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Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki (1956)

Chapter: THE COMPARABILITY OF IRRADIATION SUBCLASSES

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Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
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Page 53
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 54
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 55
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 56
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 57
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 58
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 59
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 60
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 61
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 62
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 63
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 64
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 65
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 66
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 67
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 68
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 69
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 70
Suggested Citation:"THE COMPARABILITY OF IRRADIATION SUBCLASSES." National Research Council. 1956. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. Washington, DC: The National Academies Press. doi: 10.17226/18776.
×
Page 71

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Chapter V THE COMPARABILITY OF IRRADIATION SUBCLASSES THE infants examined in Hiroshima and Naga- saki during the course of this study may be apportioned among 25 subclasses on the basis of the radiation exposure categories of their fathers and mothers, as these categories were defined in the preceding chapter. The crux of our problem is a comparison of the characteris- tics of the infants comprising these subclasses. As has been emphasized several times already, all of the indicators of possible genetic damage utilized in this investigation may also be in- fluenced by a variety of other factors. It will be the purpose of this chapter to undertake a detailed comparison of the parents of the in- fants comprising these subclasses with respect to certain possible differences which might in- fluence the outcome of pregnancy. Of the many possible differences which could be explored, we shall restrict ourselves to those which in our opinion are most pertinent to the problem at hand and for which we have more nearly satis- factory data. In the comparisons which will be presented, usually no allowance has been made for the fact that because of repeated pregnancies the same couple may be represented more than once among the parentage of a subclass. The tests of significance that follow assume no duplicate registration and thus yield underestimates of the errors of differences. It might be pointed out that, in the main, we should underestimate variances in the parental population more than in the offspring population. 5.1 Consanguinity. — It is generally recog- nized that the offspring of consanguineous marriages more often exhibit the consequences of genetic homozygosity than do the offspring of non-consanguineous unions. To the extent that there is a recessive, incompletely recessive, or semi-dominant genetic component in the etiology of congenital defect, stillbirth, or neo- natal death, such homozygosity might be ex- pected to alter the frequency of these events sufficiently to obscure real irradiation differ- ences or to create spurious ones. The occurrence within the populations under study of a non- random distribution of consanguineous mar- riages thus might introduce a source of bias into the findings. This, then, was the theoretical consideration which led to the inclusion of an item in the Genetics Short Form regarding parental consanguinity. The problem seemed of special importance because of the relatively high frequency of consanguineous unions in Japan (Neel, Kodani, Brewer, and Anderson, 1949). In Tables 5.1 and 5.2 the present data are examined as regards a relationship between ex- posure subclass and the frequency of consan- guinity.1 Although all known degrees of con- sanguinity were recorded by the clerks, in the analysis attention has been restricted to mar- riages of first cousins, first cousins once re- moved, and second cousins. A few uncle-niece unions, and some involving more remote de- grees of consanguinity than second cousin marriages, have been recorded during the study; all such unions have been excluded from these considerations because of the uncertainty regard- ing the exhaustiveness of the ascertainment. There is significantly more consanguineous marriage in Nagasaki than in Hiroshima, this presumably a reflection of social and cultural differences between the two localities. Moreover, within the cities there is heterogeneity among exposure subclasses. In general this consists in less consanguineous marriage among the "ex- posed" (categories 2, 3, 4, 5) than among the 1 The differing forms utilized in the presentation of the results of the analysis of the various tables will be evident following the reading of Chapter VI. 53

54 Chapter V Genetic Effects of Atomic Bombs TABLE S.I CONSANGUINITY (FIRST COUSIN, FIRST COUSIN ONCE REMOVED, SECOND COUSIN) BY CITY AND PARENTAL EXPOSURE Hiroshima Fathers ' 1 2 3 4-5 Total f fn 18,723 1,611 648 422 21,404 Mr IP 1,242 97 42 23 1,404 .0663 .0602 .0648 .0545 .0656 [n 5,721 1,993 416 264 8,394 2V [p 311 117 27 16 471 .0544 .0587 .0649 .0606 .0561 a (n 2,320 451 545 161 3.477 u .£. 3 r IP 97 23 16 4 140 £ .0418 .0510 .0294 .0248 .0403 fn 1,208 217 116 127 1,668 4-5^ r U 77 9 6 6 98 .0637 .0415 .0517 .0472 .0588 f n 27,972 4,272 1,725 974 34,943 TotaU r 1,727 246 91 49 2,113 IP .0617 .0576 .0528 .0503 .0605 Nagasaki Fathers • 1 2 3 4-5 Total f fn 16,338 2,420 258 149 19,165 Mr IP 1,541 211 13 8 1,773 .0943 .0872 .0504 .0537 .0925 h 10,141 4,483 301 188 15,113 2ir U 683 293 22 10 1,008 .0674 .0654 .0731 .0532 .0667 a fn 823 298 109 39 1,269 jj 3 r U 69 14 7 4 94 i .0838 .0470 .0642 .1026 .0741 4-5Jr (n .596 129 35 30 790 U 33 10 — 2 45 .0554 .0775 — .0667 .0570 1 n 27,898 7,330 703 406 36,337 TotaU r 2,326 528 42 24 2,920 Ip .0834 .0720 .0597 .0591 .0804 ' In this and subsequent tables, the term "Fathers" will be used as an abbreviation for Father's Exposure Category, and the term "Mothers" similarly.

The Comparability of Irradiation Subclasses 55 unexposed (category 1), although the tendency is statistically significant only with respect to the mothers. There is also a significant city- mother interaction. Category 1 contains a high proportion of persons who did not legally re- side in either of the two cities at the time of the bombings. It may be surmised that a sub- stantial proportion of these persons have rural antecedents; the frequency of consanguinity is known to be higher in rural communities (Neel etal.,1949). ables, parental age 2 and parity,3 and most of the indicators of possible genetic damage herein studied is attested to by a voluminous literature (e.g., Ciocco, 1938; Yerushalmy, 1938; Pen- rose, 1939; Murphy, 1947; Landtman, 1948; Record and McKeown, 1949; Sutherland, 1949; Carter, 1950; Lowe and McKeown, 1950; Worcester, Stevenson, and Rice, 1950; Heg- nauer, 1951; Karn and Penrose, 1951; Novitski, 1953; Salber and Bradshaw, 1953; MacMahon and Gordon, 1953; Myers, 1954). Our own TABLE 52 CHI-SQUARE ANALYSIS OF THE FREQUENCY OF CONSANGUINEOUS MARRIAGES BY CITY AND PARENTAL EXPOSURE Source DF Total 31 261.453 Interactions, first order CM 3 16.913 CF 3 1.610 MF 9 6.317 Main Effects City" Mother's exposure — 1 1 101.499 Mother's exposure — 2 1 10.257 Mother's exposure — 3 1 22.672 Mother's exposure — 4, 5 1 0.031 Mother" Hiroshima (H) 3 37.775 Nagasaki (N) 3 83.002 Father ° (H) Mother's exposure — 1 3 1.783 Mother's exposure — 2 3 1.292 Mother's exposure— 3 3 4.156 Mother's exposure — 4, 5 3 2.123 (N) Mother's exposure — 1 3 9.581 Mother's exposure — 2 3 0.947 Mother's exposure — 3 3 4.950 Mother's exposure — 4, 5 3 3.210 Sum 24 28.042 • Adjusted for mothers. (The meaning of the term "adjusted" is explained in Sec. 6.5.) b Adjusted for cities. * Adjusted for cities and mothers. ^ < .001 <.001 .50-.70 .70-.80 <.001 .001-.01 <.001 .80-.90 <.001 <.001 .20-.30 In Nagasaki, the bomb was detonated over that area of the city in which there was'the high- est concentration of Christians; Schull (1953) has shown that there is less consanguineous mar- riage among Christian (Catholic) Japanese in Nagasaki than among non-Christians. Thus, it may be surmised that among the non-Christian Japanese, the differences in frequency of con- sanguineous unions between Hiroshima and Nagasaki are even more striking than shown in Table 5.1. 5.2 Age and parity. — A probable or cer- tain relationship between the correlated vari- analysis of these relationships in the present data will be published elsewhere. Suffice it to say at this point that significant associations can be readily demonstrated. The findings in these data with respect to mean maternal age and parity differences among the mothers of the children falling into the subclasses are shown in Tables 5.3 various 2 The terms "parental age," "maternal age," or "paternal age" as here used refer simply to age of parent(s) at birth of child. •The term "parity" refers simply to total number of conceptions, including the present.

56 Chapter V Genetic Effects of Atomic Bombs TABLE S3 MEAN MATERNAL AGE BY CITY AND PARENTAL EXPOSURE (Based on unrelated parents only) Hiroshima Fathers 1 2 3 4 5 Total .fn 17,481 \x 27.0469 1,514 27.3250 606 136 263 20,000 27.1013 27.5165 27.4853 28.2700 2/n 5,410 \x 26.8366 1,876 30.1311 389 108 28.0926 140 7,923 27.7883 29.2956 28.7500 ,fn 2,223 '\x 26.9523 428 29.1402 529 30.9981 81 30.0123 76 29.0395 3.337 27.9961 Mothers 4/n 388 \x 27.7861 88 45 29.6667 24 31.1667 19 29.6842 564 28.2340 28.3636 fn 743 120 29.3667 65 26 28.5385 52 31.4808 1,006 27.7972 '\x 27.1252 29.3385 ~ . ./n 26,245 7°talix 27.0087 4,026 28.9091 1,634 29.1989 375 28.5147 550 32,830 27.3988 Nagasaki Fathers 28.8509 1 2 3 4 5 Total .fn 14,797 \x 28.5427 2,209 29.1421 245 29.5265 41 100 30.2800 17,392 28.6425 28.4878 -fn 9,458 \x 27.6087 4,190 30.8477 279 30.3118 51 30.1176 127 29.8976 14,105 28.6540 ,/n 754 \x 27.6578 284 29.8415 102 12 31.5833 23 30.6522 1,175 28.6204 | 31.5294 i 4/n 105 lx 29.9333 35 30.4857 14 34.6429 4 32.0000 3 161 34.6667 30.6025 ,fn 458 \x 26.7445 84 28.4762 21 29.1905 1 20 29.4000 584 27.1490 13.0000 Ml 285i447 6,802 30.2207 661 30.2648 109 29.5780 273 33,417 28.6299 30.1172

The Comparability of Irradiation Subclasses 57 through 5.8. It will be noted that the compari- son is restricted to unrelated parents. In the fol- lowing chapter we shall advance reasons for excluding children born to related parents from the analysis. Because of the potential great im- portance of age-parity differences in this analy- 2, 3, 4, or 5) than when non-exposed (cate- gory 1). This appears to be true with reference to fathers' but not mothers' exposure in Naga- saki. An obvious explanation of the findings with regard to the relation between paternal ex- posure and mean maternal age is the fact that TABLE 5.4 ANALYSIS OF VARIANCE: MOTHER'S AGE BY CITY AND PARENTAL EXPOSURE (Unrelated parents) (In this and subsequent tables, one asterisk will be used to denote a value significant at the 5 per cent level, and two asterisks, a value significant at the 1 per cent level.) Source Main effects City (C) Sums of squares of deviations DF 1 21,983321551 Father (F) 43 4oi 030323 4 Mother (M) 947 687594 4 Interactions First order CF 74.432938 4 CM 3,107.667017 4 MF 18,682.813301 16 Higher orders 871.870114 16 Between classes . . 94,513.849388 49 Within classes 1,751,484.087605 66 197 Mean square 21,983.3216 10,850.2576 236.9219 18.6082 776.9168 1,167.6758 54.4919 1,928.8541 26.4587 830.86** 410.08** 8.95** 1.42 29.36** 44.13** 2.06** 72.90** Total 1,845,997.936993 66,246 TABLE 5.5 THE DISTRIBUTION OF MEAN SQUARES FOR MATERNAL AGE BY CITY, SEX OF INFANT, AND PARENTAL EXPOSURE (Unrelated parents) (The sample numbers are the same as in Table 5.3. The form of the analysis Hiroshima Fathers Sex 1 22.160 2 27.336 24.205 3 29.653 29.271 4-5 25.529 23.310 , I o 1 O 21.628 '8 Kl 21.999 22.327 28.964 29.351 33.690 28.247 34.122 Mothers 40.519 24.216 23.381 29-592 29.429 32.618 31.245 25.009 36.640 ."{s 26.112 24.226 28.495 36.713 47.317 27.148 35.253 36.738 x! =121.021** DF = 15 y ' — 144.251** DF = 15 Xo — will be discussed in Chapter VI.) Nagasaki Fathers Sex 1 /(? 25.376 \? 25.822 2 36.213 3 40.472 32.491 4-5 38.920 32.455 33.257 fcf 28.335 z\8 26.361 37.926 38.289 43.489 42.377 31.397 40.381 Mothers , /<? 30.266 *\? 29.384 49.061 39.629 42.831 37.398 18.423 31.729 x./C? 27.956 \? 27.720 28.292 48.456 32.515 28.743 55.269 Xrff =222.236** Xo' =192.154** DF=15 DF=15 39.000 sis, it has seemed wise to anticipate this decision with respect to this tabulation. Not only do the cities differ but there is also significant heterogeneity within cities among exposure subclasses as regards both mean ma- ternal age and mean parity. In Hiroshima there is a clear tendency for maternal age to be greater when the mother or father is exposed (category the younger males tended to be in military service while the older males remained at home (and so were exposed), and mother's age is correlated with father's. Heterogeneity between the subclasses is also indicated by the fact that most of the interaction terms are also significant. No less variable than the mean maternal ages and parities are the mean squares (variance esti-

Genetic Effects of Atomic Bombs Chapter V TABLE 5.6 MEAN PARITY BY CITY AND PARENTAL EXPOSURE (Based on unrelated parents only) Hiroshima Fathers 1 2 3 4 5 Total r j fn 17,481 1,514 606 136 263 20,000 lx 2.4228 2.4108 2.3762 2.3676 2.4677 2.4207 2 /" 5.410 1,876 389 108 140 7,923 2 ix 2.4222 3.6151 3.2339 2.7963 2.9429 2.7588 3 {" lx 2,223 2.4368 428 529 81 3.9136 76 3.3158 3,337 E 3.2897 3.9187 2.8370 -s •< 4 /" ix 388 88 45 24 19 564 S 2.6031 3.2273 3.4889 3.8750 3.3684 2.8511 ?{x 743 120 3.5333 65 26 3.4231 52 1,006 2.6680 2.4078 3.0615 3.5192 Total/ " I'x 26,245 2.4261 4,026 3.1167 1,634 3.1377 375 550 2.8364 32,830 2.5596 Nagasaki Fathers 2.9947 1 2 3 4 5 Total f , fn 14,797 2,209 245 41 100 17,392 ' lx 2.9008 3.0946 3.1551 2.4878 3-1500 2.9295 , fn 9,458 4,190 279 51 127 14,105 2 ix 2.7294 3.9754 3.6810 3.2941 3.6457 3.1287 3 {.» lx 754 2.8594 284 3.7254 102 12 5.0000 23 1,175 3.2060 a 4.0000 3.6957 i fn 105 35 14 4 3 161 a ix 3.4762 3.8000 5.3571 4.7500 6.3333 3.7950 . fn 458 84 21 1 20 584 5 ix 2.6201 3.1667 3.6190 1.0000 3.7500 2.7705 Total/" lx 25,572 2.8335 6,802 3.6680 661 3.5688 109 3.2110 273 3.5055 33,417 3.0247

The Comparability of Irradiation Subclasses 59 mates) for these two variables.* From Tables 5.5 and 5.8 we note a significant heterogeneity among exposure classes, within each sex and city, in the variance estimates. It can also be shown that the variance estimates differ signifi- cantly between cities. In general, the variance in post-war Japan, those persons closer in having suffered in material ways to a greater extent than those farther out. Economic status appears to be related to some of the indicators of radiation effect here under consideration, notably still- birth frequency, birthweight, and neonatal TABLE 5.7 ANALYSIS OF VARIANCE: PARITY BY QTY AND PARENTAL EXPOSURE (Unrelated parents) Sums of squares Source of deviations DF Mean square F Main effects City (C) 1,663.729494 1 1,663.7295 531.52** Father (F) 6,053.779421 4 1,513.4449 483.51** Mother (M) 852.862735 4 213.2157 68.12** Interactions First order CF 181.504471 4 45.3761 14.50** CM 62.510339 4 15.6276 4.99** MF 2,637.923744 16 164.8702 52.67** Higher orders 77.508327 16 4.8443 1.55 Between classes 13,593.325165 49 2,774.1480 886.27** Within classes 207,206.531342 66,197 3.1302 — 66,246 Total 220,799.856507 TABLE 5.8 THE DISTRIBUTION OF MEAN SQUARES FOR PARITY BY CITY, SEX OF INFANT, AND PARENTAL EXPOSURE (Unrelated parents) (The sample numbers are the same as in Table 5.6.) Hiroshima Fathers Set 1 2 3 4-5 '{1 2.255 2.076 2.156 2.311 2.360 1.691 2.067 2.217 Kf 2.242 2.232 3.438 3.840 4.023 3.659 2.286 2.729 rt 2.361 2.134 3.610 3.274 4.460 3.785 4.286 4.251 "{I 2.239 2.206 4.171 4.526 4.999 3.884 5.328 3.441 xj: = 281.717** DF=15 X ' = 324.417** DF=15 Sex Nagasaki -Jo i 0 2.867 2.899 *y \ O s O 3.022 2.795 Kl 3.059 3.624 •>{? 3.258 3.434 *; = 337.847** Fathers 4.111 4.036 4.933 5.183 4.849 4.647 2.967 4.878 4-5 = 397.544** 4.717 3.297 3.266 2.328 4.652 4.284 3.984 3.992 4.306 4.474 5.862 3.350 4.434 4.529 6.495 5.359 DF= 15 DF=15 estimates increase with increasing conjoint parental exposure. 5.3 Economic status.—On a priori grounds it seemed quite possible that there might be a correlation between distance from the hypocenter at the time of the explosion and economic status * The effect of heterogeneity of the variances on the tests given in Tables 5.5 and 5.7 will be discussed in Section 6.6. death (e.g., Ebbs et al., 1942a,b; Balfour, 1944; Antonov, 1947; Smith, 1947; Burke et al., 1949; Dean, 1950; Nixon, 1950). It therefore seemed advisable to make some at- tempt to evaluate this possibility. The economic status of the home into which the child was born was estimated for all preg- nancies terminating abnormally, as well as every pregnancy whose registration number ended in

60 Chapter V Genetic Effects of Atomic Bombs TABLE 5.9 ECONOMIC STATUS BY CITY AND PARENTAL EXPOSURE (The figure given for economic status is proportion of homes falling into the "poor" and "very poor" categories.) Hiroshima Fathers 1 2 3 4-5 Total [n 1,770 143 65 46 2,024 Mr 144 4 6 — 154 IP .0814 .0280 .0923 — .0761 fn 569 171 47 28 815 21r 49 24 4 2 79 IP .0861 .1404 .0851 .0714 .0969 12 |n 218 26 56 19 319 £. 31r 14 5 6 1 26 o IP .0642 .1923 .1071 .0526 .0815 I" 103 21 10 11 145 4-5-^ r IP 9 1 1 1 12 .0874 .0476 .1000 .0909 .0828 In 2,660 361 178 104 3,303 TotaH r 216 34 17 4 271 I IP .0812 .0942 .0955 .0385 .0820 Nagasaki Fathers 1 2 3 4-5 Total r in 1,459 227 27 14 1,727 Hr 226 33 8 — 267 IP .1549 .1454 .2963 — .1546 fn 894 387 33 14 1,328 2V 125 74 5 1 205 IP .1398 .1912 .1515 .0714 .1544 e I" 61 29 10 6 106 u Hr 7 5 2 2 16 i IP .1148 .1724 .2000 .3333 .1509 (n 56 12 4 3 75 4-5^ r IP 9 2 1 — 12 .1607 .1667 .2500 — .1600 (n 2,470 655 74 37 3,236 TotaK r IP 367 114 16 3 500 .1486 .1740 .2162 .0811 .1545

The Comparability of Irradiation Subclasses 61 zero, in connection with the use of the Genetics Long Form (Secs. 2.2 and 2.3). This evalua- tion was made according to a very rough scoring system admitting of five economic classifica- tions: very poor, poor, average, well-to-do, and rich. The evaluation was carried out by the Japanese physician at the time of the home visit. The physicians were instructed that it was ex- pected that most homes would be graded as average, i.e., that existing rather than pre-bomb- ing standards should serve as the yardstick of comparison. Inasmuch as in the course of time a physician employed in the program found himself in all sections of the city, it was felt that this crude system of rating would pick up any marked differences between exposure cate- gories. The findings are given in Tables 5.9 and 5.10. The data are presented in simplified form, in terms of proportion of all homes graded as "poor" or "very poor." In view of the subjective nature of the ratings, it is difficult to attach sig- nificance to the apparent difference between the two cities. There is no apparent relation between economic status and mother's exposure category, nor is there a relation between father's category and economic status. At first glance this observa- tion would seem to be counter to common sense, since it would seem obvious that persons close to the hypocenter would have suffered greater material losses than those more distant, losses •which would reflect themselves in economic level. However, the effect of the atomic bomb was but one of a number of sources of severe economic dislocation in post-war Hiroshima and Nagasaki. The obvious conclusion from the findings summarized in this section would be that these other causes of economic readjustment tended to complicate and even to nullify the effects of the bombs. 5.4 Frequency of positive serological test for syphilis.—In view of the well-known relation- ship between syphilis and stillbirth and neonatal death, a serological test for syphilis was carried out in the ABCC laboratories on each woman whose registration number terminated in "0," as well as for any woman whose pregnancy terminated abnormally. In about 3 per cent of the terminations no test was performed, usually because of the disinclination of the mother to submit to venipuncture. The tests used were the cardiolipin microflocculation and the Kline. Tables 5.11 and 5.12 present the findings. There is a significant difference between cities, but no indication of heterogeneity between parental exposure classes. 5.5 Frequency of induced abortions and of dilatation and carettage of the uterus (D and C). — During the post-war years, in an effort to control birth rates, the Japanese government relaxed the indications for legal "therapeutic" abortion. Exact figures on the frequency with which abortions were performed are impossible to obtain for a variety of reasons. However, be- cause of the possibility that the late complica- tions of uterine infection following an induced TABLE 5.10 CHI-SQUARE ANALYSIS OF THE DISTRIBUTION OF ECONOMIC STATUSES BY CITY AND PARENTAL EXPOSURE (Unrelated parents) Source Total DF 31 x1 P Interactions, first order CM 120.378 < 0.001 3 2.268 .50-70 CF 3 0 365 90-.95 MF 9 17 683 02-05 Main effects Cities (C) 1 82.529 < 0.001 Fathers (F)« Hiroshima 3 3.782 .20-.30 Nagasaki 3 6.262 .05-. 10 Sum 6 10 044 10- 20 Mothers (M)« Hiroshima 3 3 354 30- 50 Nagasaki 3 0 028 > 99 Sum 1 Adjusted for cities. 3.382 .70-.80 abortion might influence pregnancy termination, an attempt was made to obtain some informa- tion on this point through the use of the Genet- ics Short Form. Each registrant was questioned concerning the occurrence of abortions. The abortions which were reported were divided into two categories, depending on occurrence before or after the date of the atomic bombing, and further subdivided as to whether they were spontaneous or induced. The findings concern- ing induced abortions are shown in Tables 5.13 and 5.14. The figures refer to the proportion of women reporting one or more induced abor- tions. Each mother is scored only once, on the basis of the first registered pregnancy. Induced abortions are reported with a significantly greater frequency in Hiroshima than in Naga- saki and, in both cities, appear to be more

62 Chapter V Genetic Effects of Atomic Bombs TABLE 5.11 FREQUENCY OF POSITIVE SEROLOGY BY PARENTAL EXPOSURE, CITY, AND GROUP (Unrelated "zero" parents only) Hiroshima Fathers 1 2 3 4-5 Total fn 1,610 131 60 41 1,842 lit 61 3 5 2 71 [p .0379 .0229 .0833 .0488 .0385 fn 509 145 43 26 723 2-< r 12 10 4 2 28 [p .0236 .0690 .0930 .0769 .0387 a {n 197 25 51 18 291 jj. r 5 1 1 1 8 ^ p .0254 .0400 .0196 .0556 .0275 fn 84 18 9 11 122 4-5 jr 5 [p .0595 — .1111 1 .0909 1 .0574 7 — fn 2,400 319 163 96 2,978 TotaN r 83 [p .0346 .0439 14 .0675 11 .0625 6 .0383 114 Nagasaki Fathers 1 2 3 4-5 Total fn 1,401 214 26 14 1,655 14 I 70 11 4 — 85 [p .0500 .0514 .1538 — .0514 fn 853 363 32 11 1,259 2-jr 42 23 2 — 67 [p .0492 .0634 .0625 — .0532 | [n 62 3*U 11 [p .1774 25 10 6 11 .1068 103 fn 55 12 4 1 72 4-5^ r 3 [p .0545 — — — .0417 3 — — — ( n 2,371 614 72 32 3,089 TotaK r 126 Ip .0531 .0554 34 .0833 6 — .0537 166 —

The Comparability of Irradiation Subclasses common following the bombing than before. However, there is no apparent, consistent rela- tion to exposure history. Three of the interac- tion terms are significant. In view of the possibility that it might be easier to obtain a history of a "therapeutic" D and C than of an induced abortion, a question concerning D and C was included in the Ge- netics Long Form. The findings in those termi- nations where the registration number ended in "0" are shown in Tables 5.15 and 5.16. The figures refer to the proportion of women report- ing one or more D and C's, with no reference TABLE 5.12 CHI-SQUARE ANALYSIS OF THE FREQUENCY OF POSITIVE SEROLOGIES BY CITY AND PARENTAL EXPOSURE (Unrelated parents) Source Total Interactions, first order CM CF MF Main effects DF 31 3 3 9 X' 60.330 6.645 3.522 12.876 ^ P .001-.01 .05-.10 .30-.50 .10-.20 .001-.01 Fathers (F)' 3 6.469 .05-. 10 3 3.106 .30-.50 Sum 6 9.575 .10-.20 Mothers (M)" 3 2.136 .50-.70 Nagasaki 3 6.099 .10-.20 Sum 6 8.235 .20-.30 • Adjusted for cities. as to whether the event preceded or followed the bombings. There is a striking difference be- tween the cities, similar in direction to that re- ported with respect to induced abortions, but much greater in magnitude. However, no differ- ence with respect to exposure groups is apparent, nor are any of the interaction terms significant. 5.6 The frequency of repeat registrations. — Depending upon the number of pregnancies which she experienced during the period cov- ered by this study, a woman residing in Hiro- shima or Nagasaki could bear one, two, three, four or even more infants whose examination fell within the scope of the program. Table 5.17 summarizes the mean number of infants per mother in relation to the exposure categories of mother and father, by city. There is a tend- ency towards a higher average number of preg- nancies in Nagasaki than in Hiroshima. Fur- thermore, particularly with respect to mothers' exposure in Nagasaki, there is apparent a tend- ency for the more heavily irradiated mothers to have borne more children. 5.7 Parental cooperation. — If for any reason one group of parents was more cooperative than another in permitting an examination of their newborn child, herein lies a source of bias. Fortunately, parental cooperation was excellent throughout the course of this study. Refusals to permit the ABCC physician to examine a child were infrequent, so infrequent that no analysis of the phenomenon has been carried out. It should in this connection be pointed out that such refusals could influence only the data on malformation, since sex, birthweight, and the occurrence of stillbirth were reported by the midwife, and since, further, it would be im- practical to attempt to conceal a neonatal death. In Japan as in the United States, the birth of a malformed child tends to stigmatize the par- ents in the lay mind. In a country where mar- riages are still often arranged to a large extent by the families concerned, and where the koseki (census register) is freely consulted when a marriage is under consideration, there are at work social factors encouraging the concealment of congenital abnormality. In this connection, the possibility has to be recognized of subtle influences tending to make one of the groups under study more cooperative than another group. More specifically, one had to recognize the possibility that some of the "exposed" group, learning from the newspapers that con- genital abnormalities were a possible aftermath of exposure to an atomic bomb, would cooperate more completely than the controls, and thus introduce a bias. The chief opportunity for concealing major congenital defect lay in children who were still- born or died shortly following birth, and whose bodies were disposed of without being seen by an ABCC physician. As mentioned earlier (Sec. 2.5), an attempt was made to obtain autopsies on as many children who were stillborn or died during the neonatal period as possible. In 1950 and 1951, when the autopsy program was in full stride in Hiroshima, autopsies were obtained on approximately 50 per cent of all children who were stillborn or died during the neonatal period. Another 15 per cent of all children who were stillborn or died during the neonatal

64 Chapter V Genetic Effects of Atomic Bombs TABLE 5.13 FREQUENCY OF MOTHERS REPORTING ONE OR MORE INDUCED ABORTIONS BY PARENTAL EXPOSURE, CITY, AND TIME (Unrelated parents) Hiroshima — before Aug. 6, 1945 Fathers 1 2 3 4-5 Total r fn 4,738 310 115 79 5,242 H* 207 16 4 4 231 IP .0437 .0516 .0348 .0506 .0441 fn 1,037 902 137 78 2,154 2< r 42 28 6 1 77 IP .0405 .0310 .0438 .0128 .0357 fn 437 165 281 83 966 Ji - ' l r 19 3 6 1 29 1 IP .0435 .0182 .0214 .0120 .0300 fn 186 73 62 66 387 4-5-i r 2 7 4 — 13 IP .0108 .0959 .0645 — .0336 fn 6,398 1,450 595 306 8,749 TotaU r 270 54 20 6 350 IP .0422 .0372 .0336 .0196 .0400 Hiroshima — after Aug. 6, 1945 Fathers 1 2 3 4-5 Total r fn 10,599 799 426 223 12,047 1 J r 581 50 20 19 670 IP .0548 .0626 .0469 .0852 .0556 fn 2,860 402 128 85 3,475 21r 187 18 9 4 218 IP .0654 .0448 .0703 .0471 .0627 e J" 1,185 127 99 42 1,453 77 8 7 — 92 o IP .0650 .0630 .0707 _ .0633 s Jn 599 51 39 19 708 45 4 7 — 56 IP .0751 .0784 .1795 — .0791 fn 15,243 1,379 692 369 17,683 TotaU r IP 890 80 43 23 1,036 .0584 .0580 .0621 .0623 .0586

The Comparability of Irradiation Subclasses 65 TABLE 5.13—Continued Nagasaki — before Aug. 9, 1945 1 2 Fathers 3 4-5 Total f" 5,616 706 65 34 6,421 Mr 121 17 — — 138 IP .0215 .0241 — — .0215 fn 1,918 2,322 128 80 4,448 21r 27 27 3 1 58 IP .0141 .0116 .0234 .0125 .0130 e f- 171 120 58 29 378 J. Hr — 1 — 1 2 I IP — .0083 — .0345 .0053 *— • fn 87 48 21 10 166 4-5^r IP — — - — 1 1 — — — .1000 .0060 f" 7,792 3,196 272 153 11,413 TotaK i 148 45 3 3 199 1 IP Nagasaki — .0190 after Aug. .0141 9, 1945 .0110 .0196 .0174 1 2 Fathers 3 4-5 Total f " 7,953 1,073 129 85 9,240 Mr 182 23 2 — 207 IP .0229 .0214 .0155 — .0224 fn 4,692 1,028 90 55 5,865 21r 98 20 3 — 121 IP .0209 .0195 .0333 — .0206 8 (n 361 120 25 3 509 a Hr 4 4 — — 8 _C . IP 1 .0111 .0333 — — .0157 fn 291 56 13 8 368 4-5<r IP 5 1 — — 6 .0172 .0179 — — .0163 fn 13,297 2,277 257 151 15,982 TotaU r IP .0217 289 .0211 48 .0195 5 — .0214 342 —

66 Chapter V Genetic Effects of Atomic Bombs TABLE 5.14 CHI-SQUARE ANALYSIS OF THE FRE- QUENCY OF MOTHERS REPORTING ONE OR MORE INDUCED ABORTIONS BY PARENTAL EXPO- SURE, QTY, AND TIME (Unrelated parents) Source DP x' P Total 63 574.384 < .001 Interactions, first order CT 1 3.057 .05 -.10 TM 3 16.265 .001-.01 TF 3 3.725 .20 -.30 CM 3 10.087 .01 -.02 CF 3 2.616 .30 -.50 MF 9 30.308 < .001 Main effects Cities (C) Before bombing . . . 1 95.230 < .001 After bombing . . . 1 270.261 <.001 Sum 2 365.491 < .001 Time (T) Hiroshima (H) . . 1 40.677 < .001 Nagasaki (N) ... 1 5.401 .02 -.05 Sum 2 46.078 < .001 Mothers (M) (H) Before bomb- ing 3 6.191 .10 -.20 After bomb- ing 3 9.001 .02 -.05 (N) Before bomb- ing 3 15.700 .001-.01 After bomb- ing 3 0.459 .90 -.95 Fathers (F) (H) Before bomb- ing 3 5.039 .10 -.20 After bomb- ing 3 3.127 .30 -.50 (N) Before bomb- ing 3 3.898 .20 -.30 After bomb- ing 3 0.851 .80 -.90 Sum 12 12.915 30. -.50

The Comparability of Irradiation Subclasses 67 TABLE 5.15 FREQUENCY OF DILATATION AND CURETTAGE BY PARENTAL EXPOSURE AND CITY: ZERO TERMINATIONS Hiroshima Fathers ' 1 2 3 4-5 Total ' fn 1,770 143 65 46 2,024 li* 266 19 10 5 300 U .1503 .1329 .1538 .1087 .1482 fn 569 171 47 28 815 21r 75 16 5 6 102 IP .1318 .0936 .1064 .2143 .1252 fn 218 26 56 19 319 i IP 34 1 11 1 47 -. .1560 .0385 .1964 .0526 .1473 fn 103 21 10 11 145 4-5^r U 17 4 2 1 24 .1650 .1905 .2000 .0909 .1655 f" TotaN r 2,660 392 .1474 361 40 .1108 178 28 104 13 3,303 473 .1432 U Nagasaki .1573 .1250 Fathers 1 2 3 4-5 Total fn 1,459 227 27 14 1,727 1J r 25 3 1 — 29 IP .0171 .0132 .0370 — .0168 fn 894 387 33 14 1,328 24 i 12 12 1 1 26 IP .0134 .0310 .0303 .0714 .0196 g fn 61 29 10 6 106 jj _ ' i r — 1 1 — 2 I IP — .0345 .1000 — .0189 [" 56 12 4 3 75 IP — — — — — fn 2,470 655 74 37 3,236 Total \ r 37 16 3 1 57 IP .0150 .0244 .0405 .0270 .0176

68 Chapter V Genetic Effects of Atomic Bombs TABLE 5.16 CHI-SQUARE ANALYSIS OF THE FRE- QUENCY OF DILATATION AND CURETTAGE BY PARENTAL EXPOSURE AND CITY: ZERO TERMINATIONS (Unrelated parents) Source Total DP x' P Interactions, first order CM 31 372 060 < .001 . 3 3.099 .30-.50 CF . 3 7.426 .05-.10 MF . 9 10.799 .20-.30 Main effects Cities (C) . . . 1 346.140 < .001 Mothers (M)' Hiroshima 3 3.212 .30-.50 Nagasaki 3 1.718 .50-.70 Stun 6 4930 50-.70 Fathers (F)« Hiroshima , 3 4.034 .20-.30 Nagasaki , 3 5.185 .10-.20 Sum . 6 9.219 .10-.20 * Adjusted for cities. TABLE 5.17 MEAN NUMBER OF REGISTERED PREGNANCIES PER MOTHER BY PARENTAL EXPOSURE AND CITY Hiroshima 1 - Fathers 1 2 3 4-5 Total l/° 13,577 1,155 490 301 15,523 lx 1.288 1.311 1.237 1.326 1.288 fn 3,964 1,472 308 189 5,933 lx 1.365 1.274 1.263 1.312 1.335 12 3f n 1,653 318 420 121 2,512 « \x i• 1.345 1.346 1.260 1.298 1.328 3 4-5/n lx 821 1.378 156 1.333 82 1.341 99 1.222 1,158 1.356 Total/" lx 20,015 1.311 3,101 1.298 1,300 1.257 710 1.303 25,126 1.307 Nagasaki Fathers 1 2 3 4-5 Total f r{" lx 10,581 1.398 1,582 1.396 166 97 12,426 1.400 1.476 1.454 , fn 6,246 2,971 188 122 9,527 \x 1.514 1.410 1.484 1.459 1.481 g Cn 476 196 75 20 767 •£• o 3\x 1.632 1.449 1.360 1.750 1.532 4-5/n 345 1.632 81 24 1.458 21 1.333 471 1.582 lx 1.469 Total/" lx 17,648 1.449 4,830 1.408 453 1.459 260 1.469 23,191 1.441

The Comparability of Irradiation Subclasses 69 period were seen by a physician in the employ of the ABCC but did not come to autopsy. It follows that opportunities for the concealment of defect existed with respect to only 35 per cent of all stillbirths and neonatal deaths. In 1952 and 1953 the efficiency of the autopsy program increased, to the point where some 60-70 per cent of the possible material was being autop- sied, with a corresponding decrease in oppor- tunities for concealment. Tables 13.1 through 13.4 analyze the material coming to autopsy with reference to its randomness. It can be shown that there is no detectable bias as regards the exposure history of the parents. Since this autopsy material includes the majority of the stillbirths and neonatal deaths, it seems unlikely that there exists the possibility of a serious bias as regards parental exposure among the still- births and neonatal deaths who were not seen. If, for instance, unirradiated mothers of still- bom (malformed) children were especially prone to dispose of these infants without their coming to the attention of the ABCC, then, since approximately 10 per cent of stillborn children are malformed, this should depress the representation of unexposed mothers in the parents of the autopsy material; such a dispro- portion was not observed. On the other hand, the data are of course not sufficiently extensive to exclude small biases in this direction. In this connection, however, it must be borne in mind that all of the infants falling in this 25 per cent were seen by a Japanese midwife or obstetrician, which provides a partial safeguard against the concealment of defect, even though there were occasionally encountered striking shortcomings in midwife reporting. 5.8 Late sequelae of exposure to the bombs. — Reference has already been made (Sec. 4.1) to the occurrence among the parents of the in- fants under study of certain late sequelae of exposure to the atomic bombs. The best docu- mented of these late effects are cataracts (Cogan, Martin, and Kimura, 1949; Sinsky, 1955) and leukemia (Policy, Borges, and Yamawaki, 1952; Lange, Moloney, and Yamawaki, 1954; Moloney and Lange, 1954; Moloney and Kas- tenbaum, 1955). Refractory anemia may also be a delayed manifestation of radiation injury (Lange, Wright, Tomonaga, Kurasaki, Mat- suoke, and Matsunaga, 1955). These events occur with a frequency which cannot be ignored in a study of this type. Thus, the findings with respect to leukemia are given in Table 5.18. To date, the over-all frequency of this disease in individuals who at one time displayed one or more of the three radiation symptoms, epilation, petechiae, or gingivitis, is 0.5 per cent. While the occurrence of cataracts would not be expected to influence pregnancy outcome, there is little doubt that a disease with the systemic manifestations of leukemia has pro- found effects. Whether in addition to leukemia there are other serious sequelae which have so far escaped detection cannot be said. Fillmore (1952) was not able to detect any significant sequelae in a general medical examination of 78 persons who had received sufficient radiation at the time of the bombings to develop, later, radiation cataracts. On the other hand, Lorenz and his collaborators (1954) have demonstrated a shortened life span in a variety of animals exposed to chronic irradiation, associated with the development of such conditions as pancyto- penia and lymphoid, pulmonary, ovarian, and mammary tumors. Whether there are compar- able effects in man is not yet known. Whereas techniques exist for coping with the age-parity and consanguinity differences be- tween the groups of parents with whom we are concerned, it is much more difficult in any plan of analysis to make allowance for the somatic effects of irradiation which might influence the outcome of a pregnancy. These somatic effects should be exerted largely through the mother. Thus, "effects" apparently consequent upon maternal radiation which are not confirmed by a corresponding analysis with regard to pa- ternal radiation history must be viewed with reservations. 5.9 The changing proportion of control and irradiated from year to year. — Table 2.1 pre- sented a summary of the number and propor- tion of registrations with at least one parent falling into categories 4 or 5 for the years 1948 through 1953. There was apparent a recent de- crease in both the absolute and the relative representation of the more heavily irradiated. If there were any marked tendency for the level of diagnostic accuracy or parental cooperation with respect to congenital malformation to change during the course of the study, or if be- cause of post-war improvements in medical and economic levels the stillbirth or the neonatal death rate fell appreciably or the birthweight increased, then here again are factors capable of introducing a source of spurious conclusions. Tables 5.19 and 5.20 summarize our annual

70 Chapter V Genetic Effects of Atomic Bombs TABLE 5.18 INCIDENCE OF LEUKEMIA IN THE HIROSHIMA SURVIVORS OF THE ATOMIC BOMBING AS RELATED TO DISTANCE FROM THE HYPOCENTER AND THE PRESENCE OF SEVERE RADIATION COMPLAINTS (After Moloney and Kastenbaum, 1955) Distance from Population * (meters) SRC" NRCC Total 0- 999 750 450 1,200 1,000-1 499 . 2 250 8 250 10,500 1 500-1 999 1 750 16950 18,700 2,000-2,499 950 16,250 17,200 2,500 and over. . . . 850 49,650 50,500 Total 6,550 91,550 98,100 Cases of leukemia Incidence SRC NRC Total SRC NRC Total 14 1 15 1: 53 1: 450 1: 80 15 9 24 1:150 1: 917 1: 438 3 2 5 1:583 1: 8,475 1: 3,740 1 1 2 1:950 1:16,250 1: 8,600 0 4 4 — 1:12,412 1:12,625 33 17 5O 1:198 1: 5,385 1,962 * Population estimated and rounded off to the nearest 50 persons. These population figures were based on the Commission's 1949 radiation census and the Japanese national census (1950). Numbers of survivors with severe radia- tion complaints were estimated from an analysis of the pregnancy registration data. "SRC: severe radiation complaints (heavily irradiated). 0 NRC: no radiation complaints (lightly irradiated). TABLE 5.19 THE FREQUENCY OF MALFORMATIONS BY YEAR AMONG THE OFFSPRING OF PARENTS NEITHER OF WHOM WAS EXPOSED TO THE ATOMIC BOMBS Hiroshima Total births 1948 1949 1950 1,756 4,005 3,602 1951 3,324 1952 3,084 Total 15,771 Malformations 14 34 34 36 35 153 Percentage 0.80 0.85 0.94 1.08 1.13 0.97 X' = 2.496 DF= 4 0.70 Nagasaki 0.50 1948-49 1950 3,934 3,243 1951 3,189 1952 Total Total births 3,123 13,489 31 36 45 32 144 Pcrcentace . 0.79 1.11 1.41 1.02 1.07 x' = 6.584 DF = 3 0.10 > P>0.05

The Comparability of Irradiation Subclasses 71 TABLE 5.20 THE FREQUENCY OF STILLBIRTHS BY YEAR AMONG THE OFFSPRING OF PARENTS NEITHER OF WHOM WAS EXPOSED TO THE ATOMIC BOMBS Hiroshima 1948 . . 1,742 1949 1950 1951 1952 Total Total births 3,971 87 2.19 3,564 3,287 3,037 64 58 61 1.80 1.76 2.01 15,601 321 2.06 Stillbirths 51 Percentage . . 2.93 X2 = 9.544 DF = 4 I 0.05 > P > 0.02 Nagasaki 1948-49 1950 1951 1952 Total Total births ............... 3,902 3,200 3,134 3,084 13,320 Stillbirths ................. 63 61 49 67 240 Percentage ................. 1.61 1.91 1.56 2.17 1.80 X ' = 4.372 DF=3 0.30 >P> 0.20 figures for the frequency of gross malformations and stillbirths for the first five years of the study among the offspring of parents neither of whom was exposed to the atomic bombs. The fre- quency of malformations and stillbirths appears to remain sufficiently constant from year to year, that time trends should not complicate the analysis of these two indicators. On the other hand, we shall in a subsequent section (Sec. 10.4) present evidence that time trends may be of importance in the birthweight analysis. 5.10 The background of group 1 individuals. — There remains one final problem for dis- cussion. There are important differences in back- ground between the parents in radiation cate- gory 1 and those in categories 2 through 5. The latter have all been urban dwellers since 1945 or before. The former parents, although in part composed of residents of Hiroshima and Naga- saki who were away at the time of the bombings, and also of urbanites who have come to Hiro- shima and Nagasaki from the other cities of Japan, in addition include a high proportion of emigrants from rural areas and repatriates from Manchuria, Korea, and Formosa. In addi- tion, among the men there are many with ex- tensive overseas military service. Although there are well-known urban-rural differences with respect to the indicators of possible genetic effect here considered, it is by no means clear to what extent these are apparent and to what extent real, and if the latter, whether they are socio-economic or biological in origin. Finally, if biological, there are no data as to how long they persist after urbanization. In the face of this situation, one can only conclude that the significance of any finding based solely on a difference between category 1 and categories 2 through 5 collectively must be viewed with reservations. 5.11 Summary. — Of the differences between the individuals in the various exposure subcate- gories which have come to light in the forego- ing analysis, some appear to be inconsequential, of such a nature that they can be ignored with safety. Others of the differences appear to repre- sent sources of potentially significant bias. These latter differences fall into a natural dichotomy, depending on whether or not allowance can be made for them in an analysis. Thus, one way or another, differences in the frequency of con- sanguinity, age, and parity can be circumvented. This is not so either with respect to the occur- rence of late sequelae of the bombing among the more heavily irradiated, the possible implica- tions of the progressive decline during the six years covered by this study in the proportion of category 4's and 5's among the registrants, or the differences in background among persons falling into category 1 as opposed to categories 2 through 5. In the following chapter, the steps taken to meet this situation will be described.

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