Maternal fatty acid status in pregnancy and childhood atopic manifestations: KOALA Birth Cohort Study.

BACKGROUND: Prevalence of atopic disorders has increased rapidly, but aetiological factors responsible for this increase are still largely unknown. Prenatal exposure to a pro-inflammatory fatty acid status is hypothesized although little research has been carried out. OBJECTIVE: To investigate whether prenatal fatty acid exposures are associated with atopy in childhood. METHODS: In the KOALA Birth Cohort Study, maternal blood samples (n=1275) at 34-36 weeks of pregnancy were assayed for n-6 and n-3 long-chain polyunsaturated fatty acids (LCPs). The full spectrum of offspring atopic manifestations (wheeze, asthma, allergic rhinoconjunctivitis, eczema, atopic dermatitis, allergic sensitization, and high total IgE) until the age of 6-7 years was assessed by repeated parental questionnaires and measurements of total and specific IgE. Associations of maternal fatty acid status with child atopic outcomes were analysed using multivariable logistic regression and generalized estimating equations for repeated measurements. RESULTS: High ratio of maternal n-6 vs. n-3 LCPs was associated with a lower risk of eczema in the child (P for trend 0.012). More specifically, we found a decreased risk of eczema in the first 7 months of life with increasing arachidonic acid levels (P for trend 0.013). No associations were found between maternal fatty acids and offspring airway-related atopic manifestations, sensitization, or high total IgE. CONCLUSION AND CLINICAL RELEVANCE: The development of atopic disorders in early childhood is associated with prenatal exposure to n-6 vs. n-3 fatty acids, but with inconsistencies between different manifestations. Further exploration of associations with maternal diet and genetic variants in genes regulating fatty acid metabolism are required. This study shows that the influence of prenatal exposure to fatty acids on the risk of eczema in the child is limited to the first year of life.

Vitamin E supplementation during the dry period in dairy cattle. Part I: adverse effect on incidence of mastitis postpartum in a double-blind randomized field trial.

A randomized, controlled field trial with dairy cows demonstrated an adverse effect of vitamin E supplementation during the dry period on mastitis incidence in early lactation. This study was conducted on farms with historically high rates of mastitis to investigate the benefit of vitamin E supplementation on udder health; however, the outcome showed an adverse effect. The aim of the study was to evaluate whether daily supplementation of 3,000 IU of vitamin E to dairy cows during the dry period could improve udder health in commercial herds with a high incidence of mastitis. On 5 dairy farms, dry cows were randomly divided into 2 experimental groups: a high and a low group. Both groups received a dry cow mineral mix providing 3,000 or 135 IU of vitamin E/cow per day, respectively, between dry-off and calving for a mean period of 8 wk. Providing 3,000 IU of vitamin E exceeds NRC standards, but this amount has been used in previous studies. The experiment, as well as the majority of the statistical analysis, were carried out blinded. Blood was sampled 3 times before calving and on calving day. Serum was analyzed for vitamin E and cholesterol. Vitamin E and the vitamin E:cholesterol ratio were analyzed as dependent variables in mixed models and Student's t-tests to study trends in time and differences between groups. Relative risk calculation and survival analysis were used to study the effect of supplementation on mastitis incidence in the first 3 mo of lactation. The results showed that vitamin E supplements increased both absolute vitamin E and the ratio of vitamin E to cholesterol in blood. In the high group, significantly more subclinical and clinical cases occurred, showing the same trend on all farms. In this study, an initial vitamin E level at dry off above 14.5 µmol/L was a risk factor for clinical mastitis, suggesting that the vitamin E status at the start of the dry period is important. It is recommended to work out exactly at what threshold vitamin E is harmful for udder health before new trials with high dosages of vitamin E are started. Additionally, further research is required to investigate the mechanism by which vitamin E affects udder health.

Vitamin E supplementation during the dry period in dairy cattle. Part II: oxidative stress following vitamin E supplementation may increase clinical mastitis incidence postpartum.

The aim of this study was to evaluate, retrospectively, which physiological states influenced the effect of vitamin E supplements during the dry period on the level of oxidative stress at 2 wk antepartum. Furthermore the effect of oxidative stress at 2 wk antepartum on the risk of clinical mastitis in early lactation was investigated. Cows experience oxidative stress around calving. Vitamin E is able to decrease oxidative stress by scavenging free radicals. Normally, vitamin E radicals formed when vitamin E reacts with free radicals are regenerated by a network of other antioxidants, termed the "vitamin E regeneration system" (VERS). In case of vitamin E supplementation, VERS should be sufficient to regenerate formed vitamin E radicals; if not, oxidative stress might increase instead of decrease. Additionally, the level of oxidative stress and vitamin E might be important physiological states to evaluate before supplementation. In a clinical trial, 296 cows on 5 farms were randomly divided into 2 groups, supplemented with a mineral mix between dry off and calving that supplied 3,000 or 135 IU/d, respectively. Blood samples collected at dry off and 2 wk antepartum were analyzed for vitamin E, reactive oxygen metabolites, ferric-reducing ability of plasma, glutathione peroxidase, and malondialdehyde. Cows were allocated retrospectively into 8 subgroups based on the level of oxidative stress, vitamin E, and VERS status at dry off. To evaluate whether differences in physiological states at dry off influenced the effect of vitamin E supplementation on the level of oxidative stress, group effects (supplemented vs. control) were studied with Student's t-test for all 8 subgroup at 2 wk antepartum. Differences in physiological states at dry off influenced the effect of vitamin E supplements. In 2 insufficient VERS subgroups, the supplemented group had higher levels of free radicals at 2 wk antepartum compared with the control group. Relative risk calculation was used to study the effect of oxidative stress at 2 wk antepartum on the incidence of mastitis in the first 100 d of lactation. Higher levels of oxidative stress at 2 wk antepartum were related to higher risk of clinical mastitis. In conclusion, not every dry cow responded well to high vitamin E supplementation. This subgroup analysis provides a possible explanation for the unexpected adverse effects observed in the clinical trial.

Effects of vitamin E supplementation on and the association of body condition score with changes in peroxidative biomarkers and antioxidants around calving in dairy heifers.

The objective of this study was to investigate the effect of vitamin E supplementation on oxidative status in blood, liver, milk, and ovarian follicular fluid in periparturient heifers. Vitamin E supplementation started 8 wk before calving and continued until 8 wk postpartum. Grass silage was the main forage fed during the experiment. In addition, supplemented heifers (n=9) received 3,000I U of vitamin E daily on a carrier food; control heifers (n=9) consumed only the carrier food. Blood samples and liver biopsies were taken frequently throughout the study and ovarian follicular fluid was sampled at 8 wk postpartum. Body condition score was scored weekly and milk yield was measured daily. A marker of oxidative damage, determinable reactive oxygen metabolites (d-ROM), and a set of antioxidants were measured in blood, liver, milk, and ovarian follicular fluid. Control heifers had a low vitamin E status, and selenium status was marginal in control and supplemented heifers. Vitamin E supplementation increased vitamin E concentrations in blood, liver, and ovarian follicular fluid and increased triacylglycerol in liver. Serum d-ROM were not reduced by vitamin E supplementation. Superoxide dismutase and glutathione peroxidase activity in red blood cells and liver and glutathione peroxidase activity in ovarian follicular fluid were not affected by vitamin E supplementation and they were not increased around calving. Protein thiol groups and ratio of reduced glutathione to oxidized glutathione were also not increased around calving. These results suggest that heifers around calving experience a low level of oxidative processes. This might be caused by lower than expected milk production attributed to a low forage intake. Serum d-ROM were negatively correlated with protein thiol groups and positively correlated with the activity of glutathione peroxidase in red blood cells, oxidized glutathione, and the ratio of reduced glutathione and oxidized glutathione in serum. The lack of treatment effects allowed estimation of the effects of body condition 4 wk before calving and the loss of body condition on markers of lipid peroxidation and antioxidants. A trend that a body condition of >or=3 might result in more oxidative damage measured by serum d-ROM was observed, but fatter heifers had a significantly higher ratio of reduced glutathione to oxidized glutathione.