O14.1 TIME TO PREGNANCY AMONG FEMALE GREENHOUSE WORKERS

N. Roeleveld, R. Bretveld, G. Zielhuis.Department of Epidemiology and Biostatistics, University Medical Centre, Nijmegen, the Netherlands

Introduction: Fertility problems are a rising public health issue in industrialised countries, with an estimated incidence of 15% for infertility. Exposure to pesticides with endocrine disrupting properties is a possible risk factor for infertility and subfertility, which can be measured by time to pregnancy (TTP). As female greenhouse workers constitute a major occupational group of workers exposed to pesticides at childbearing age, a study was performed among female greenhouse workers (n = 484) and a reference group of female workers not exposed to pesticides (n = 679).

Methods: Data were collected through postal questionnaires with detailed questions about TTP and pregnancy outcomes of the last pregnancy, as well as questions on lifestyle (such as smoking habits, and coffee and alcohol consumption), work tasks, and occupational exposures of the women and their partners in the 6 months before conception of the last pregnancy. The relationship between TPP and exposure to pesticides was studied by means of the Cox proportional hazards model. In addition, we evaluated the different sources of bias that may occur in studies on TPP.

Results: The crude fecundability ratio (FR) for pesticide exposure was 1.18 (95% confidence interval 1.03 to 1.35), but after correction for confounding, the FR decreased to 1.10 (0.90 to 1.35). The evaluation of potential biases showed that these results were biased by the reproductively unhealthy worker effect. Therefore, we analysed only primigravidae, and stratified on work status in the final analyses. The crude FR for full time workers exposed to pesticides while trying to get pregnant for the first time was 0.65 (0.43 to 0.98) and the confounder adjusted FR was 0.63 (0.41 to 0.95). The crude FR for part time primigravidae was 1.72 (65 to 4.51), but this FR was based on small numbers, which precluded correction for confounding.

Conclusions: The results of this study show that female greenhouse workers who are exposed to pesticides and work full time take longer to conceive their first pregnancy than other working women. An explanation for these findings might be that the female hormone system is especially susceptible to the hormone disrupting properties of some pesticides prior to the initial conception.

O14.2 IMMUNOLOGICAL EXPOSURES IN NORWEGIAN AGRICULTURE AND PRE-ECLAMPSIA

K. C. Nordby¹, L. M. Irgens², P. Kristensen¹.¹National Institute of Occupational Health, Oslo; ²Medical Birth Registry, Bergen; Norway

Introduction: Immunological mechanisms are involved in pre-eclampsia. We hypothesised that immunomodulating substances such as mycotoxins or endotoxins might affect pre-eclampsia risk. Associations between indicators of immunomodulating exposures in agriculture and pre-eclampsia are reported.

Methods: In a Norwegian cohort of contributors to agricultural censuses conducted in1969–1989 by Statistics Norway, 65 777 pregnancies to female farmers (annual farm work input of >500 hours) were followed in the Medical Birth Registry of Norway. Cases were defined by ICD-8 637: pre-eclampsia and hypertension during pregnancy. Data on farm production and fungal warnings 1973–1990 (a marker of temperate and humid climate known to favour fungal growth and mycotoxin formation) was obtained and allocated to each farm. Prevalences were studied in strata of exposure indicators using Poisson regression models adjusted for maternal age and parity. Rate ratios (RR) and 95% confidence intervals (CI) were computed.

Results: We identified 4508 cases, implying an RR of 6.9 % (95% CI 6.7 to 7.1). Preeclampsia showed moderate associations with grain production (RR 1.19; 95% CI 1.11 to 1.26), animal farming (1.08; 1.00 to 1.17) fungal warnings (1.05 (0.97 to 1.13) in the stratum of 12−18 warnings, and 1.19 (1.11 to 1.27) in the stratum of 19–46 warnings) with 0–11 warnings as reference. Associations with indicators of pesticide use, horticulture, farm size, agricultural education by the farmer, weighted family income from the farm, and work input by the baby’s father all showed confidence intervals including 1.0.

Conclusions: Exposure to immunomodulating substances as indicated by grain farming, animal farming, and fungal warnings could possibly have a small but significant effect on pre-eclampsia incidence, thus supporting the study hypothesis. Our use of exposure proxies as surrogates for actual exposures to immunomodulating substances introduces a non-dependent misclassification of the exposure that would attenuate any true exposure–response association, thus underestimating the true strength of associations. The use of exposure proxies also warrants that inferences from the study should be made with caution.

O14.3 REPRODUCTIVE OUTCOME AMONG SWEDISH RUBBER INDUSTRY EMPLOYEES

Z. Mikoczy, L. Hagmar, K. Jakobsson.Department of Occupational and Environmental Medicine, Lund University Hospital, Lund, Sweden

Introduction: Work in the rubber industry may involve exposure to a wide range of toxic agents, many of which are mutagenic. Enhanced risks for bladder cancer, lung cancer, and leukaemias among rubber industry workers have been reported. Very little is however known of the reproductive health among these workers.

Objective: To investigate whether employment in the Swedish rubber industry had a negative impact on reproductive health.

Methods: The identity of 18 308 children born between 1973 and 2001 to a cohort of 18 518 former and current male and female employees in the Swedish rubber industry was obtained from Statistics Sweden. Information on maternal background variables and birth outcome was obtained from the Medical Birth Register. Continuous maternal employment during the 9 months before childbirth, and paternal employment during the sperm maturation period (9–12 months before childbirth) were considered as exposed periods. As a reference group we used 33 414 children of female food industry workers. Student’s t test was used for group comparisons of continuous variables, and logistic regression for dichotomised variables.

Results: Involuntary childlessness for 1 year or more was reported in 7.3% of births with any parent ever employed in the rubber industry, compared with 5.5 % among food industry workers, corresponding to a prevalence odds ratio (POR) of 1.35 (95% confidence interval (CI) 1.16 to 1.57). The sex ratio was reversed when the mother was a rubber industry employee, with 52% girls, compared with 48% among the referents. The POR for having a girl was 1.13 (1.03 to 1.26). With both parents as active rubber industry employees, the proportion of multiple births was increased, (1.87; 1.16 to 3.02). Girls with both parents in rubber employment had a reduced birth weight compared with the reference group, with medians of 3400 g v 3440 g (p = 0.02). Information on smoking and ethnicity was available only for births during the period 1983–2001. After adjustment for these covariates and sex, the mean birth weight among children with maternal rubber industry employment was as a mean 46 g (95% CI 11 to 82) less than among referents.

Conclusion: Even with this crude assessment of exposure, we can see some effects on the reproductive outcome among employees in the Swedish rubber industry. Further investigations with a more detailed exposure classification are under way.

O14.4 REPRODUCTION TOXIC EFFECTS AMONG NURSES EXPOSED TO ANTINEOPLASTIC DRUGS

W. Fransman¹, S. Peelen², N. Roeleveld², H. Kromhout¹, D. Heederik¹.¹Environmental and Occupational Health Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; ²Department of Epidemiology and Biostatistics, University Medical Centre Nijmegen, Nijmegen, The Netherlands

Introduction: Nurses are exposed to antineoplastic drugs during their work activities.

Objective: To describe the relationship between dermal exposure to antineoplastic drugs and toxic effects on reproduction among nurses in the Netherlands.

Methods: Self administered questionnaires were completed by nurses retrospectively selected over the period between 1990 and 1997 (based on job title and department) in 83 (68.6%) Dutch hospitals, with a response rate of 79.2%. Questions were asked on lifestyle, pregnancy outcomes, and work related exposures. Nurses’ exposure levels were assessed using a database containing task based measured dermal exposure levels, which were multiplied by self reported task frequencies. Nurses were subsequently divided into three exposure categories based on tertiles. Time to pregnancy (TTP) was modelled using a Cox proportional hazard regression model, and odds ratios (with 95% confidence intervals) were calculated to study the reproductive outcomes for the exposure categories compared with the reference group using multiple logistic regression analysis. In addition, generalised linear models were used to study continuous outcomes (such as pregnancy duration and birth weight).

Results: The results showed an increased risk of toxic effects on reproduction (such as spontaneous abortion, stillbirth, early birth, low birth weight, and congenital anomalies) for nurses with highest exposure to antineoplastic drugs compared with referent nurses, although only statistically significant (p<0.05) for low birth weight (adjusted odds ratio 2.4; 95% confidence interval (CI) 1.0 to 5.5). Modelling pregnancy duration and low birth weight on a continuous scale did not alter these conclusions. TTP was somewhat extended for high exposure nurses compared with the reference group (adjusted hazard ratio for the ‘hazard’ of getting pregnant was 0.9; 95% CI 0.7 to 1.0).

Conclusions: This study indicates that there is an increased risk for spontaneous abortion, stillbirth, early birth, low birth weight, congenital anomalies and time to pregnancy among nurses with high level dermal exposure to antineoplastic drugs.