American Journal of Epidemiology Copyright O 1991 by The Joins Hopkins Urwersrty School of Hygiene and Pubic Health All rights reserved
Vol. 133, No. 7 Printed In US A.
A BRIEF ORIGINAL CONTRIBUTION
Cigarette Smoking, Tea and Coffee Drinking, and Subfecundity
Jorn Olsen
A population-based survey of life-style factors and subfecundity (prolonged time to pregnancy) was conducted between 1984 and 1987 in two cities in Denmark. Altogether, 11,888 women filled out a questionnaire in the last trimester of pregnancy (an 86 percent response rate). After exclusion of women who had been treated for infertility or who did not respond to the question on infertility, 10,886 subjects remained. Among nonsmokers, no association was found between subfecundity (defined as a waiting time of 1 year or more from cessation of contraception to achievement of pregnancy) and consumption of hot caffeinated beverages. For women who smoked and also consumed at least 8 cups of coffee per day (or an equivalent amount of tea), a statistically significant association was seen (odds ratio = 1.35, 95% confidence interval 1.02-1.48) for a wait of 1 year or more. Consumption of coffee was closely related to smoking habits and to a number of social factors, such as education and peer group acceptance, which may play a rote in subfecundity. Am J Epidemiol 1991 ;133:734-9. caffeine; coffee; fertility; pregnancy; smoking, tea
Caffeine is a pharmacologically active substance with stimulant effects. It is a plant alkaloid (1,3.7-trimethylxanthine) related to uric acid, adenine, and guanine (1) and is rapidly absorbed and diffused to all tissue compartments, including the preimplantation blastocyst (2, 3). Caffeine has a number of general effects, such as catecholamine release, mobilization of free fatty acids, stimulation of the central nervous system, in-
Received for publication December 4,1989, and in final form October 16, 1990. Abbreviations: Cl, confidence interval; OR, odds ratio. From the Institute of Social Medicine, University of Aarhus, Hoegb-GuWbergs Gade 8, DK-8000 Aarhus C, Denmark. (Reprint requests to Dr. Jam Olsen at this address.) This study was supported by Helsefondet, Egmont Fondet, the Danish National Board of Health, the County of Funen, Denmark, and the Comrte consuttatif de Gestion et de Cordination as part of its European studies on infertility. The author thanks Dr. Donna Baird for her valuable comments.
734
creased gastric secretion, heart rate, and basal metabolic rate, altered blood pressure, diuresis, and relaxation of smooth muscles (4). In experimental animal studies, caffeine interferes with insect reproduction (5), and reduced pregnancy rates have been observed among exposed mice (6). Caffeine is known to decrease DNA polymerase activity in human embryonic lung cells and to affect DNA excision repair (7). Thus, caffeine may modify the effect of other potential mutagens such as those found in tobacco smoke. Tobacco use has been implicated in the occurrence of a number of reproductive anomalies, the best documented being low birth weight (8). Female rats fed small doses of nicotine exhibit reduced fertility and deliver smaller litters (9). A higher frequency of sperm abnormalities has been shown in smokers relative to nonsmokers in some studies (10, 11), and female smoking has been associated with infertility as well as subfecundity (11, 12).
Smoking, Tea and Coffee Drinking, and Subfecundity
Since the metabolism of caffeine differs even among primates (10, 13), epidemiologic studies are the best approach to exploring any association between caffeine intake and fertility in humans. Furthermore, the use of coffee, tea, and in some countries also caffeinated soft drinks is very frequent, and even a modest effect on fertility could have public health and clinical relevance. Women drinking more than three cups of coffee per day during the first trimester of pregnancy have shown an increased risk of miscarriage in some studies (4). Decreased fertility has been reported for women who consume more than one cup of coffee per day while trying to become pregnant (14). It has been suggested that such an effect could be mediated via the tuberoinfundibular dopamine pathway controlling the release of prolactin (15). However, a recently published paper failed to show any risk of delayed conception associated with caffeinated beverages (16). The purpose of this analysis was to estimate the association between caffeine intake and time to pregnancy for smokers and nonsmokers among all women in the last trimester of pregnancy in two well-defined geographic areas in Denmark. Caffeine intake was measured by consumption of coffee and tea.
MATERIALS AND METHODS
All pregnant women in two cities in Denmark (Odense and Aalborg) were given a questionnaire on cigarette smoking, alcohol drinking, and eating habits. The questionnaire was handed out in the 36th week of pregnancy, and the study period ran from April 1984 to April 1987. The aim was to study the impact of social conditions and life-style factors on the outcome of pregnancy, but the questionnaire also had items on time to pregnancy and on smoking and drinking habits during the time before pregnancy. The questionnaire included questions on the father's smoking and drinking habits during the pregnancy. More than 95
735
percent of all women in the third trimester of pregnancy in the region (n = 13,815) received the questionnaire, and 11,888 participated in the study (86 percent). After the 903 women who had been treated for infertility and the 99 who did not respond to the question on infertility treatment were excluded from the data set, 10,886 subjects remained. The women were asked how many cups of coffee they usually drank per day before becoming pregnant. A similar question was also posed for tea. The question had three answer categories (0-3 cups, 4-7 cups, and 8 cups or more). Similarly, the women were asked about their consumption of beer, wine, and liquor before pregnancy. Since one bottle of beer, one glass of wine, and one serving of liquor in Denmark usually all contain the same amount of alcohol (about 12 g), all of these data were grouped into the item "number of drinks consumed per week." The question on smoking also concerned the time before pregnancy, whereas the fathers' smoking and drinking habits were only recorded as present habits (when the wife was pregnant). In Denmark, almost all coffee drunk is filter coffee. Coffee contains 14—489 mg of caffeine per serving, and tea contains 8-107 mg (17); in the analysis in this study, two cups of tea was assumed to be equivalent to one cup of coffee, which is similar to the approach taken in an earlier study (14). Time to pregnancy was recorded according to the question, "For how many months did you and your partner attempt to achieve conception; that is, how much time elapsed from when you stopped using contraception until you became pregnant?" The question had the answer categories 0-6 months, 7-12 months, and 1 year or longer. Time to pregnancy is a measure closely related to fecundity, i.e., the cycle-specific probability of conception. In the analysis, the measure was dichotomized at 6 months or at 12 months, including women who became pregnant in spite of the use of contraceptives among rapid conceivers. Table 1 shows the basic characteristics of the study participants.
736
Olsen
TABLE 1. Basic characteristics of the 10,886 couples In a study of cigarette smoking, tea and coffee drinking, and subfecundrty, Denmark, 1984-1987 Variable
Mother's age (years) *19 20-29 30-39 240 Father's age (years) 519 20-29 30-39 240 No. of previous pregnancies 0 1
2 23
1-4 5-9 10-14 15-19 220 Coffee/tea drinking (cups/ day)t
0-3 4-7 28
Time to pregnancy} 0-6 months 7-12 months 1 year or longer Planned pregnancy Yes No Don't know
Not pregnant within 6 AH months women*
Variable
No. of couples
%
No.
343 7,669 2,782 92
70 26
3
23 4,471 5,388 1,004
0 41 50 9
3,967 3,732 1,942 1,245
37 34 18 11
1
Mother's smoking (cigarettes/day)*
0
TABLE 2. Prevalence of subfecundrty according to selected variables, Denmark, 1984-1987
Mother's age (years) 15-24 25-34 235 Father's age (years) 15-24 25-34 235 Shift work (mother) No Yes Mother's education (years) 8 Father's smoking (cigarettes/day) 0 1-9 10-19 220 Coffee/tea (cups/day):J: 0-3 4-7 >8 Father's smoking (cigarettes/day) 0 1-9 10-19 >20 Mother's smoking (cigarettes/day) 1-4 5-9 10-14 15-19 >20
>6 months
>12 months
ORt
95% Clf
OR
95% O
1.00§ 1.02 3.92
0.88-1.78 0.71-1.19
1.00 1.05 0.98
0.87-1.27 0.70-1.37
1.00 1.16 1.32 1.32
0.95-1.41 1.10-1.58 0.96-1.80
1.00 1.34 1.39 1.11
1.05-1.72 1.10-1.75 0.72-1.71
1.00 3.98 1.08
0.84-1.14 0.91-1.30
1.00 1.03 1.35
0.90-1.41 1.02-1.48
1.00 1.09 1.34 1.62
0.90-1.31 1.15-1.56 1.28-2.05
1.00 1.13 1.23 1.71
0.9O-1.41 1.02-1.48 1.31-2.34
1.00 1.89 .84 .68 .67
1.41-2.49 1.40-2.41 1.26-2.24 1.21-2.31
1.00 1.83 1.84 1.75 1.70
1.28-2.61 1.31-2.58 1.22-2.50 1.15-2.53
• Logistic regression including no. of pregnancies (0,1, 2, 3, and £4), mother's and father's age (15-24,25-34, and £35 years), mother's and father's alcohol drinking (0-9, 10-19, and a20 drinks/week), shift work (mother yes/no), mother's education (
Vol. 133, No. 7 Printed In US A.
A BRIEF ORIGINAL CONTRIBUTION
Cigarette Smoking, Tea and Coffee Drinking, and Subfecundity
Jorn Olsen
A population-based survey of life-style factors and subfecundity (prolonged time to pregnancy) was conducted between 1984 and 1987 in two cities in Denmark. Altogether, 11,888 women filled out a questionnaire in the last trimester of pregnancy (an 86 percent response rate). After exclusion of women who had been treated for infertility or who did not respond to the question on infertility, 10,886 subjects remained. Among nonsmokers, no association was found between subfecundity (defined as a waiting time of 1 year or more from cessation of contraception to achievement of pregnancy) and consumption of hot caffeinated beverages. For women who smoked and also consumed at least 8 cups of coffee per day (or an equivalent amount of tea), a statistically significant association was seen (odds ratio = 1.35, 95% confidence interval 1.02-1.48) for a wait of 1 year or more. Consumption of coffee was closely related to smoking habits and to a number of social factors, such as education and peer group acceptance, which may play a rote in subfecundity. Am J Epidemiol 1991 ;133:734-9. caffeine; coffee; fertility; pregnancy; smoking, tea
Caffeine is a pharmacologically active substance with stimulant effects. It is a plant alkaloid (1,3.7-trimethylxanthine) related to uric acid, adenine, and guanine (1) and is rapidly absorbed and diffused to all tissue compartments, including the preimplantation blastocyst (2, 3). Caffeine has a number of general effects, such as catecholamine release, mobilization of free fatty acids, stimulation of the central nervous system, in-
Received for publication December 4,1989, and in final form October 16, 1990. Abbreviations: Cl, confidence interval; OR, odds ratio. From the Institute of Social Medicine, University of Aarhus, Hoegb-GuWbergs Gade 8, DK-8000 Aarhus C, Denmark. (Reprint requests to Dr. Jam Olsen at this address.) This study was supported by Helsefondet, Egmont Fondet, the Danish National Board of Health, the County of Funen, Denmark, and the Comrte consuttatif de Gestion et de Cordination as part of its European studies on infertility. The author thanks Dr. Donna Baird for her valuable comments.
734
creased gastric secretion, heart rate, and basal metabolic rate, altered blood pressure, diuresis, and relaxation of smooth muscles (4). In experimental animal studies, caffeine interferes with insect reproduction (5), and reduced pregnancy rates have been observed among exposed mice (6). Caffeine is known to decrease DNA polymerase activity in human embryonic lung cells and to affect DNA excision repair (7). Thus, caffeine may modify the effect of other potential mutagens such as those found in tobacco smoke. Tobacco use has been implicated in the occurrence of a number of reproductive anomalies, the best documented being low birth weight (8). Female rats fed small doses of nicotine exhibit reduced fertility and deliver smaller litters (9). A higher frequency of sperm abnormalities has been shown in smokers relative to nonsmokers in some studies (10, 11), and female smoking has been associated with infertility as well as subfecundity (11, 12).
Smoking, Tea and Coffee Drinking, and Subfecundity
Since the metabolism of caffeine differs even among primates (10, 13), epidemiologic studies are the best approach to exploring any association between caffeine intake and fertility in humans. Furthermore, the use of coffee, tea, and in some countries also caffeinated soft drinks is very frequent, and even a modest effect on fertility could have public health and clinical relevance. Women drinking more than three cups of coffee per day during the first trimester of pregnancy have shown an increased risk of miscarriage in some studies (4). Decreased fertility has been reported for women who consume more than one cup of coffee per day while trying to become pregnant (14). It has been suggested that such an effect could be mediated via the tuberoinfundibular dopamine pathway controlling the release of prolactin (15). However, a recently published paper failed to show any risk of delayed conception associated with caffeinated beverages (16). The purpose of this analysis was to estimate the association between caffeine intake and time to pregnancy for smokers and nonsmokers among all women in the last trimester of pregnancy in two well-defined geographic areas in Denmark. Caffeine intake was measured by consumption of coffee and tea.
MATERIALS AND METHODS
All pregnant women in two cities in Denmark (Odense and Aalborg) were given a questionnaire on cigarette smoking, alcohol drinking, and eating habits. The questionnaire was handed out in the 36th week of pregnancy, and the study period ran from April 1984 to April 1987. The aim was to study the impact of social conditions and life-style factors on the outcome of pregnancy, but the questionnaire also had items on time to pregnancy and on smoking and drinking habits during the time before pregnancy. The questionnaire included questions on the father's smoking and drinking habits during the pregnancy. More than 95
735
percent of all women in the third trimester of pregnancy in the region (n = 13,815) received the questionnaire, and 11,888 participated in the study (86 percent). After the 903 women who had been treated for infertility and the 99 who did not respond to the question on infertility treatment were excluded from the data set, 10,886 subjects remained. The women were asked how many cups of coffee they usually drank per day before becoming pregnant. A similar question was also posed for tea. The question had three answer categories (0-3 cups, 4-7 cups, and 8 cups or more). Similarly, the women were asked about their consumption of beer, wine, and liquor before pregnancy. Since one bottle of beer, one glass of wine, and one serving of liquor in Denmark usually all contain the same amount of alcohol (about 12 g), all of these data were grouped into the item "number of drinks consumed per week." The question on smoking also concerned the time before pregnancy, whereas the fathers' smoking and drinking habits were only recorded as present habits (when the wife was pregnant). In Denmark, almost all coffee drunk is filter coffee. Coffee contains 14—489 mg of caffeine per serving, and tea contains 8-107 mg (17); in the analysis in this study, two cups of tea was assumed to be equivalent to one cup of coffee, which is similar to the approach taken in an earlier study (14). Time to pregnancy was recorded according to the question, "For how many months did you and your partner attempt to achieve conception; that is, how much time elapsed from when you stopped using contraception until you became pregnant?" The question had the answer categories 0-6 months, 7-12 months, and 1 year or longer. Time to pregnancy is a measure closely related to fecundity, i.e., the cycle-specific probability of conception. In the analysis, the measure was dichotomized at 6 months or at 12 months, including women who became pregnant in spite of the use of contraceptives among rapid conceivers. Table 1 shows the basic characteristics of the study participants.
736
Olsen
TABLE 1. Basic characteristics of the 10,886 couples In a study of cigarette smoking, tea and coffee drinking, and subfecundrty, Denmark, 1984-1987 Variable
Mother's age (years) *19 20-29 30-39 240 Father's age (years) 519 20-29 30-39 240 No. of previous pregnancies 0 1
2 23
1-4 5-9 10-14 15-19 220 Coffee/tea drinking (cups/ day)t
0-3 4-7 28
Time to pregnancy} 0-6 months 7-12 months 1 year or longer Planned pregnancy Yes No Don't know
Not pregnant within 6 AH months women*
Variable
No. of couples
%
No.
343 7,669 2,782 92
70 26
3
23 4,471 5,388 1,004
0 41 50 9
3,967 3,732 1,942 1,245
37 34 18 11
1
Mother's smoking (cigarettes/day)*
0
TABLE 2. Prevalence of subfecundrty according to selected variables, Denmark, 1984-1987
Mother's age (years) 15-24 25-34 235 Father's age (years) 15-24 25-34 235 Shift work (mother) No Yes Mother's education (years) 8 Father's smoking (cigarettes/day) 0 1-9 10-19 220 Coffee/tea (cups/day):J: 0-3 4-7 >8 Father's smoking (cigarettes/day) 0 1-9 10-19 >20 Mother's smoking (cigarettes/day) 1-4 5-9 10-14 15-19 >20
>6 months
>12 months
ORt
95% Clf
OR
95% O
1.00§ 1.02 3.92
0.88-1.78 0.71-1.19
1.00 1.05 0.98
0.87-1.27 0.70-1.37
1.00 1.16 1.32 1.32
0.95-1.41 1.10-1.58 0.96-1.80
1.00 1.34 1.39 1.11
1.05-1.72 1.10-1.75 0.72-1.71
1.00 3.98 1.08
0.84-1.14 0.91-1.30
1.00 1.03 1.35
0.90-1.41 1.02-1.48
1.00 1.09 1.34 1.62
0.90-1.31 1.15-1.56 1.28-2.05
1.00 1.13 1.23 1.71
0.9O-1.41 1.02-1.48 1.31-2.34
1.00 1.89 .84 .68 .67
1.41-2.49 1.40-2.41 1.26-2.24 1.21-2.31
1.00 1.83 1.84 1.75 1.70
1.28-2.61 1.31-2.58 1.22-2.50 1.15-2.53
• Logistic regression including no. of pregnancies (0,1, 2, 3, and £4), mother's and father's age (15-24,25-34, and £35 years), mother's and father's alcohol drinking (0-9, 10-19, and a20 drinks/week), shift work (mother yes/no), mother's education (
