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Periconceptional smoking and the male to female ratio in the offspring—re-assessment of a recently proposed hypothesis

Periconceptional smoking and the male to female ratio in the offspring—re-assessment of a... Sirs—The male to female ratio has declined from the middle of the last century in some European countries.1,2 It has recently been suggested that the usual suspect—smoking—is the culprit of this development.3 Maternal as well as paternal smoking around the time of conception reduced the male:female ratio in the offspring towards fewer boys, they say. If true this finding has wide-ranging implications since it indicates that smoking has an impact on conception itself or the risk of early abortions. Participants, methods, results We examined whether parental smoking around the time of conception influences the sex ratio in the offspring in two Danish pregnancy cohorts of liveborn singletons. One cohort consisted of 10 926 children born in Odense and Aalborg from 1984 to 1987. In this cohort the mothers completed a questionnaire in pregnancy which included information on smoking around the time of conception for both partners (response rate 85%). The second cohort included 31 678 children born in Aarhus from 1990 to 1999 with data on maternal smoking around the time of conception (response rate 95%). Information on maternal smoking around the time of conception was available throughout the study period (response rate 95%). During the period from 1990 to 1992 information on smoking habits of the father was also included (N = 5064, response rate 60%). Sex ratio according to the number of cigarettes in both partners from both cohorts is shown in Table 1. We found no association between paternal and maternal smoking habits around the time of conception and sex ratio in the offspring (Table 1). When neither of the parents smoked the male:female ratio was 1.06 compared with 1.04 when both parents smoked ≥20 cigarettes. When all data on maternal smoking (N = 42 604) were analysed together, we found 7% fewer boys among women who smoked ≥20 cigarettes (95% CI: 0–13%) but no sign of a dose–response effect. Comment In conclusion, we failed to corroborate Fukuda’s strong association between periconceptional smoking and a low male: female ratio in the offspring. Heavy smoking is closely linked to social or dietary factors, environmental exposures or stress.4 A marginal effect may easily be due to confounding. Other types of bias may explain the association found in the Japanese cohort. The male:female ratio among non-smoking parents in the Japanese cohort was 1.21, which indicate that this is a selected group. If this sex ratio was representative for non-smoking parents one would expect to find a much higher sex ratio in countries with few smokers. Table 1 Parental smoking habits around the time of conception and sex ratio in the offspring . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) Open in new tab Table 1 Parental smoking habits around the time of conception and sex ratio in the offspring . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) Open in new tab References 1 Parazzini F, La Vecchia C, Levi F, Franceschi S. Trends in male:female ratio among newborn infants in 29 countries from five continents. Hum Reprod 1998 ; 13 : 1394 –96. 2 Møller H. Change in male:female ratio among newborn infants in Denmark. Lancet 1996 ; 348 : 828 –29. 3 Fukuda M, Fukuda K, Shimizu T, Andersen CY, Byskov AG. Parental periconceptional smoking and male:female ratio of newborn infants. Lancet 2002 ; 359 : 1407 –08. 4 Hansen D, Møller H, Olsen J. Severe periconceptional life events and the sex ratio in offspring: follow up study based on five national registers. BMJ 1999 ; 319 : 548 –49. Authors’ Response Misao Fukuda5 Misao Fukuda5 5 Fukuda Ladies Clinic, 30-9 Kariya, Ako, Hyogo 678-0239, Japan. Kiyomi Fukuda5 Kiyomi Fukuda5 5 Fukuda Ladies Clinic, 30-9 Kariya, Ako, Hyogo 678-0239, Japan. Takashi Shimizu6 Takashi Shimizu6 6 Shimizu Women’s Clinic, 2–2–4 Minamiguchi, Takarazuka, Hyogo 665–0011, Japan. Claus Yding Andersen7 Claus Yding Andersen7 7 Laboratory of Reproductive Biology, University Hospital of Copenhagen, Section 5712, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Anne Grete Byskov7 Anne Grete Byskov7 7 Laboratory of Reproductive Biology, University Hospital of Copenhagen, Section 5712, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Sirs—Obel and colleagues failed to find similar effects of maternal and paternal smoking habits on the offspring sex ratio, using two Danish pregnancy cohorts from 1984–1987 and 1990–1992 respectively. Although the Danish data include more cases than our study1 (15 990 versus 11 815 children), the group in which the father smoked >20 cigarettes per day and the mother was a non-smoker is considerably smaller in the Danish data as compared with ours (370 versus 5775). We observed the most pronounced effect particularly in the group of heavy smoking fathers (i.e. >20 cigarettes per day) and suggest that the lack of a significant decline in the offspring sex ratio in the Danish data may be related to the relatively small number of heavy smokers. This may actually be supported in the Danish data by the trend towards a decreasing sex ratio in relation to increasing number of cigarettes the parents smoked. Moreover, the data from an old study published in 1912 actually suggest an even more pronounced effect on the offspring sex ratio than we reported: the offspring sex ratio in paternal smokers was found to be 0.783 (2333:2981), whereas that of non-smokers was 1.326 (4185:3154).2 These old data are also important in evaluation of possible confounders especially in relation to stress as suggested by Obel and colleagues. We agree that stress also is of importance in affecting the offspring sex ratio,3 but imagine that the nature of stress around 1912 was different, although perhaps not lower than today, and maintain that paternal smoking around the time of conception seems to influence the offspring sex ratio. However, we accept that smoking habits could be linked to other lifestyle parameters that may affect the offspring sex ratio, and our study did not provide information on whether those who suffer from stress tend to smoke cigarettes. The Danish study found 7% fewer boys in the group of women who were heavy smokers. These data also corroborate with the Japanese statistics in 2000 where it was found that maternal smoking, irrespective of paternal smoking, resulted in the sex ratio 0.998 (492:493) as compared with 1.063 (4287:4087) in non-smokers.4 In combination with the data we published, which showed a significant decline in the offspring sex ratio1 when maternal smoking was considered, these data collectively show an unequivocal trend towards the birth of fewer boys with maternal smoking around the time of conception. We accept that the cohort of Japanese mothers included in our study may differ from that of the Danish study, which may explain more subtle differences. However, we maintain that the smoking habits of the mother around the time of conception seem to be of importance for the offspring sex ratio, although the data on paternal smoking show a more prominent effect. Obel and colleagues claim that our offspring sex ratio of non-smoking couples is high and suggest that our cohort is a selected group. However, as described above, the sex ratio of non-smokers was 1.326,2 which is even higher than our value of non-smokers of 1.214. Moreover, the natural offspring sex ratio in baboons is reported to be 1.20.5 This value corroborates what was observed in the group in our study in which neither of the couple smoked. References 1 Fukuda M, Fukuda K, Shimizu T, Yding Andersen C, Byskov AG. Parental periconceptional smoking and male: female ratio of newborn infants. Lancet 2002 ; 359 : 1407 –08. 2 Tidswell HH. The Tobacco Habit: Its History and Pathology. London: J & A Churchill, 1912, pp. 219–21. 3 Fukuda M, Fukuda K, Shimizu T, Møller H. Decline in sex ratio at birth after Kobe earthquake. Hum Reprod 1998 ; 13 : 2321 –22. 4 Kaneda I. The Physical Values for Japanese Infants and Preschool Children in 2000 (in Japanese). Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 2002, pp. 54–56. 5 Packer C, Collins DA, Eberly LE. Problems with primate sex ratios. Philos Trans R Soc Lond B Biol Sci 2000 ; 355 : 1627 –35. © International Epidemiological Association 2003 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Epidemiology Oxford University Press

Periconceptional smoking and the male to female ratio in the offspring—re-assessment of a recently proposed hypothesis

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Publisher
Oxford University Press
Copyright
© International Epidemiological Association 2003
ISSN
0300-5771
eISSN
1464-3685
DOI
10.1093/ije/dyg089
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Abstract

Sirs—The male to female ratio has declined from the middle of the last century in some European countries.1,2 It has recently been suggested that the usual suspect—smoking—is the culprit of this development.3 Maternal as well as paternal smoking around the time of conception reduced the male:female ratio in the offspring towards fewer boys, they say. If true this finding has wide-ranging implications since it indicates that smoking has an impact on conception itself or the risk of early abortions. Participants, methods, results We examined whether parental smoking around the time of conception influences the sex ratio in the offspring in two Danish pregnancy cohorts of liveborn singletons. One cohort consisted of 10 926 children born in Odense and Aalborg from 1984 to 1987. In this cohort the mothers completed a questionnaire in pregnancy which included information on smoking around the time of conception for both partners (response rate 85%). The second cohort included 31 678 children born in Aarhus from 1990 to 1999 with data on maternal smoking around the time of conception (response rate 95%). Information on maternal smoking around the time of conception was available throughout the study period (response rate 95%). During the period from 1990 to 1992 information on smoking habits of the father was also included (N = 5064, response rate 60%). Sex ratio according to the number of cigarettes in both partners from both cohorts is shown in Table 1. We found no association between paternal and maternal smoking habits around the time of conception and sex ratio in the offspring (Table 1). When neither of the parents smoked the male:female ratio was 1.06 compared with 1.04 when both parents smoked ≥20 cigarettes. When all data on maternal smoking (N = 42 604) were analysed together, we found 7% fewer boys among women who smoked ≥20 cigarettes (95% CI: 0–13%) but no sign of a dose–response effect. Comment In conclusion, we failed to corroborate Fukuda’s strong association between periconceptional smoking and a low male: female ratio in the offspring. Heavy smoking is closely linked to social or dietary factors, environmental exposures or stress.4 A marginal effect may easily be due to confounding. Other types of bias may explain the association found in the Japanese cohort. The male:female ratio among non-smoking parents in the Japanese cohort was 1.21, which indicate that this is a selected group. If this sex ratio was representative for non-smoking parents one would expect to find a much higher sex ratio in countries with few smokers. Table 1 Parental smoking habits around the time of conception and sex ratio in the offspring . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) Open in new tab Table 1 Parental smoking habits around the time of conception and sex ratio in the offspring . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) . . . . Mother’s smoking No. of cigarettes . . . . . 0 . 1–19 . 20+ . Odense/Aalborg-cohort N = 10 926 Born 1984–1987 Father’s smoking No. of cigarettes 0 males:females odds ratio 2115:1953 1(ref.) 970:933 0.96(0.86–1.07) 89:88 0.93(0.69–1.26) 1–19 males:females odds ratio 746:729 0.95(0.84–1.07) 1327:1229 1.00(0.90–1.1) 121:147 0.76(0.59–0.97) 20+ males:females odds ratio 64:63 0.94(0.66–1.34) 115:129 0.82(0.64–1.07) 59:49 1.11(0.76–1.63) Aarhus cohort N = 5064 Born 1990–1992 Father’s smoking No. of cigarettes 0 males:females odds ratio 932:911 1(ref.) 373:350 1.04(0.88–1.24) 87:89 0.96(0.70–1.30) 1–19 males:females odds ratio 318:300 1.04(0.86–1.24) 349:376 0.91(0.76–1.08) 94:96 0.96(0.71–1.29) 20+ males:females odds ratio 112:131 0.84(0.64–1.09) 184:164 1.10(0.87–1.38) 97:101 0.94(0.70–1.30) Both cohorts N = 15 990 Father’s smoking No. of cigarettes 0 males:females odds ratio 3047:2864 1(ref.) 1343:1283 0.98(0.90–1.08) 176:177 0.94(0.76–1.17) 1–19 males:females odds ratio 1064:1029 0.97(0.88–1.07) 1676:1605 0.98(0.90–1.07) 215:243 0.84(0.69–1.01) 20+ males:females odds ratio 176:194 0.86(0.70–1.07) 299:293 0.97(0.82–1.15) 156:150 0.97(0.90–1.04) Open in new tab References 1 Parazzini F, La Vecchia C, Levi F, Franceschi S. Trends in male:female ratio among newborn infants in 29 countries from five continents. Hum Reprod 1998 ; 13 : 1394 –96. 2 Møller H. Change in male:female ratio among newborn infants in Denmark. Lancet 1996 ; 348 : 828 –29. 3 Fukuda M, Fukuda K, Shimizu T, Andersen CY, Byskov AG. Parental periconceptional smoking and male:female ratio of newborn infants. Lancet 2002 ; 359 : 1407 –08. 4 Hansen D, Møller H, Olsen J. Severe periconceptional life events and the sex ratio in offspring: follow up study based on five national registers. BMJ 1999 ; 319 : 548 –49. Authors’ Response Misao Fukuda5 Misao Fukuda5 5 Fukuda Ladies Clinic, 30-9 Kariya, Ako, Hyogo 678-0239, Japan. Kiyomi Fukuda5 Kiyomi Fukuda5 5 Fukuda Ladies Clinic, 30-9 Kariya, Ako, Hyogo 678-0239, Japan. Takashi Shimizu6 Takashi Shimizu6 6 Shimizu Women’s Clinic, 2–2–4 Minamiguchi, Takarazuka, Hyogo 665–0011, Japan. Claus Yding Andersen7 Claus Yding Andersen7 7 Laboratory of Reproductive Biology, University Hospital of Copenhagen, Section 5712, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Anne Grete Byskov7 Anne Grete Byskov7 7 Laboratory of Reproductive Biology, University Hospital of Copenhagen, Section 5712, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Sirs—Obel and colleagues failed to find similar effects of maternal and paternal smoking habits on the offspring sex ratio, using two Danish pregnancy cohorts from 1984–1987 and 1990–1992 respectively. Although the Danish data include more cases than our study1 (15 990 versus 11 815 children), the group in which the father smoked >20 cigarettes per day and the mother was a non-smoker is considerably smaller in the Danish data as compared with ours (370 versus 5775). We observed the most pronounced effect particularly in the group of heavy smoking fathers (i.e. >20 cigarettes per day) and suggest that the lack of a significant decline in the offspring sex ratio in the Danish data may be related to the relatively small number of heavy smokers. This may actually be supported in the Danish data by the trend towards a decreasing sex ratio in relation to increasing number of cigarettes the parents smoked. Moreover, the data from an old study published in 1912 actually suggest an even more pronounced effect on the offspring sex ratio than we reported: the offspring sex ratio in paternal smokers was found to be 0.783 (2333:2981), whereas that of non-smokers was 1.326 (4185:3154).2 These old data are also important in evaluation of possible confounders especially in relation to stress as suggested by Obel and colleagues. We agree that stress also is of importance in affecting the offspring sex ratio,3 but imagine that the nature of stress around 1912 was different, although perhaps not lower than today, and maintain that paternal smoking around the time of conception seems to influence the offspring sex ratio. However, we accept that smoking habits could be linked to other lifestyle parameters that may affect the offspring sex ratio, and our study did not provide information on whether those who suffer from stress tend to smoke cigarettes. The Danish study found 7% fewer boys in the group of women who were heavy smokers. These data also corroborate with the Japanese statistics in 2000 where it was found that maternal smoking, irrespective of paternal smoking, resulted in the sex ratio 0.998 (492:493) as compared with 1.063 (4287:4087) in non-smokers.4 In combination with the data we published, which showed a significant decline in the offspring sex ratio1 when maternal smoking was considered, these data collectively show an unequivocal trend towards the birth of fewer boys with maternal smoking around the time of conception. We accept that the cohort of Japanese mothers included in our study may differ from that of the Danish study, which may explain more subtle differences. However, we maintain that the smoking habits of the mother around the time of conception seem to be of importance for the offspring sex ratio, although the data on paternal smoking show a more prominent effect. Obel and colleagues claim that our offspring sex ratio of non-smoking couples is high and suggest that our cohort is a selected group. However, as described above, the sex ratio of non-smokers was 1.326,2 which is even higher than our value of non-smokers of 1.214. Moreover, the natural offspring sex ratio in baboons is reported to be 1.20.5 This value corroborates what was observed in the group in our study in which neither of the couple smoked. References 1 Fukuda M, Fukuda K, Shimizu T, Yding Andersen C, Byskov AG. Parental periconceptional smoking and male: female ratio of newborn infants. Lancet 2002 ; 359 : 1407 –08. 2 Tidswell HH. The Tobacco Habit: Its History and Pathology. London: J & A Churchill, 1912, pp. 219–21. 3 Fukuda M, Fukuda K, Shimizu T, Møller H. Decline in sex ratio at birth after Kobe earthquake. Hum Reprod 1998 ; 13 : 2321 –22. 4 Kaneda I. The Physical Values for Japanese Infants and Preschool Children in 2000 (in Japanese). Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 2002, pp. 54–56. 5 Packer C, Collins DA, Eberly LE. Problems with primate sex ratios. Philos Trans R Soc Lond B Biol Sci 2000 ; 355 : 1627 –35. © International Epidemiological Association 2003

Journal

International Journal of Epidemiology – Oxford University Press

Published: Jun 1, 2003

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