Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

Maternal asthma symptoms during pregnancy on child behaviour and executive function: A Bayesian phenomics approach.

OBJECTIVE: Maternal history of inflammatory conditions has been linked to offspring developmental and behavioural outcomes. This phenomenon may be explained by the maternal immune activation (MIA) hypothesis, which posits that dysregulation of the gestational immune environment affects foetal neurodevelopment. The timing of inflammation is critical. We aimed to understand maternal asthma symptoms during pregnancy, in contrast with paternal asthma symptoms during the same period, on child behaviour problems and executive function in a population-based cohort. METHODS: Data were obtained from 844 families from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Parent asthma symptoms during the prenatal period were reported. Asthma symptoms in children were reported longitudinally from two to five years old, while behavioural problems and executive functioning were obtained at seven years old. Parent and child measures were compared between mothers with and without prenatal asthma symptoms. Generalized linear and Bayesian phenomics models were used to determine the relation between parent or child asthma symptoms and child outcomes. RESULTS: Children of mothers with prenatal asthma symptoms had greater behavioural and executive problems than controls (Cohen's d: 0.43-0.75; all p < 0.05). This association remained after adjustments for emerging asthma symptoms during the preschool years and fathers' asthma symptoms during the prenatal period. After adjusting for dependence between child outcomes, the Bayesian phenomics model showed that maternal prenatal asthma symptoms were associated with child internalising symptoms and higher-order executive function, while child asthma symptoms were associated with executive function skills. Paternal asthma symptoms during the prenatal period were not associated with child outcomes. CONCLUSIONS: Associations between child outcomes and maternal but not paternal asthma symptoms during the prenatal period suggests a role for MIA. These findings need to be validated in larger samples, and further research may identify behavioural and cognitive profiles of children with exposure to MIA.

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.

Parental, Perinatal, and Childhood Risk Factors for Development of Irritable Bowel Syndrome: A Systematic Review.

Background/Aims: Adverse early life experiences are associated with the development of stroke, cancer, diabetes, and chronic respiratory and ischemic heart diseases. These negative experiences may also play a role in the development of irritable bowel syndrome (IBS)--a functional gastrointestinal disease. This review discusses the research to date on the parental, perinatal, and childhood risk and protective factors associated with the development of IBS. Methods: A literature search was completed for studies published between 1966 and 2018 that investigated premorbid factors occurring during the perinatal and childhood periods as well as parental factors that were associated with the development of IBS. Results: Twenty-seven studies fulfilled the review criteria. Risk factors that appeared in more than one study included: (1) parental IBS, substance abuse, parental punishment, and rejection as parental risk factors; (2) low birth weight as a perinatal risk factor; and (3) crowded living conditions in low-income families, childhood anxiety, depression, or child abuse as childhood risk factors. Protective factors for IBS were emotional warmth from the parents and being born to an older mother. Conclusions: More effort is needed to identify what fetal and maternal factors are associated with low birth weight and IBS. A well-executed prospective birth cohort with a collection of bio-samples and functional data will provide a better understanding of how adversity and the interplay between genetics, epigenetics, and numerous risk factors affect the development of IBS.

Challenges of managing food allergy in the developing world.

Food allergy (FA) is currently a significant health care problem in the developing world. Widely varying study populations and methodologies, the use of surrogate markers such as self report or hospitalization rates due to anaphylaxis rather than objective methods, limits robust estimation of FA prevalence in low income settings. Also, allergy is under-recognized as a clinical specialty in the developing world which compromises the chance for accurate diagnosis. In this review, most published data on food allergens from developing or low income countries are displayed. The diagnostic challenges and limitations of treatment options are discussed. It seems that FA is an under-appreciated health care issue in the developing world, and accurate determination of its burden in low-income settings represents an important unmet need. Multicenter surveillance studies, using standardized methodologies, are, therefore, needed to reveal the true extent of the problem and provide epidemiological clues for prevention. Preventive strategies should be tailored to fit local circumstances in different geographic regions. In addition, studying the gene environment interactions and impact of early life microbiota on the expression of FA in developing communities would be worthwhile. Efforts and resources should be directed toward public health education and training of health care providers dealing with food allergic patients.

Anaphylaxis - Lessons learnt when East meets West.

The rapidly increasing prevalence of allergic disorders over the past 2 decades highlights the need to understand the epidemiology of anaphylaxis. In Europe, the United States, and Australia, the incidence of anaphylaxis is estimated to be between 60 and 950 cases per 100 000 population, with a lifetime prevalence of anaphylaxis of 0.05%-2%. The incidence appears to be increasing over time. Although the existing Asian literature is heterogeneous and limited by under-reporting, it also suggests a similar increasing trend in anaphylaxis incidence in Asia. Anaphylaxis triggers in Asia, such as the predominance of shellfish and wheat in older children and adolescents, differ from those seen in Western populations. Triggers unique to Asia such as traditional Chinese medications, galacto-oligosaccharides, and food delicacies have also been reported. Low usage of adrenaline as first-line treatment of anaphylaxis is evident across all countries and is particularly concerning. There is a need to establish prospective, standardized protocols for anaphylaxis data collection and reporting, to enhance the collective understanding of anaphylaxis and its burden, gaps in management and to identify areas for future research and intervention in each region. Understanding of the underlying reasons explaining the difference between East and West will facilitate future primary preventive strategies.

Prevention of food allergy in the real life.

The prevalence of food allergy has increased exponentially in the last decade and is fast becoming the second wave of the allergy epidemic. Secondary prevention methods such as treatment of accidental exposures and immunotherapy are still fraught with difficulties and unanticipated adverse events still occur. The future of food allergy management may lie in primary prevention, of which practical strategies and current evidence are summarized in this review. No maternal dietary restrictions are required during pregnancy and lactation. High risk infants should be exclusively breastfed for at least 4 to 6 months with early introduction of complementary solid foods. Hydrolyzed formulas may be used for high risk infants who are not exclusively breastfed. A healthy balanced diet inclusive of fresh fruits, vegetables and vitamins may play an important role in prevention of allergies and has myriad advantages to general health and well-being. There remains a need for large scale randomized controlled trials for all other nutritional interventions in the hope that more can be done for the primary prevention of allergies in the future.

Factors predictive of outcome in childhood stroke in an Asian population.

INTRODUCTION: While paediatric strokes are fairly uncommon, they are often associated with significant long-term disability. Diagnosis is often delayed because of the need to exclude conditions that mimic stroke. Understanding the outcomes related to stroke in children is important in the development of secondary prevention strategies. The aim of this study was to evaluate the epidemiology of childhood stroke in a tertiary paediatric unit in Singapore and to assess factors influencing outcome in these children. MATERIALS AND METHODS: A retrospective case-note review of all childhood strokes presenting to the Children's Medical Institute (CMI) at the National University Hospital (NUH), Singapore between October 1999 and May 2006. Data collected include demographic factors, clinical presentation, diagnosis, subsequent management and follow-up using specific outcome measures. RESULTS: Twenty-six children with a median age of 8.0 years at presentation were identified, comprising 15 ischaemic strokes (57.7%), 10 haemorrhagic strokes (38.5%) and 1 patient with both ischaemic and haemorrhagic lesions. The most common symptoms at presentation were seizures (15/26, 57.7%), lethargy (11/26, 42.3%), hemiparesis (10/26, 38.5%) and altered levels of consciousness (10/26, 38.5%). Vascular abnormalities accounted for 50% of strokes in our study population. The average length of follow-up was 33.2 months (range, 1 to 120) with only 11 children (11/26, 42.3%) achieving full recovery. Significant prognostic factors include altered consciousness and seizures at presentation, lesions in both cortical and subcortical locations, systemic disease aetiology, neurological deficits at discharge and seizures at the time of discharge. CONCLUSION: Long-term neurological, neuropsychological and functional impairment are common in survivors of paediatric strokes. Certain clinical features and lesion characteristics are useful indicators of prognosis in these children.

Cystic neoplasms of the pancreas: current diagnostic modalities and management.

Cystic neoplasm of the pancreas is a relatively uncommon condition covering a wide spectrum of pathology. The increasing incidence as a result of routine imaging tests in asymptomatic patients presents a diagnostic and therapeutic problem to the clinician. This paper discusses the role of the various investigative modalities in the management of cystic neoplasia of the pancreas.

Epinephrine auto-injector prescriptions as a reflection of the pattern of anaphylaxis in an Asian population.

This study surveyed the prescription patterns of adrenaline auto-injectors (AAs) in Singapore to examine the frequency, triggers, and demographic pattern of anaphylaxis requiring such prescriptions. A 6-year retrospective review of 417 consecutive patients prescribed AAs in Singapore from January 1999 to December 2004, as identified from hospital pharmacy records. There were 417 patients identified, consisting of 295 (70.7%) Singaporeans with the remaining being non-Singaporean residents. Based on population census, the frequency of AA prescriptions was estimated at 1 per 10,000 Singaporeans. Demographic factors associated with AA prescriptions were male gender (OR = 1.361; p = 0.002); minority ethnic groups, which included Eurasians, Caucasians, Koreans, and Japanese (OR = 15.873; p < 0.001); and children <15 years of age (OR = 2.593; p < 0.001). The most common food allergens resulting in AA prescriptions were peanut (41.9%) and shellfish allergy (28.5%). Multiple logistic regression analysis showed that peanut allergy was independently associated with Eurasian ethnicity (OR = 5.045; p = 0.021); and shellfish allergy with Indian ethnicity (OR = 2.757; p = 0.034). The estimated frequency of AA prescriptions in Singapore is relatively low at 0.01%. The incidence of peanut and shellfish allergy in the Asian population appears to differ from that seen in Western populations.