Healthcare systems across the world face major challenges due to allergic diseases, known to affect people of all ages. In Singapore, two prominent cohort studies, Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO), have made notable advancements to our knowledge and understanding of allergic diseases. These cohorts, which comprised of healthy mother-infant dyads recruited from the healthy Singapore population, have shed light on the complex connections between factors influencing health in early life, preconception and pregnancy, on the pathogenesis of allergic disorders in offspring. GUSTO highlighted significant risk factors in antenatal and early life, such as maternal diet, health and lifestyle choices, as well as infant environmental influences, that contributed to the risk of allergic diseases in the Asian Singaporean population. It also identified differential patterns of allergic disease in comparison to other populations, particularly the role of the microbiome in predicting atopic outcomes. Meanwhile, S-PRESTO further explores the long-term maternal and child outcomes associated with preconception health. Findings seem to suggest that prevention of offspring allergic conditions can be achieved through optimizing maternal health and lifestyle choices before conception. Both studies underscore the significance of early life interventions, preconception health, and personalized approaches to effectively manage and prevent allergies. By leveraging the insights and promising findings from GUSTO and S-PRESTO, future work can drive development of preventative strategies and personalized interventions to reduce burden of allergic diseases in the Singapore population.

The Asia Allergy Birth Cohort (A2BC) network consolidates data from multiple independently established birth cohorts across Asia to enhance research on host-environment interactions in allergic diseases. These cohorts, established at different times with various methodologies, are reliable data sources. Our aim is to introduce the content, variables, and outcomes of these cohorts while highlighting their differences, laying the groundwork for future collaborative research. The A2BC network includes 10 cohort studies on allergic diseases from six Asian countries. Enrollment criteria, study aims, and an initial inventory were discussed and confirmed through five business meetings. A common database was developed to assess the study characteristics of these observational cohorts on allergic diseases, though harmonization efforts are retrospective. Five studies collected data on specific immunoglobulin E responses to various inhalant and food allergens, while six cohorts conducted skin prick tests. Lung function measurements were included in some studies, but without standardized procedures across cohorts. Asthma and allergic rhinitis were primarily assessed using questionnaires or doctor diagnoses, while assessments of eczema and food allergies varied across studies. The A2BC network also examines early-life environmental factors such as delivery mode, antibiotic usage, diet, and air pollutants, although these exposures were measured differently across the cohorts. Despite differences in the origins, methods, and objectives of each cohort, pooling data and conducting joint analyses offer valuable insights into the relationship between environmental exposures and allergic disease outcomes in Asian children. This approach can serve as a foundation for future collaborative research.

INTRODUCTION:Anaphylaxis was the first serious adverse event (AE) of special interest surfaced in Singapore following coronavirus disease 2019 (COVID-19) vaccination. Individuals who developed physician-diagnosed severe allergic reactions to the mRNA vaccines would be medically ineligible for mRNA vaccines and offered non-mRNA alternatives. This paper describes anaphylaxis reports received by the Health Sciences Authority (HSA) and presents a review of individuals who received heterologous COVID-19 vaccination. METHODS:Reports of anaphylaxis associated with the COVID-19 vaccines received till 31 July 2022 were reviewed and adjudicated using the Brighton Collaboration case definition criteria by an HSA-appointed expert panel. Additional review was conducted for cases with heterologous vaccination for any subsequent reactions until administration of third dose of COVID-19 vaccines. RESULTS:Among 112 adjudicated anaphylaxis cases, majority occurred in females, adults and persons with allergy histories, which were consistent with global observations. Most cases (71%) occurred within 30 minutes of vaccination. The reporting incidence rates (IRs) of 0.67 and 0.55 per 100,000 administered doses for Comirnaty and Spikevax vaccines, respectively, were comparable with IRs reported overseas, whereas the IRs for non-mRNA vaccines (Sinovac-CoronaVac and Nuvaxovid) were much higher at 4.14 and 29.82 per 100,000 administered doses, respectively, likely due to selection bias. Review of the 20 cases following heterologous vaccination found varying reactions to subsequent vaccinations. CONCLUSION:Anaphylaxis is a rare but serious AE in which outcomes can be mitigated with timely medical intervention. The case review helped to guide vaccination strategies and added to the cumulative knowledge of safety with heterologous vaccination.

Strategies for prevention of atopic dermatitis (AD) are likely most effective with the help of skin biomarkers to identify high-risk infants in the pre-disease stage. This study aimed to identify early skin microbiome and metabolome signature predictive of infantile AD at 6 and 18 months of life.

BACKGROUND:We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES:We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS:Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS:Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS:Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

In spite of major scientific advances in the field of allergy and immunology in recent decades, there are still several caveats in diagnosis and management. This is mainly due to the lack of training of health professionals, ignorance among the public and indiscriminate exploitation for purely financial benefits. Unfortunately, these unscientific methods are expanding in their influence through social media and this is disturbing to the scientific community. Hence, efforts are being made to educate the health professional, the patients, their families and society.

The allergy skin prick test (SPT) is still the test of choice to confirm an underlying allergic disease. However, in certain specific conditions measurement of specific IgE or the more recently developed component-resolved diagnostics (CRD) is a better choice. Indications for specific IgE and CRD will be covered. The value of specific IgE determination will be compared to the SPT. Although CRD has not established its exact place in the diagnostic work-up of an allergic disease in daily practice yet and is still mainly a subject of intense research, it is a promising test that will allow improvement of treatment (mainly of specific immunotherapy) and might become a useful tool in predicting the long-term outcome of an allergic disease.

BACKGROUND AND AIMS:There are significant changes to the maternal inflammatory profile across pregnancy. Recent studies suggest that perturbations in maternal gut microbial and dietary-derived plasma metabolites over the course of pregnancy mediate inflammation through a complex interplay of immunomodulatory effects. Despite this body of evidence, there is currently no analytical method that is suitable for the simultaneous profiling of these metabolites within human plasma. MATERIALS AND METHODS:We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the high-throughput analysis of these metabolites in human plasma without derivatization. Plasma samples were processed using liquid-liquid extraction method with varying proportions of methyl tert-butyl ether, methanol, and water in a 3:10:2.5 ratio to reduce matrix effects. RESULTS:LC-MS/MS detection was sufficiently sensitive to quantify these gut microbial and dietary-derived metabolites at physiological concentrations and linear calibration curves with r2 > 0.99 were obtained. Recovery was consistent across concentration levels. Stability experiments confirmed that up to 160 samples could be analyzed within a single batch. The method was validated and applied to analyse maternal plasma during the first and third trimester and cord blood plasma of 5 mothers. CONCLUSION:This study validated a straightforward and sensitive LC-MS/MS method for the simultaneous quantitation of gut microbial and dietary-derived metabolites in human plasma within 9 minutes without prior sample derivatization.

Background: Childhood wheezing isa highly heterogeneous condition with an incomplete understanding of the characteristics of wheeze trajectories, particularly for persistent wheeze.Objective: To characterize predictors and allergic comorbidities of distinct wheeze trajectories in a multiethnic Asian cohort.Methods: A total of 974 mother-child pairs from the prospective Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were included in this study. Wheeze and allergic comorbidities in the first 8 years of life were assessed using the modified International Study of Asthma and Allergies in Childhood questionnaires and skin prick tests. Group -based trajectory modeling was used to derive wheeze trajectories and regression was used to assess associations with predictive risk factors and allergic comorbidities.Results: There were 4 wheeze trajectories derived, including the following: (1) early-onset with rapid remission from age 3 years (4.5%); (2) late-onset peaking at age 3 years and rapidly remitting from 4 years (8.1%); (3) per-sistent with a steady increase to age 5 years and high wheeze occurrence until 8 years (4.0%); and (4) no or low wheeze (83.4%). Early-onset wheezing was associated with respiratory infections during infancy and linked to subsequent nonallergic rhinitis throughout childhood. Late-onset and persistent wheeze shared similar origins characterized by parent-reported viral infections in later childhood. However, persistent wheezing was generally more strongly associated with a family history of allergy, parent-reported viral infections in later childhood, and allergic comorbidities as compared with late-onset wheezing.Conclusion: The timing of viral infection occurrence may determine the type of wheeze trajectory development in children. Children with a family history of allergy and viral infections in early life may be predisposed to persistent wheeze development and the associated comorbidities of early allergic sensitization and eczema.(c) 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Following initial reports of anaphylaxis linked to the Pfizer/BioNTech COVID-19 vaccine (Pfizer vaccine),1 vaccine excipient polyethylene glycol (PEG) was the suspected candidate causing these reactions. Later on, polysorbate 80 (PS-80) was included due to theoretical concerns about cross-reactivity between PEG and PS-80 contained in viral vector vaccines.2 The UK and USA Medicines and Healthcare Products Regulatory Agency initially recommended halting mRNA vaccinations in patients with “a history of a significant allergic reaction to a vaccine, medicine, or food or who have been advised to carry an adrenaline autoinjector”3 resulting in governments worldwide establishing triage systems to survey vaccine safety. These initial recommendations were extremely broad and were quickly revised. A nationwide strategy in Singapore was put in place to evaluate individuals deemed at risk of vaccine allergy prior to receiving mRNA COVID-19 vaccination through a Ministry of Health (MOH) sanctioned vaccine allergy clinics nationwide. This initially included all patients with a history of anaphylaxis to food or drugs but was later revised to include only those with a history of vaccine allergy. Criteria for referral were any prior vaccine allergy including to non-COVID-19 vaccines. At inception of this referral pathway, there was limited universal experience with skin testing using mRNA-based COVID-19 vaccines, and there remains no consensus among allergists regarding the true sensitivity and specificity of these tests.2, 4 This approach was particularly important for pediatric patients where vaccine hesitancy was greater and prior allergy history was often used to defer vaccination.5 Currently, there are no countries that restrict COVID-19 vaccination for anyone with allergies unrelated to the COVID-19 vaccines. This is a prospective observational study of vigilance undertaken in adults and children who were referred to the Adult and Paediatric Allergy & Immunology units of two tertiary academic medical centers between April 2021 and November 2021 for evaluation of suitability to receive the Pfizer vaccine. This study was approved by the institutional ethics committee (DSRB Reference Number 2021/00375), and informed consent was obtained from all patients. Basic demographics, personal and family allergy history, nature of reported prior vaccine allergy, and tolerance of subsequent vaccines were collected. Patients with histories consistent with an IgE-mediated allergic reaction underwent skin prick (SPT) and intradermal tests (IDT) with the Pfizer vaccine and representative drugs to screen for sensitization to known excipients. SPTs (1:1 concentration) and IDTs (1:100 and 1:10 concentrations) to the Pfizer vaccine, PS-20 (Havrix® Hepatitis A vaccine), PEG-3350/PS-80 (Medroxyprogesterone Acetate), and PS-80 (Optive® Advanced Eyedrops) were performed according to Banerji et al.6 Patients with negative skin tests were offered a two-step graded provocation test to the Pfizer vaccine. The provocation test was performed in two steps: step 1 administered 0.1 mL, step 2 administered the remaining 0.2 mL, with a cumulative dose of 0.3 mL (full vaccine dose). Patients were observed for 1 h in between doses, and for 2 h after the last dose. Patients with positive skin tests were counseled to choose between a two-step provocation test to the Pfizer vaccine or vaccination with Sinovac, the only non-mRNA COVID-19 vaccine alternative available in Singapore at the time. A safety phone call was made 48–72 h after provocation to monitor for any delayed reactions. Of a total of 635 patients referred for evaluation, 43.0% were deemed to be eligible for direct vaccination in the community upon review of the referral information. These included patients whose reaction to the index vaccine were consistent with side effects (e.g., fever and myalgia) rather than allergy. Another 23.1% were cleared by an allergist for vaccination after consultation. These patients had symptoms inconsistent with an allergy or had subsequently tolerated the same vaccine or other vaccines containing the excipients of interest. The remaining 31.2% required closer evaluation (Figure 1). It is important to note that cross-reactivity between PS-80 and PEG is theoretical and remains unproven, thus tolerating a vaccine containing one does not accurately allow us to conclude that the individual would tolerate both. Of the patients undergoing further evaluation, we enrolled 190 individuals (Table 1). Patient age ranged from 12 to 83 years with a median age in the pediatric group (defined as age < 18 years) of 14 years (n = 39) and 46 years in adults (n = 151). Only children 12 years and above were eligible for COVID-19 vaccination during this period. Most patients reported symptoms consistent with a type 1 hypersensitivity reaction to the vaccines, including urticaria or angioedema (56.33%) or anaphylaxis (9%) based on physician reporting on the national electronic database and patient history taken during the specialized allergy consultation. All SPTs to the Pfizer vaccine were negative. Fourteen patients had an immediate positive IDT [1:10 Pfizer vaccine (five adults, three children) and 1:10 PS-80 (five adults, two children)] and three had delayed positive IDTs (48 h after testing). Seven patients had only one positive skin test, while seven others had several positive results. There was no relationship between positive skin tests and family history of allergy, personal medical history, type of reaction to vaccines, or other demographic variables. Patients with negative skin tests (n = 109) were offered provocation tests. Of these, seven patients reported mild reactions (nausea and urticaria being the most common). One patient developed anaphylaxis7 characterized by generalized urticaria, wheezing, and shortness of breath, 5 min after the first dose of the graded challenge, requiring treatment with one dose of intramuscular adrenaline. Eight of the 17 patients with positive skin tests (including seven positives to the Pfizer vaccine) tolerated the provocation tests with the Pfizer vaccine without any immediate or delayed reactions. Seven patients chose non-mRNA alternatives (Sinovac–CoronaVac was the only non-COVID-19 mRNA vaccine available at the time). Two patients deferred COVID-19 vaccination. At a safety phone call made 48–72 h of post vaccination, mild reactions were reported in 13.7% of patients, 18% for children and adults, respectively. No severe reactions were reported in either age group. The proportion of pediatric patients with skin test positivity and tolerance of graded challenge is similar in adults and children. While there was one anaphylactic episode in the adult group, none of the children developed a reaction during graded challenge. To our knowledge, allergy referrals in patients with suspected prior non-COVID-19 vaccine allergies was not routinely done in other countries. We demonstrate that within our study population, (i) skin testing with vaccine and excipients prior to vaccination with mRNA COVID-19 vaccines was not a useful predictor of mRNA vaccine tolerance and provocation tests should be recommended as gold standard; (ii) a history of reported vaccine allergy did not correlate with excipient skin test positivity, even in those with convincing type 1 hypersensitivity reactions, and (iii) a history of prior vaccine allergy did not predict successful vaccination with the mRNA COVID-19 vaccine. Our findings were consistent with previous reports2, 8 demonstrating poor correlation between allergy skin-testing to excipients and mRNA COVID-19 vaccination tolerance. This could be in part due to an irritant concentration of the Optive Advanced eye drops used to test for sensitization to PS-80 and low cross-reactivity between PEG and PS-80. Furthermore, other nonallergic mechanisms could play a role in the vaccine adverse events reported such as complement activation-related pseudo allergic reaction (CARPA). If CARPA is responsible for a subset of the adverse reactions seen, this could explain why most patient with a previous reaction subsequently tolerate the same vaccine. We are limited by the patient-reported nature of the past vaccine allergies, which may inadvertently have included patients with nonallergic reactions. Careful history was taken to exclude patients with inconsistent allergy symptoms. Patients who were cleared for direct vaccination after a review of history alone received their vaccinations at the community vaccine centers and could not be followed up as they were not recruited into the study. However, none of these patients were referred back to us for COVID-19 vaccine-related reactions. Although the Brighton criteria7 has been used to define anaphylaxis in vaccine-related reactions, the criteria has been reevaluated as the inclusion of subjective symptoms could account for higher reports of adverse events following immunization.9 This is not applicable to the anaphylactic reaction within our study as it presented with objective symptoms but could have played a role in overestimating the severity of the initial vaccine allergic reaction for which the patients were referred to the vaccine clinic. Our study shows that prior vaccine allergy history is not a risk factor for vaccination with COVID-19 mRNA vaccines, a concern both among physicians and patients, which is still a cause of hesitancy for vaccination in the general population. The strengths of our study include the prospective recruitment and follow-up of patients undergoing allergy review, work up and provocation tests in the pediatric population, providing a comprehensive overview of the utility of such an allergy referral workflow in predicting COVID-19 mRNA vaccine allergies. Our study is the first to describe a systematic allergy testing approach in subjects under 18 years of age. A previously published series of three patients also demonstrates that children with immediate first-dose reactions to mRNA COVID-19 can safely receive their second injection in a graded challenge without the need for premedication.10 The subjects presented with cutaneous symptoms after vaccination which were managed with oral antihistamines. Contrary to our study, cutaneous allergy tests where not performed; the authors performed basophil activation tests which did not predict the outcome. Another study in adolescents and young adults with a history of acute lymphoblastic leukemia and allergy to PEG-asparaginase retrospectively analyzed data from 32 patients who received the Pfizer-BioNTech vaccine in a specialized vaccination clinic without any allergic reaction.11 No allergy tests or allergy visits were performed for these patients in order not to delay vaccination. Robust data on pediatric population are still lacking, but these studies and our own data show that prevaccination testing is of limited use in this age group. There have been little pediatric data regarding potential vaccine allergy and the utility of testing in children published so far, necessitating extrapolation of adult data to the pediatric context. Our study includes allergy testing in pediatric subjects, a strategy which has not been done in other countries. This initial screening program for adolescents helped reassure the public of the continued safety of COVID-19 vaccination in children. As we demonstrated a low utility of allergy testing both in the adult and adolescent age groups with suspected past vaccine allergies prior to mRNA COVID-19 vaccination, along with rising evidence on the limitations of allergy testing to predict COVID-19 vaccine allergy, government policy on the eligibility for vaccination with mRNA COVID-19 vaccines in these patients was revised,12 allowing them to receive full dose vaccinations without prior testing or graded challenges. When the COVID-19 vaccination drive was opened up to children under the age of 12 years in Singapore, they were able to follow this revised vaccination guidance. Currently, COVID-19 vaccination is freely available in Singapore for all age groups 6 months and above. Referral to the allergy specialist is indicated only in patients with a history of prior reaction to mRNA COVID-19 vaccine or its excipients. Overall, we do not recommend excipient testing in either adult or pediatric patients receiving the mRNA COVID19 vaccination, supporting the validity of common recommendation across the age groups, and we conclude that a history of prior vaccine allergy should not preclude vaccination with the mRNA COVID-19 vaccine. Carmen Riggioni was involved in Conceptualization (lead), Recruitment(equal), Writing-review (lead), editing (equal); Kee Fong Phang: Recruitment(equal), review & editing (equal); Sen Hee Taywas involved in Recruitment(equal), review & editing (equal); Hugo Van Bever was involved in Recruitment(equal), review & editing (equal); Serene Xu was involved in Recruitment(equal), review & editing (equal); Sylvia Oh was involved in Recruitment(equal), review & editing (equal); Angela Bueno was in involved in Recruitment(equal), review & editing (equal); Ruth Chua was involved in Recruitment(equal), review & editing (equal); Si Hui Goh was involved in review & editing (equal), Kok Wee Chong was involved in review & editing (equal), Elizabeth Huiwen Tham was involved in Conceptualization (lead), Recruitment(equal), Writing-review (lead), editing (lead); Amelia Santosa was involved in Conceptualization (lead), Recruitment(equal), Writing-review (lead), editing (lead). All authors have no conflicts of interest to disclose. The peer review history for this article is available at https://publons.com/publon/10.1111/pai.13923. The peer review history for this article is available at https://publons.com/publon/10.1111/pai.13923.

Singapore (15.2%) (all P < 0.001). By contrast, asthma prevalence was similar in Australian Caucasian and Asian children (12.7% vs 11.1%, P = 0.68) and lower in Singapore (4.6%, P < 0.001). HDM sensitization was highest in Asian children in Australia (41.2%) followed by Singapore (34.4%, P = 0.02) and lowest in Caucasian children (21%, P < 0.001). Eczema diagnosis in the fi rst year of life was the top risk factor for asthma in GUSTO but 7th in the HealthNuts Asians. Time of egg introduction into diet was the top risk factor for rhinitis and HDM sensitization in HealtNuts Asians and GUSTO respectively. Conclusion : At age 5 – 6 years, prevalence of asthma, rhinitis and HDM sensitization was higher in Australia compared to Singapore, particularly in Australian Asian children. Our fi ndings highlight the variable contribution of risk factors to allergic disease pathogenesis in different populations, suggesting the need for tailored approaches to allergic disease treatment and prevention

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Singapore (15.2%) (all P < 0.001). By contrast, asthma prevalence was similar in Australian Caucasian and Asian children (12.7% vs 11.1%, P = 0.68) and lower in Singapore (4.6%, P < 0.001). HDM sensitization was highest in Asian children in Australia (41.2%) followed by Singapore (34.4%, P = 0.02) and lowest in Caucasian children (21%, P < 0.001). Eczema diagnosis in the fi rst year of life was the top risk factor for asthma in GUSTO but 7th in the HealthNuts Asians. Time of egg introduction into diet was the top risk factor for rhinitis and HDM sensitization in HealtNuts Asians and GUSTO respectively. Conclusion : At age 5 – 6 years, prevalence of asthma, rhinitis and HDM sensitization was higher in Australia compared to Singapore, particularly in Australian Asian children. Our fi ndings highlight the variable contribution of risk factors to allergic disease pathogenesis in different populations, suggesting the need for tailored approaches to allergic disease treatment and prevention

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.

BackgroundAllergic 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.MethodsWe 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.ResultsAmong 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)], cesarean 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)].ConclusionEarly 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.