Hall Book Ch 12 (Effects of Radiation on the Embryo and Fetus)

Question 1

Doses that have little effect on adults can produce catastrophic effects on the developing ( ).

The effects depend on the ( ).

Gestation is divided into ( ).

Answer 1

embryo and fetus

stage of gestation, the dose, and the dose rate

preimplantation, organogenesis, and the fetal period

In humans, these periods correspond to about 0 through 9 days, 10 days through 6 weeks, and 6 weeks through term, respectively.

Question 2

The principal effects of radiation on the developing embryo and fetus, aside from cancer, are ( ).

Answer 2

embryonic, fetal, or neonatal death; congenital malformations; growth retardation; and functional impairment, such as mental retardation

Question 3

Irradiation during preimplantation leads to potential death of the embryo.

At doses less than 100 mGy, such lethal effects will be infrequent in humans.
Growth retardation or malformations are not seen in animals from irradiation
at this time. The human data are consistent with this conclusion.
In animals, embryos exposed to radiation in early organogenesis exhibit the
most severe intrauterine growth retardation, from which they can recover
later (i.e., temporary growth retardation). Irradiation in the fetal period leads
to the greatest degree of permanent growth retardation.
In animals, lethality from irradiation varies with stage of development. The
embryonic 50% lethal dose is lowest during early preimplantation; at this
stage, embryos killed by radiation suffer a prenatal death and are resorbed. In
organogenesis, prenatal death is replaced by neonatal death—death at or
about the time of birth. During the fetal stage, the 50% lethal dose approaches
that of the adult.
In animals, the peak incidence of teratogenesis, or gross malformations, occurs
if the fetus is irradiated in organogenesis. For practical purposes, the risk of
malformations for doses well below 100 mGy would not be expected.
In contrast to what is observed in experimental animals, radiation-induced
malformations of body structures other than the central nervous system are
uncommon in the Japanese survivors irradiated in utero, although they have
been reported in patients exposed to therapeutic doses of medical radiation.
In the Japanese survivors, irradiation in utero resulted in small head size
(microcephaly) and mental retardation.
Mental retardation from irradiation occurred primarily at 8 to 15 weeks of
gestational age, with a smaller excess at 16 to 25 weeks. It is thought to be
caused by radiation effects on cell migration within the brain.
The incidence of severe mental retardation as a function of dose is apparently
linear at 8 to 15 weeks, with a risk coefficient of 0.4 per Gy. The incidence is
about 4 times lower at 16 to 25 weeks. The data are also consistent with a
dose threshold of 0.3 Gy.
Small head circumference was more common than mental retardation.
Data on atomic bomb survivors indicate that microcephaly can result from
347
exposure at 0 to 7 and 8 to 15 weeks postovulation but not at later times.
There is little evidence for a threshold in dose.
Various effects have been documented in experimental animals after
irradiation during fetal stages, including effects on the hematopoietic system,
liver, and kidney, all occurring, however, after quite high radiation doses.
There is an association between exposure to diagnostic x-rays in utero and the
subsequent development of childhood malignancies, although there are
particular uncertainties concerning the risk involved.
The original study of diagnostic x-ray exposure in utero and subsequent
malignancies, principally leukemia, was done by Stewart and Kneale at
Oxford University, but the same association was observed in the United
States by MacMahon. If x-rays are the causative agent, these studies imply
that radiation at low doses in utero increases the spontaneous cancer
incidence in the first 10 to 15 years of life by 50%—that is, by a factor of 1.5.
It has been argued for years whether radiation is the causative agent or whether
there are other factors involved.
A study of twins born in the 1930s and early 1940s also found an increase in
childhood cancers in children who had been irradiated in utero which
supports the causal nature of the childhood cancers in the earlier studies
because in twins, most x-rays in those days were not ordered for medical
reasons but simply to observe progress in the pregnancy.
Doll and Wakeford in 1997 summarized all of the evidence for and against the
calculated risks and concluded that an obstetric x-ray examination,
particularly in the third trimester, increased the risk of childhood cancer by
40%. The risk is increased by a dose of only 10 mGy. The excess absolute
risk is about 6% per Gy, which is not very different from the risk estimates
from the atomic bomb survivors for adult exposure.
Until a pregnancy is declared, no special limits apply to women other than
those applicable to any radiation worker. Once a pregnancy is declared, the
maximum permissible dose to the fetus is 0.5 mSv per month.
Once a pregnancy is declared, the duties of a radiation worker should be
reviewed to ensure that this limit is not exceeded.
A sufficiently large dose to the embryo or fetus during the sensitive period of
gestation (10 days to 25 weeks) may be justification for considering a
therapeutic abortion to avoid the possibility of an anomalous child. Not
348
everyone would agree with this, and the decision to terminate a pregnancy
should be flexible and must depend on many factors in addition to dose.