Debra J. Palmer

The importance of early complementary feeding in the development of oral tolerance: concerns and controversies.

Rising rates of food allergies in early childhood reflect increasing failure of early immune tolerance mechanisms. There is mounting concern that the current recommended practice of delaying complementary foods until 6 months of age may increase, rather than decrease, the risk of immune disorders. Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a ‘critical early window’ of development. Although the timing of this window is not clear in humans, current evidence suggests that this is most likely to be between 4 and 6 months of life and that delayed exposure beyond this period may increase the risk of food allergy, coeliac disease and islet cell autoimmunity. There is also evidence that other factors such as favourable colonization and continued breastfeeding promote tolerance and have protective effects during this period when complementary feeding is initiated. This discussion paper explores the basis for concern over the current recommendation to delay complementary foods as an approach to preventing allergic disease. It will also examine the growing case for introducing complementary foods from around 4 months of age and maintaining breastfeeding during this early feeding period, for at least 6 months if possible.

Early regular egg exposure in infants with eczema: A randomized controlled trial

BACKGROUND Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. OBJECTIVE We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. METHODS In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. RESULTS A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had egg-specific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P = .11). Egg-specific IgG4 levels were significantly (P < .001) greater in the egg group at both 8 and 12 months. CONCLUSION Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

Cord Blood 25-Hydroxyvitamin D3 and Allergic Disease During Infancy

OBJECTIVE: There has been growing interest in vitamin D insufficiency as a predisposing factor for allergy development based on immunoregulatory properties and epidemiological studies. The aim of this study was to investigate the association between vitamin D exposure in utero and allergic outcomes in the first year of life. METHODS: Cord blood (CB) vitamin D was measured in 231 high-risk infants from an Australian prospective birth cohort. CB 25-hydroxyvitamin D3 (25[OH]D3) concentration was analyzed in relation to maternal vitamin D intake and the development of infant eczema, allergen sensitization, and immunoglobulin E-mediated food allergy. RESULTS: Maternal intake of supplemental vitamin D was significantly correlated with CB 25(OH)D3 concentration (ρ = 0.244, P = .003), whereas dietary vitamin D did not influence CB levels. There was significant seasonal variation in CB 25(OH)D3 concentration suggesting that sunlight exposure was an important determinant. Lower CB vitamin D status was observed in infants that developed eczema (P = .018), and eczema was significantly more likely in those with concentrations <50 nmol/L in comparison with those with concentrations ≥75 nmol/L (odds ratio 2.66; 95% confidence interval 1.24–5.72; P = .012). This association remained significant after adjustment for multiple confounding factors. The associations between CB 25(OH)D3 concentration and allergen sensitization, immunoglobulin E-mediated food allergy, and eczema severity (SCORing Atopic Dermatitis) were not significant. CONCLUSIONS: Reduced vitamin D status in pregnancy may be a risk factor for the development of eczema in the first year of life, reinforcing the need to explore the role of vitamin D exposure during development for disease prevention.

Randomized controlled trial of early regular egg intake to prevent egg allergy.

Background: The ideal age to introduce egg into the infant diet has been debated for the past 2 decades in the context of rising rates of egg allergy. Objective: We sought to determine whether regular consumption of egg protein from age 4 to 6 months reduces the risk of IgE‐mediated egg allergy in infants with hereditary risk, but without eczema. Methods: Infants aged 4 to 6 months were randomly allocated to receive daily pasteurized raw whole egg powder (n = 407) or a color‐matched rice powder (n = 413) to age 10 months. All infants followed an egg‐free diet and cooked egg was introduced to both groups at age 10 months. The primary outcome was IgE‐mediated egg allergy defined by a positive pasteurized raw egg challenge and egg sensitization at age 12 months. Results: There was no difference between groups in the percentage of infants with IgE‐mediated egg allergy (egg 7.0% vs control 10.3%; adjusted relative risk, 0.75; 95% CI, 0.48–1.17; P = .20). A higher proportion of participants in the egg group stopped taking the study powder because of a confirmed allergic reaction (25 of 407 [6.1%] compared with 6 of 413 [1.5%]). Egg‐specific IgG4 levels were substantially higher in the egg group at 12 months (median, 1.22 mgA/L vs control 0.07 mgA/L; P < .0001). Conclusions: We found no evidence that regular egg intake from age 4 to 6 months substantially alters the risk of egg allergy by age 1 year in infants who are at hereditary risk of allergic disease and had no eczema symptoms at study entry.

Diet of lactating women and allergic reactions in their infants.

Purpose of reviewTo evaluate whether the diet of lactating women modulates the development of allergic disease in their children. Recent findingsAlthough maternal avoidance of common food protein allergens was previously recommended for lactating women with infants predisposed to allergic disease, recent expert reviews have concluded that there is no strong evidence to support this position. A recent well-controlled study, using egg as an allergen, confirmed that the appearance of food proteins in human milk is common, but this can be highly variable between women even after consuming the same challenge (dose) food. On the other hand, preliminary data suggest that increasing dietary n−3 fatty acids may offer protection from the development of some childhood allergies. A recent animal study offers mechanistic support, indicating that perinatal diets high in n−3 fatty acids can induce oral neonatal tolerance more effectively compared with diets predominating in n−6 fatty acids. SummaryCurrent data do not support the use of maternal antigen-avoidance diets during lactation as a strategy to prevent childhood allergies. Controlled trials are required to evaluate the efficacy of maternal dietary n−3 fatty acid interventions in preventing allergic disease in at-risk infants.

25-hydroxyvitamin D3 status is associated with developing adaptive and innate immune responses in the first 6 months of life

Vitamin D (25[OH]D3) status in early life has been linked to the risk of allergic disease in multiple observational studies. While immunomodulating properties are well recognized, there are few longitudinal studies of 25(OH)D3 status, immune function and allergic disease in infants.

Nutritional influences on epigenetic programming: asthma, allergy, and obesity.

Observational studies show consistent links between early-life nutritional exposures as important risk factors for the development of asthma, allergy, and obesity. Reliance on increasing use of dietary supplementation and fortification (eg, with folate) to compensate for increased consumption of processed foods is also influencing immune and metabolic outcomes. Epigenetics is providing substantial advances in understanding how early-life nutritional exposures can effect disease development. This article summarizes current evidence linking the influence of early-life nutritional exposures on epigenetic regulation with a focus on the disease outcomes of asthma, allergy, and obesity.

Prenatal fish oil supplementation and allergy: 6-Year follow-up of a randomized controlled trial

BACKGROUND AND OBJECTIVE: Evidence from randomized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA) reduces the incidence of allergic disease characterized by an immunoglobulin E (IgE) response. We aimed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy. METHODS: Six-year follow-up of children (n = 706) with a family history of allergic disease from the Docosahexaenoic Acid to Optimize Mother Infant Outcome (DOMInO) trial. Women were randomly allocated to receive n-3 LCPUFA-rich fish oil capsules (800 mg/d docosahexaenoic acid DHA and 100mg/d eicosapentaenoic acid) or vegetable oil capsules (without n-3 LCPUFA). Allergic disease symptoms including eczema, wheeze, rhinitis, and rhino-conjunctivitis, were assessed using the International Study of Asthma and Allergies in Childhood questionnaire and sensitization to allergens was measured by skin prick test. RESULTS: There was no difference in the percentage of children with any IgE-associated allergic disease between the n-3 LCPUFA and control groups (116/367 [31.5%] vs 106/336 [31.5%]; adjusted relative risk, 1.04; 95% confidence interval, 0.82–1.33; P = .73). There was a reduction in the percentage of children sensitized to house dust mite Dermatophagoides farinae (49/367 [13.4%] vs 68/336 [20.3%]; adjusted relative risk, 0.67, 95% confidence interval, 0.44–1.00; P = .0495). CONCLUSIONS: Prenatal n-3 LCPUFA supplementation did not reduce IgE-associated allergic disease at 6 years of age. Secondary outcomes were suggestive of a protective effect of the intervention on the incidence of D. farinae sensitization.

Elevated IL‐5 and IL‐13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema

Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen‐specific T‐cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure.

Maternal Folic Acid Supplementation during Pregnancy and Childhood Allergic Disease Outcomes: A Question of Timing?

Since the early 1990s, maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy, to reduce the risk of infant neural tube defects. In addition, many countries have also implemented the folic acid fortification of staple foods, in order to promote sufficient intakes amongst women of a childbearing age, based on concerns surrounding variable dietary and supplementation practices. As many women continue to take folic acid supplements beyond the recommended first trimester, there has been an overall increase in folate intakes, particularly in countries with mandatory fortification. This has raised questions on the consequences for the developing fetus, given that folic acid, a methyl donor, has the potential to epigenetically modify gene expression. In animal studies, folic acid has been shown to promote an allergic phenotype in the offspring, through changes in DNA methylation. Human population studies have also described associations between folate status in pregnancy and the risk of subsequent childhood allergic disease. In this review, we address the question of whether ongoing maternal folic acid supplementation after neural tube closure, could be contributing to the rise in early life allergic diseases.