RADIATION IN PREGNANCY

2014. 3. 18.

차의과학대학교강남차병원 산부인과

조 연 경

• Ionizing Radiation IS a Teratogen!

• What is a teratogen?

• What is ionizing radiation?

• What are possible sources of ionizing radiation?

• When are the critical periods during pregnancy that ionizing radiation could affect the fetus?

• What are the levels of ionizing radiation that could affect the fetus?

• What could result if exposed to a high level of ionizing radiation during pregnancy?

• How can I protect myself from ionizing radiation poisoning?

Ionizing & Non-ionizing Radiation

Commonly used measurements for ionizing radiation and their units

(Nuclear Wastelands, Makhijani et al., eds., Cambridge: MIT Press, 1995)

Units Description equivalent

Rem(roentgen equivalent man)

A unit of equivalent absorbed dose of radiation with relative biological effectiveness

rem = rad x Q

Sievert (Sv) A unit of equivalent absorbed dose equal to 100 rem.

1 Sv = 100 remSv = Gy x Q

Rad(radiation absorbed dose)

A unit of absorbed dose of radiation. Rad is a measure of the amount of energy deposited in tissue

1 rad = 100erg/gram

Gray (Gy) A unit of absorbed radiation dose equal to 100 rad. Gray is a measure of deposition of energy in tissue

1 Gy = 100 rad

Health impact of high-dose radiation from a nuclear

disaster• Cell death

– Alter DNA of normal cells

– Uncontrolled cell divisions

– Induce cancer

• Damage organs

– Acute radiation sickness (coagulopathy, immunity disorders)

– Diarrhea

– Fever, burns, coordination & equilibrium disturbances

Ionizing radiation from Natural source

Ionizing radiation from Natural source

(World Nuclear Association)

Effects of Prenatal Radiation

Exposure

Effects of radiation in pregnancy

• Pregnancy loss• Malformation• Neurobehavioral abnormalities• Fetal growth restriction --- deterministic effect --- Threshold or NOAEL (No-Adverse-Effect Level)

• Cancer --- Stochastic effect --- More radiation, greater the chance of the disease --- No defined threshold

Effects of radiation in pregnancy

- Deterministic effect

• Radiation dose, the trimester of the pregnancy

Ex) Pregnancy loss• During the 1st 2 weeks after conception, 100-200mGy

(10-20 rad)• Shortly thereafter, 250-500 mGy (25-50 rad)• 18weeks, 5000mGy (500 rad)• At term, 20, 000mGy

(2000rad)

Exposure groups Preimplantation Embryo Fetus

Spontaneous abortion

++ ± -

Congenital malformation

- + -

Intrauterine growth restriction

- + +

Mental retardation - + +

Effects of Radiation (1Gy) Prenatal Exposure in Rodents

(Schull WJ and Otake al. 1999)

Gestational age

Weeks after conception

Fetal Dose

Observed Effect

Preimplantation 0-2 5-10 radAnimal data suggest possibility of prenatal death

Major organogenesis

1-8 20-25 radAnimal 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 radSmall head size, seizures, decline in IQ points: 25points/100 rad

After organogenesis and rapid neuron development

15-term >10 radAssociated with increased frequency of childhood cancer

>50 rad Severe mental retardation observed at 16-25wk

Effects of Radiation Exposure

Ionizing radiation & CNS malformations

Malformations Estimated threshold doseGestational age at

greatest risk

Microcephaly >20Gy 8-15 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 IQ 0.1Gy 8-15 week

Other malformations (skeleton, genitals, eyes)

>0.2Gy 3-11 week

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

Radiation exposure & Cancer

Cancer incidence (1950-1984) and A-Bomb radiation

exposureDS86 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 per 100,000 22.4 32.5 77.8 97.0

Esstimated 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 To 10 years

Gestational exposure 1/2000 1.5 <10 years

U.S. white children <15

y.o.1/2800 1 To 10 years

(Brent RL, Teratology, 1986)

Type of riskSpontaneous risk(0 rad exposure)

Additional risk from 5 rad

Risk of very early pregnancy loss before the first missed period

350,000/106 pregnancies 0

Risk of spontaneous abortion in known pregnant women

150,000/106 pregnancies 0

Risk of major congenital malformation 30,000/106 pregnancies 0

Risk of several mental retardations 5,000/106 pregnancies 0

Risk of childhood leukemia/year 40,000/106 pregnancies/year

<?1-3/106 year

Risk of early or late-onset genetic disease 110,000/106 pregnancies Very low risk: the risk in the next generation and is not measurably increased

with small populations

Prematurity 40,000/106 pregnancies 0

Growth retardtaion 30,000/106 pregnancies 0

Stilbirth 20-2,000/106 pregnancies 0

Infertility 7% of couples 0

Spontaneous Risk Vs Additional Risk

Probability of birth with no malformation and no childhood

cancerDose to

conceptus (mGy)

No malformation

(%)

No childhood cancer(%)

No malformation

and No 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 et al. 1982)

Health impact of high-dose radiation from a nuclear

disaster• ICRP (The International Commission on Radiological Protection)

– < 100mGy (10 rad)

: Not medical ground for termination

• ACOG – Threshold for medical concern ~ 50mGy (5 rad)– > 1000mGy (100 rad)

: Serious risk to fetus’ CNS---severe mental retardation– Single diagnostic radiation exposure? –10rad? 5 rad?

Estimated fetal radiation per procedure or event

Clinical suspicion Procedure Estimated fetal absorption (mGy)

Estimated fetal absorption (rad)

pnemonia X-ray chest < 0.01 <0.001

Pulmonary embolism

CT scan 0.06-0.96 0.006-0.096

Appendicitis CT scan 8-49 0.85-4.9

Nephrolithiasis Pyelogram 1.7-10 0.17-1

Breast nodule Mammogram 0.07-0.2 0.007-0.02

Colon pathology X-ray abdomen 1-4.2 0.1-0.42

Barium enema 7 0.7

Spine injury X-ray lumbar spine

6 0.6

X-ray skull <0.001 <0.001

(Groen RS et al, 2012)

Estimated fetal radiation per procedure or event

Clinical suspicion Procedure Estimated fetal absorption (mGy)

Estimated fetal absorption (rad)

Pelvic injury X-ray pelvis 1-1.4 0.11-0.4

CT scan pelvis 20-79 2.0-79

Background radiation

None 1 mSv 0.1rem

Commercial flight Round trip(toronto~frankfurt)

0.1mSv 0.01rem

100h of commercial flying

1mSv 0.1rem

(Groen RS et al, 2012)

Health impact of high-dose radiation from a nuclear

disaster• Radioactive iodine

• Fetal thyroid : extremely active from >16 weeks• Begins the uptake of iodine↑• Hypothyroidism/hyperthyroidisim• Cretinism (esp. 16-25 weeks)

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 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

2.6:1000

Leukemia1:75,000-100,000

Ovarian cancer1:10,000-100,000

Colorectal cancer 1:13,000

Site N %

Breast 298 26

Cervical 294 26

Leukemia 174 15

Lymphoma 119 10

Melanoma 193 8

Thyroid 45 4

Miscellaneous 111 11

Total 1,134 100

Radiotherapy during pregnancy

malignancy

No. Treatment dose(Gy,median)

Fetal dose(Gy, median)

GA at RT

No. of adverse outcomes

Brain7

40.0–54.0(42.0) 0.00270–0.08000

(0.03000)

18–28(21)

1

Breast23 30.0–78.0(41.0

0.03900–0.16000

(0.15000)

2–24(17.5)

2

Hodgkin’s lymphoma 58

6.0–44.0(36.0) 0.00100–10.00000(0.08500)

1–33(20)

3

NHL 32.0–52.0(26.0)

0.01800–0.10000

(0.06000)

4–30(23)

1

(Luis SA et al, J Med Imaging Radat Oncol 2009)

Radiotherapy during pregnancy : Cases with adverse

outcomesmalignancy Region treated Tx dose

(Gy)Fetal dose

(Gy)GA at

RTNo. of adverse

outcomes

BrainBrain

54.0 0.00270 20 Died in utero

Breast chest, axilla Perinatal death

Hodgkin’s lymphoma

Mediastinum,Supraclavicular

fossa

28 Slow learner, spontaneous

abortion

NHL Mediastinum, chest wall 26 <0.1 30

Fetal distress, short stature,

attention deficit, delayed motor development

(Luis SA et al, J Med Imaging Radiat Oncol 2009)

Radiation exposure on infants and lactating women

• Direct exposure to radiation on breast• Ingestion of radioactive pharmaceuticals

• Mammogram ---- breastfeeding (O)

• The highest radiation conc. in breast milk– 3-4 hours after adm. of radioactive pharmaceuticals– radiation absorbed by fetus < 3-10% of the total dose absorbed

by a woman– But, no negligible dose !– 1 Gy in infant :thyroid cancer(x10)

• CDC: if radioactive iodine ----stop breastfeeding !

Protection of pregnant women and fetuses from

radiation exposure• Maintaining a safe distance• Shielding one’s body from exposure• Avoiding ingestion of food and water contaminated

with radioactive particles in the air, rain, or soil

• In disaster, minimize the exposure• Lead-containing vest• In radioactive pharmaceuticals, hydration + voiding!

• If safe protocol, < 1mSv /year

Gestational age

Fetal Absorbed Dose

<5 rad 5-15 rad >15 rad

<2 wk Recommended Recommended Recommended

2-8 wk Recommended

Maybe consider termination (in presence of other severe risks)

Maybe consider termination (in presence of other risks)

8-15 wk Recommended

Maybe consider termination (in presence of other risks)

Higher risk conditions exist, but termination is not necessarily recommended

15 wk to term Recommended Recommended Recommended

Wagner LK et al : Exposure of the pregnant patient to diagnostic radiations, 1997

Continuing a pregnancy after exposure