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in the present work, no evidence was observed of a protective effect of maternal antioxidant intake during pregnancy against the development of type 1 diabetes in the offspring. lower ends of the ci for the hr per twofold increase in total intake of each analyzed antioxidant nutrient – which represents a large proportion of the total variation of intake within the study population – varied between 0.70 and 0.90, excluding substantial inverse associations. although all the sociodemographic and lifestyle variables analyzed were

associated with the maternal diet, there was no confounding as their relationships with the endpoint variable were weak. among the other baseline characteristics, genetic risk group, diabetes in a first-degree relative and gestational age were associated with pre-type 1 diabetes, but they did not confound the etiologic associations.

the associations were analyzed in a large, prospective, population-based study cohort with a reasonable number of cases. the variation in the intakes of the antioxidant nutrients within the study population was substantial, even if high supplementary intakes were uncommon among the pregnant mothers of the cohort.

dietary intake during pregnancy was assessed using a detailed ffQ validated specifically for the purposes of the present study (Erkkola et al. 2001). Despite acceptable repeatability and validity of the ffQ, measurement error is still likely to persist in dietary intake figures. For example, the time interval of a few months between the reference period and the completion of the ffQ may lead to memory errors. most likely, the associations reported are to some degree attenuated towards no association by random measurement error, as is usual in epidemiologic analyses (Willett 1998). a systematic between-person error – overestimation of dietary consumption – was observed in the validation study (erkkola et al. 2001), but such an error has no effect on the measure of association with the endpoint variable. systematic within-person errors may result, for example, if food items important for the responder are missing from the food list of the questionnaire, or are misinterpreted. systematic within-person errors may also exist in the present data, but as long as they are not associated with the outcome variable, they will not bias the results (Willett 1998).

the validity of the ffQ was tested against food records, which in general provide the best available reference method (Willett and lenart 1998). however, as both methods use the same dietary database to calculate nutrient intakes on the basis of food consumption, a potential error in this phase could lead to overestimation of the validity of the ffQ. for example, the bioavailability of selenium seems to differ according to the source (finley 2006), which is not taken into account in assessing the nutrient intakes. therefore both the ffQ and food records could be inaccurate measures of bioavailable selenium, and consequently the association of estimated selenium intake with pre-type 1 diabetes could be attenuated. however, as the differences in bioavailability seem to be modest (finley 2006), a major attenuation is unlikely.

in trying to assess the effects of potential differences in the bioavailability of nutrients from different food groups, it is useful to analyze the associations of dietary sources of each nutrient with the disease of interest. in the present study, the consumption of none of the main dietary sources of antioxidant nutrients during pregnancy was associated with pre-type 1 diabetes in the child. among all foods, only low-fat spreads, coffee and berries showed an inverse association after appropiate adjustments, and none of these stands out

6 dIscussIoN

as an important source of the antioxidant nutrients studied.

in theory, maternal antioxidant intake during pregnancy could affect the future risk of type 1 diabetes in the offspring by at least two different mechanisms. the most likely explanation is that maternal intake determines the antioxidant status of the newborn, which, in turn, is expected to be associated with his or her risk of developing the disease. correlations between the blood concentrations of antioxidant nutrients between mother and newborn infant have been observed in several studies (vobecky et al. 1982, tsuchiya et al. 1984, Wasowicz et al. 1993, lee et al. 1995, dimenstein et al. 1996, karakilcik et al. 1996, Zapata et al. 1997, dejmek et al. 2002, Gazala et al. 2003, takser et al. 2004). however, the baby’s own dietary intake is likely to become the most important determinant of his/her antioxidant status soon after birth, or at least as soon as he or she starts to consume other foods than breast milk. probably type 1 diabetes starts to develop during the fetal or neonatal period in only a minority of cases who will later be affected by pre-type 1 diabetes, and therefore no association with maternal intake is seen. clinical type 1 diabetes may manifest even several years after the seroconversion to autoantibody positivity (daneman 2006). as the time span from the fetal time to the endpoint is much longer than for prediabetes, it is not very likely that maternal antioxidant intake is associated with overt disease. in fact, no evidence for such an association was observed in the present study.

an alternative potential mechanism of protection against type 1 diabetes by antioxidants could be fetal programming analogous to what has been proposed for chronic metabolic diseases of adulthood (barker et al. 1989). according to this hypothesis, low maternal intake of antioxidant nutrients causes permanent metabolic or structural alterations in the fetus, thereby predisposing it to type 1 diabetes later in life. at present, there is no evidence to support this view. as antioxidants are hypothesized to exert their action by protecting the β-cells against free radical action, fetal programming seems a less liss likely mechanism of protection than a direct effect of antioxidants in the islets.