The maternal diet index in pregnancy is associated with offspring allergic diseases: the Healthy Start study.

BACKGROUND: A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. METHODS: Data came from Healthy Start, a Colorado pre-birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. RESULTS: The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one-unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72-0.94]), atopic dermatitis (0.77 [0.69-0.86]), asthma (0.84 [0.74-0.96]), and wheeze (0.80 [0.71-0.90]), but not food allergy (0.84 [0.66-1.08]). CONCLUSIONS: This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero.

Associations between child filaggrin mutations and maternal diet with the development of allergic diseases in children.

BACKGROUND: Filaggrin (FLG) loss-of-function mutations in children and maternal diet in pregnancy have been implicated in child allergy outcomes. This paper studies the questions: "do FLG mutations modify the effect of maternal diet on the odds of development of allergic diseases?" and "which factor leads to the highest rate of diagnosis allergic diseases over time, maternal diet, or FLG mutations?". METHODS: Exact logistic regressions studied effect modification. Cox proportional hazard models compared the rate of allergic disease development in three groups (N = 624): (1) children with FLG mutation, (2) children without FLG mutation whose mothers did not eat an allergy preventive diet, and (3) children without FLG mutation whose mothers ate an allergy preventive diet. Maternal diet was classified using a validated index. RESULTS: Cox models showed the development of atopic dermatitis, asthma, and wheeze was significantly higher for children in group 1 versus 3 (HR = 2.40 [1.32, 4.37], HR = 2.29 [1.05, 4.97], and HR 2.10 [1.004, 4.38], respectively), but not significantly higher for children in group 1 versus 2 (HR = 1.30 [0.74, 2.29], HR = 1.27 [0.61, 2.63], and HR = 1.29 [0.65, 2.58], respectively). Development of allergic rhinitis was significantly higher for group 1 versus 2 and 3 (1 vs. 2: HR = 2.29 [1.10, 4.76]; 1 vs. 3: HR = 3.21 [1.46, 7.08]). There was no significant effect modification for any outcome. CONCLUSION: Children with FLG mutation had similar risk of atopic dermatitis, asthma, and wheeze as children without an FLG mutation whose mothers did not eat an allergy preventive diet during pregnancy. Child FLG mutation did not modify the effect of maternal diet. The results suggest that maternal diet in pregnancy, a modifiable risk factor, could be a target for preventive interventions.

Advanced glycation end product intake during pregnancy and offspring allergy outcomes: A Prospective cohort study.

BACKGROUND: Associations have been shown between concurrent assessment of dietary intake of advanced glycation end products (AGEs) and childhood allergic outcomes. We examined the association between maternal AGEs intake and development of offspring asthma, wheeze, atopic dermatitis, allergic rhinitis and food allergies, and sought to determine whether the intake of AGEs was associated with cord sera cytokines/chemokines. METHODS: Pregnant women ≥16 years were recruited in the Healthy Start study, a prospective pre-birth cohort from Colorado (N = 1410). The analysis included 962 dyads with adequate diet (≥2 recalls) and allergy outcome details. AGEs intake was estimated for each mother by matching intakes reported using 24-h dietary recalls during pregnancy to a reference database of commonly consumed foods' AGEs values. Child diagnoses of asthma and allergies up to 8 years were obtained from electronic medical records. Cord sera cytokines and chemokines were analysed in a subset (N = 462) of children. RESULTS: The median [IQR] AGEs intake for the overall sample was 11,919 kU/day [8293, 16,573]. Unadjusted analysis showed a positive association between maternal AGEs intake in pregnancy and rhinitis up to 8 years of age (HR = 1.03; 95% CI: 1.01, 1.06), but the association was attenuated and no longer significant in adjusted models (HR = 1.01; 95% CI: 0.98, 1.04). Both adjusted and unadjusted models showed no associations between AGEs intake in pregnancy and any of the other outcomes (p > .05). There were no significant associations between any cytokine or chemokine measured and AGEs intake or any of the outcomes studied (p > .05). CONCLUSION: The study showed that maternal AGEs intake was not associated with offspring asthma and allergy outcomes. AGEs exposure during pregnancy may not have the same impact on child development as postnatal exposure.

Dietary factors during pregnancy and atopic outcomes in childhood: A systematic review from the European Academy of Allergy and Clinical Immunology.

RATIONALE: Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non-allergen-specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring. METHODS: We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case-control studies and meta-analysis performed from RCTs. RESULTS: We identified 95 papers: 17 RCTs and 78 observational (case-control, cross-sectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta-analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56-0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega-3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45-1.08). Omega-3 supplementation was also associated with a non-significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56-1.04). Neither vitamin D nor omega-3 fatty acids were associated with an altered risk of AD or food allergy. CONCLUSIONS: Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.

Elevated double negative T cells in pediatric autoimmunity.

PURPOSE: Autoimmune diseases are thought to be caused by a loss of self-tolerance of the immune system. One candidate marker of immune dysregulation in autoimmune disease is the presence of increased double negative T cells (DNTs) in the periphery. DNTs are characteristically elevated in autoimmune lymphoproliferative syndrome, a systemic autoimmune disease caused by defective lymphocyte apoptosis due to Fas pathway defects. DNTs have also been found in the peripheral blood of adult patients with systemic lupus erythematosus (SLE), where they may be pathogenic. DNTs in children with autoimmune disease have not been investigated. METHODS: We evaluated DNTs in pediatric patients with SLE, mixed connective tissue disease (MCTD), juvenile idiopathic arthritis (JIA), or elevated antinuclear antibody (ANA) but no systemic disease. DNTs (CD3(+)CD56(-)TCRαß(+)CD4(-)CD8(-)) from peripheral blood mononuclear cells were analyzed by flow cytometry from 54 pediatric patients including: 23 SLE, 15 JIA, 11 ANA and 5 MCTD compared to 28 healthy controls. RESULTS: Sixteen cases (29.6 %) had elevated DNTs (≥2.5 % of CD3(+)CD56(-)TCRαß(+) cells) compared to 1 (3.6 %) control. Medication usage including cytotoxic drugs and absolute lymphocyte count were not associated with DNT levels, and percentages of DNTs were stable over time. Analysis of multiple phenotypic and activation markers showed increased CD45RA expression on DNTs from patients with autoimmune disease compared to controls. CONCLUSION: DNTs are elevated in a subset of pediatric patients with autoimmune disease and additional investigations are required to determine their precise role in autoimmunity.

Incidence and timing of offspring asthma, wheeze, allergic rhinitis, atopic dermatitis, and food allergy and association with maternal history of asthma and allergic rhinitis.

BACKGROUND: Studying the developmental precursors of allergy may help explain the mechanisms (or etiology) of allergic disease. We studied childhood respiratory and allergic diseases in a pre-birth cohort from the United States. OBJECTIVE: We assessed the associations between maternal history of asthma and the development of respiratory and allergic diseases in offspring. We also assessed associations with maternal history of allergic rhinitis. METHODS: Maternal history of asthma and allergic rhinitis was self-reported during early pregnancy. Offspring respiratory and allergy information was obtained from electronic medical records. Adjusted Cox proportional hazard models assessed the associations between maternal history of asthma and development of respiratory and allergic diseases in the offspring up to 8 years. A similar approach was used for maternal history of allergic rhinitis. RESULTS: Children born to women with a history of asthma had a 77% greater risk of developing asthma, a 45% greater risk of atopic dermatitis/eczema, and a 65% greater risk of wheeze (all p < 0.01), but no significantly increased risk of allergic rhinitis or food allergies, compared to children born to women with no history of asthma. Maternal history of allergic rhinitis was not associated with any child allergy outcome, and maternal history of both asthma and allergic rhinitis was associated with child atopic dermatitis/eczema only. CONCLUSIONS: Maternal history of asthma was significantly associated with offspring respiratory and allergic diagnoses. The association between maternal history of asthma and offspring asthma and atopic dermatitis is a novel finding. Our findings may guide physicians who counsel families with a history of maternal asthma and allergic rhinitis about their child's risk of developing respiratory and allergic diseases.