Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal.

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring, compared to those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7-9 years of age in C: hildren born during the trial. 841 children (80% of the cohort) were seen at mean±sd 8.5±0.4 years. Technically successful spirometry results were obtained in 793 (94.3%) children, 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95% CI) difference in z-scores (supplementation minus control) was -0.08 (-0.19-0.04), -0.05 (-0.17-0.06) and -0.04 (-0.15-0.07) for forced expiratory volume in 1 s (FEV1), forced vital capacity and FEV1/FVC, respectively. Compared with healthy white children, FEV1 and FVC in the "healthy" Nepalese children were ∼1 (∼13%) z-score lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age.

Maternal vitamin D and E intakes during pregnancy are associated with asthma in children.

Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74-0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81-1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31-0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81-0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications.

Complex effects of vitamin E and vitamin C supplementation on in vitro neonatal mononuclear cell responses to allergens.

Low maternal dietary vitamin E (but not vitamin C) intake during pregnancy has been associated with increased in vitro cord blood mononuclear cell (CBMC) proliferative responses, childhood wheezing and asthma. We investigated whether these associations reflect direct effects of vitamin E by investigating the effects of supplementing CBMC cultures with physiological concentrations of vitamin E. CBMC from seventy neonates were cultured supplemented with either nothing, α-tocopherol or ascorbic acid. Proliferative, IFN-γ, IL-4, IL-10 and TGF-ß responses were measured. In general, vitamin E supplementation was associated with a trend for reduced proliferative responses after stimulation with antigens and house dust mite, and with increased proliferation after stimulation with timothy grass allergen. There was a trend for CBMC cultures to exhibit decreased secretion of IFN-γ, IL-10 and IL-4. Supplementation with vitamin C had no effect on CBMC proliferation, but increased IFN-γ and IL-4 production, and decreased IL-10 production. In conclusion, in vitro vitamin E and C supplementation of CBMC modifies neonatal immune function, but not in a manner predicted by observational epidemiological studies. The observed associations between vitamin E and childhood respiratory disease are complex, and the nature and form of nutritional intervention need to be carefully considered before inclusion in trials.

A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day.

Associations have been reported between suboptimal maternal vitamin E intake during pregnancy and childhood asthma. This pilot study conducted in 2008/2009 investigated the feasibility and acceptability of a food-based randomized controlled trial in pregnant women to optimize dietary vitamin E intake to 15 mg/day. A food-based intervention using "food exchanges" to individually optimize dietary vitamin E intake to 15 mg/day was developed and included in an advice booklet. Forty-three pregnant women with a personal/partner history of asthma were recruited at 12 weeks gestation and randomized to food-based intervention or a control group until 20 weeks gestation. A registered dietitian assessed the vitamin E intake of 22 women and provided tailored advice on food-based exchanges to optimize their intake to 15 mg/day. The 21 control women were not given dietary advice. The food-based intervention was completed by 19 women and increased mean vitamin E intake: food diary data, 7.13 mg/day (95% confidence interval: 5.63 to 18.6) to 17.4 mg/day (95% confidence interval: 14.4 to 20.5) (P<0.001). This pilot study demonstrates the feasibility and acceptability of a food-exchange-based intervention to optimize dietary vitamin E intake during pregnancy. Additional work is required to determine whether this intervention, if sustained for the rest of pregnancy, reduces the likelihood of childhood asthma. The methodology used in the design of this novel food-based intervention could be transferred to other nutrients.

Diet and asthma: nutrition implications from prevention to treatment.

Asthma is characterized by lung airway inflammation initiated and perpetuated by an inappropriate immune response, increased airway responsiveness, and variable airflow obstruction. In Western countries there has been a marked increase in asthma prevalence such that it has become a public health concern. It has been hypothesized that the increase may be due to changing antioxidant intake, increasing dietary ratio of n-6:n-3 polyunsaturated fatty acids (PUFA), and vitamin D deficiency (and supplementation). Observational studies have reported associations between asthma and dietary antioxidants (vitamin E, vitamin C, carotenoids, selenium, polyphenols, and fruit), PUFA, and vitamin D. However, supplementing the diets of adults with asthma with antioxidants and n-3 PUFA has minimal, if any, clinical benefit. Currently there is insufficient evidence to support the use of nutrient supplements to complement conventional treatment; however, results of ongoing studies are awaited, and additional research is required, particularly in children. Interest in the potential of dietary intervention during pregnancy to reduce the likelihood of childhood asthma has increased. A small number of cohort studies have highlighted associations between childhood asthma and reduced maternal intake of some nutrients (vitamin E, vitamin D, selenium, zinc, and PUFA) during pregnancy. Although vitamin D intervention studies during pregnancy are ongoing and two intervention studies suggest that dietary PUFA manipulation during pregnancy may be advantageous, further trials are needed to establish if modification of maternal nutrient intake during pregnancy can be used as a healthy, low cost, public health measure to reduce the prevalence of childhood asthma.

Session 1: Allergic disease: Nutrition as a potential determinant of asthma.

Asthma is characterised by chronic lung airway inflammation, increased airway responsiveness and variable airflow obstruction. In Westernised countries asthma is a public health concern because of its prevalence, associated ill health and high societal and healthcare costs. In recent decades there has been a marked increase in asthma prevalence, particularly in Westernised countries. It has been proposed that changing diet has contributed to the increase in asthma. Several dietary hypotheses exist; the first relates the increase in asthma to declining dietary antioxidant intake, the second to decreased intake of long-chain n-3 PUFA and increasing intake of n-6 PUFA. Vitamin D supplementation and deficiency have also been hypothesised to have contributed to the increase in asthma. Observational studies have reported associations between asthma and dietary antioxidants (vitamin E, vitamin C, carotenoids, Se, flavonoids, fruit), lipids (PUFA, butter, margarine, fish) and vitamin D. However, supplementing the diets of adults with asthma with antioxidants and lipids has minimal, if any, clinical benefit. There is growing interest in the possibility that childhood asthma is influenced by maternal diet during pregnancy, with studies highlighting associations between childhood asthma and maternal intake of some nutrients (vitamin E, vitamin D, Se, PUFA) during pregnancy. It has been suggested that maternal diet during pregnancy influences fetal airway and/or immune development. Further intervention studies are needed to establish whether modification of maternal nutrient intake during pregnancy can be used as a healthy low-cost public health measure to reduce the prevalence of childhood asthma.

Early life events in asthma--diet.

It has been hypothesized that the recent increase in the prevalence of asthma may, in part, be a consequence of changing diet. There is now increasing interest in the possibility that childhood asthma may be influenced by maternal diet during pregnancy and/or diet during early childhood. A number of observational studies and a childhood fish oil supplementation study provide little support for the notion that early childhood intake of polyunsaturated fatty acids (PUFAs) influence the development of childhood asthma. Recent work however, suggests that supplementation of maternal diet with fish oil is associated with altered neonatal immune responses to allergens. Further work is required to establish whether this immunological observation is translated into clinical outcomes. Two birth cohorts have now reported reduced maternal intake of vitamin E, zinc and vitamin D during pregnancy to be associated with increased asthma and wheezing outcomes in children up to the age of 5 years. Early life diet could modulate the likelihood of childhood asthma by affecting fetal airway development and/or influencing the initial early life interactions between allergens and the immune system. In animal models, vitamin E, zinc and vitamin D have been shown to modify fetal lung development and vitamin E, zinc, vitamin D and PUFA can modulate T-cell responses. Further research, particularly, early life intervention studies need to be carried out to establish whether early life dietary intervention can be used as a public health measure to reduce the prevalence of childhood asthma.

Diet as a risk factor for atopy and asthma.

It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified.