BACKGROUND. The rate of recurrence of a broad range of birth defects may decrease among women who change residence after the birth of their first infant. The aim of the present study was to determine the effect of changing residence on the recurrence of congenital facial-cleft defects. METHODS. We identified 4189 women who had infants with facial-cleft defects by linking a data base comprising the records of children with facial clefts born between 1952 and 1987 with the Central Person Registry in Denmark. Among the 4189 mothers, 1902 each had additional children after the first child with a facial-cleft defect. A total of 2692 younger siblings were identified. We compared the proportion of infants with facial-cleft defects among the younger siblings between mothers who had changed municipalities or sexual partners and those who had not. RESULTS. Changing the municipality of residence did not decrease the frequency with which facial-cleft defects recurred in younger siblings. Among the 907 infants of mothers who changed municipalities but not partners, 29 (3.2 percent) had facial-cleft defects, as compared with 48 (3.4 percent) of 1425 infants of mothers who changed neither municipality nor partner (relative risk, 0.9; 95 percent confidence interval, 0.6 to 1.5). However, a change of partner reduced the recurrence risk significantly. Among 236 infants of mothers who changed partners, 1 (0.4 percent) had a facial-cleft defect, as compared with 77 (3.3 percent) of 2350 infants of mothers who did not change partners (relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). CONCLUSIONS. Recurrence of facial-cleft defects is not linked to the residence of the mother, but having a different partner reduced a woman's risk of having a second child with this defect.
During 1992-1995, 430 Danish couples were recruited after a nationwide mailing of a letter to 52,255 trade union members who were 20-35 years old, lived with a partner, and had no children. The couples were enrolled into the study when they discontinued birth control, and they were followed for six menstrual cycles or until a clinically recognized pregnancy. At enrollment and each month throughout the follow-up, both partners completed a questionnaire that asked them about their smoking, alcohol consumption, and intake of caffeinated beverages. The effect of current smoking and smoking exposure in utero was evaluated by using a logistic regression model with pregnancy outcome of each cycle in a Cox discrete model calculating the fecundability odds ratio. After adjustment for female body mass index and alcohol intake, diseases in female reproductive organs, semen quality, and duration of menstrual cycle, the fecundability odds ratio for smoking women exposed in utero was 0.53 (95% confidence interval (CI) 0.31-0.91) compared with unexposed nonsmokers. Fecundability odds ratio for nonsmoking women exposed in utero was 0.70 (95% CI 0.48-1.03) and that for female smokers not exposed in utero was 0.67 (95% CI 0.42-1.06). Exposure in utero was also associated with a decreased fecundability odds ratio in males (0.68, 95% CI 0.48-0.97), whereas present smoking did not reduce fecundability significantly. It seems advisable to encourage smoking cessation prior to the attempt to conceive as well as during pregnancy.
Antidepressants appear to promote tumor growth in experimental studies; however, results from epidemiologic studies are inconclusive. We used a population-based cohort study to estimate the incidence of cancer after antidepressant treatment in 39,807 adult users of antidepressants identified in the Prescription Database of the County of North Jutland, Denmark between January 1, 1989 and December 31, 1995. Information on cancer occurrence was obtained from the Danish Cancer Registry. We categorized exposure according to use of tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, or monoamine oxidase inhibitors. In the follow-up period beginning 1 year after first known prescription, there were 966 cancers among users of antidepressants; our population estimate suggested an expected number of 946 for an overall standardized incidence ratio of 1.0 (95% confidence interval = 1.0-1.1). Users of tricyclic antidepressants had an excess of non-Hodgkin's lymphoma, with the risk increasing with the number of prescriptions of tricyclic antidepressants. The standardized incidence ratio was 2.5 (95% confidence interval, 1.4-4.2) for those with five or more prescriptions. Our results provide little evidence that antidepressants promote cancer at other sites, except for a possible effect of tricyclic antidepressants and tetracyclic antidepressants on non-Hodgkin's lymphoma.
The effects of caffeine consumption on delayed conception were evaluated in a European multicenter study on risk factors of infertility. Information was collected retrospectively on time of unprotected intercourse for the first pregnancy and the most recent waiting time episode in a randomly selected sample of 3,187 women aged 25-44 years from five European countries (Denmark, Germany, Italy, Poland, and Spain) between August 1991 and February 1993. The consumption of caffeinated beverages at the beginning of the waiting time was used to estimate daily caffeine intake, which was categorized as 0-100, 101-300, 301-500, and > or = 501 mg. Risk of subfecundity (> or = 9.5 months) and the fecundability ratio, respectively, were assessed by logistic regression and Cox proportional hazard analyses, adjusting for age, parity, smoking, alcohol consumption, frequency of intercourse, educational level, working status, use of oral contraceptives, and country. A significantly increased odds ratio (OR) of 1.45 (95% confidence interval (CI) 1.03-2.04) for subfecundity in the first pregnancy was observed for women drinking more than 500 mg of caffeine per day, the effect being relatively stronger in smokers (OR = 1.56, 95% CI 0.92-2.63) than in nonsmokers (OR = 1.38, 95% CI 0.85-2.23). Women in the highest level of consumption had an increase in the time leading to the first pregnancy of 11% (hazard ratio = 0.90, 95% CI 0.78-1.03). These associations were observed consistently in all countries as well as for the most recent waiting time episode. The authors conclude that high levels of caffeine intake may delay conception among fertile women.
Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At enrollment and in six cycles of follow-up, both partners filled out a questionnaire on different factors including smoking habits and their intake of coffee, tea, chocolate, cola beverages, and chocolate bars. In all, 1596 cycles and 423 couples were included in the analyses. The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [95% confidence interval (CI) 0.60-1.31], whereas women with a higher caffeine intake had a FR = 0.63 (95% CI 0.25-1.60) after adjusting for female body mass index and alcohol intake, diseases of the female reproductive organs, semen quality, and duration of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake.
Increased occurrences of malignancies of the lymphatic and haematopoietic tissues have been reported from industries in which employees are potentially exposed to styrene. The aim of the study reported here was to describe cancer incidence in the reinforced plastics industry in Denmark. A total of 64,000 employees of 552 Danish companies assessed to have produced reinforced plastics at any time since the 1960s were identified from a public administrative registry of all Danish employers and wage earners. Cancer incidence in the population was compared with similar rates for the population at large. No excess risk for all neoplasms was observed. Among male employees, increased risks were found for cancer of the lung (396 cases; relative risk [RR], 1.15; 95% confidence interval, 1.04-1.27), of the pleura (20 cases; RR, 2.33; 1.42-3.60), of the nasal cavities (nine cases; RR, 1.55; 0.71-2.94), of non-Hodgkin's lymphoma (61 cases; RR, 1.27; 0.97-1.63) and for leukaemia (61 cases; RR, 1.15; 0.88-1.48). Among female employees, a reduced risk for non-Hodgkin's lymphoma was observed (one case; RR, 0.16; 0.00-0.88). Some support was thus found for previous reports of increased risk for respiratory cancers and for malignancies of the lymphatic and haematopoietic tissues. The results must be interpreted with caution, however, owing to shortcomings in the design of the study.
We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.
Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+ in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17911 patients who received at least one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned.