Immunological exposures in Norwegian agriculture and pre-eclampsia

Immune system perturbations are involved in pre-eclampsia pathophysiology. We hypothesised that immunomodulating substances, such as mycotoxins, endotoxins or pesticides, affect pre-eclampsia risk. Associations between indicators of immunomodulating exposures in agriculture and pre-eclampsia are reported. In a Norwegian family cohort based on participants in agricultural censuses conducted by Statistics Norway 1969-89, 183 313 pregnancies to farmers were identified in the Medical Birth Registry of Norway. Cases notified as pre-eclampsia as well as pregnancies indicated by hypertension in combination with proteinuria were included. Data on farm production and meteorologically based fungal forecasts 1973-90 (a marker of temperate and humid climatic conditions known to favour fungal growth and mycotoxin formation in grain) were obtained and allocated to each farm. Pre-eclampsia prevalence rates were studied in strata of exposure indicators using Poisson regression models. Adjusted rate ratios (RR) and 95% confidence intervals [CI] were computed. We identified 4912 cases, equivalent to 26.8 pre-eclampsia cases per 1000 pregnancies [95% CI 26.1, 27.6]. Pre-eclampsia showed moderate associations with animal farming, RR 1.14, [95% CI 1.07, 1.22] and moderate negative associations with grain production, RR 0.93, [95% CI 0.86, 1.01], and two or more fungal forecasts appearing in any year 1973-90, RR 0.90 [95% CI 0.84, 0.97], using no years with two or more forecasts as reference. Exposure to immunomodulating substances as indicated by grain farming, animal farming and fungal warnings could possibly have moderate effects on pre-eclampsia risk, thus supporting the study hypothesis. The use of exposure indicators as surrogates for real exposures may introduce a non-differential misclassification of the exposure that would attenuate any true exposure-outcome association. The use of exposure proxies warrants that inferences from the study should be made with caution.