Dual effect of short interval between first and second birth on ductal breast cancer risk in Finland.

OBJECTIVE: A short interval between the first and second birth was associated with an increased risk of advanced ductal breast cancer among women with 5+ childbirths in our previous study. We now evaluated the significance of this risk factor and its relation to the age at first birth among mothers with 2-4 children. METHODS: The cohort of 190,949 Finnish women with 2-4 children comprised 3,834 women with ductal breast cancer diagnosed before 2009. Conditional logistic regression for case-control design nested within the cohort was used to estimate proportional hazard ratios (HR) associated with the birth interval. Controls were matched for age and number of children. Age at the first birth and the interval from the last birth to cancer were co-variables. RESULTS: Among women with the first birth <30 years, the HR of advanced ductal breast cancer at 50+ years for a short (<1.5 years) versus long (>3 years) interval between the first and second birth was 0.48 (95% Confidence Interval 0.33-0.70). Among women with the first birth at 30+ years, the HR of this cancer type diagnosed before the age of 50 years for a short versus long interval between the first and second birth was 5.83 (95% CI 2.30-14.8). CONCLUSION: The interval between first and second birth strongly influences the risk of ductal breast cancer. Because second pregnancy soon after the first one decreased the risk of ductal breast cancer in young primiparas but increased the risk in older primiparas, it is likely that in such circumstances second pregnancy continues the actions initiated by the first pregnancy/breast-feeding.

Birth intervals and breast cancer risk.

BACKGROUND: The interval between successive births (birth interval) may affect breast cancer risk, whereas interval from last birth to cancer onset may modify its behaviour. METHODS: The study cohort consisted of 29 488 Finnish grand multiparous (GM) women, including 628 women with breast cancer. Conditional logistic regression for case-control design nested within the cohort was used to estimate proportional hazards (referred as relative risks, RR). Age at first birth and parity were co-variables. RESULTS: Short interval (<1 year) between first and second birth increased the risk of advanced ductal breast cancer at ages < 50 years (RR=5.29; 95% CI 2.00-14.0) as compared to interval 3+ years. The risk of advanced ductal cancer was also large (RR = 4.00; 95% CI 1.19-13.4) shortly (<3 years) after last birth as compared with the period 15+ years. CONCLUSIONS: Short birth interval-associated excess breast cancer risk may be related to stimulatory effects of female steroid hormones produced during two closely connected pregnancies, or defective breast maturation owing to failures in breastfeeding.

Moulds, bacteria and cancer among Finns: an occupational cohort study.

BACKGROUND: Some environmental moulds and bacteria produce carcinogenic toxins. AIM: To study associations between work-related exposure to moulds and bacteria and cancers in Finland. METHODS: A cohort of all economically active Finns in the population census in 1970 were followed-up for 30 million person-years. Subsequent cancer cases were identified through record linkage with the Finnish Cancer Registry. Observed and expected numbers of cancer cases were calculated by occupation, sex, birth cohort and period of observation. Exposures to moulds of agricultural and industrial origin and to bacteria of non-human origin were estimated with the Finnish Job-Exposure Matrix. RESULTS: Men with the highest mould and bacterial exposure had a reduced relative risk for lung cancer (RR 0.7, 95% CI 0.6 to 0.9 for moulds and RR 0.9, 95% CI 0.8 to 1.0 for bacteria). Women in the highest mould and bacterial exposure category had RRs of 3.1 (95% CI 1.0 to 9.2) and 2.6 (95% CI 1.5 to 4.7) for cervical cancer, respectively. The respective RRs for lip cancer were 2.4 (95% CI 1.2 to 5.1) and 1.6 (95% CI 1.2 to 2.2). CONCLUSIONS: Exposures at the investigated concentrations to either moulds or bacteria are unlikely to be major risk factors of cancer, although suggestions of risk increases were observed for some cancer types. It has been suggested previously that the decreased risk for lung cancer is due to the protective effect of endotoxins.

Scholastic achievements of children with brain tumors at the end of comprehensive education: a nationwide, register-based study.

BACKGROUND: Cancer treatment may affect school performance. Scholastic achievements after childhood brain tumors have not been previously reported on the level of actual grades. PATIENTS AND METHODS: Patients with brain tumor (n = 300) were identified from the Finnish Cancer Registry. Population controls (n = 1,473) were matched for age, gender, and place of living. Their ninth grade school reports were obtained from Statistics Finland. Age at diagnosis and cranial irradiation (CRT) were considered in analyses, and the level of parental education was taken into model as a covariate. RESULTS: Six percent of patients did not finish their comprehensive school at the usual age. Patients had lower overall averages than their controls (95% CI for the difference -0.30, -0.16). Girls differed from their controls independently of the age at diagnosis or CRT. Boys treated with CRT at school age, but not before school age, had poorer results than their controls (95% CI -0.65, -0.18). The grades of patients were significantly lower in each school subject, and differed most in foreign language. Young girls with CRT had greatest differences from their controls (95% CI -1.73, -0.86) in this subject. In mathematics, patients diagnosed before school age had greatest difference from their controls. In their mother tongue, patients differed less from their controls. CONCLUSIONS: Few patients with brain tumor missed the ninth grade certificate at the age of 16. Grades in foreign language (representing verbal performance) were most affected. However, the patients fared poorer than controls in each subject. The difference was most pronounced among girls. Girls were more sensitive to the adverse effects of irradiation.

Nordic biological specimen banks as basis for studies of cancer causes and control--more than 2 million sample donors, 25 million person years and 100,000 prospective cancers.

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

Occupational exposure to eight organic dusts and respiratory cancer among Finns.

BACKGROUND: There is inconclusive evidence concerning cancer risks of organic dusts. AIM: The carcinogenic exposures are mainly inhalatory and the authors therefore studied associations between occupational exposure to eight different organic dusts and respiratory cancers in Finland. METHODS: The authors followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person-years during 1971-95. Incident cases of nasal, laryngeal, and lung cancer and mesotheliomas were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to eight organic dusts with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as a product of prevalence, level, and estimated duration of exposure. Standardised incidence ratios (SIR) and 95% confidence intervals (CI) adjusted for age, period, and social class were calculated for each organic dust using the economically active population as the reference. RESULTS: A total of 20 426 incident cases of respiratory cancer were observed. Slightly increased risk was observed among men exposed to wood dust for nasal cancer (SIR 1.42, 95% CI 0.79 to 2.44). For laryngeal cancer, men exposed to plant dust (mainly grain millers) had a raised SIR in the high exposure class (SIR 3.55, 95% CI 1.30 to 7.72). Men exposed to wood dust had a raised SIR for lung cancer, but only in the low exposure class (SIR 1.11, 95% CI 1.04 to 1.18). Women exposed to wood dust showed an increased SIR for mesotheliomas in the low exposure class (SIR 4.57, 95% CI 1.25 to 11.7) and some excess in the medium exposure category. CONCLUSIONS: Exposure to organic dusts is unlikely to be a major risk factor of respiratory cancer. Even exposure to wood dust which is a major exposure in Finland seems to have minor effect for nasal cancer. The authors found suggestive evidence that exposure to grain dust may increase the risk of laryngeal cancer, and some support to the hypothesis that exposure to textile dust, and to plant and animal dust (agricultural dusts) may decrease the risk of lung cancer.

A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland.

Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86 978 GM women. Standardised incidence ratios (SIR) were calculated from the numbers of observed and expected cases. Interval analyses by parity, age at first birth and average birth interval were done using multivariate Poisson regression. Seroprevalence of human papillomavirus (HPV) 16 and Chlamydia trachomatis was tested among 561 GM women and 5703 women with 2-4 pregnancies. The incidence among GM women was slightly above the national average for squamous cell carcinoma of cervix uteri (SIR 1.21, 95% CI 1.05-1.40) and CIN3 (1.37, 95% CI 1.17-1.58), but lower for adenocarcinoma (SIR 0.77, 95% CI 0.52-1.10). The seroprevalence of HPV16 and Chlamydia trachomatis among GM women was lower than in the reference population, except among those women who had their child under age 19. Age under 20 years at first birth increased the risk of CC and CIN3 especially in premenopausal GM women, while increasing parity had no effect. The small relative risks of CC and CIN3 among GM women in our study as compared to studies from other countries can be explained by the exceptionally low prevalence of STIs in Finnish GM women. The observed SIRs between 1.2 and 1.4 should be interpreted to represent increased risk attributable to grand multiparity. The increased incidence of CC and CIN3 among young GM women suggests causal association to HPV 16 and Chlamydia trachomatis infections.

Grand multiparity and the risk of breast cancer: population-based study in Finland.

OBJECTIVES: The significance of reproductive factors on breast cancer risk has so far been characterized in populations with 5-paras as the highest category of parity. We extended these studies to a nationwide cohort of women with at least five births (grand multiparas = GM) by assessing the significance of parity, age at first birth, and average birth interval to the risk of breast cancer. METHODS: The study cohort obtained from the Population Register of Finland comprised 86,978 GM-women; the incidence of cancer cases was obtained from the populated-based Finnish Cancer Registry. During a follow-up of about 2 million person-years, 1508 breast cancers were obtained. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cases by the number expected on the basis of national rates. RESULTS: In the GM cohort the incidence of breast cancer was low (SIR 0.55, 95% confidence interval 0.52-0.58). The relative risk decreased significantly from 5-paras (SIR 0.60, adjusted for the other study variables) to 8-paras (SIR 0.40). The increase in the age at first birth from less than 20 years to 30+ years nearly doubled the risk (SIR from 0.40 to 0.73). Parity was a significant risk determinant only in ductal cancer, while shortening the birth interval was protective only in lobular cancer. The incidence of advanced breast cancer among GM-women exceeded the population rate in premenopausal women and in women with first birth at the age of 30 years or more. CONCLUSIONS: Our study demonstrated that young age at first birth and increasing number of births were independent and powerful protective factors from the fifth child onwards, while birth interval was weak in this respect. The tumor morphology and the clinical advancement of malignancy modified the dependence of breast cancer risk on reproductive variables.

Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland.

Reports on the prognosis of familial breast cancer patients have been contradictory. True differences in survival, if they exist, would have important implications for genetic counselling and in treatment of hereditary breast cancer. We assessed the survival rates of 359 familial breast cancer patients (32 patients from BRCA1-positive families, 43 patients from BRCA2-positive families and 284 patients from BRCA1/2-negative breast cancer families) and compared them with those of all other breast cancer patients diagnosed in Finland from 1953 to 1995 (n = 59,517). Cumulative relative survival rates (RSR) were calculated by dividing the observed survival rates by the expected ones. The expected survival rates were derived from the sex, age and calendar year specific life-tables of the general population in Finland. Regression model was used to calculate relative excess risk of death (RR) and to adjust for confounding factors. The overall 5-year RSR of the patients in the BRCA1 families, BRCA2 families, non-BRCA1/2 families and among sporadic cases was 67%, 77%, 86% and 78%, respectively. However, we found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population. In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63--2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39--1.57) than among the general breast cancer patient population. The RR among patients in the non-BRCA1/2 families did not differ from that of the general patient population.

Familial cancer risks in affected sibships: results from the Swedish family-cancer database.

We used the nationwide Swedish Family-Cancer Database to assess familial risks to sibs in sibsibs where at least two sibs had concordant cancer and their parents either concordant or discordant cancer. Familial relative risks (FRRs) were calculated by comparing to concordant sib-pairs whose parents had no cancer. Cancer sites were included if at least ten such concordant sib-pairs were found. In situ cancers were included in order to increase the numbers of cases. Concordant triads, one parent and the sib-pair affected, had an FRR over 100 for thyroid (FRR 399), colon, all bowel, and ovarian cancer. In these cancers, some 40% or more of the concordant sib-pairs belonged to this group. Melanoma and cancer of the nervous system showed FRRs of about 20, and invasive breast cancer of only 2. 9; in these cancers no more than 10% of the concordant sib-pairs belonged to the concordant triads. Discordant family sets, one or two parents presenting with a cancer discordant from that of the sib-pair, showed an FRR of about 3.0 and breast cancer about 2.0, suggesting the involvement of familial effects shared by many forms of cancer.

Cognitive deficits after cryptogenic infantile spasms with benign seizure evolution.

Between 1989 and 1994, 18 children with cryptogenic infantile spasms-defined by normal development before onset of spasms, symmetrical hypsarrhythmia or multifocal spikes, and typical spasms on presentation, and no abnormal findings on aetiological studies including neuroradiology-were diagnosed and treated. To assess the risk of cognitive impairment later in life, 15 of these 18 children whose spasms completely resolved within the first year of life were studied. Age at onset of spasms varied between 4.4 and 9.8 months (mean 6.5 months). Children were effectively treated with adrenocorticotrophic hormone (10 children), pyridoxine (three), vigabatrin (one), or sodium valproate (one). Spasms lasted between 11 and 138 days (mean 50 days) and stopped between the age of 6.3 and 10.2 months(mean 8.1 months). EEGs normalized between the age of 7.1 and 13.2 months (mean 9.4 months). Early development was assessed on presentation and within a few months after spasms had stopped. A detailed neuropsychological assessment was performed between the age of 4.0 and 5.9 years. Twelve children had normal intelligence; specific cognitive deficits were found in five. Three children had mild learning disability. Abnormal developmental status at age 8 to 15 months after complete resolution of spasms and EEG abnormalities was associated with cognitive deficits at age 4 to 6 years.

Parental age and risk of sporadic and familial cancer in offspring: implications for germ cell mutagenesis.

We used the nationwide Swedish Family-Cancer Database to analyze the effect of parental age on cancer in offspring at ages 15-53 years. We studied 13 cancer sites, including 37,877 people. Data on familial and sporadic cancers were analyzed separately. We adjusted for age of spouse, year of diagnosis, and birth order. Rate ratios (RRs) were calculated by Poisson regression. Maternal age was associated with sporadic melanoma and leukemia, causing a 30% excess if mothers were more than 40 years vs. less than 20 years of age. A marginal effect of about 10% of both maternal and paternal age was observed for sporadic breast cancer. Paternal age increased the RR of sporadic nervous system cancer by about 15%. Accumulation of chromosomal aberrations and mutations during the maturation of germ cells may be a mechanism for these findings. In familial cancers of colon, melanoma, and thyroid, higher age showed an apparent protective effect, which was also noted for sporadic cervical cancer and melanoma. The results argue against major age-induced mutagenic/carcinogenic effects on germ cells as well as against age-induced adverse cancer-related hormonal effects during pregnancy. Because two or more mutations are required for adult cancers, however, these cancers may be an insensitive indicator of germ cell mutagenesis.

Reduced fertility among female wood workers exposed to formaldehyde.

BACKGROUND: The aim of the study was to investigate whether exposure to formaldehyde, organic solvents or other chemicals in the wood-processing industry affects the fertility of women. METHODS: For this purpose, a retrospective study on time to pregnancy was conducted among female wood workers who had given birth during 1985-1995. Data on pregnancy history, time to pregnancy, occupational exposures, and potential confounders were collected by a questionnaire; 64% (699/1,094) participated. The exposure assessment was conducted by an occupational hygienist. The data on time to pregnancy were analyzed with the discrete proportional hazards regression. RESULTS: Exposure to formaldehyde was significantly associated with delayed conception: adjusted fecundability density ratio, FDR, was 0.64 (95% CI 0.43-0.92). At high exposure if no gloves were used, the FDR was 0.51 (% CI 0.28-0.92). Exposure to phenols, dusts, wood dusts, or organic solvents was not related to the time to pregnancy. Additionally, an association was observed between exposure to formaldehyde and an increased risk of spontaneous abortion (concerning previous spontaneous abortions, reported by the women). Associations between exposure to formaldehyde or to organic solvents and endometriosis, and between exposure to organic solvents or to dusts and salpingo-oophoritis were also suggested. CONCLUSIONS: The study suggests that a woman's occupational exposure to formaldehyde has an adverse effect on fertility.

Modification of cancer risk in offspring by parental cancer (Sweden).

OBJECTIVES: Familial cancer risks were studied in offspring whose parents had a similar (concordant) or a different (discordant) cancer in order to assess the modification of cancer risks from one generation to another. METHODS: We used the nation-wide Swedish Family-Cancer Database to calculate familial rate ratios (FRRs) to the offspring when their parents had concordant and discordant cancers. Cancer sites were included if there was at least one pair of parents with the same cancer. In situ cancers were included in a separate analysis in order to increase the numbers of cases. RESULTS: The risk of colon, all bowel, lung and breast cancer and melanoma increased 1.1-1.2 times when one parent and 1.3-1.6 times when two parents had any discordant cancer, suggesting involvement of environmental and hereditary effects shared by many forms of cancer. When both parents had colon cancer or melanoma, the respective risks in the offspring were 3.0 and 9.3 but only based on single triplets. For all bowel cancer the risk was 3.4, approximately multiplicative from the familial one parent-offspring risk. For concordant lung and breast cancer triplets the risk in offspring was 11.8 and 29.4, respectively. CONCLUSIONS: Even discordant cancer in parents increased cancer risk in offspring. This may be due to environmental and hereditary causes, and deserves consideration in epidemiological studies. The high risks in families where both parents had the same cancer suggest interactions of hereditary and environmental factors.

Parental age as a risk factor of childhood leukemia and brain cancer in offspring.

We use here the Swedish Family-Cancer Database to analyze the time trends in childhood leukemia and brain cancer between 1960 and 1994 and the effect of parental age on childhood leukemia and brain cancer of some 1500 cases each. The database includes all persons born in Sweden after 1940 with their biological parents, over 6 million individuals, whose cancers were retrieved from the Swedish Cancer Registry from years 1958-1994. Incidence in cancer increased from 1960 to 1994; low grade astrocytoma accounted for most of the increase, whereas high grade astrocytoma has not increased in incidence. There has been a moderate increase in leukemia to about 1980. We found a parental age effect for both leukemia and brain cancer, with the former (of about 50% excess in those over 35 years) being mediated by maternal age and the latter (of about 25% excess) by paternal age. Accumulation of chromosomal aberrations and mutations during the maturation of germ cells is a likely mechanism for these findings. They can help to explain partially the secular trends of these malignancies and the excess risks in offspring of the well educated.

Incidence of death in patients with intractable epilepsy during nitrazepam treatment.

PURPOSE: Increased risk of death has been reported in patients with intractable epilepsy (IE) taking nitrazepam (NZP). METHODS: Between January 1983 and March 1994, 302 patients with IE were entered into a NZP compassionate-plea protocol. NZP was discontinued if there was < 50% seizure reduction or significant side effects. In some patients with > 50% reduction, it also was discontinued for lack of sufficient effect. At the end of follow-up for this study, 62 patients remained taking NZP. Patients took NZP from 3 days to 10 years. RESULTS: Twenty-one of 302 patients died after institution of NZP. Fourteen of 21 of these were taking NZP at death, and in five of 21, the NZP had been discontinued. Two patients were excluded from analysis, because it is unclear whether NZP had been discontinued before death. Six other patients were lost from follow-up. Of the 14 deaths with NZP, seven were sudden, six were of pneumonia, and one was of cystinosis. Nine had at least one contributing factor, such as dysphagia, gastroesophageal reflux, or recurrent aspirations. The 294 patients took NZP for a total of 704 patient years (ptyrs), and were discontinued for a total of 856 ptyrs. There were 1.98 deaths/ 100 ptyrs on NZP compared with 0.58 deaths/100 ptyrs without NZP, most of the former being associated with side effects of NZP. Mortality in patients younger than 3.4 years was 3.98 with NZP compared with 0.26 deaths/100 ptyrs without NZP (p = 0.0002). Corresponding figures in patients 3.4 years or older were 0.50 and 0.86 deaths/100 ptyrs, respectively. CONCLUSIONS: NZP therapy for epilepsy apparently increases the risk of death, especially in young patients with IE. This should be considered in antiepileptic drug (AED) management decisions.

Age-specific familial risks in common cancers of the offspring.

Quantitative data on familial cancer risks are important for clinical, psychological and scientific reasons. The available estimates carry many uncertainties due to sample size and possible bias in data collection and often refer to first-degree relatives of unspecified age and sex. We calculated sex- and age-specific familial hazard ratios (FHRs) of cancer in offspring aged 15-53 years of cancer probands at 16 male and 17 female cancer sites, based on registered nation-wide data, free from bias. The familial risks in offspring were high, > 5 for thyroid (FHR 10.7 in all offspring, CI 95% 6.9-16.6), and testicular cancer (FHR 5.4, CI 95% 2.6-11.3), or intermediate, FHR 2-5, for colon, rectal, lung, breast, cervical, uterine, ovarian, skin (melanoma and squamous cell) and other endocrine gland cancers. FHRs < 2.0 were observed for stomach, renal and nervous system cancers, lymphomas and leukemias. Some sex differences were observed: FHRs for male breast (only 2 cases) and thyroid cancers were over 2 times higher than the respective female ones. When parents were diagnosed before age 50 years, offspring were at an increased risk of familial breast, renal, skin (melanoma), nervous system, thyroid and non-thyroid endocrine gland cancers, particularly affecting young (< 40 years) individuals. The parental diagnostic age also affected offspring's risk of colon, rectal, uterine and ovarian cancers, but young individuals were not at a particular risk. No effect of age was noted for cervical cancer and lymphoma.

Time to pregnancy among the wives of men exposed to organic solvents.

OBJECTIVES: To assess whether paternal exposure to organic solvents is associated with decreased fertility. METHODS: A retrospective time to pregnancy study was conducted among men biologically monitored for organic solvents. The workers were classified into exposure categories on the basis of work description and the use of solvents as reported in the questionnaires, and on biological exposure measurements. The relative fecundability density ratios (FDR--an analogue of incidence density ratio of clinically recognised pregnancies) were calculated with discrete proportional hazards regression. RESULTS: After three mailings 316 (72.1%) wives of the monitored men participated. The final study population consisted of 282 couples who did not use contraception at the beginning of pregnancy. The FDRs, adjusted for potential confounders, were 0.80 (95% confidence interval (95% CI) 0.57 to 1.11) and 0.74 (95% CI 0.51 to 1.06) for high or frequent and low or intermediate exposure, respectively. High or frequent and low or intermediate exposure were related to decreased fecundability among primigravida (FDRs 0.36; 95% CI 0.19 to 0.66 and 0.53; 95% CI 0.27 to 1.04) but not among couples with at least one previous pregnancy (FDRs 0.96; 95% CI 0.62 to 1.49 and 0.77; 95% CI 0.47 to 1.24). CONCLUSIONS: The findings of the study provide limited support for the hypothesis that paternal exposure to organic solvents might be associated with decreased fertility. Further studies with careful design are warranted.

Validity aspects of exposure and outcome data in reproductive studies.

Some validity aspects related to various sources on pregnancy outcome and exposure are discussed. Register-based data on outcome and exposure are compared with workers' own reports. The problems in the use of personal interview data on pregnancies are related to the possible selection in recognition and reporting the pregnancy outcome. The best way of avoiding misclassification of outcome is to resort to medical records whenever possible. Misclassification of exposure is most likely a common reason for discrepancies in results in reproductive studies. The misclassification of exposure deflates the power of the study to detect the true difference between exposed and nonexposed subjects, particularly when the prevalence of exposure is low. It is of great importance to confirm, if possible, the exposure status by using two or more independent sources of data.

Time to pregnancy among women occupationally exposed to lead.

A retrospective time-to-pregnancy study was conducted among women biologically monitored for exposure to lead. The women were participants of a previous study on spontaneous abortion. They were classified into exposure categories on the basis of questionnaire information, and individual blood lead (B-Pb) measurements. The adjusted incidence density ratios (IDR) of clinically recognized pregnancies were .93 (95% confidence interval [CI] .56 to 1.57) for very low (B-Pb < .5 mumol/L), .84 (CI .48 to 1.45) for low (B-Pb .5 to .9 mumol/L), and .80 (CI 0.42 to 1.54) for higher (B-Pb > or = 1.0 mumol/L) exposure compared with no exposure, in the discrete proportional hazards analysis. Exposure to inorganic lead was not associated with fecundability at current, low-exposure levels. The suggestive finding among the eight most heavily exposed women (B-Pb 1.4 to 2.4 mumol/L, IDR .53; CI .19 to 1.52) should be confirmed or refuted in a larger study.