Risks to Embryo and Fetus

Embryo and fetus risks are both

deterministic and stochastic

If we are talking about embryo/fetus risks, we are talking about

post conception

Embryo/fetus deterministic risks

Death of the embryo

Abnormalities with organ formation (congenital)

General growth disturbance (baby born w low weight)

Embryo/fetus stochastic risks

Childhood cancer

Potentially microcephaly

What are the factors that influence radiation risks to the embryo/fetus?

Dose

Dose rate

Gestational period

Like cancer and heritable effects, embryo/fetus effects are modeled how?

Relative risk

At birth, what is the natural incidence of congenital malformations

6%

In older children, what is the incidence of malformations?

12%

Radiation only increases the

risk that already exists in the general population

What are the three phases of fetal development

Preimplantation

Organogenesis

Fetal Period

Gestational time period for preimplantation

0-9 days

Gestational time period for organogenesis

Day 9-6 weeks

Gestational time period for fetal period

6 weeks to birth

Preimplantation marks the time between fertilization and

the egg attaching to the uterine wall

Organogensis marks the period of

major organ development

foundational work!!

fetal period refers to the growth

of existing structures

embryo-fetus

Preimplantation stage is most sensitive to what from radiation exposure

Prenatal death

Irradiation during the preimplantation phase results in a

all or nothing effect

In preimplantation, the radiation will either cause

too many cell death killed by radiation so the embryo dies and is reabsorbed

or

the embryo attaches and develops normally

In the preimplantation phase, the cells are too undifferentiated to result in

birth defects

What happened to the mice during irradiation in the preimplantation phase?

A decrease in litter size

NO observable growth disturbances

NO observable increase in congenital malformations

In the preimplantation the phase, the embryo will either die or

develop normally during this phase if irradiated

Organogenesis stage is most sensitive to what from radiation exposure

Organ malformations and temporary growth disturbances

What is happening during the organogenesis phase?

The embryonic cells are differentiating into whatever organ they will eventually become

Irradiation during organogenesis may induce

congenital malformations by depleting the cells in the developing body organs or structures

Irradiation during EARLY organogenesis may result in

temporary growth disturbance, although normal adult weight is possible

If death is going to occur as a result of radiation exposure during organogenesis, it is most likely

neonatal death

What were the congenital malformations seen in mice during organogenesis?

Exencephaly (brain outside skull)

Eviseration (organs outside body)

Anencephaly (absence of brain tissue)

Growth stunting

Microphthalmus (small eye)

Anophthalmus (Absence of eye)

Preimplantation vs. Organogenesis

Fetal period stage is most sensitive to what from radiation exposure

PERMANENT growth disturbances

(ex: low birth weight)

Irradiation during the fetal period can have a large impact on what for the offspring?

fertility

Natal lethality during the fetal period occurs at

MUCH HIGHER DOSES than preimplantation or organogenesis

Graph of all stages of development from when mice received a dose of 2 Gy at different stages

What is the threshold for radiation effects in preimplantation?

100 mGy for prenatal death

What is the threshold for radiation effects in organogenesis?

100 mGy for malformations

What is the threshold for radiation effects in fetal period?

Doses below 100 mGy appear to have no significance to intellectual disability

What happened to pre-atomic bomb, early rad therapy studies?

Involved in-utero exposure as a consequence of pelvic radiation therapy to the moth

Describe the fetal effects seen in studies on individuals exposed to radiation therapy treatments in utero

-Large doses (2.5 Gy) delivered before 2-3 weeks did not produce organ abnormalities

-Irradiation between 4-11 weeks produced severe organ abnormalities

-Irradiation after 30 weeks did not produce significant organ abnormalities

As well as

-MICROCEPHALY

-INTELLECTUAL DISABILITY

Microcephaly quick summary

structural abnormality

small head size

impairment of glial cell development

intellectual disability summary

functional abnormality

decreased cognition

impairment of neuron development

Majority of the effects seen in early rad tx studies (microcephaly and intellectual disability) between

11-25 weeks gestation

the atomic bomb survivors give us some evidence about human

preimplantation effects

-First, there were too few children born that would have been less than 4 weeks in utero at the time of the blast

-Second, there was no birth defects observed in individuals who were more than 15 days in utero

the atomic bomb survivors prove the

all or nothing effect in preimplantation

Microcephaly results in

small head size

What is a permanent form of growth disturbance?

Microcephaly

Microcephaly was mostly observed in survivors that were within

1,500 m (1 mile) from the blast epicenter

Microcephaly was only seen in those that were exposed

before 15 weeks

Microcephaly appears to be what type of effect?

Stochastic because there was little evidence for a dose threshold

Since microcephaly does not have a threshold, the data implies that microcephaly also has a

GENETIC COMPONENT or some other factor that leads to stochastic rather than deterministic

Intellectual disability appears to be

deterministic

There is a 40% chance of intellectual disability at a dose of

1 Gy

What is the threshold for intellectual disability?

300 mGy

For atomic bomb survivors, intellectual disability was only seen in children exposed between

8-25 weeks

Children with IQ less than 68 (avg is usually 90-110)

Both microcephaly and intellectual disability are seen with irradiation between

8-15 weeks gestation

Microcephaly occurs without intellectual disability from weeks

0-7

Intellectual disability occurs without microcephaly from weeks

16-25

8-15 weeks is a

critical time for protecting brain development

What is the threshold for intellectual disability as observed in the atomic bomb survivors?

300 mGy

Increased risk of childhood cancer is always a concern, regardless of

timing of irradiation

Risk appears to be slightly increased for childhood cancer with irradiation in

last trimester

What is the most common cancer associated with in-utero exposure

Childhood leukemia

Doll and Wakeford's review on childhood cancer risk

1997 summary paper

Tells us that obstetric x-ray exam leads to excess relative risk of 40%

Doses of 10 mGy increase cancer risk

Absolute risk is 6% per Gy

Obstetric x-ray exam leads to excess relative risk of

40%

Doses of how much increase cancer risk

10 mGy

Absolute risk is

6% per Gy

Childhood cancer estimates are highly uncertain, but not

zero

data is controversial due to confounding factors

Childhood cancer in atomic bomb survivors

The relative cancer risk for individuals exposed in utero was observed to be 1 per Gy of dose (100% increase)

For childhood cancer in atomic bomb survivors, however:

there was no statistically significant increase in the number of childhood cancers (less than 15 years)

the risk was higher if exposed as an infant of young child rather than in utero!!!

According to atomic bomb data, the relative cancer risk exposed in utero

observed to be 1 per Gy of dose (100%)

NRC fetal dose limit

500 mrem for the entire pregnancy

NRCP occupational fetal dose

50 mrem per month

The dose limits for occupational exposure to the embryo and fetus are designed to

minimize the risk of cancer, malformations, and growth disturbances

Embryo/fetal dose limit is

VOLUNTARY

Declared pregnancy woman

Means a woman who has voluntarily informed the licensee, in writing, of her pregnancy and the estimated date of conception. The declaration remains in effect until the declared pregnant woman withdraws the declaration in writing or is no longer pregnant.

The regulatory term for a radiation worker who has officially requested fetal monitoring.

Recommendations for pregnant individuals working in medical radiation professions

No I-131 admin by pregnant employees

Reduce or eliminate admin of other therapeutic radiopharmaceuticals

Pregnant employees should not be involved in radiation emergency response

Pregnant employees in intense fluoro departments should consider the possibility of reducing caseload

All pregnant employees should practice ALARA

What can pregnant women not administrate?

I-131

Patients should be asked about

possible pregnancy before receiving routine diagnostic scans, and answer should be documented

If the procedure is high dose or therapeutic, what is required?

BLOOD pregnancy test (BETA HCG)

If the patients medical condition warrants intentional exposure, the decision must be made in collaboration with the

physician

if a pregnant patient is accidentally exposed...

careful dosimetry should be performed by qualified expert

small doses pose a very low

deterministic risk (malformations)

-less than 100 mSv during preimplantation and organogensis

-less than 300 mSv during fetal period

Stochastic risk is always

a concern at ANY dose levels

higher doses may require a

tough conversation