John Molloy

Cohort Profile: The Barwon Infant Study

The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological samples and measures include: maternal blood, faeces and urine during pregnancy; infant urine, faeces and blood at regular intervals during the first 4 years; lung function at 1 month and 4 years; cardiovascular assessment at 1 month and 4 years; skin-prick allergy testing and food challenge at 1 year; and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au].

The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field.

The skin barrier function gene SPINK5 is associated with challenge-proven IgE-mediated food allergy in infants

A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions.

Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study

Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE‐mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge‐proven food allergy.

Genetic Variation at the Th2 Immune Gene IL13 is Associated with IgE-mediated Paediatric Food Allergy

Food allergies pose a considerable world‐wide public health burden with incidence as high as one in ten in 12‐month‐old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.

Persistent Food Allergy and Food Allergy Coexistent with Eczema Is Associated with Reduced Growth in the First 4 Years of Life.

BACKGROUND Food allergy has been associated with lower weight and height in cross-sectional studies in children; however, this has not been investigated in longitudinal studies to explore growth over time, and previous studies have not accounted for coexisting eczema. OBJECTIVE The objective of this study was to examine the association of IgE-mediated food allergy and eczema with anthropometric measures at 1 and 4 years of age. METHODS In the HealthNuts population-based cohort, infants recruited at age 1 year underwent a skin prick test to egg, peanut, and sesame; those sensitized had oral food challenges. Food challenges repeated at 4 years determined food allergy persistence or resolution. Eczema was defined as parent report of eczema diagnosis. Parent-reported weight and height and child health record data were used to calculate age- and sex-adjusted percentiles from World Health Organization charts. Multivariable linear regression models were fitted to examine the effect of food allergy and eczema on weight and height controlling for potential confounders. RESULTS Children with both food allergy and eczema at age 1 had lower percentiles for mean weight (51.3 vs 58.3 percentile, P = .001) and height (48.4 vs 53.4, P = .028) at age 1 compared with those with neither condition. There was no difference for children with only food allergy or eczema at age 1. By age 4, children with persistent food allergy and persistent eczema, but not those with resolved food allergy, were still shorter and lighter. CONCLUSIONS Children with both food allergy and eczema were shorter and lighter throughout early childhood, with more pronounced differences in those with persistent food allergy.

Is Low Vitamin D Status A Risk Factor For Food Allergy? Current Evidence And Future Directions.

Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis; and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.

Prevalence of challenge-proven IgE-mediated food allergy in infants in the Barwon Region, Victoria, Australia

Methods The Barwon region, located approximately 100 km south of Melbourne, is centred around the city of Geelong and has metropolitan, rural and coastal communities. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1069 infants). As part of the 12 month review infants undergo skin prick testing to five foods: cow’s milk, raw egg, peanut, cashew and sesame. Those with any detectable wheal size are offered a formal in-hospital oral food challenge using a validated protocol to determine their clinical allergy status.

Maternal antenatal folate levels and offspring risk of IgE-mediated food sensitisation

Background The prevalence of IgE-mediated food allergy has increased in the developed world, particularly among children less than 5 years of age. Widespread folate supplementation during pregnancy commenced in the 1980’s in an attempt to decrease the rate of neural tube defects. This introduction corresponded with the increase in inflammatory disease in children, including allergic conditions. Elevated maternal folate has been associated with allergic disease development in mice, yet there is conflicting evidence in humans as to whether elevated levels, associated with folic acid supplementation in pregnancy, may be associated with allergic airway disease in children.