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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.

Introduction: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

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.

Introduction: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

Introduction: 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., Materials and Methods: 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., Results: 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., Conclusion: 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.

Introduction: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented., Methods: Completed RIX4414 trials have been reviewed., Results: Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated., Conclusion: These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.

Introduction: Asthma and atopy are complex traits, the phenotypes being influenced by the interaction of both genetic and environmental factors. In view of the growing evidence for inter-ethnic differences in genetic susceptibility to complex diseases such as asthma and atopy, we have assessed genetic factors for these diseases in the local population., Methods: The genetic analysis of asthma and atopy is being approached by candidate gene analysis as well as linkage studies for mapping of susceptibility loci. We reviewed published studies, which include data from our population on some candidate genes, as well as our preliminary data on susceptibility locus mapping for linkage to chromosome 5q31-33., Results: In local studies of the interleukin-4 receptor and tumour necrosis factor polymorphisms, we failed to find associations with genetic variants previously implicated to be associated with asthma and atopy. Evaluation of markers on chromosome 5q31-32 identified novel loci for susceptibility to asthma and atopy in addition to loci already described by others., Conclusion: Both the published literature and our own findings indicate that there are inter-ethnic differences in genetic susceptibility to asthma and atopy.

The allergens of domestic pets such as cats, dogs and birds, have been known to sensitive predisposed individuals. In Singapore, approximately 25% to 35% of our atopic populations are sensitised to cat, dog or bird feather allergens. It is not known, however, if the presence of such domestic pets would translate to higher rates of sensitisation, or more importantly, give rise to increased respiratory symptoms. This study evaluated the association between the presence of domestic pets at home and the prevalence of respiratory symptoms among asthmatic children in Singapore. The parents of 1517 doctor-diagnosed asthmatic children were interviewed using the American Thoracic Society-Division of Lung Diseases respiratory questionnaire. More than 20% were found to have domestic pets (cats, dogs or birds) at home. Of these, those with exposure to passive smoke in the home were excluded. A total of 188 current pet owners (cats, dogs and birds) were demographically-matched for sex, race and socio-economic status (type of housing) to those without pets, past or current. Compared to those without pets, asthmatic children with pets at home had a higher prevalence of coughing with cold [relative risk (RR) 1.30; 95% confidence interval (CI) 1.01 to 1.69]; wheezing with cold (RR 1.42; CI 1.07 to 1.90), wheezing with shortness of breath (RR 1.33; CI 1.00 to 1.82), exercise-induced wheezing (RR 1.68; CI 1.10 to 2.56); and increased phlegm production or congestion with cold (RR 1.38; CI 1.00 to 1.91). This study suggests that the presence of domestic pets increases the prevalence of respiratory symptoms in asthmatic children. Those with predisposition to these allergens should avoid having these pets in the home or take specific precautions in avoiding their allergens.

Evaluation of minimal residual disease (MRD) in acute lymphoblastic leukaemia (ALL) is important for disease prognostication and early relapse detection. In this study, the rearranged third complementarity-determining-region (CDR-III) of immunoglobulin heavy chain (IgH) was used as a surrogate tumour marker for MRD evaluation. DNA obtained from marrows at diagnosis was amplified by the polymerase chain reaction (PCR) using a pair of consensus primers. After 2 rounds of DNA amplification and polyacrylamide gel separation, the nucleotide sequences of 87.5% (21/24) consecutive children with B-lineage ALL were obtained by automated sequencing. There were between 1-4 rearrangements per patient. Although the J5 and J6 joining regions were preferentially used, the rearranged sequences were unique for all 25 sequences obtained. Oligoprobes to the DNJ region were constructed and quantitation in 7 patients showed a detection sensitivity of 1 leukaemic cell in 10(4) to 10(5) normal cells compared to 3 in 100 using conventional morphological criteria. Serial bone marrow showed progressive decrease in the quantity of leukaemic cells, and no leukaemic sequences were detected during cessation of therapy in 4/7 patients. One patient with detectable MRD, absconded treatment and eventually relapsed. These results are consistent with the need to eliminate the leukaemic clones below MRD detection levels before the end of therapy at 2 years. In conclusion, this study describes a novel, simplified and sensitive method of MRD detection in childhood leukaemia.

Food allergy is perhaps the most controversial area of clinical immunology. The literature is filled with anecdotal reports. Food allergy refers to an untoward immune-mediated reaction caused by ingestion of food antigens. It should be distinguished from non-immunological adverse reactions to food since their therapeutic and prognostic implications are different. This review article examines some of the important issues with regards to the pathogenesis, symptomatology, diagnosis and treatment of food allergy.

Drugs and their metabolites may act as haptens resulting in hypersensitivity reactions. These reactions occur less frequently in children than adults. As most pathogenetic mechanisms of drug hypersensitivity reactions (DHRs) and drug metabolic pathways are unknown, there are few diagnostic tests for DHRs. The patient's history, with particular emphasis on the type of reaction invoked by the drug is therefore, still of utmost importance in evaluation. Diagnostic tests are confined mainly to IgE-mediated DHRs, of which tests for penicillin allergy is the most established. Several factors are known to influence the occurrence of DHRs. Anaphylaxis is less common with orally administered drugs compared to those administered parenterally, and atopic persons appear to have an increased susceptibility to anaphylactic reaction. In the paediatric population, antibiotics, especially the penicillins, are common agents involved in DHRs. However, the fine erythematous macular papular rash frequently evoked by ampicillin, should not be mistaken for an allergic reaction with the associated risk of anaphylaxis. Other drugs commonly involved in DHRs in children are sulfonamides, aspirin, and vaccines, especially those against measles, mumps and rubella.

Thirty-two cases of hydronephrosis caused by pelvi-ureteric junction obstruction, presenting to the Department of Paediatric Surgery in the last 6 years were reviewed. In both infants and older children a palpable abdominal mass was the most common mode of presentation. Anderson-Hynes pyeloplasty was performed in a total of 31 kidneys. In 4 children, whose kidneys were severely hydronephrotic and with hardly any renal parenchyma present a primary nephrectomy was performed. Of the two children who required further operation on the same kidney, a repeat pyeloplasty for persistent obstruction was required in 1 patient, the other patient underwent nephrectomy subsequent to pyeloplasty as a severe pyonephrosis had developed. Twenty-nine of the 31 kidneys were assessed postoperatively by tube nephrogram, intravenous pyelogram (IVP), or diuretic renography. Four kidneys were found to be non-functional or severely damaged.

We studied the distribution of HLA-DR and MT1, MT2, MT3 genotypes in 23 Chinese children with insulin-dependent diabetes mellitus (IDDM). The frequency of DR3 was 48% in IDDM children compared to 14% of normal controls (corrected p = 0.0098, RR = 5.70). The frequency of DR4 was not increased. These differences when compared with the results of Western populations may contribute to the relative rarity of IDDM among Chinese children.

Singaporean Chinese IDDM was significantly associated with AW33, BW58, DR3 and DR4. AW33, BW58 and DR3 being in strong linkage disequilibrium among the Chinese, were associated most strongly with IDDM whose onset was less than or equal to 10 years. The strength of this association showed a significant inverse relationship with age of onset. The frequency of DR4 was significantly elevated on in the 11-20 year IDDM group. The importance of DR3 in Chinese IDDM was also reflected in the observations of joint occurrences of DR antigens. In the less than or equal to 10 years subgroup, the significant association were either DR3/DRW9, DR3/DR4 or DR3/BLANK. In the 11-20 years subgroup, DR4 appeared to be more important and DR4/DR3 and DR4/BLANK were strongly associated with IDDM in this subgroup.

Nineteen children with insulin-dependent diabetes mellitus in the University Department of Paediatrics were assessed for complications of diabetes. 36.8% showed marked growth stunting, and half of the patients who attained puberty had a delayed onset of puberty. 42% showed limited joint mobility. Almost all the patients developed hypertrophic lipodystrophy while only 5 patients developed reversible lipoatrophy. Abnormal nerve conduction velocities were found in all 17 patients tested, with more of sensory nerve involvement. A significant correlation was found between duration of disease and the extent of neuropathy. Evidence of nephropathy was found in 5 patients, 2 of whom showed impaired renal function. One patient had background retinopathy, another had proliferative retinopathy and 2 patients developed cataracts. The high prevalence of microangiopathic complications in these children is probably related to their previous poor diabetic control and it is hoped that with home blood glucose monitoring to improve their control, these complications may be arrested or minimized.