Prevalence, risk factors and parental perceptions of gastroesophageal reflux disease in Asian infants in Singapore

INTRODUCTION@#Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents.@*METHODS@#Mother-infant dyads in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort were prospectively followed from preconception to 12 months post-delivery. GERD diagnosis was ascertained through the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) administered at 4 time points during infancy. Data on parental perceptions and lifestyle modifications were also collected.@*RESULTS@#The prevalence of infant GERD peaked at 26.5% at age 6 weeks, decreasing to 1.1% by 12 months. Infants exclusively breastfed at 3 weeks of life had reduced odds of GERD by 1 year (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.97, P=0.04). Elimination of "cold or heaty food" and "gas producing" vegetables, massaging the infant's abdomen and application of medicated oil to the infant's abdomen were quoted as major lifestyle modifications in response to GERD symptoms.@*CONCLUSION@#Prevalence of GERD in infants is highest in the first 3 months of life, and the majority outgrow it by 1 year of age. Infants exclusively breastfed at 3 weeks had reduced odds of GERD. Cultural-based changes such as elimination of "heaty or cold" food influence parental perceptions in GERD, which are unique to the Asian population. Understanding the cultural basis for parental perceptions and health-seeking behaviours is crucial in tailoring patient education appropriately for optimal management of infant GERD.

Economic value of using partially hydrolysed infant formula for risk reduction of atopic dermatitis in high-risk, not exclusively breastfed infants in Singapore

<p><b>INTRODUCTION</b>Previous trials have demonstrated reductions in atopic dermatitis (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were fed until four months of age with 100% whey-based partially hydrolysed formula (PHF-W) versus standard cow's milk formula (CMF). We assessed the cost-effectiveness of this intervention in Singapore.</p><p><b>METHODS</b>Modelling techniques were used to simulate, from birth to Month 30, the incidence and clinical/economic burden of AD in high-risk, non-exclusively breastfed infants fed with PHF-W or CMF for up to four months. Epidemiologic and clinical data were from a local comparative trial. Expert opinion informed AD treatment patterns and outcomes. Outcomes included reduction in AD risk, time spent with AD, days without AD flare, quality-adjusted life years (QALYs) and direct/indirect costs. Multivariate probabilistic sensitivity analysis was used to assess model parameter uncertainty.</p><p><b>RESULTS</b>Over 30 months, with the use of PHF-W instead of CMF, the proportion of children who developed AD and the time spent with AD decreased by 16.0% (28.3% vs. 44.3%) and 6.4 months, respectively, while time without AD flare and QALYs increased by 14.9 days and 0.021 QALYs per patient, respectively. Estimated AD-related discounted costs per child for PHF-W and CMF were SGD 771 and SGD 1,309, respectively (net savings: SGD 538). PHF-W was less expensive and more effective than CMF for 73%, and cost less than SGD 50,000 per QALY for 87% of all multivariate simulations.</p><p><b>CONCLUSION</b>Early short-term nutritional intervention with PHF-W instead of CMF may reduce AD incidence and costs for healthy, high-risk, non-exclusively breastfed infants in Singapore.</p>

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore

<p><b>INTRODUCTION</b>Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer.</p><p><b>METHODS</b>A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore.</p><p><b>RESULTS</b>Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV.</p><p><b>CONCLUSION</b>AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.</p>

Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants

<p><b>INTRODUCTION</b>This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life.</p><p><b>MATERIALS AND METHODS</b>Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed.</p><p><b>RESULTS</b>Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups.</p><p><b>CONCLUSION</b>Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.</p>

Shellfish and House Dust Mite Allergies: Is the Link Tropomyosin?

Crustacean shellfish allergy is an important cause of food allergy and anaphylaxis in Asia. The major allergen in shellfish allergy is tropomyosin, a pan-allergen that is also found in house dust mites and cockroaches. Tropomyosins from house dust mites (HDMs) have a high sequence homology to shellfish tropomyosins, and cross-reactivity between HDM and shrimp tropomyosins has been demonstrated. Exposure to inhaled tropomyosins from house dust mites has been postulated to be the primary sensitizer for shellfish allergy, in a reaction analogous to the oral allergy (inhalant-food) syndrome. This notion is supported by indirect data from the effects of HDM immunotherapy on shellfish allergy, and strong correlations of shellfish and HDM sensitization. HDM immunotherapy has been reported to induce both shrimp allergy in non-allergic patients and shrimp tolerance in shrimp-allergic patients. Epidemiological surveys have also demonstrated a strong correlation between shellfish and HDM sensitization in both hospital-based and community-based studies. Unexposed populations have also been shown to develop sensitization-shellfish sensitization in orthodox Jews with no history of shellfish consumption was associated with HDM sensitization. Reciprocally, HDM sensitization in an Icelandic population living in a HDM-free environment was associated with shrimp sensitization. In vitro IgE inhibition studies on sera in shrimp-allergic Spanish patients indicate that mites are the primary sensitizer in shrimp-allergic patients living in humid and warm climates. Current data supports the hypothesis that tropomyosin is the link between HDM and shellfish allergies. The role of tropomyosin in HDM and shellfish allergies is a fertile field for investigation as it may provide novel immunotherapeutic strategies for shellfish allergy.

Relationship between all fevers or fever after vaccination, and atopy and atopic disorders at 18 and 36 months

BACKGROUND: Studies have reported that early febrile episodes and febrile episodes with infections are associated with a decreased risk of developing atopy. OBJECTIVE: To examine further the association between presence of and number of febrile episodes are with atopy and atopic diseases and if there was a difference between all fevers and fever after vaccination. METHODS: We studied 448 infants in a Singapore mother-offspring cohort study (Growing Up in Singapore Towards Healthy Outcomes) which had complete data for the exposures and outcomes of interest. Fever was defined as more than 38.0℃ and was self-reported. The presence of and number of febrile episodes were examined for association with outcome measures, namely parental reports of doctor-diagnosed asthma and eczema, and rhinitis, which was evaluated by doctors involved in the study at 18 and 36 months. These outcomes were considered atopic if there were 1 or more positive skin prick tests. RESULTS: The presence of all fevers from 0–6 months of age was associated with reduced odds of having atopy at 36 months of age (unadjusted odds ratio [OR], 0.628; 95% confidence interval [CI], 0.396–0.995). The presence of fever after vaccination from 0–24 months of age was associated with reduced odds of having atopy at 36 months of age (OR, 0.566; 95% CI, 0.350–0.915). The presence of all fevers from 0–6 months of age was associated with reduced odds of having atopic eczema at 36 months (OR, 0.430; 95% CI, 0.191–0.970). Fever was associated with increased odds of having doctor-diagnosed asthma and rhinitis. CONCLUSION: There was an inverse relationship between the presence of all fevers from 0–6 months of age and the development of atopy and eczema at 36 months of age. Fever after vaccination might be considered a subclinical infection that did not show the same effect in early life.

Carbohydrates as food allergens

The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are two distinct groups, each with unique characteristics and geographical distribution. Anaphylaxis and acute allergic reactions related to the carbohydrate galactose-α-1,3-galactose (α-Gal) epitope that are present in the monoclonal antibody, cetuximab and red meat have been described in the United States and Europe populations where tick bites have been found to be the primary sensitizer. Another carbohydrate inducing anaphylaxis is galacto-oligosaccharides in commercial milk formula which has been described in the several Asian populations including Singapore. The latter is unique in that the allergen is a pure carbohydrate. We summarize the current literature on carbohydrate-induced food allergy, and evaluate the two new groups of carbohydrate allergy that have defied previous findings on carbohydrates and their role.

Food allergy in Asia: how does it compare?

Asia is a populous and diverse region and potentially an important source of information on food allergy. This review aims to summarize the current literature on food allergy from this region, comparing it with western populations. A PubMed search using strategies "Food allergy AND Asia", "Food anaphylaxis AND Asia", and "Food allergy AND each Asian country" was made. Overall, 53 articles, published between 2005 and 2012, mainly written in English were reviewed. The overall prevalence of food allergy in Asia is somewhat comparable to the West. However, the types of food allergy differ in order of relevance. Shellfish is the most common food allergen from Asia, in part due to the abundance of seafood in this region. It is unique as symptoms vary widely from oral symptoms to anaphylaxis for the same individual. Data suggest that house dust mite tropomysin may be a primary sensitizer. In contrast, peanut prevalence in Asia is extremely low compared to the West for reasons not yet understood. Among young children and infants, egg and cow's milk allergy are the two most common food allergies, with prevalence data comparable to western populations. Differences also exist within Asia. Wheat allergy, though uncommon in most Asian countries, is the most common cause of anaphylaxis in Japan and Korea, and is increasing in Thailand. Current food allergy data from Asia highlights important differences between East and West, and within the Asian region. Further work is needed to provide insight on the environmental risk factors accounting for these differences.

Allergies in Asia: are we facing an allergy epidemic?

No abstract available.

Erratum: Rhinitis in children less than 6 years of age: current knowledge and challenges

In the original publication, we created a mistake in typing the name. Thus it was spelled as Antony Hadjojo when submitted to the publisher. We request for a correction of the author name into Antony Hardjojo.

The methodology of the GUSTO cohort study: a novel approach in studying pediatric allergy

Growing Up in Singapore Towards healthy Outcomes (GUSTO) is Singapore's largest birth cohort study to date. The main aim of GUSTO is to evaluate the role of developmental factors in the early pathways to metabolic compromise. Detailed data is collected for a range of environmental exposures in the parents and offspring, and allergic disorders are among a number of outcomes assessed in infancy and childhood. Under the Allergy domain of GUSTO, this integrated study will describe the epidemiology of allergic manifestations and different phenotypes in the Asian context and help shed light on the association of metabolic disease to allergy. Epigenetic mechanisms and associations with other childhood disorders will also be explored. The aim of this report is to focus on methodology of GUSTO, and to suggest similar approaches (i.e., integrated cohort studies on pediatric allergy) worldwide. Recruitment commenced in 2009 with a cohort of 1,163 pregnant mothers in their first trimester. The mothers and children were followed throughout pregnancy and follow-up will continue until the child reaches 3 years of age. Preliminary results showed that 39.8% of the mothers had a personal history of having at least one allergic disease, which included asthma, eczema and allergic rhinitis. Further data collection and analyses are still ongoing. Allergy is a complex spectrum of disorders with numerous poorly-understood aspects. The ongoing GUSTO cohort study, with its longitudinal design and multi-disciplinary nature, may provide new insights into developmental influences on allergy. As a Singapore-based study, it will be the first integrated allergy cohort in Southeast Asia, of which recruitment started during pregnancy.

Rhinitis in children less than 6 years of age: current knowledge and challenges

Rhinitis is a disease of the upper airway characterized by runny and/or blocked nose and/or sneezing. Though not viewed as a life threatening condition, it is also recognized to impose significant burden to the quality of life of sufferers and their caretakers and imposes an economic cost to society. Through a PubMed online search of the literature from 2006 to September 2011, this paper aims to review the published literature on rhinitis in young children below the age of 6 years. It is apparent from epidemiology studies that rhinitis in this age group is a relatively common problem. The condition has a heterogenous etiology with classification into allergic and non-allergic rhinitis. Respiratory viral infections may play a role in the pathogenesis of long standing rhinitis, but definitive studies are still lacking. Treatment guidelines for management are lacking for this age group, and is a significant unmet need. Although the consensus is that co-morbidities including otitis media with effusion, adenoidal hypertrophy and asthma, are important considerations of management of these children. Pharmacotherapy is limited for young children especially for those below the age of 2 years. This review underscores the lack of understanding of rhinitis in early childhood and therefore the need for further research in this area.

Childhood food allergy: a Singaporean perspective

Food allergy is defined as reaction to a food which has an immunologic mechanism. Its prevalence is increasing in children globally and is therefore of increasing clinical importance. A useful clinical approach is to distinguish food allergic reactions by the timing of clinical reaction in relation to food exposure and classified as immediate (generally IgE-mediated) and delayed (generally non-IgE-mediated), with the exception of eczema and eosinophilic gastrointestinal disease, which, when associated with food allergy may be associated with either mechanism. This review is aimed at providing the clinician with a Singaporean perspective on the clinical approach and management of these disorders.

An update of paediatric intussusception incidence in Singapore: 1997-2007, 11 years of intussusception surveillance

<p><b>INTRODUCTION</b>Understanding baseline epidemiology of intussusception (IS) in different geographical settings is important for the safety assessment of rotavirus vaccines. This paper presents IS surveillance data from Singapore between 1997 and 2007, including the period between November 2005 and December 2007 when rotavirus vaccines (primarily Rotarix) were available to newborns in Singapore.</p><p><b>MATERIALS AND METHODS</b>Case ascertainment, collection, analyses and presentation of IS data was done as per recommendations of the Brighton Collaboration Working Group. For estimating the IS incidence rate in infants, live births for the years of the study were used as denominators, while for incidence in children age <2 years, the expected numbers of infant deaths occurring between 1 and 2 years of age was deducted from the combined live births for the 2 years, to obtain the denominator.</p><p><b>RESULTS</b>The incidence of IS among children aged <1 year throughout this 10-year period was higher than the incidence of IS in children between 1 and 2 years of age. In 2005, 2006 and 2007, the incidence of IS per 100,000 was 39.9, 26.4 and 35.6 in children aged <1 year and 26.2, 23.8 and 28.7 in children <2 years.</p><p><b>CONCLUSION</b>This IS surveillance study provides reassuring preliminary evidence that there is no increase in the incidence of IS in Singapore after the introduction of rotavirus vaccines (including Rotarix) in Singapore.</p>

The Influence of Breastfeeding and Weaning Practices on the Development of Allergic Disease Review of Current Evidence / 소아알레르기및호흡기학회지

Food allergies and atopic diseases are on the rise worldwide. There have been several published practice guidelines on the primary prevention of these diseases. One aspect of these guidelines is the recommendations on infant nutrition, as food allergen exposure and other nutritional factors may influence allergen sensitization. This article aims to review the current international recommendations on infant diet and weaning practices in the primary allergy prevention of infants. The conclusions drawn are as follows: (1) Breastfeeding is considered the gold standard for infant nutrition, especially since exclusive breastfeeding confers some protection against the development of allergic diseases. However, large cohort studies have not been carried out in Asian populations. (2) Maternal avoidance of allergenic food substances during pregnancy and lactation has not been proven to reduce the risk of allergies and is not recommended as a primary prevention strategy. (3) Hydrolyzed formulas have not been shown to have an advantage over breastfeeding, although they have some protective value against atopic eczema in at risk infants when compared to regular cows milk based infant formula. (4) Soy formula is also not recommended for prevention of atopic diseases. (5) Weaning to semisolids should be undertaken between the ages of 4 to 6 months as weaning before the age of 4 months is associated with increased of allergy symptoms. (6) The age for introduction of certain highly allergenic foods have been arrived at empirically and included in some guidelines. These comprise the initiation of dairy products at 12 months, eggs at 24 months, and peanuts, nuts and fish at 36 months.

The epidemiology of paediatric intussusception in Singapore: 1997 to 2004

<p><b>INTRODUCTION</b>The world's first rotavirus vaccine, Rotashield or RRV-TV, was registered in the US in 1998, but withdrawn within a year because of an observed association with intussusception (IS). Surveillance for IS has consequently become important in safety monitoring of new-generation rotavirus vaccines during development. Post-marketing surveillance is also important, and requires the availability of local baseline epidemiology data on IS.</p><p><b>MATERIALS AND METHODS</b>An eight-year study of IS in children under 2 years of age in Singapore was performed by retrospective review of admissions to KK Women's and Children's Hospital, the main paediatric hospital, from 1997 to 2001, followed by prospective surveillance of all hospitals from 2001 to 2004, using the case definition of the Brighton Collaboration Intussusception Working Group.</p><p><b>RESULTS</b>The average IS incidence was 60 per 100,000 in under-ones, and 32 per 100,000 in under-twos, with a downward trend between 1999 and 2004. Ninety-two per cent of subjects were aged below one year, with 51% aged 6 months to 11 months. The mean age at which IS occurred increased from 6.4 months to 12.5 months over the study period. The male-to-female ratio was 1.3:1. No trend in IS numbers was observed over different months of the year.</p><p><b>CONCLUSION</b>IS in Singapore shows no seasonality, but has demonstrated a trend of decreasing incidence in recent years. While highest in the first year of life, the risk of IS is increasing in the second year of life. Males have a slightly higher risk.</p>