임신 중 방사선(X-ray) 노출이 태아에 어떤 영향을 미칠까?
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Transcript of 임신 중 방사선(X-ray) 노출이 태아에 어떤 영향을 미칠까?
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Radiation in pregnancy
CHA의대
강남차병원 산부인과
조 연 경
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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
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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
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Effects of radiation (1Gy) prenatal exposure in rodents
Exposure group Preimplantation Embyo Fetus
Spontaneous
Abortion
++ ± -
Congenital
Malformation
- + -
Intrauterine
growth restriction
- + +
Mental
retardation
- + +
(Schull WJ & Otake. 1999)
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Effects of radiation exposure
(Schull WJ & Otake. 1999)
Gestational age Weeks after
conception
Fetal dose Observed effects
Preimplantation 0-2 0.05-0.1Gy Animal data:prenatal death
major
organogenesis
1-8 0.2-0.25 Gy sensitive stage for growth restriction
2-15 Small head size
< 8weeks :intellectual deficit (-)
Most sensitive time for induction of
childhood cancer
Rapid neuron
development and
migration
8-15 > 0.1 Gy Small head size, seizure, IQ point ↓
(↓25/0.1 Gy)
After
organogenesis and
rapid neuron
development
15- term >0.1 Gy Increased frequency of childhood cancer
> 0.5 Gy Severe mental retardation (16-25 weeks)
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Ionizing radiation & malformation
Malformation Estimated threshold dose Gestational age at
greatest risk
Microcephaly > 20Gy 8-15 weeks
mental 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 weeks
Other malformation > 0.2 Gy 3-11 weeks
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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
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Cancer incidence (1950-1984) & A-bomb radiation exposure
DS86 maternal uterine dose (Gy)
0 0.01-0.29 0.30-0.59 > 0.6
Mean dose (Gy) 0.000 0.087 0.416 1.372
No. at risk 710 682 129 109
Person –years 21770 21659 4095 3287
Cancer cases 5 7 3 3
Adjusted
rate/100,000
22.4 32.5 77.8 97.0
Estimated RR 1.00 1.24 2.18 4.78
[1.01-2.10] [1.06-6.32] [1.19-7.93]
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Risks of leukemia in various groups
Group Approximate risk Increased risk over
control population
occurrence
Siblings of leukemic
children
1/720 4 ~ 10 years
Gestational exposure 1/2000 1.5
U.S white children
< 15 y.o.
1/2800 1
(Brent RL, Teratology, 1986)
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Estimated conceptus doses from radiographic and fluoroscopic examinations
examinations Typical conceptus dose (mGy)
Cervical spine < 0.001
Extremities <0.001
Chest 0.002
T-spine 0.003
Abdomen
21cm patient thickness 1
33cm patient thickness 3
L-spine 1
Limited IVP 6
Small bowel study 7
Barium enema 7
(McCollough CH 2007)
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Estimated conceptus doses from single CT & Nuclear medicine exam
(Pavlidis NA, 2002)
Examinations Typical conceptus doses (mGy)
Extra-abdominal
Head CT 0
Chest CT 0.2
Abdominal
Abdomen, routine 4
Abdomen/pelvis, routine 25
Early 1st trimester End of 1 st trimester
Bone scan 5 4
Whole body PET scan 15 10
Thyroid scan 0.2 0.1
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Probability of birth with no malformation and no childhood cancer
(Wagner LK 2002)
Doses to conceptus
(mGy)
No malformation
(%)
No childhood
cancer(%)
No malformation
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
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Spontaneous risk vs additional risk
Type of risk Spontaneous risk
(0Gy exposure)
Additional risk
from 0.05Gy
Spontaneous abortion 150,000/106 pregnancies 0
Major ongenital
malformation
30,000/106 pregnancies 0
Severe mental retardation 5,000/106 pregnancies
0
childhood leukemia/year 40,000/106
pregnancies/year
<?1-3/106year
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
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Cancer in pregnancy
Tumot type incidence
Breast cancer 1: 3,000-10,000
Cervical cancer 1.2 : 10,000
Hodgkin’s disease 1: 1,000-6,000
Malignant melanoma 2.6: 1,000
leukemia 1: 75,000-100,000
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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
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Repeated Dx doses of x-ray/US :prenatal effect
Exposure
groups
Body weight Body length Head length Brain weight
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/US
during organogenesis)
(Hande MP, 1995)
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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)
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Continuing a pregnancy after exposure
Gestational age
Control
Fetal absorbed dose
< 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)
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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
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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
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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
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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
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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
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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
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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)
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Counseling patients exposed to ionizing radiation
during pregnancy
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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)
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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
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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
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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
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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