1. Radiation in pregnancy 2009. 03. 24 Kangnam CHA General Hospital Cho Yeonkyung

2. Non-ionizingIonizing Extremely low frequency Radio Microwave InfraredUltraviolet X-ray Γ- ray Broken bondsOpticalThermalNon-thermal Induces low currents Induces high currents Excites electrons Damage DNA Photo chemical effects Heating??? Static field Power line AM radio FM radio TV Microwave oven Heat lamp Tanning booth Medical x-ray Visible light

3. MeasureDefinitionUnit Exposure Dose Number of ions produced by X-rays per kilogram of air Amount of energy deposited per kilogram of tissue Roentgen (R) Rad (rad) Roentgen (R) Gray (Gy) 1 Gy = 100 rad Relative Effective dose Amount of energy deposited per kilogram of tissue normalized for biological effectiveness Roentgen equivalents man (rem) Sievert (Sv) 1 Sv = 100 rem Wiliams obstetrics. 21 st ed. New york (NY): McGraw-Hill; 2001 Definition

4. Ionizing radiation from Natural source 1. Radioactive substances in the earth's crust 2. Emanation of radioactive gas from the earth 3. Cosmic rays from outer space 4. Trace amounts of radioactivity in the body Natural background radiationAverage Annual Whole Body Dose Cosmic29 mrad/year Terrestrial29 mrad/year Radon200 mrad/year Internal (K-40, C-14, etc.)40 mrad/year

5. Average Annual Whole Body Dose in USA Radiation SourceWhole Body Dose Natural Cosmic 29 mrad/year Terrestrial 29 mrad/year Radon 200 mrad/year Internal (K-40, C-14, etc.) 40 mrad/year Man-made Diagnostic X-ray 39 mrad/year Nuclear Medicine 14 mrad/year Consumer Products 11 mrad/year All others Fallout Air travel Occupational…etc 2 mrad/year Average annual total360 mrad/year + Tobacco + 280 mrad

7. Exposure groupsPreimplantationEmbryoFetus Spontaneous abortion ++±- Congenital malformation -+- Intrauterine growth restriction -++ Mental retardation-++ Effects of radiation (1Gy) prental exposure in rodents (Schull WJ et al. 1999)

8. Gestational age Weeks after conception Fetal DoseObserved Effect Preimplantation0-25-10 radAnimal data suggest possibility of prenatal death Major organogenesis 1-820-25 rad Animal and NBS data suggest that this is the most sensitive stage for growth retardation 2-15 NBS data indicate small head size; those exposed before 8 wk did not display any intellectual deficit even with small head; most sensitive time for induction of childhood cancer Rapid neuron development and migration 8-15>10 rad Small head size, seizures, decline in IQ points: 25points/100 rad After organogenesis and rapid neuron development 15-term>10 rad Associated woth increased frequency of childhood cancer >50 radSevere mental retardation observed at 16-25wk NBS = nuclear bombing survivor from Hiroshima an Nagasaki Effects of radiation exposure

9. ProcedureWiliamsOthers Dental0.06 mrad Chest X-ray (2 views)0.02 – 0.07 mrad0.5 mrad Abdominal film (single view)100 mrad250 mrad Intravenous pyelography ≥ 1 rad ̽ 0.4 – 0.5 rad Hip film (single view)200 mrad120 mrad Mammography7 – 20 mrad < 10 mrad Barium enema or small bowel series2 - 4 rad0.9 rad CT scan of head or chest< 1 rad 0 - 0.016 rad CT scan of abdomen and lumbar spine3.5 rad2.0 – 2.5 rad 131 I - Thyroid imaging (15% uptake)10 mrad 131 I - Thyroid therapy - thyrotoxcisis50 – 2000 mrad 131 I - Thyroid therapy – thyroid cancer7.5 – 15 rad Estimated fetal exposure

10. Type of risk Spontaneous risk (0 rad exposure) Additional risk from 5 rad Risk of very early pregnancy loss before the first missed period 350,000/10 6 pregnancies0 Risk of spontaneous abortion in known pregnant women150,000/10 6 pregnancies0 Risk of major congenital malformation30,000/10 6 pregnancies0 Risk of several mental retardations5,000/10 6 pregnancies0 Risk of childhood leukemia/year40,000/10 6 pregnancies/year<?1-3/10 6 year Risk of early or late-onset genetic disease110,000/10 6 pregnanciesVery low risk: the risk in the next generation and is not measurably increased with small populations Prematurity40,000/10 6 pregnancies0 Growth retardtaion30,000/10 6 pregnancies0 Stilbirth20-2,000/10 6 pregnancies0 Infertility7% of couples0 Spontaneous Risk Vs Additional Risk

11. Ionizing radiation and malformtions MalformationsEstimated threshold dose Gestational age at greatest risk Microcephaly>20Gy8-15 week Mental retardation 0.06-0.31Gy between 8 and 15 wks 0.25-0.28 Gy between 16 and 25 wks >0.5Gy between 8 and 15 wks 8-15 week Reduction of the IQ0.1Gy8-15 week Other malformations (skeleton, genitals, eyes) >0.2Gy3-11 week

12. Cancer incidence (1950-1984) and A-Bomb radiation exposure DS86 maternal uterine dose (Gy) 00.01-0.290.30-0.59>0.6 Mean dose (Gy)0.0000.0870.4161.372 No. at risk710682129109 Person-Years217702165940953287 Cancer cases5733 Adjusted rate per 100,00022.432.577.897.0 Esstimated RR1.001.242.184.78 [1.01-2.10][1.06-6.32]1.19-7.93

13. It is estimated that about 3,500 new cases of cancer are diagnosed annually in pregnant women in the U.S., which is equivalent to one case every 1,000 gestations Pavlidis NA. Coexistence of Pregnancy and Malignancy. Oncologist 2002 Tumor typeIncidence Breast cancer1:3,000-10,000 Cervical cancer1.2:10,000 Hodgkin’s disease1:1,000-6,000 Malignant melanoma2.6:1000 Leukemia1:75,000-100,000 Ovarian cancer1:10,000-100,000 Colorectal cancer1:13,000 SiteN% Breast29826 Cervical29426 Leukemia17415 Lymphoma11910 Melanoma1938 Thyroid454 Miscellaneous11111 Total1,134100

14. Maternal doseFetal dose TrimesternDelivery Breast carcinoma 5000 rad16 rad21Healthy boy 5000 rad14-18 rad31Healthy boy 4600 rad3.9 rad11Healthy boy Hodgkin’s disease 3500-4000 rad1.4-5.5 rad1-316Healthy babies/No malignant disease 1900 rad10-13.6 rad31Healthy child at age 8 years 1500-2000 rad2-5 rad2-37Healthy children at age 6-11 years 3500 rad<10 rad21Healthy child Outcome of Pts undergoing RTx

15. Maternal doseFetal doseTrimesternDelivery Brain tumor, head and neck cancer 6400 rad2.7-8.6 rad21Healthy baby 4500 rad2 rad11 2500 rad0.15-0.31 rad31 3000 rad0.3 rad21Healthy boy at age 3 years 6800 rad6 rad31Healthy girl at age 2.5 years 7820 rad3 rad31Healthy girl at age 1.5 years 6600 rad3.3-8.6 rad31 Outcome of Pts undergoing RTx

16. Exposure groups% fetal mortality % microphthalmia% growth restricted fetuses Control6.223.983.32 X+U6.407.375.79 U+X6.638.28 X+X6.124.606.58 U+U7.468.068.60* Repeated exposures to Dx doses of X-ray/US : prenatal effects (18-day mouse fetuses after repeated exposures to diagnostic doses of X-ray /US during organogenesis) Hande MP. Teratogenic effects of repeated exposures to X-ray /US in mice. Neurotoxicology and teratology 1995

17. Exposure groups Body weightBody lengthHead lengthBrain weight Control1.25± 0.01025.62±0.0948.10±0.0420.086±0.001 X+U1.22± 0.01225.38±0.0128.08±0.0410.085±0.001 U+X1.20 ± 0.011*25.12±0.2018.07±0.0460.086±0.001 X+X1.22± 0.01525.34±0.1888.09±0.0400.086±0.001 U+U1.19± 0.013 *25.03±0.205 *7.97±0.0450.083±0.001 Repeated exposures to Dx doses of X-ray/US : prenatal effect (18-day mouse fetuses after repeated exposures to diagnostic doses of X-ray /US during organogenesis) Hande MP. Teratogenic effects of repeated exposures to X-ray /US in mice. Neurotoxicology and teratology 1995

18. Exposure groups% postnatal mortality Sex ratio% brain weight-body weight ratio Control11.810.981.57±0.17 X+U16.451.031.55±0.19 U+X18.670.881.56±0.19 X+X16.001.051.55±0.18 U+U20.00*0.941.45±0.18 Repeated exposures to Dx doses of X-ray/US : postnatal effects (18-day mouse fetuses after repeated exposures to diagnostic doses of X-ray /US during organogenesis) Hande MP. Teratogenic effects of repeated exposures to X-ray /US in mice. Neurotoxicology and teratology 1995

19. Repeated exposures to Dx doses of X-ray/US : postnatal effects Hande MP. Teratogenic effects of repeated exposures to X-ray /US in mice. Neurotoxicology and teratology 1995

20. Gestational age Fetal Absorbed Dose <5 rad5-15 rad>15 rad <2 wkRecommended 2-8 wkRecommended Maybe consider termination (in presence of other severe risks) Maybe consider termination (in presence of other risks) 8-15 wkRecommended Maybe consider termination (in presence of other risks) Higher risk conditions exist, but termination is not necessarily recommended 15 wk to termRecommended Wagner LK et al : Exposure of the pregnant patient to diagnostic radiations, 1997 Continuing a pregnancy after exposure

23. 1.X-ray exposure from a single diagnostic procedure does not result in harmful effects 2.Concern about effect of high-dose ionizing radiation exposure should not prevent indicated diagnostic X-ray 3. US / MRI are not associated with known adverse fetal effects Guidelines for Diagnostic Imaging During Pregnancy

24. 4. Consultation with an expert in dosimetry calculation 5. Use of radioactive isotope of iodine is contraindicated during pregnancy 6. Radiopaque and paramagnetic contrast agent are unlikely to cause harm Guidelines for Diagnostic Imaging During Pregnancy