Radiation in pregnancy

CHA의대

강남차병원 산부인과

조 연 경

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

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

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)

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)

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

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

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]

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)

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)

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

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

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

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

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

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)

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)

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)

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

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

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

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

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

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

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)

Counseling patients exposed to ionizing radiation

during pregnancy

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)

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

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

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

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