final Flashcards
Artificial Radiation:
-50% man’s annual exposure
-3.2 mSv/yr
-2% consumer products
<1% industrial, security, medical, educational and research
<1% occupational exposure
48% medical and dental procedures
Radiation:
- can cause leukemia, cancer, and/or genetic effects in ALL living organisms
- amount required to produce these long term effects is unknown
- genetic = high dose (not diagnostic)
ORP
Optimizing radiation protection (ALARA)
Natural Radiation (Background) (ubiquitous): -man has no control -3 sources: Terresterial - from soil Cosmic - sun and stars Bodies - radionuclides
Artificial Radiation Medical Procedures: 24% CT 12% Nuclear Medicine 7% Interventional Fluoroscopy 5% Conventional Radiography & Fluoroscopy
Terrestrial Radiation:
- 37% of man’s annual exposure comes from radon and thoron (soils)
- 2.0 mSv / yr
- second leading cause of lung cancer
Radium:
replaces calcium in bones, exsists in some well water (leads to osteoporosis)
Cosmic Radiation:
- from sun and stars
- .5 - 1 mrem per hour of air travel
- greater in higher atmosphere
Annual Natural (ubiquitous background) Exposure:
- 50% of man’s annual dose
- 3.0 mSv/yr
- 37% radon and thoron
- 3% other terrestrial
- 5% space (cosmic)
- 5% internal
Biologic Damage: (intra cellular tissue) -cellular level: major or microscopic lethal or sub-lethal immediate or delayed -interaction: completely absorbed partially absorbed direct transmission
BERT:
- Background Equivalent Radiation Time
- Chest: 0.08 mSv/ 8 mrem / 10 days BERT
- Lumbar 3.0 mSv/ 300 mrem / 1 yr BERT
ORP:
-optimization for radiation protection
(ALARA)
Diagnostic Efficacy:
degree with which a diagnostic exam accurately reveals presence or absence of a disease
NCRP 160:
Addresses radiation dose from all sources to the US population
The amount of radiation actually received by patient from a diagnostic x-ray procedure may be indicated in terms such as:
Entrance skin exposure, bone marrow dose, gonadal dose
Which of the following processes is the foundation of the interaction of x-rays with human tissue
Ionization
Why are the long-term effects such as increased incidence of cancer in the exposed population living near Japan’s Fukushima nuclear plant unable to be accurately determined
It was difficult to measure amounts of radiation people recieved
According to the most recent available data what percentage of natural background radiation exposure comes from radon and thoron
37
Which of the following are natural sources of ionizing radiation
Radioactive elements in the crust of the earth and in the human body
And equivalent dose as low as 250 Millie sieverts delivered to the whole body may cause which of the following within a few days
A substantial decrease within a few days in the number of lymphocytes or white blood cells that are the body’s primary defense against disease
Which of the following is the total average annual radiation equivalent dose from man-made and natural radiation
6.3 mSv per year
Which of the following is recognized as the main adverse health effects from the 1986 share noble nuclear power accident
Increase in the incidence of thyroid cancer and children and adolescents
Radiation
Transfer of energy due to radioactive decay or interaction with the particle (electron)
AlARA
As low as reasonably achievable
Bert
Background equivalent radiation time
Ionizing radiation
Radiation that produces positively and negatively charged particles (ions) when passing through matter
Direct transmission
Primary x-ray photons that traverse a patient without interacting
Diagnostic efficacy
Degree with which a diagnostic exam accurately reveals presence or absence of a disease
Background radiation
Natural radiation
ubiquitous
man has no control
Radon
First decay products of radium a colorless odorless heavy radioactive gas that is always present in the air
Norm
Naturally occurring radioactive materials
photoelectron:
freed electrons energy equals the incoming photon energy minus the electrons binding energy
characteristic photon:
- aka Fluorescent radiation (secondary)
- is created when electrons move to fill shell vacancies
Photodisintegration:
- High dose radiation therapy
- greater than 10 meV
- nucleus absorbs radiation
- excess radiation is emitted in the form of a neutron
Photodisintegration:
- High dose radiation therapy
- greater than 10 meV
- nucleus absorbs radiation
- excess radiation is emitted in the form of a neutron
indirect transmission:
primary photons that undergo Compton and or coherent interactions and are scattered or deflected while passing through a patient and then still reach the image receptor
A decrease in contrast of the image by adding an unwanted additional exposure results from which of the following interactions between X radiation and matter
Compton scattering
Photoelectric absorption
Process whereby the kinetic energy of the incident photon is completely absorbed as it interacts with an Adam any checks an inner shell electron in its orbit
Compton scatter
Energetic electron dislodged from the outer shell of an Adam of the irradiated object as a result of Compton interaction with an incoming x-ray photon
Coherent Interaction:
- photon changes direction without energy change
- usually occurs below 10 kVp
- produces small amount of scatter (1%)
- aka: classical, Thompson, unmodified, and simple
Photoelectric Interaction:
- incoming photon gives up ALL of its energy
- interaction with inner (K) shell electron
- occurs between 23 and 150 kVp
Probability of PE increases as:
- energy of incoming photon decreases ( dec kVp)
- atomic # inc
- tissue mass density inc
- tissue thickness inc
Compton Interactions:
- interaction with outer shell electron
- incoming photon gives up part of its energy and is scattered (incoming photon after change of direction has occurred)
- responsible for scatter
Probability of Compton Int increases:
- due to decrease in PE interactions when kVp increases
- not affected by atomic #
Primary Radiation:
Radiation that emerges directly from the x-ray tube collimator and moves without deflection
Secondary Radiation:
The radiation that results from the interaction between primary radiation and the atoms of the irradiated object and the off-focus or leakage radiation that penetrates the x-ray tube protective housing. (scattered radiation is included)
scatter:
all radiation that arises from the interaction of an x-ray beam with the atoms of a patient or any other object in the path of the beam, X-ray photons undergo a change in direction after interaction
attenuation:
reduction in radiation intensity that results from absorption and scattering
Exit or image formation radiation is composed of which of the following
Non-interacting and small angle scattered photons
Which of the following contribute significantly to the exposure of the radiographer
Compton scattered photons
Which of the following defines attenuation
Absorption and scatter
In the radiographic killer voltage range which of the following structures undergoes the most photoelectric absorption
Compact bone
When I hi atomic number solution is either swallowed or injected into human tissue or a structure to visualize it during an imaging procedure which of the following occurs
Photo electric inner action become significantly in Hanst leading to an increase in the absorb those in the body tissues or structures that contain the contrast medium
Which of the following characteristics primarily differentiates the probability of occurrence of the various interactions of x-radiation with human tissue
Energy of the incoming photon
Binding energy
Force that holds the components of an atom or nucleus together
Photo disintegration
Interaction that occurs in high energy radiation therapy treatment machines
Pair production
Interaction between an incoming photon in an atom of a radiated biologic tissue in which the photon approach is strongly interacting with the nucleus of the Adam of the radiated tissue and disappears in the process the energy is transformed into a negatron and a positron
Auger effect:
energy released from inner shell is transferred to another electron instead of forming characteristic radiation
Pair Production:
- aka: annihilation method
- doesn’t occur diagnostically (Nuc med, PET)
- occurs at 1.022 meV
- interaction with nucleus causes photon to split into positron and negatron
- negatron absorbed by body, positron interacts with another electron and annihilates it
- energy forms 2 photons of .511 meV each
remnant radiation:
All radiation exiting the patient during exposure and ultimately striking the receptor
direct transmission:
primary xray photons that traverse a patient without interacting
absorption:
transference of electromagnetic energy from an xray beam to the atoms or molecules of the matter through which it passes (patients biological tissue)
Which of the following influences attenuation
Affective atomic number of the absorber, mass density, thickness of the absorber
The interactions of x-ray photons with any Adam of biologic matter are
Random so the effects of such interactions cannot be predicted with certainty
Indirect transmission
Primary photons that undergo Compton and or coherent interactions and are scattered or deflected while passing through a patient and still reaching image receptor
Coherent scatter
Process where in a low energy photon interacts with an atom of human tissue and does not lose kinetic energy
Air Kerma
SI method used to quantify beam intensity
Radiation concentration transferred in a point
SI unit replacing exposure
Calculation of radiation intensity in the air
•deci =
.1 or 1/10
•centi =
.01 or 1/100
Air Kerma
- SI method used to quantify beam intensity
- Radiation concentration transferred in a point
- SI unit replacing exposure
- Calculation of radiation intensity in air
- Kinetic energy released in a mass
- Measured in Gray
- Gya
EQUIVALENT DOSE cont:
•1 REM = 1/100 Sv or .01 Sv
•1 Sv = 100 REM
Linear energy transfer
How fast it’s transferred to the patient
Right energy is transferred from ionizing radiation to soft tissue per unit length
exposure
- traditional method used to quantify beam intensity
- amount of radiation an object is exposed to
- measurement of ionizations of X and gamma radiation in air
DAP
- Dose area product
- •amount of energy delivered to the patient
- area of tissue irradiated
Kerma air product=
entrance air kerma x cross sectional area of beam
EQUIVALENT DOSE cont •AD x WR = EqD •RAD x WR = REM •GRAY x WR = SIEVERT •the AD of any type of ionizing radiation produces the same biological damage as 1 RAD of x-rays
EFFECTIVE DOSE (EfD) •Combines both type of radiation and the radiosensitivity of the body part •Tissue Weighting factor (WT) •AD x WR = EqD then •EqD X WT = EfD
Collective Effective Dose Equivalent (ColEfD)
•Describes radiation exposure of a population from various sources
•Person Sievert
- decrease energy =
- decrease penetration = increase damage
- like alpha particles, they have high QF, high LET, and high WR
Which of the following is the unit of collective effective dose
Person Sievert
What is the SI radiation unit coulomb per kilogram used to specify
Radiation exposure in air only
How is the SI unit for dose area product usually specified
Sievert
•kilo =
1,000
•milli =
.001 or 1/1000
exposure -traditional unit = Roentgen -SI unit = coulomb / kg -1R = 2.58 x 10-4 Coulomb/kg Calibrate equipment
Entrance Air Kerma (EAK)
- measurement of amount of radiation intensity incident on patient having exam and measured at point where beam would enter the patient
- actual mAs, kVp, and SID are set
- patient is replaced with an ionization chamber
- many doses are estimated like organ dose and fetal dose
absorbed dose (d)
-amount of radiation transferred from ionizing radiation to the object
•increase atomic # = increase absorption and damage
•Bone atomic # 13.8; soft tissue 7.4
•increase photon energy = decrease absorption and damage to patient
absorbed dose
•traditional unit = RAD (radiation absorbed dose)
•SI unit = Gray
•measures all forms of ionizing radiation in all materials
•1 RAD = 1/100 Gy or .01 GY
•1 GY = 100 RAD
Equivalent Dose (EqD)
-quantifies biologic damage from different types of radiation
•calculates the absorbed dose for all forms of ionizing radiation at a precise point
•Exposure when person receives various types of radiation
•Radiation weighting Factor (WR) adjusts the Absorbed Dose (AD) value
•D x (WR) = EqD
Equivalent Dose (EqD) •Product of absorbed dose for tissue or organ and its radiation weighting factor (WR) •traditional unit = REM •SI unit = Sievert
TEDE
•Total Effective Dose Equivalent - sum of effective dose equivalent from external and Committed Effective Dose Equivalent (internal radiation) exposures
ACTIVITY
•measures the # of disintegrations per second of a radioactive material
•traditional unit - curie (Ci)
•SI unit - becquerel_ (Bq)
Linear Energy Transfer (LET)
•rate energy is transferred from ionizing radiation to soft tissue per unit length
•Shows need for a Quality factor
•measured in kev per micrometer
•High LET, high QF, a lot of damage in a small area (Alpha)
•Low LET, low QF, damage is spread out over a long area (X & Gamma)
- increase energy =
- increase penetration = decrease damage
- like X-ray and gamma ray, they have a low QF, low LET, and low WR
Which of the following was used as the first measure of exposure for ionizing radiation
Skin erythema
The concept of tissue waiting factor is used to do which of the following
Account for the risk to the entire organism brought on by irradiation of individual tissues and organs
To convert the number of gray into Millie gray the number of gray must be
Multiplied by 1000
Which of the following radiation quantities accounts for some biologic tissues being more sensitive to radiation damage than other tissues
Effective dose
If 100 people received an average affective dose of .35 Sv what is the collective effective dose
35 person sieverts
Traditional unit
Roentgen and REM
Tolerance dose
Occupational exposure to radiation that will not cause any apparent harmful a cute effect
Skin erythema dose
Amount of radiation it takes to redden in the skin
Exposure
Amount of radiation an object is exposed to
Method used to quantify beam intensity
Measurement of ionizations of X and gamma radiation in air
Dose Area Product (DAP)
Amount of energy delivered to the patient
Equivalent dose
Quantity attempting to numerically specified the differences in transferred energy and therefore potential biologic harm that are produced by different types of radiation
Collective effective dose equivalent
Describes radiation exposure of a population from various sources
Person Sievert
Total effective dose equivalent
Some of effective dose equivalent from external in cumulative effective dose equivalent exposures
Activity
Measures the number of disintegration per second of a radioactive material
Absorbed dose
Amount of radiation transferred from ionizing radiation to the object
ICRP
•International Commission on Radiological Protection
NCRP
• National Council on Radiation Protection and Measurements
NAS/NRC-BEIR
• National Academy of Sciences / National Research Council - on the Biological Effects of Ionizing Radiation
NRC (REGULATORY)
• Nuclear Regulatory Commission
-“right to know” workplace hazards
- Agreement States - TEXAS MEDICAL BOARD (REGULATORY)
- Department of State Health Services (TEXAS)
EPA (REGULATORY)
•Environmental Protection Agency
FDA (REGULATORY)
•Food & Drug Administration
OSHA (REGULATORY)
•Occupational Safety & Health Administration
RADIATION SAFETY OFFICER •Nuclear Regulatory Commission publishes title 10 Code of Federal regulations (10 CFR) to enforce duties of RSO •Develop RADIATION safety program •Oversee operation •Identify problems •Provide corrective action
1968 Radiation Control for Health and Safety Act
•Protect public from hazards of electronic products that release radiation
•Led to Center for Devices and Radiologic Health
•1974 Code of Standards for Diagnostic X-Ray Equipment
white paper
•2010 FDA
•Patient should receive right procedure, at right time, with right radiation dose
Consumer Patient Radiation Health and Safety Act of 1981
•established minimum standards for accrediting radiology programs
•DSHS (TDH/MRT) division requires 24 hr CE credits/2 years
•ARRT requires 24 hr CE credits/2 years
care bill
Will amend and enforce the Consumer-Patient Radiation Health & Safety Act
Currently does not have penalties for states who do not comply
CARE bill will make compliance a condition of getting Medicare payment
Radiographer - this means certification and ARRT registration which includes CE
tissue effect
Radiation Induced Response
-responses (previously called deterministic effect)
-•a somatic effect which increases in severity with increases in the absorbed dose
•ex. cataracts, blood changes, sperm count reduction
•requires high doses - threshold
stochastic effect
Radiation Induced Response
-(probabilistic) effects
-non threshold
•the probability of occurrence increases with the increased absorbed dose, but the severity does not depend on the amount
•ex. cancer and genetic effects at low doses
CURRENT PHILOSOPHYn(general) •based on the assumption that there is a linear, non threshold dose response relationship between radiation dose and biological effects
Basis for Occupational Exposure Limits
•the NCRP believes that the level of protection provided for radiation workers should, as far as possible, be comparable with that of other “safe” industries
Effective Dose Limit
•upper boundary for the amount of radiation anyone can receive and only have negligible damage
cumulative effective dose •(CumEfD) •lifetime dose •H = (age X 10 mSv) •H = (age X 1 rem)
- Annual occupational Effective Dose Limit
- 50 mSv or 5 rem per year total
NCRP DOSE LIMITS
•OCCUPATIONAL LIMITS
•Lens of eye 150 mSv (15 rem )
•Other organs 500 mSv (50 rem )
NCRP DOSE LIMITS •FETUS of TECHNOLOGIST •entire time 5 mSv (.5 rem ) •per month .5 mSv (.05 rem) •educational 1 mSv (.1 rem)
NCRP DOSE LIMITS •PUBLIC LIMITS 1 mSv (.1 rem) •infrequent 5 mSv (.5 rem) •NEGLIGIBLE DOSE .01 mSv (.001 rem
ACTION LIMIT
•Point of exposure where investigation occurs
•LIT action limit is 5 mSv (500 mrem)
Which of the following agencies is responsible for enforcing radiation safety standards
NRC
Biological effects such as cataracts that result from exposure to ionizing radiation appear to have which of the following
Sigmoid threshold dose response curve
For radiation workers such as medical imaging personnel occupational risk may be equated with which occupational risk in which of the following
Other industries that are generally considered reasonably safe
Revised estimates derived from more recent reevaluation’s of those symmetric studies on the atomic bomb survivors of Hiroshima and Nagasaki indicate which of the following
An increase in the number of solid tumors in the survivor population
organs tissue abundance
12%
bone marrow tissue abundance
4.2%
subcutaneous tissue abundance
5.8%
chromosome breakage
interacts with DNA
muscle tissue abundance
43%
fat tissue abundance
14%
skeletal tissue abundance
10%
blood tissue abundance
7.7%
skin tissue abundance
2.9%
cells
combine to form tissues
tissues
combine to form organs
organs
combine to form systems
ionizing radiation
causes damage by removing electrons from atoms when it tries to stabilize
-different cells have different sensitivity levels
Linear Energy Transfer (LET)
rate energy is transferred from beam to tissue
-increased LET = increased sensitivity
Relative Biological Effectiveness
- increased RBE = increased sensitivity
Fractionation
if dose is spread over several small doses sensitivity decreases
Portacted
if large dose is given all at once sensitivity increases
Oxygen Enhancement Ratio (OER)
increased oxygen content increases sensitivity of low LET radiation, but does not effect high LET radiation
aerobic
high oxygen
hypoxic
low oxygen
apoxic
no oxygen
Age
increased age decreases sensitivity until old age
Sex
females are 5 - 10% more resistant than males
Chemicals
radiosensitizers and radioprotectors
= increased sensitivity
- increase dose
- increased stress
- increased area exposed
= decreased sensitivity
increased body weight
Law of Bergonie and Tribondeau
- increased reproduction rate = increased radiosensitivity
- increased specialization= decreased sensitivity
- increased metabolism = increased sensitivity
Leukocytes (WBC) (HIGHLY SENSITIVE)
lymphocytes - live 24 hrs -10 -25 rad to decrease, 50 - 100 rad to destroy
thrombocytes (platelets) (HIGHLY SENSITIVE)
30 days, 50 rad decreases #
erythrocytes (RBC) (HIGHLY SENSITIVE)
live 120 days, 50 rad to decrease
germ cells (HIGHLY SENSITIVE) 200 rad temporary sterilize, 500 - 600 rad permanently
INTERMEDIATE SENSITIVITY -epithelial tissue digestive system -eyes - 200 rad cataracts in some, 700 rad cataracts in all -cardiovascular system -liver
LOW SENSITIVITY
- lungs - 1000 rad pneumonitis or fibrosis
- muscle tissue
- nervous tissue - 5000 rad death
Direct Effect (5% of interactions are direct) hits the molecule itself
- ionizing radiation acts directly on a macromolecule like DNA, RNA, protein, or enzyme
- greater chance of occurrence with high LET radiation
RADIOLYSIS OF WATER
- forms ion pair (HOH+ & E-)
- ion pair can recombine causing no damage or combine with another water molecule and form a negatively charged water molecule (HOH-)
- this molecule can break apart into free radicals (H & OH)
- free radicals can travel and cause distance ionizations or form hydrogen peroxide (H2O2)
Indirect effect (95% occurrence) it hits the water and then the water hits it Free radical from irradiated water molecule interacts with macromolecule like DNA, RNA, proteins, or enzymes
point mutation
chemical bond is ruptured and sugar phosphate chain is broken
-incoming x ray photon hits edge of sugar phosphate chain of DNA and causes it to break (repairable)
double strand break
more than one break
-can be at one or more levels
-not repairable if they are at same level
mutation
nitrogenous base is changed or lost
crosslinking
two atoms share an electron
-damage has occurred and 2 atoms link up and now share an electron
-occurs from high dose radiation
CHROMOSOME DAMAGE
rejoin original configuration
-create an aberration
-join another broken chromosome and make a new chromosome (cross linking)
TARGET THEORY
some molecules can be damaged in a cell and it will not be noticed, but there are key molecules that if hit by radiation the cell will die. This occurs only by chance. The key molecule is believed to be DNA.
instant death
100,000 rad in a few minutes
reproductive death
100 - 1,000 rad unable to reproduce
interphase death-
does not try to reproduce
mitotic or genetic death
dies after 1 or more divisions
mitotic delay
1 rad
Causes of Short Term Effects early martyrs in radiology accidents in industry & labs Pacific testing grounds 1945 Hiroshima & Nagasaki Human experimentation 1979 Three Mile Island (TMI) 1986 Chernobyl 1999 Japan 2011 Tsunami Japan - Fukushima Daiichi
SOMATIC
short term - acute
long term - late
FUKUSHIMA DAI-ICHI
March 11, 2011 - Tsunami hit Japan
March 12 - explosion Unit 1
March 14 - explosion Unit 3
March 15 - explosion Units 2 & 4
Dose rate gradually reduced over time but there remained some “hot spots” where it accumulated
Indoor exposure 1/10 of the outdoor exposure
prodromal
symptoms occur within hours of exposure
latent period
no symptoms - increase dose = decrease latent
manifest illness
visible symptoms
acute radiation syndrome
recovery or death
HEMATOPOIETIC 100 - 1000rad ( 1-10 Gy) latent period can be 4 weeks blood cells decrease and death occurs from infection & hemorrhage bone marrow syndrome
GASTROINTESTINAL 600-1000rad (6-10 Gy) latent period 3-5 days damage to lining of small intestine death usually occurs within 2 weeks
CEREBROVASCULAR over 5000 rad (50 Gy) May occur as low as 20 Gy swelling of blood vessels in brain death occurs in 3 days
LD 50/30 lethal dose to kill 50 % of those exposed in 30 days 300 rad ( 3Gy) LD 100/30 = 600rad (6 Gy)
REPAIR ENZYMES enable repair and recovery recovery depends on amount of functional damage exposure has cumulative effect 10% irreparable, 90% recovery
4 classes long term effects
- cataractogenesis (cause of cancer)
- life span shortening
- carcinogens
- birth effects (teratogenic)
Causes of long term effects
- single small dose
- several small doses
- large dose survivors
CANCER
- 5-30 year latent period
- occurs naturally in nature
- early martyrs (Curie, Roentgen, Dally)
- survivors of acute radiation syndrome (nagasaki, Hiroshima)
- Low doses at diagnostic levels
LEUKEMIA
- linear, non-threshold
- latent period 4-7 years
- at risk for 20 years
- early radiologists (over 117 cases) (aprecious anemia)
- ankylosing spondylitis (bamboo spine)
- survivors of atomic bombs (117 cases)
- Survivors of Chernobyl (50% increase in child and adult in Gomel region)
- Liquidators who cleaned up Chernobyl
BONE CANCER
Radium dial painters (ingesting radium based paint by painting radioactive Rolex watches in earlier days)
LUNG CANCER
Bohemian pitchblend & Colorado uranium miners (breathing radon)
LIVER CANCER
- Thorotrast for angiography (1925 - 1940) (had thorium in it)
- latent period 15-20 yrs
SKIN CANCER
- early radiologists
- radiation therapy patients
- 5-10 year latent period
- small threshold
BREAST CANCER
- tuberculosis patients
- Japanese atomic bomb survivors
THYROID CANCER
- Ann Arbor & Rochester series
- Rongelap Atoll 1954 (Marshall Islands)
- Chernobyl children (over 982 cases in children)
CATARACTS
- cataractogenisis (clouding of lens of eye)
- radiosensitivity depends upon age
- 5-30 year latent period
- rad threshold for one large dose
- 1000 rad for several small doses
CYCLOTRON
- Ernest and John Lawrence
- Bombarded elements with high speed electrons to create radioisotopes
- biggest group of people that had cataractogenesis
TECHNOLOGIST SURVEY
- Minnesota School Public Health
- National Cancer Institute
- ARRT
- Technologists who began working before 1950
RESULTS
- of the 90,305 survey completers there were 1283 cancer deaths
- technologists who worked before 1940 had a higher elevation of cancer rates
- technologists who began working before1950 have had higher rates of leukemia, multiple myeloma, lymphoma, and deaths when compared to those who began working after 1950
- Technologists who began working before1940 have had a higher rate of cancer deaths
TERATOGENIC EFFECTS (radiation to fetus)
- Preimplantation — often results in spontaneous abortion(before attaching to uterine wall as fertilized egg)
- organogenesis- fetal death, congenital abnormality, sense organ damage, growth defects( Conception- week 7)
- Fetal stage- skeletal abnormality, childhood leukemia, functional defects (week 8-delivery)
