Abstract
The Fukushima Health Management Survey, conducted by Fukushima Prefecture since the 2011 Great East Japan Earthquake (GEJE), has not identified any health effects from radiation exposure. Complete blood counts (CBC), which are sensitive to radiation exposure, have not shown lymphocytopenia, neutropenia, anemia, or thrombocytopenia, but the white blood cell fractions have not yet been analyzed since 2011. We classified 25,885 residents (11,383 male, 14,502 female;age range, 16-84 years) in evacuation areas with external exposure dose estimates based on behavioral surveys conducted 4 months after the GEJE into two groups (0-1 [≥0 and <1] and ≥1 mSv) and analyzed changes in CBC and leukocyte fractions from fiscal year (FY) 2011 to FY2017 and their influencing factors. Compared with FY2011, no significant increase in the number of residents with leukopenia was seen, but the rate of male residents with anemia increased through 2017, regardless of the radiation exposure dose, but factors contributing to the development of anemia were more critical in males. No links were found between the development of anemia and smoking, evacuation, or heavy alcohol drinking, whereas significant associations were found with thinness and older age. These findings suggest that malnutrition is a cause of anemia, especially in males.
Introduction
To investigate the effects of radiation from the nuclear power plant accident resulting from the 2011 Great East Japan Earthquake (GEJE), Fukushima Prefecture is estimating external radiation doses based on a behavioral survey of all prefectural residents for 4 months after the GEJE1,2). The response rate as of March 31, 2020 was about 28%3,4), but the analysis of 466,367 residents excluding radiation workers and those with movement records covering less than 4 months from 26.4% (541,653/2,055,533) of eligible residents as of June 30, 2014, found that the effective radiation dose due to external exposure (EDEE) of 93.8% of the residents was less than 2 mSv, while that of 99.8% was less than 5 mSv3,4). Furthermore, the mean, median, and maximum exposure doses were 0.8 mSv, 0.6 mSv, and 25 mSv, respectively3,4).
On the other hand, we previously examined the results of the Comprehensive Health Check (CHC) from the Fukushima Health Management Survey (FHMS), which was conducted on residents of 13 municipalities who were mandated to evacuate by the government because of the GEJE and the resultant accident at the Fukushima Daiichi Nuclear Power Plant1,5). Our examinations of the residents demonstrated that evacuation is a risk factor for obesity6), hypertension7,8), diabetes mellitus9,10), hypo-high-density lipoprotein cholesterolemia11), metabolic syndrome12), kidney disease13), liver dysfunction14), polycythemia15,16), and hyperuricemia17,18). Furthermore, no differences in white blood cell counts (WBC;neutrophil and lymphocyte counts) within 1 year after the GEJE were observed by evacuation area19).
Although the number of residents analyzed for EDEE represented only about a quarter of the eligible number of residents of Fukushima Prefecture, the relationship between the EDEE and the results of health checks was analyzed for residents for whom both types of data were available. For residents with incomplete results from the movement survey for 4 months after the GEJE, we supplemented their EDEE data with similar evacuation movements using multiple imputation. Consequently, no external radiation dose effect was found in the results of health checkups from 2011 to 2017 using the results from 2011 as a baseline20). An analysis of peripheral blood cell counts, i.e., complete blood count (CBC), which are particularly sensitive to radiation exposure21), showed no relationship between the EDEE and anemia, neutropenia, lymphopenia, or thrombocytopenia20).
As expected from the low EDEE, CBC was not affected by radiation exposure, but the relationship between the EDEE and leukocyte fractions has not yet been analyzed;therefore, we would like to reveal that the leukocyte fractions are also not affected by radiation exposure.
Subjects and methods
Study Population and Design
The participants of the present study were nearly 210,000 residents of all ages living in the following communities near the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture: Tamura, Minami-Soma, Kawamata, Hirono, Naraha, Tomioka, Kawauchi, Okuma, Futaba, Namie, Katsurao, Iitate, and Date. All of the residents of Hirono, Naraha, Tomioka, Kawauchi, Okuma, Futaba, Namie, Katsurao, and Iitate, and some of the residents of Tamura, Minami-Soma, Kawamata, and Date were forced to evacuate their homes after the disaster because of a governmental order (Figure 1). The detailed methods of the CHC have been reported elsewhere1-3). The study participants received (1) annual health check-ups with additional items in specified health check-ups conducted by each municipality, (2) annual group health check-ups conducted by Fukushima Medical University, or (3) individual health check-ups at designated medical institutions within and outside of Fukushima Prefecture.
Follow-up medical examinations were conducted annually from fiscal year (FY) 2012 through FY2017 as a part of the CHC. Because the evacuees have moved to all over the country, the follow-up medical examination was conducted by the designated medical institutions nationwide if the evacuees were living outside the prefecture.
The number of medical examinees in FY2011 was 72,867 (31,982 men;40,885 women). We excluded participants who had missing for outcome for each analysis at FY2011 CHC as baseline. Examinees who were <16 or ≥85 years of age as of of the physical examination, or who had deficient or total leukocyte fractions of less than 99% and more than 101%, or incomplete data for leukocyte fractions, or had incomplete EDEE, were excluded from the study. In addition, in regard to hematological disease analyses, participants with a history of anemia at baseline or and chronic renal failure at each CHC were also excluded. Therefore, the total number of participants for the baseline analysis was 25,885 (11,383 male;14,502 female;Figure 2).
This epidemiological study was approved by community representatives and conducted according to the guidelines of the Council for International Organizations of Medical Science, as well as the Ethics Committee of Fukushima Medical University (No. 1319).
Estimation of EDEE
The Basic Survey is conducted to estimate EDEE for individuals who were registered residents of Fukushima Prefecture from March 11 to July 1, 2011. Details of the Basic Survey are given elsewhere3). Briefly, as we reported previously20), the Basic Survey is a self-administered questionnaire that asks residents to record and send back information on their behavior (including time spent indoors and outdoors and the timing of any moves) in the first 4 months after the GEJE, which occurred on March 11, 2011. The respondents’ behavior records were then digitalized, and individual EDEEs were calculated by superimposing the behavior records with daily ambient dose rate maps using a computer program. The dose rate maps were based on available measurement data and created as a 2 km × 2 km mesh. The dose rate was assumed to be uniform within each mesh area. Considering the above method, the calculation of the EDEE is considered to involve some amount of uncertainties related to the dose rate maps, as well as the residents’ memories about their behaviors. Because the Basic Survey is regarded as the only method available for estimating individual external doses at an early stage after the GEJE, it is difficult to check the accuracy of EDEE by comparing it with that estimated by another method. However, municipality-averaged doses estimated from the Basic Survey results were in reasonable agreement with personal dosimeter measurements4).
Measurements and Definitions
In the CHC, the standard values for peripheral blood were as follows:in males, a red blood cell (RBC) count of 400-579 × 104/µL, hemoglobin (Hb) level of 13.1-17.9 g/dL, and hematocrit (Ht) level of 38.0%-54.9%;and in females, an RBC of 370-549 × 104/µL, Hb level of 12.1-15.9 g/dL, and Ht level of 33.0%-47.9%. Polycythemia was diagnosed if any one of these items was greater than the standard value. In the CHC, the definition of anemia is an Hb level of ≤13.1 g/dL in males and ≤12.1 g/dL in females. Thrombocytopenia was defined as a platelet count (PLT) <15 × 104/µL. Leukocytopenia was defined as a WBC count <3,000/µL. Leukocyte fractions were analyzed automatically by the instrument. Height in stocking feet and weight in light clothing were measured. Body mass index (BMI) was calculated as the weight (kg) / height (m)2, and obesity and thinness were defined as a BMI ≥25 kg/m2 and ≤18.5 kg/m2, respectively. We obtained histories for cigarette smoking and weekly alcohol intake in “go” units, which is a traditional Japanese unit of volume corresponding to 20 g of ethanol, which was subsequently converted to grams per day. Participants who consumed ≥40 g of ethanol per day were classified as heavy drinkers. Evacuees were defined as residents who lived in evacuation zones in the above-mentioned 13 municipalities, as reported previously (Figure 1)20). Age was divided into four groups:16-19, 20-39, 40-59, and ≥59 years, with those aged ≥65 years considered to be older adults.
Statistical Analysis
All statistical analyses were conducted using SAS version 9.4 (SAS Institute, Cary, NC). A comparison of means for age, WBC and their fractions (neutrophils, lymphocytes, eosinophils, monocytes, and basophils), RBC, Hb, Ht, and PLT counts was performed using one-way analysis of variance (ANOVA;Dunnett’s test) for each result in FY2012 through FY2017 with those of FY2011 as a baseline in two separate EDEE by gender classified into the following two groups:0-1 (≥0 and <1) and ≥1 mSv. In addition, we compared the frequencies of anemia, polycythemia, and leukopenia in FY2012 through FY2017 using a generalized linear model, with those of FY2011 as a control. Furthermore, within the two EDEE groups by gender, the above blood cell counts were performed using ANOVA (Dunnett’s test) for older adults (age ≥65 years) and the following factors:smoking, heavy drinking, evacuation, obesity, and thinness. The incidence of anemia was then compared between genders, age groups, older adults, smoking, heavy drinking, evacuation, obesity, and thinness in each year from FY2011 to FY2017 in the two EDEE groups. Consequently, univariate and multivariate logistic regression analyses were performed on the relationship between those factors and the presence of anemia, and then odds ratios (ORs) were calculated. To identify trends in mean blood test results over time, regression analysis was conducted by sex and the EDEE, with FY of the CHC as the explanatory variable and mean blood test results as the objective variable. All tests were two-tailed, and p-values <0.05 were considered to indicate statistical significance.
Results
The purpose of the present study was to investigate changes in WBC counts and their fractions after the GEJE, while simultaneously analyzing changes in RBC and PLT counts. In a previous report on the relationship between the results of health checkups and EDEE20), the number of subjects was larger than that in the present analysis because the previous analysis included residents who had no movement records for the 4 months after the GEJE. Therefore, in the present study, the participants were divided into two groups, 0-1 mSv and ≥1 mSv, because the number of subjects with an EDEE ≥2 mSv would be smaller if they were divided into three groups, as in the previous analysis20):<1 mSv, 1-2 mSv, and ≥2 mSv.
The number of male subjects in FY2011 was 6,064 for <1 mSv and 3,964 for ≥1 mSv. The number of female subjects was 8,160 for the former and 4,226 for the latter. The reason why the number of subjects analyzed for the PLT count was lower than that for the other items was that some municipalities did not include this item in the complete blood count (CBC). WBC counts and their fractions (neutrophil, lymphocyte, eosinophil, basophil, and monocyte), as well as RBC, Hb, Ht, and PLT counts from FY2011 to FY2017 are shown in Table 1A-D, and their changes are shown in Figure 3 A-D. Both EDEE groups, 0-1 mSv and ≥1 mSv, showed similar changes between years, although many showed significant differences in the CBC for each year compared with 2011 (Table 1A-D). Basophil counts in both males and females increased from FY2011 to FY2012, but the cause of this increase is unknown.
Of note, both groups of males with an EDEE of 0-1 mSv or ≥1 mSv showed an increase in the incidence of anemia each year through FY2017 compared with FY2011 (Table 1A and 1B). On the contrary, the rate of residents with polycythemia, which was found to increase among evacuees in previous reports15,16), showed a decreasing trend in the group with an EDEE of 0-1 mSv (Table 1A), but no significant change in the group with an EDEE of ≥1 mSv (Table 1B). No significant changes in the rate of residents with leukopenia were found, except for the group with an EDEE of ≥1 mSv in FY2015 and FY2016 (Table 1A and 1B). As for females, the rate of residents with anemia increased in both EDEE groups (0-1 mSv and ≥1 mSv;Table 1C and 1D), except for a decrease in FY2014 (Table 1D). No significant change in the rate of residents with polycythemia or leukopenia were seen in either EDEE group from FY2011 to FY2017 (Table 1C and 1D).
Therefore, the CBC examinations from FY2011 to FY2017 indicated an increase in the rate of residents with anemia in both genders for both EDEE groups.
In addition to the EDEE, the effects of age, smoking, heavy drinking, evacuation, obesity, and thinness on CBC and leukocyte fractions were analyzed in the two EDEE groups. Age was analyzed based on the criteria for older adults, i.e., <65 and ≥65 years (Supplementary table 1A-D). We further compared the mean values of CBC and leukocyte fractions in the two EDEE groups from FY2011 to FY2017 and found no significant differences (Supplementary table 2A, 2B, and 2C).
Next, because the rate of residents with anemia has generally increased since FY2011, we analyzed the relationship between anemia and the factors assumed to be responsible for this increase (gender, age, obesity, thinness, evacuation, smoking, heavy drinking, and EDEE) (Table 2). The rate of female residents with anemia has been notably higher since 2011, but no upward trend in this rate has been observed. In contrast, the rate of male residents with anemia has increased since 2012. A comparison of the four age groups (16-19, 20-39, 40-59, and 60-84 years) indicated that the rate of residents with anemia, especially those aged 60-84 years, increased annually. Furthermore, when comparing residents aged ≥65 and <65 years, the rate of residents with anemia increased in the former group. Among residents with anemia, the rate of those with obesity was generally 20%-25%, the rate of those with thinness was generally around 10%, and the rate of evacuees was generally 50%-60%. Regarding the relationship between smoking and anemia, the number of smokers increased in FY2014, as did the rate of smokers among residents with anemia;however, both the number of smokers and the rate of residents with anemia decreased after FY2015. The rate of residents with anemia among heavy drinkers was generally 2%. In terms of the relationship between anemia and the EDEE, the lower dose group accounted for 65%-70% of the residents with anemia. These results indicate that anemia is more common among females and older adults. In addition, the rate of residents with anemia increased after FY2012 among males.
Next, univariate logistic regression analysis of the relationship between the above factors and anemia was performed to calculate ORs (Supplementary table 3). The factors related to the development of anemia from FY2011 to FY2017 were older age (≥65 years), female, and thinness. We then performed a multivariate logistic regression analysis of the relationship between the above factors and anemia to calculate ORs by gender (Table 3A and 3B). Thinness and older age were more common among females from FY2011 to FY2017 (Supplementary tables 3 and 4). Older age (≥65 years) and thinness were risk factors for anemia in both male and female, but this was especially true in male;no relationship was found between evacuation, smoking, heavy drinking, or the EDEE and the development of anemia. On the other hand, thinness and older age were more common among females from FY2011 to FY2017 (Supplementary tables 4 and 5).
In summary, no significant changes in leukocyte fractions were found in residents of the evacuated areas from FY2011 to FY2017, and anemia was more common in females who were older and thinner. However, older age and thinness had a stronger effect on anemia in male than in female.
Discussions
The results of the present study indicated no significant increase in the number of residents with leukopenia and no significant change in leukocyte fractions until FY2017 compared with FY2011 for both males and females, which was expected, given that the EDEE was not related to neutropenia and lymphopenia in a previous report20).
It is noteworthy that in the present study, the rate of residents with anemia increased through FY2017 compared with FY2011, especially among males, regardless of the EDEE. However, the main factor contributing to the development of anemia is female gender, possibly due to the higher rate of thinness and old age in females (Supplementary tables 4 and 5). It is also of interest that aging and smoking were not associated with the development of anemia. Furthermore, the fact that evacuation and heavy drinking did not contribute to the development of anemia was inferred from the increase in residents with obesity among the evacuees6), which suggests that sufficient amounts of food are consumed among heavy drinkers.
Therefore, considering that undernourishment usually leads to anemia, it is easy to assume that thinness contributes to the increased incidence of anemia. In a report by Yamamoto et al.22), residents with anemia increased in the year after the GEJE and then decreased in young adult females aged 20-45 years with a BMI <23 kg/m2 and no history of smoking or drinking. This is thought to be a temporary phenomenon due to the lack of sufficient food supplies for health-conscious young females with thinness in the immediate aftermath of the GEJE. On the other hand, the reason why the rate of residents with anemia showed a decreasing trend from FY2013 to FY2018 is thought to be the extremely low health checkup rate in the CHC, especially in the younger generation, who were mostly male, smokers, or residents with anemia after FY2012, leading to the possibility of overlooking unhealthy populations23). Furthermore, a study on the relationship between lifestyle and malnutrition in older residents reported that non-evacuees, residents with no exercise habits, and residents with poor physical activity levels were more likely to become malnourished after the GEJE24). Therefore, the significant relationship identified between old age or thinness and anemia might be due to malnutrition accompanied by decreased physical activity levels. Nutritional deficiency, chronic inflammation or chronic renal disease, and unexplained anemia each accounted for one-third of the causes of anemia in persons 65 years and older analyzed in the United States25). It is interesting to note that there is a fairly large prevalence of anemia with unknown causes in the elderly.
Because females in Japan have a longer life expectancy than males26), the number of female participants in the CHC was also higher. Therefore, if there were more older females, the rate of those who were less active and ate less would increase; this could have led to the increased rate of residents with anemia.
The results of this study must be considered in light of some limitations. First, in the CHC, the participation rate among residents was relatively low (30%);thus, the results might not be representative of the general population. Second, the data set used in this study could not be linked to data from before the GEJE. Therefore, the baseline data could not be compared with those before the GEJE. This situation might be a natural consequence of longevity and not a major social problem.
Finally, although no health problems have been recognized as direct effects of radiation exposure following the nuclear power plant accident, more than 10 years have passed since the GEJE, and the rate of health checkups has declined further, which suggests that health checkup strategies need to be reconsidered.
Acknowledgments
We would like to thank the staff of the Fukushima Health Management Survey for their cooperation. The findings and conclusions of this article are the sole responsibility of the authors and do not represent the official views of the Fukushima Prefectural Government. This survey was supported by the National Health Fund for Children and Adults Affected by the Nuclear Incident.
Conflict of interest
The authors declare that they have no competing interests.
Author contributions
AS, HN, and HK designed the study and contributed to writing the manuscript. HN collected the data and performed the statistical analysis. KO, MS, TO, TI, MT, MH, AT, JJK, SH, KW, GK, HS, HT, FH, and MN contributed to the planning of the health screening program. HO and SY contributed to the scientific review. All authors read and approved the final manuscript.
References
- 1. Yasumura S, Hosoya M, Yamashita S, et al. for the Fukushima Health Management Survey Group. Study protocol for the Fukushima Health Management Survey. J Epidemiol, 22:375-383, 2012.
- 2. Yasumura S, Ohto H, Kamiya K. Updated study protocol and achievements of the Fukushima Health Management Survey. J Epidemiol, supp, 32:S3-S10, 2022.
- 3. Kamiya K, Ohto H, Yasumura S. Report of the Fukushima Health Management Survey 2011-2020. Radiation medical Science Center for the Fukushima Health Management Survey, Fukushima Medical University. Fukushima, 17-50, 2021.
- 4. Ishikawa T, Yasumura S, Akahane K, et al. External doses available for epidemiological studies related to the Fukushima Health Management Survey −First four-month individual doses and municipality-average doses for the first year−. J Epidemiol, supp, 32:S11-S22, 2022.
- 5. Kawasaki Y, Hosoya M, Yasumura S, et al. The Basic Data for residents aged 16 years or older who received a Comprehensive Health Check examinations in 2011-2012 as a part of the Fukushima Health Management Survey after the Great East Japan Earthquake. Fukushima J Med Sci, 60:159-169, 2014.
- 6. Ohira T, Hosoya M, Yasumura S, et al. Effect of evacuation on body weight after the Great East Japan Earthquake. Am J Prev Med, 50:553-560, 2016.
- 7. Ohira T, Hosoya M, Yasumura S, et al. Evacuation and risk of hypertension after the Great East Japan Earthquake:The Fukushima Health Management Survey. Hypertension, 68:558-564, 2016.
- 8. Nagai M, Ohira T, Takahashi H, et al. Impact of evacuation on trends in the prevalence, treatment, and control of hypertension before and after a disaster. J Hypertension, 36(4):924-932, 2018.
- 9. Satoh H, Ohira T, Hosoya M, et al. Evacuation after the Fukushima Daiichi Nuclear Power Plant accident is a cause of diabetes:Results from the Fukushima Health Management Survey. J Diabetes Res, 2015:627390, 2015.
- 10. Satoh H, Ohira T, Nagai M, et al. Evacuation is a risk factor for diabetes development among evacuees of the Great East Japan earthquake:A 4-year follow-up of the Fukushima Health Management Survey. Diabetes Metab, 45:312-315, 2019.
- 11. Satoh H, Ohira T, Nagai M, et al. Hypo-high-density lipoprotein cholesterolemia is caused by evacuation after the Fukushima Daiichi Nuclear Power Plant accident:Results from the Fukushima Health Management Survey. Intern Med, 55:1967-1976, 2016.
- 12. Hashimoto S, Nagai M, Ohira T, et al. Influence of post-disaster evacuation on incidence of metabolic syndrome:The Fukushima Health Management Survey. J Atheroscler Thromb, 24:327-337, 2017.
- 13. Hayashi Y, Nagai M, Ohira T, et al. The impact of evacuation on the incidence of chronic kidney disease after the Great East Japan Earthquake:The Fukushima Health Management Survey. Clin Exp Nephrol, 21:995-1002, 2017.
- 14. Takahashi A, Ohira T, Yasumura S, et al. Effect of evacuation on liver function after the Fukushima Daiichi Nuclear Power Plant accident. J Epidemiol, 27:180-185, 2017.
- 15. Sakai A, Ohira T, Hosoya M, et al. Life as an evacuee after the Fukushima Daiichi Nuclear Power Plant accident is a cause of polycythemia:The Fukushima Health Management Survey. BMC Public Health, 14:1318, 2014.
- 16. Sakai A, Nakano H, Ohira T, et al. Persistent prevalence of polycythemia among evacuees 4 years after the Great East Japan Earthquake:a follow-up study. Prev Med Rep, 5:251-256, 2017.
- 17. Hashimoto S, Nagai M, Ohira T, et al. Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima prefecture;the Fukushima Health Management Survey. Clin Exp Nephrol, 24:1025-1032, 2020.
- 18. Honda K, Okazaki K, Tanaka K, et al. Evacuation after the Great East Japan Earthquake is an independent factor associated with hyperuricemia:the Fukushima Health Management Survey. Nutr Metab Cardiovasc Dis, 31:1177-1188, 2021.
- 19. Sakai A, Ohira T, Hosoya M, et al. White blood cell count and its subpopulations in individuals in the evacuation zone designated by the government after the Fukushima Daiichi Nuclear Power Plant accident:The Fukushima Health Management Survey. J Epidemiology, 25:80-87, 2015.
- 20. Sakai A, Nagao M, Nakano H, et al. Effects of radiation exposure resulting from the nuclear accident at the Fukushima Daiichi Nuclear Power Plant on the health of residents in the evacuation zones in Fukushima prefecture:the Fukushima Health Management Survey. J Epidemiology, supp, 32:S84-S94, 2022.
- 21. ICRP, 1984. Non-stochastic effects of irradiation. ICRP Publication 41. Ann. ICRP 14(3).
- 22. Yamamoto K, Takita M, Kami M, et al. Changes in the proportion of anemia among young women after the Great East Japan Earthquake:The Fukushima Health Management Survey. Scientific Rep, 12:10805, 2022.
- 23. Yamamoto K, Takita M, Kami M, et al. Loss of participation among evacuees aged 20-37 years in the disaster cohort study after the Great East Japan Earthquake. Scientific Reports, 12:19600, 2022.
- 24. Okazaki K, Ohira T, Sakai A, et al. Lifestyle factors associated with undernutrition in older people after the Great East Japan Earthquake. A prospective study. International J Environmental Research and Public Health, 19:3399, 2022.
- 25. Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States:evidence for a high rate of unexplained anemia. Blood, 104:2263-2268, 2004.
- 26. World Health Oraganization. THE GLOBAL HEALTH OBSERVATORY, World Health Statistics, Life expectancy and life tables, Life expectancy at birth (years):https://www.who.int/data/gho/data/indicators/indicator-details/GHO/life-expectancy-at-birth-(years) (in Japanese).
