Radiation is an important health concern during pregnancy for both the mother and fetus. Exposures are possible in a variety of forms, including in the workplace and at home, along with diagnostic and therapeutic medical interventions. Due to its widespread use, the exquisite sensitivity of the developing embryo, and potential for damaging exposure without knowledge, understanding the potential impacts and methods to safeguard pregnant women against radiation is critical.

Radiation is energy emitted as waves or particles and divided into two general types. Nonionizing radiation includes microwave, visible and ultraviolet light, ultrasound, and low frequency radiofrequency. The majority of studies, however, have not found a causal link between nonionizing radiation and undesired fetal effects.^1,2,3

Nonionizing radiation is utilized frequently during assessment of in utero development. Ultrasound is routinely used in pregnancy, and causal relationships between prenatal ultrasonography and adverse effects have not been observed.^4,5 Magnetic resonance imaging (MRI) is another commonly used imaging modality utilized during pregnancy, especially when ultrasound findings are equivocal, and has also not demonstrated adverse outcomes.^6,7

Ionizing radiation, on the other hand, has the ability to directly interact with molecules and can either directly or indirectly alter DNA. Actively dividing cells are more sensitive to the effects of radiation and, therefore, cells in the M and G1 cell phases of division are the most radiosensitive, whereas S-phase cells are the least sensitive due to their ability to repair DNA damage. Ionizing radiation causes both single- and double-strand DNA breaks. Single-strand DNA breaks are typically repairable in an otherwise healthy cell; double-strand DNA breaks can lead to genetic alterations, including chromosomal alterations.⁸

Biological effects of radiation depend on the amount or radiation dose, defined as the energy absorbed per unit mass and measured in gray (Gy). In addition, both the type of radiation and the total amount of absorbed energy exert effects. To account for the role of different radiation types, the biological effect of radiation is expressed through the unit sievert (Sv) and is the product of the radiation dose (Gy) and radiation weighting factor for the type of radiation. For example, alpha particles, which cause a significant amount of damage in small places, have a weighting factor of 20, compared to photons, which are typically used in diagnostic and therapeutic radiation.⁸

Classically, the effects of ionizing radiation are separated into deterministic and stochastic.⁹ Stochastic effects of radiation result from insults to the DNA that do not impede the replicative capacity of the cell. These alterations in the DNA can lead to potential consequences, including development of future malignancies. While stochastic effects increase linearly with the radiation dose, there is no minimum absorbed dose. This means that a single radiation-induced DNA change could potentiate a malignant transformation and strongly argues for limiting radiation expose to as low as reasonably achievable. The risk of stochastic effects is the basis for current radiation-related protection practices and standards.¹⁰

Deterministic effects, on the other hand, are characterized by a threshold dose and begin to occur once the threshold dose is achieved. Deterministic effects are caused by cell death at the time of exposure and in pregnancy can lead to abortion, congenital malformations, growth delay, and neurobehavioral
abnormalities. Once the threshold dose is encountered, the likelihood and severity of deterministic effects increases with increased dose, although below the threshold there appears to be no observed effect.^9,11

The majority of our understanding about the effects of radiation during fetal development comes from animal studies, human exposures to diagnostic and therapeutic radiation, and large-scale radiation exposures, including the Chernobyl nuclear power plant exposure and atomic bomb detonations in Hiroshima and Nagasaki during World War II. The majority of published data around radiation dose during pregnancy is from study of these events, and there are limited recent data due to broad implementation of strategies to limit in utero radiation exposure. Although these high-dose exposures provide the majority of available data in humans, they may or may not accurately represent findings at lower doses with lower dose rates.¹² It is also often difficult to accurately quantify risks due to the complexity of the fetal developmental process, which remains incompletely understood.

The risks to the fetus associated with radiation exposure are related to the absorbed dose of radiation and the stage of fetal development at which the exposure occurred, and can be carcinogenic, teratogenic, or mutagenic. Because carcinogenic effects are stochastic, these can, theoretically, occur with any amount of exposure. Noncarcinogenic effects, however, are not believed to be observed when the fetus receives a threshold dose below 0.05 Gy. In practice, however, the believed threshold dose increases from 0.1 to 0.2 Gy for an embryo to 0.5 to 0.7 Gy for the fetus at 16 weeks.¹³ Due to the significant changes in radiation sensitivity and outcomes, noncarcinogenic radiation effects on the fetus are categorized into preimplantation, organogenesis, and early fetal growth. Significant efforts in animal models during fetal development have subsequently been correlated to human fetal development. Irradiation with 2 Gy of photons delivered through gestation is depicted graphically in Figure 9.1 along with estimates for the equivalent human embryonic developmental stages.

Prior to implantation, the embryo is exquisitely sensitive to radiation. The primary deleterious effect observed is implantation failure and is felt to occur with doses as low as 0.1 Gy. Failure to implant is believed to represent an “all or nothing” type of event, and (noncarcinogenic) deleterious effects from radiation are not typically observed if an embryo undergoes successful implantation.^14,15 However, it can be challenging to accurately identify radiation as the causative agent in implantation failure due to the fact that a significant percentage of fertilized embryos do not implant, even in the absence of a known injury.

The period of organogenesis is also highly sensitive to the effects of radiation. The most commonly linked noncarcinogenic effects include mental retardation, microcephaly, and growth restriction.^16,17,18,19 Studies from atomic bomb survivors suggest that fetuses between weeks 8 to 15 exposed in utero to doses above 1 Gy had a 3% to 4% reduction in height¹⁷ and that there was a threshold dose of 0.3 Gy for an increased risk of mental retardation.^18,19 Microcephaly was observed in fetuses exposed up to 15 weeks’ gestation and increased with radiation dose without evidence for a threshold dose.¹⁹ Mental retardation was observed in fetuses exposed from weeks 8 to 25 with the most sensitive period during 8 to 15 weeks. The relationship between absorbed dose and mental retardation appears linear and suggests a probability of 40% chance of mental retardation with a dose of 1 Gy and a
threshold of at least 0.3 Gy.²⁰ Based on available data, microcephaly and mental retardation occur with radiation exposure during the critical period of 8 to 15 weeks. Microcephaly also occurs earlier in gestation, while mental retardation can occur later, with significantly higher exposure. However, it can be challenging to determine the specific impact of radiation on early fetal development because 15% of known pregnancies end in spontaneous abortions and 3% of babies have a major congenital malformation in the general population.²¹

Studies have attempted to understand more subtle changes in mental capacity due to radiation exposure using IQ tests. Osei et al evaluated radiation exposure in 50 pregnant women who underwent radiological examinations of the pelvis using risk coefficients and developed a model that suggested that a 30-point IQ decline occurred per 1 Gy of radiation received during weeks 8 to 15 of gestation.²² It is very challenging to assess these sublethal endpoints, especially when the effects of radiation may not be observable early in life.¹² Figure 9.2 charts risk of known adverse perinatal and neonatal outcomes after radiation exposure at specific gestational ages, based on data from animal studies and human exposure studies, taking into account the limitations of the available human data.

Unlike noncarcinogenic effects of radiation on the fetus, which are highly dependent on the gestational age, carcinogenic effects of radiation can occur from radiation exposure any time throughout the pregnancy. While initially reported in 1956 that in utero exposure to radiation was associated with an increased risk of childhood malignancies, controversy remains regarding whether radiation exposure is the causative agent of childhood cancers due to limited data. Correlation between increased risk of childhood malignancy, especially leukemia, and in utero doses of 0.2 Gy has been demonstrated.^23,24 Another estimate places the risk at 1 to 2 cases of childhood malignancies for 3000 in utero exposures of 0.1 Gy.²⁵ A systematic review of 40 years of research suggests in utero radiation-induced risk of childhood malignancies with doses as low as 0.1 Gy.²⁶ Another review did not find an increased risk of childhood cancer after exposure to diagnostic x-rays²⁷; however, caution is recommended in interpreting these findings given limited data available. It is also unclear whether exposure at different times of gestation results in different carcinogenic effects, although the prevailing theory is that the risk is constant. Overall, while not conclusive, the International Commission on Radiological Protection (IRCP) suggests a relative risk of 1.4 for
development of a radiation-induced malignancy for a 10 mGy fetal exposure, which is felt to be similar to risks of childhood radiation exposure.¹³