GENETIC IMMUNIZATION APPROACHES ON THE CONTROL OF ALLERGIC INFLAMMATION

Ph.DDOCTOR OF PHILOSOPH

Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort

Background Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Methods The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. Results Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. Conclusions We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.Peer reviewe

Atopic dermatitis in early life: evidence for at least three phenotypes? Results from the GUSTO study

10.1159/000381342International Archives of Allergy and Immunology1664273-279GUSTO (Growing up towards Healthy Outcomes

Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes

DOI does not function. It has been reported to the journal 28.12.2022BackgroundIncreasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infections and allergic diseases in the offspring from the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohort. MethodsMaternal perceived distress was evaluated using validated questionnaires including Beck Depression Inventory-II (BDI-II) administered during three time periods: preconception (three months apart at four timepoints), pregnancy (during each trimester) and postnatal (3 and 6 months post-delivery). Child eczema, rhinitis and wheeze outcomes were evaluated using a modified ISAAC questionnaire at ages 3, 6, 12, and 18 months. Child allergic sensitization was determined by skin prick testing at 18 months. ResultsAmong 332 mother-child pairs studied, higher maternal distress during preconception and pregnancy increased the risks of wheeze development in the first 18 months; for example, preconception and pregnancy BDI-II scores >= 20 were associated with increased risks of wheeze by 18 months [adjusted risk ratios 3.2 (95%CI 1.1-9.4) and 2.5 (1.0-5.9), respectively]. Emotional and practical support from family during preconception decreased the risks of offspring wheeze. No associations were observed between maternal distress and offspring eczema, rhinitis and allergic sensitization. ConclusionMaternal distress during critical early life periods was associated with offspring wheeze in the first 18 months of life. Supporting maternal mental health even before pregnancy could reduce the risk of offspring wheeze.Peer reviewe

House dust mite sensitization, eczema, and wheeze increase risk of shellfish sensitization

Non peer reviewe

Allergic sensitization trajectories to age 8 years in the Singapore GUSTO cohort

Background: Allergic sensitization is linked to allergy development, with early sensitization often associated with worse outcomes. We aimed to identify if distinct allergic sensitization trajectories existed within a diverse and multi-ethnic Asian cohort.Methods: We administered modified ISAAC questionnaires in the first 8 years and conducted skin prick testing at ages 18 months, 3, 5 and 8 years in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We used latent class analysis to derive allergic sensitization trajectories, and adjusted odds ratios (AOR) to evaluate predictive risk factors and associations with allergic comorbidities.Results: Among 997 children, three trajectories were identified: early food and mite sensitization (16.2%), late mite sensitization (24.2%) and no/low sensitization (59.6%). Early food and mite sensitization was associated with early eczema by 6 months [AOR (95%CI) 4.67 (1.78-12.28)], increased risk of wheeze by 3-8 years (ARR 1.72-1.99) and eczema in the first 8 years of life (ARR 1.87-2.41). Late mite sensitization was associated with female sex [AOR 0.58 (0.35-0.96)], cesar-ean section [AOR 0.54 (0.30-0.98)], early eczema by 6 months [AOR 3.40 (1.38-8.42)], and increased risk of eczema by 18 months [ARR 1.47 (1.03-2.08)] and 8 years [ARR 1.35 (1.05-1.73)].Conclusion: Early onset of eczema and early allergic sensitization were strongly associated. Early sensitization, especially to house dust mites, was associated with increased risks of developing wheeze and eczema, pointing to the importance of developing preventive perinatal interventions and effective therapeutics for sensitized toddlers.Peer reviewe

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.Peer reviewe

Age-Related Differences in Immunological Responses to SARS-CoV-2

https://doi.org/10.1016/j.jaip.2020.08.026Journal of Allergy and Clinical Immunology: In Practic

Clinical phenotype and allergen sensitization in the first 2 years as predictors of atopic disorders at age 5 years

Introduction From a birth cohort of at-risk Asian infants, we prospectively investigated the role of early onset allergen sensitization and clinical phenotypes as risk factors for atopic disorders at the age of 5 years.Methods and materials The study recruited 253 families with a history of allergic disease in a first degree relative from an antenatal clinic in Singapore. The children were followed prospectively to assess clinical outcomes and skin prick test was performed at 2 and 5 years of age.Results Allergen sensitization (food and/or house dust mites) alone at 2 years of age was not associated with increased risk of wheeze and eczema at 5 years. However, the clinical phenotype (eczema and wheeze) with or without the presence of concomitant allergen sensitization at 2 years increased this risk. For eczema, eczema alone at year 2 increased the risk of eczema at year 5 (adjOR = 7.1; 95 % CI: 1.8–27.8) and this was further increased by the presence of allergen sensitization (adjOR = 25.4; 95 % CI: 4.7–138.5) and the concomitant presence of both wheeze and allergen sensitization (adjOR = 64.9; 95 % CI: 4.7–900.0). For wheeze, wheeze alone at 2 years (adjOR = 4.5; 95 % CI: 1.4 -14.8), and wheeze with concomitant allergen sensitization and eczema (adjOR = 13.9; 95 % CI: 1.2–168.5) increased the risk of wheeze at 5 years. The exception was rhinitis, where allergen sensitization alone at 2 years (adjOR = 5.6; 95 % CI: 1.1–29.2) increased the risk of rhinitis at 5 years. Early onset of eczema at 2 years also increased the risk of rhinitis (adjOR = 6.8; 95 % CI: 2.0–23.1).Conclusion In this Asian birth cohort, the clinical phenotype (eczema and wheeze) with or without concomitant allergen sensitization in the first 2 years of life were strong predictors of atopic disorders at 5 years. Keywords: Eczema, Wheeze, Rhinitis, Allergen sensitizatio

Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes

BackgroundIncreasing evidence suggests that maternal distress is a risk factor for development of respiratory infections and allergic diseases in the offspring. We aim to evaluate the link between maternal distress during critical periods in early life, namely the preconception, pregnancy and postnatal periods, and development of respiratory infections and allergic diseases in the offspring from the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohort.MethodsMaternal perceived distress was evaluated using validated questionnaires including Beck Depression Inventory-II (BDI-II) administered during three time periods: preconception (three months apart at four timepoints), pregnancy (during each trimester) and postnatal (3 and 6 months post-delivery). Child eczema, rhinitis and wheeze outcomes were evaluated using a modified ISAAC questionnaire at ages 3, 6, 12, and 18 months. Child allergic sensitization was determined by skin prick testing at 18 months.ResultsAmong 332 mother-child pairs studied, higher maternal distress during preconception and pregnancy increased the risks of wheeze development in the first 18 months; for example, preconception and pregnancy BDI-II scores ≥20 were associated with increased risks of wheeze by 18 months [adjusted risk ratios 3.2 (95%CI 1.1–9.4) and 2.5 (1.0–5.9), respectively]. Emotional and practical support from family during preconception decreased the risks of offspring wheeze. No associations were observed between maternal distress and offspring eczema, rhinitis and allergic sensitization.ConclusionMaternal distress during critical early life periods was associated with offspring wheeze in the first 18 months of life. Supporting maternal mental health even before pregnancy could reduce the risk of offspring wheeze