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					Slama et al.                                                                  Web only material


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Appendix:


Selection of the reference area

We defined five criteria to select the reference area: 1) Location in France, near the coast; 2)

Levels of ionising radiation of natural origin that are similar to the levels in Beaumont-Hague;

3) Significantly lower environmental concentrations of radionuclides from the discharges of

the nuclear reprocessing plant than those in Beaumont-Hague; 4) Distribution of the

population into socio-economic groups that is similar to what is observed in Beaumont-

Hague; 5) Absence of industrial activity or environmental pollution likely to influence

fecundity.

To meet criteria 1 and 2, we limited the reference area to the coasts of the Armorican basin,

a Hercynian formation composed of Brittany and southern Normandy, corresponding to

geological formations from the same epoch as those of Beaumont-Hague. To meet criterion

3, we excluded the Cotentin peninsula of southern Normandy, where the values for the

dilution factors of the marine discharges originating from the reprocessing plant ranged

between 0.2 and 1.[6] To address criterion 4, we used data from the 1990 French general

population census and compared the distribution of social groups of the population of all

districts of Brittany with that of Beaumont-Hague (M. Rouxel, INSEE, personal

communication). We calculated a ‘social class index’ for each ward, measuring the

differences in the distribution of the population into social classes from that of Beaumont-

Hague (not detailed). We then focused on the five areas less than 20 km away from the

coast that were the most similar to Beaumont-Hague with respect to this social class index.

To refine the conformity with criterion 2, we used geologic maps[43] to investigate the

radioactivity of the subsoil in the five selected wards. One of the selected areas (Saint-

Renan, Finistère departement) was situated on a granite formation with a concentration of

Uranium much higher than those observed in Beaumont-Hague. Two other wards, located in

southern Brittany, have geological formations that are quite different from those in northern



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Slama et al.                                                                Web only material


Brittany and northern Cotentin, and were excluded. A more detailed geological study has

been performed for a fourth ward, composed of the districts of Langueux and Ploufragan, in

the Saint-Brieuc bay, and including ca 40,000 inhabitants, and for Beaumont-Hague. The

subsoil content in uranium (U), thorium (Th) and potassium (K), were estimated.[43] These

are the compounds which contribute most to the subsoil’s natural radioactivity.[44] For each

type of geological formation, the concentrations of U, Th and K were indirectly estimated

from the values usually observed in other sites with a similar geological nature.[43] Using the

findings of this study, we finally selected four towns (Hillion, La Méaugon, Saint-Julien and

Yffiniac) including a total of 10,509 inhabitants in 1999 and with a concentration of

radionuclides in the subsoil similar to that in Beaumont-Hague. There was no large source of

industrial pollution in these four towns (criterion 5). Together, these four towns made up our

reference area (Figure 1). They are located about 145 km away from Beaumont-Hague.




Selection bias

To study selection bias due to non-participation, we compared the characteristics of the

participating women who had had a child in the last 15 years with the census data on homes

with a child aged 15 years or less (Table S1). To study selection bias due to migration out of

the two areas during the study period, we compared, for each area, the age-standardised

number of children aged 16 years or less between women who lived in the same area in

1990 and 1999 and those who lived in the study area in 1990 but not anymore in 1999 (Table

S3).




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Slama et al.                                                                    Web only material


TABLE S1: Comparison between the characteristics of the included women who had a live

birth between January 1985 and Spring 2000 (n=1,102) and the women aged 18-59 years

living with a child aged 15 years or less (1999 census data, random sample of 1/4 of the

population).



                                             Beaumont-Hague                         Reference area
                                      Included subjects* 1999 Census        Included subjects* 1999 Census
                                          n=797 (%)       n=1632 (%)            n=305 (%)       n=1312 (%)
Education level (woman)
   No diploma                            70      (9)       208     (13)        21      (7)        124     (9)
   BEP, CEP, CAP                        360     (45)       800     (49)       140     (46)        676    (52)
   Baccalaureate (to age 18)            176     (22)       312     (19)        69     (23)        268    (20)
   Degree (baccalaureate+2 years)        79     (10)       216     (13)        39     (13)        192    (15)
   Further education                    109     (14)        96      (6)        36     (12)         52     (4)
Occupation (man)
    Farmers                              26      (3)        48      (3)         9      (3)         20     (2)
    Skilled manual workers               29      (4)        92      (6)        25      (8)        128    (10)
    White collar                        101     (13)       144      (9)        30     (10)         96     (8)
    Junior management and skilled       119     (15)       560     (37)        38     (13)        360    (29)
service sector workers
    Employees                           220     (29)       108      (7)       109     (37)        112     (9)
    Blue collar                         249     (32)       556     (36)        78     (26)        504    (41)
    Inactive                             25      (3)        20      (1)         7      (2)         16     (1)
Occupation (woman)
    Farmer                               15      (2)        32      (2)         1      (0.3)        4     (0.3)
    Skilled manual workers               15      (2)        44      (3)         6      (2)         40     (3)
    White collar                         42      (5)        80      (5)        15      (5)         36     (3)
    Junior management and skilled        99     (12)       268     (16)        40     (13)        260    (20)
service sector workers
    Employees                           383     (48)       764     (47)       180     (60)        632    (48)
    Blue collar                          32      (4)        76      (5)        13      (4)        144    (11)
    Inactive                            211     (26)       368     (23)        47     (16)        196    (15)
Woman's age (years)
  18-24                                  10      (1)        28      (2)         2      (1)          8     (1)
  25-29                                 101     (13)       192     (12)        37     (12)        112     (9)
  30-34                                 235     (29)       356     (22)       102     (33)        344    (26)
  35-39                                 264     (33)       504     (31)        88     (29)        400    (30)
  40-44                                 134     (17)       348     (21)        53     (17)        276    (21)
  45-59                                  53      (7)       204     (13)        23      (8)        172    (13)
Number of children
   1                                    157     (20)       396     (24)        62   (20)          312 (24)
   2                                    377     (47)       756     (46)       157   (51)          652 (50)
   3                                    206     (26)       376     (23)        71   (23)          284 (22)
   4 and more                            57      (7)       104      (6)        15    (5)           64   (5)
   Mean number of children                2.2                2.1                2.1                 2.1
Arrival in the ward less than 9 years
before data collection†                    427      (54)        796    (49)    159     (53)        636   (48)
* Restricted to women who had a live birth between January 1985 and the time of data collection.
†
  For included subjects, the figures correspond to women who changed home in the 9 years before the
study, even within the same town. For the census data, the figures correspond to subjects who did not
live in the same town 9 years earlier, at the time of the previous census.




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         Slama et al.                                                                                   Web only material

         TABLE S2: Description of the reproductive life events of the participating population between 1985 and 2000 according to the area of recruitment,

         for the whole period and for pregnancies conceived after the arrival of the woman in the area. Unless otherwise specified, numbers in parentheses

         are column percentages.

                                                                 From year 1985 to 2000                                            From year 1985 to 2000, after arrival in the area*
                                                    Beaumont-Hague     Reference area     Both areas                            Beaumont-Hague      Reference area          Both areas
                                                      (857 women)       (326 women)     (1,183 women)                             (857 women)         (326 women)         (1,183 women)
Pregnancies leading to a live birth
    0                                           60   (7.0)                        21   (6.4)             81   (6.8)              328 (38.3)                136   (41.7)           464   (39.2)
    1                                          296 (34.5)                        120 (36.8)             416 (35.2)               291 (34.0)                119   (36.5)           410   (34.7)
    2                                          363 (42.4)                        142 (43.6)             505 (42.7)               187 (21.8)                 56   (17.2)           243   (20.5)
    ≥3                                         138 (16.1)                         43 (13.2)             181 (15.3)                51   (6.0)                15    (4.6)            66    (5.6)
Mean number per woman                            1.7                               1.7                    1.7                      1.0                       0.9                    0.9
Twin pregnancies, (% of live births)            19   (1.3)                         3   (0.6)             22   (1.1)                7   (0.8)                 2    (0.7)             9    (0.8)
Sex (singleton births only)
    Female birth                               719 (49.9)                        269     (50.9)         988    (50.2)            409     (49.8)            138     (50.2)         547      (49.9)
    Male birth                                 722 (50.1)                        259     (49.1)         981    (49.8)            412     (50.2)            137     (49.8)         549      (50.1)
Women pregnant during interview                 36   (4.2)                        16      (4.9)          52     (4.4)             30      (3.5)             14      (4.3)          44       (3.7)
Contraceptive use at the beginning of the pregnancy†
     Yes or do not know                        177 (11.8)                        63     (11.5)           240   (11.8)            104     (12.1)             27      (9.3)         131      (11.4)
     No                                      1317 (88.2)                        484     (88.5)          1801   (88.2)            754     (87.9)            264     (90.7)        1018      (88.6)
If no contraceptive use, TTP defined†
     No                                        160 (12.1)                        60     (12.4)           220   (12.2)             93     (12.3)             36     (13.6)         129      (12.7)
          ‡
     Yes                                      1157 (87.9)                       424     (87.6)          1581   (87.8)            661     (87.7)            228     (86.4)         889      (87.3)
       and started between 1/1985 and 7/1999 1052                               392                     1444                     611                       215                    826
Spontaneous abortions
    0                                          700 (81.7)                        256     (78.5)         956    (80.8)            763 (89.0)                292   (89.6)          1055   (89.2)
    1                                          131 (15.3)                         52     (16.0)         183    (15.5)             82   (9.6)                26    (8.0)           108    (9.1)
    2                                           18   (2.1)                        12      (3.7)          30     (2.5)              7   (0.8)                 5    (1.5)            12    (1.0)
    ≥3                                           8   (0.9)                         6      (1.8)          14     (1.2)              5   (0.6)                 3    (0.9)             8    (0.7)
    Rate for 100 births or sp. abortions             12.0                                 15.3                  12.9              12.4                      14.5                   12.9
Stillbirths (rate for 100 births)               16   (1.1)                          8     (1.5)          24     (1.2)              9   (1.1)                 2    (0.7)            11    (1.0)
* For pregnancies leading to a live birth and started while the couple was not using a contraceptive method, only those for which the couple lived in the area of recruitment at the start of the
period of unprotected intercourse were taken into account. For all other pregnancies, only those for which the couple lived in the area of recruitment at the beginning of the pregnancy were
taken into account.

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           Slama et al.                                                                                  Web only material
†
    For live births and pregnancy current for more than three months at the time of interview.
‡
    Excludes couples declaring less than 4 intercourses per month at the start of the period of unprotected intercourse or using birth control methods sporadically.




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Slama et al.                                                                   Web only material

TABLE S3: Comparison of the distribution of the number of children aged 16 years or less in

1999 (standardized on the age of the woman) according to the residential address of the

woman in 1990 and her address in 1999 (column percentages). Data from the 1999 national

population census for women aged 18 to 60 years.



                                             Residential address in 1990
 Number of                  Beaumont-Hague                                 Reference area
 children ≤16    Still in the    Moved out    Overall      Still in the area   Moved out in   Overall
 years          area in 1999      in 1999*                      in 1999           1999*
  0                57%            60%          58%               62%             63%            62%
  1                20%            21%          20%               18%             16%            18%
  2                16%            13%          15%               15%             14%            14%
  3 and more        7%             7%           7%                5%              7%             6%

* Women who moved out between the 1990 and the 1999 national censuses.




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Slama et al.                                                             Web only material

FIGURE S1: Cumulative probability of pregnancy among 641 couples who started an

attempt at pregnancy in Beaumont-Hague (n=474) and in the reference area (n=167)

between 1985 and 2000. Restricted to last attempt at pregnancy.
       1.00
       0.80
       0.60
       0.40
       0.20




                                                                  Area
                                                                  Reference area
                                                                  Beaumont-Hague
       0.00




                 1   3    6    9    12          18        24                    36

                           Months since cessation of contraceptive use




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