Radiation Effects on Embryo and Fetus PDF

# Radiation effects to embryo and fetus ## Classic effects of radiation on Embryo and Fetus 1. Lethal effects - pre-implantation death - intra-uterine death - neonatal death 2. Malformations - Teratogenic effects 3. Growth disturbances ## Critical or sensitive stages in human pren...

# Radiation effects to embryo and fetus ## Classic effects of radiation on Embryo and Fetus 1. Lethal effects - pre-implantation death - intra-uterine death - neonatal death 2. Malformations - Teratogenic effects 3. Growth disturbances ## Critical or sensitive stages in human prenatal development | Periconceptual period (in weeks) | Main embryonic period (in weeks) | Fetal period (in weeks) | Full term Period | System location | Size (mm) | Direction | Maternal action | Result | |---|---|---|---|---|---|---|---|---| | 1 | 5 | 12 | 38 | Single-cell zygote | 0.1-0.2 | Not susceptible to teratogenesis | | | | 2 | 6 | 16 | | Implantation 2 | | | | | | | 7 | 17-37 | | | | | | | | | 8 | | | Morula/cleavage | 0.4-2.5 | | | | | 3 | 9 | | | Implantation 3 | 20-50 | Highly sensitive period | | | | | 10 | | | | | Less sensitive period | | | | | | | | Blastocyte | 40-9.0 | | | | | | | | | Bilaminar disc | 8.0-14 | | | | | | | | | Implantation 1 | 13-18 | | | | | | | | | | 18-31 | | | | | | | | | | 55 | | | | | | | | | | 85 | | | | | | | | | | 146 | | | | | | | | | | 163-345 | | | | | | | | | | 355 | | | | | | | | | Upper limbs | | Direct | | | | | | | | Heart | | | | | | | | | | Eye | | | | | | | | | | Skeleton | | | | | | | | | | Upper lip | | | | | | | | | | Lungs | | | | | | | | | | CNS | | | | | | | | | | Lower limbs | | | | | | | | | | Palate | | | | | | | | | | Teeth | | | | | | | | | | Immune system | | | | | | | | | | Kidneys | | | | | | | | | | External genitalia | | | | | | | 5-6 | | | Cleft lip | | | | | | | 7 | | | | | | Masculinization of female genitalia | Masculinization of female genitalia | | | 8 | | | | | | Enamel hypoplasia and staining | Enamel hypoplasia and staining | | | 9 | | | | | | Cleft palate | Cleft palate | | | | | | | | | Myasthenia gravis, severe combined immune deficiency (SCID) | Myasthenia gravis, severe combined immune deficiency (SCID) | | | | | | | | | Microphthalmia, cataracts, glaucoma | Microphthalmia, cataracts, glaucoma | | | 10 | | | | | | Respiratory anomalles | Respiratory anomalles | | | | | | | | | | Renal agenesis, renal hypoplasia, renal dysplasia and multicystic kidney, infantile polycystic kidneys, renal fusion, ectopic kidney, medullary sponge kidney, or Potter's syndrome | | | | | | | | | Amelia, adactyly, or meromelia | Amelia, adactyly, or meromelia | | | | | | | | | | Amelia, adactyly, or meromelia | | | | | | | | | Low-set malformed ears and deafness | Low-set malformed ears and deafness | | | | | | | | | | Truncus arteriosus, atrial septal defect, & ventricular septal defect | | | | | | | | | | Neural tube defects (NTDs), spina bifida | | | | | | | | | | Musculoskeletal anomalies, clubfoot | | | | | | | | | Creates susceptibility to premature birth | | | | | | | | | | | intrauterine growth retardation (small for gestational age infants) | | | | | | | | | | Placental development interruption | | | | | | | | | | Death of embryo and spontaneous abortion | | | | | | | | | | Major physical malformations (congenital anomalies) | | | | | | | | | | Mental retardation | | | | | | | | | | Physiological defects/deficiencies, impaired growth, minor physical abnormalities | | | | | | | | | Premature birth | | ## STAGES OF GESTATION - Pre-Implantation: Day 1 - 10 - Organogenesis: Weeks 3 – 7 - Growth/Foetal Stage: Week 8 – birth *Weeks are gestation weeks (GW) or postconception (PC).* - Most risk: Organogenesis - Less: 8-17 GW - Least: > 25 GW ## PRE-IMPLANTATION (<10 DAYS) - Fertilization of egg and implantation in wall of uterus occurs during this period. - The embryonic cells are rapidly growing and not well differentiated. - If exposed to radiation, it is all or nothing. - Either the embryo fails to implant and dies; or it is unaffected and survives without any risk of malformation. ## ORGANOGENESIS (WEEK 3 - 7) - Embryonic tissues are now differentiating into major organs. - A dose >100 mGy may lead to death of embryo or malformations. - Conceptus is at most risk at this stage. ## FOETAL PERIOD (contd.) - During the 8th -17th GW, the number of neurons in developing brain increases rapidly and neurons move into specific part of brain. - This high rate of mitotic activity explains the high degree of radiosensitivity in the 8th to 17th week. - After 17th week, no further cell division occurs in the foetus' brain. - *In utero* irradiation later than 25th GW does not affect the IQ of the child. - High foetal doses (100 – 1000 mGy) during late pregnancy (>25 GW) are not likely to result in malformations, since all organs have been formed. ## Comparison of human and animal data | | Preimplan-tation | Organogenesis | Fetal Period | |---|---|---|---| | Animal Studies | Prenatal Death | Congenital Anomalies <br> Neonatal Death <br> Temporary Growth Retardation | Permanent Growth Retardation | | Japanese Survivors | | | Mental Retardation <br> High Risk <br> Mental Retardation <br> 4x Lower Risk | ## TABLE 12.4. Major Events in Understanding Effects of Radiation on the Developing Embryo and Fetus | Investigators | Year | Observations | |---|---|---| | Goldstein and Murphy | 1929 | Various abnormalities, including mental retardation and small head diameter in children born to mothers who received pelvic radiation therapy during pregnancy. | | Job et al. | 1935 | Recognition that different periods of gestation differ in radiosensitivity. | | Russell | 1950 | Nature of developmental abnormality determined by gestational age at exposure. | | Russell and Russell | 1952 | Clinical implications of irradiation in pregnancy. | | Plummer | 1952 | Mental retardation and microcephaly observed in children of atomic-bomb survivors. | | Stewart and Kneale | 1952 | Leukemia and childhood cancer in children irradiated in utero with diagnostic x-rays. | | Otake and Schull | 1984 | Mental retardation caused by irradiation at 8-15 weeks of pregnancy in Japanese survivors. | ## Probability of bearing healthy children as a function of radiation dose | Absorbed dose to conceptus, mGy, above natural background | Probability that child will have no malformation, % | Probability that child will not develop cancer (age 0-19), % | |---|---|---| | 0 | 97 | 99.7 | | 0.5 | 97 | 99.7 | | 1.0 | 97 | 99.7 | | 2.5 | 97 | 99.7 | | 5 | 97 | 99.7 | | 10 | 97 | 99.6 | | 50 | 97 | 99.4 | | 100 | 97 (close to 97) | 99.1 | Note: No significant increase in probabilities below 100 mGy. ## APPROXIMATE FOETAL DOSES FROM PROCEDURES | METHOD | PROTOCOL | MEAN (mGy) | MAX (mGy) | |---|---|---|---| | X-RAY | Skull or thoracic spine | <0.01 | <0.01 | | | Chest | <0.01 | <0.01 | | | Lumbar spine / Intravenous Urogram | 1.7 | 10 | | | Abdomen | 1.4 | 4.2 | | | Pelvis | 1.1 | 4 | | FLUOROSCOPY | Barium meal (UGI) | 1.1 | 5.8 | | | Barium enema | 6.8 | 24 | | | Head CT | <0.005 | <0.005 | | CT | Chest CT | 0.06 | 1.0 | | | Lumbar spine | 2.4 | 8.6 | | | Abdomen CT | 8.0 | 49 | | | Pelvis CT | 25 | 80 | | NUCLEAR MEDICINE | Tc - Bone | 3.3 | | | | Tc - Brain | 4.3 | | Sources: Health Protection Agency (2008); J. Bushberg (2002); S. Ebina (2012)