal hypothyroidism – Generally avoided unless essential for correct diagnosis• Paramagnetic contrast agent (in MRI) – In animals, abortion, skeletal/visceral abnormalities (2-7 times the human dose)• Should be used during pregnancy only if the potential benefit justifies the potential risk
  • 22. Paternal irradiation• In Hiroshima & Nagasaki survivors, → No increase in malformation, fetal death, birth weight• Father received diagnostic x-ray exam → Insignificant decrease in birth weight (Avon Longitudinal Study of Pregnancy and Childhood)• Association between paternal pre-conceptional radiational dose and childhood leukemia has not been confirmed
  • 23. Guidelines (1) : ACOG, 2004• X-ray exposure from a single diagnostic procedure does not result in harmful effects• Concern about effect of high-dose ionizing radiation exposure should not prevent indicated diagnostic X- ray• US / MRI :not associated with known adverse fetal efects
  • 24. Guidelines (2) : ACOG, 2004• Consultation with an expert in dosimetry calculation• Use of radioactive isotope of iodine is contraindicated during pregnancy• Radiopaque and paramagnetic contrast agent : unlikely to cause harm
  • 25. Abdominal radiation in women of reproductive age• Because the risk of 0.05 Gy is so small, the medical care of the mother take priority over the risks to the embryo• X-ray studies for diagnosis and treatment should not be postponed• After diagnosis, elective procedure need not be performed on a pregnant woman• Other procedure can provide information without exposing to ionizing radiation• A period when the patient is pregnant but the pregnancy test is negative – Risk: extremely small during this period of gestation (all or none period)
  • 26. Counseling patientsexposed to ionizing radiation during pregnancy
  • 27. Risk from ionizing radiation• Spontaneous risks vs additional risks from low exposure of ionizing radiation• Diagnostic radiology (0.2 mGy-0.05Gy) – Extremely low risk to the embryo• >15%  spontaneous abortion 3%  major malformation 3%  IUGR (Brent RL , 1986)
  • 28. Case 1• Pregnant / possibly pregnant patient with clinical symptoms – Should be performed at the time clinically indicated – Should not be relegated to one portion of the menstrual cycle In follow-up study(not an emergency), – Postpone until the beginning of the next menstrual period
  • 29. Case 2• Patient has completed a diagnostic procedure that has exposed her uterus to ionizing radiation – Calculate dose to the embryo • If < 5 rad, her risks have not been increased • Threshold for birth defects > 0.2 Gy – Determine stage of pregnancy
  • 30. Case 3• A woman delivers a baby with a serious birth defect – Radiation induced malformation : confined group of malformation – < 0.05~0.1 Gy : not cause of the malformation Analysis about dose, timing, nature of the malformation – 15~25% of malformed children : genetic disease
  • 31. Case 4• When external radiation therapy / high exposures of radionuclides – Low exposure to embryo : Head, neck, upper chest, extremities – Each radionuclides: different half-life, metabolism, excretion – Expert evaluation to determine what the fetal exposure will be or has been