Search

Objectives: Evening-chronotype is associated with increased socioemotional problems among school-aged children. Inadequate sleep and increased sleep problems are also prevalent among evening-chronotype children and may underlie the relationship between chronotype and socioemotional problems. However, it is unclear whether the association between chronotype and socioemotional problems at school-age may be mediated by poorer sleep during late preschool., Methods: Our study utilized cross-sectional data to examine the relations between chronotype, sleep duration, sleep problems and socioemotional problems in preschoolers. We subsequently performed longitudinal mediation analyses to examine how the association between chronotype at preschool-age and later socioemotional problems at school-age may be mediated by sleep problems and sleep duration during late preschool. 399 children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study were included for analyses. Children's chronotype were identified with the Children's Chronotype Questionnaire at 4.5 years old. Sleep duration and problems were measured with the Children's Sleep Habits Questionnaire at 4.5 and 6 years old. Socioemotional problems were evaluated using the Child Behavioral Checklist at 4 and 7 years of age. All questionnaires were caregiver-reported., Results: Linear regressions demonstrated that eveningness was associated with concurrent sleep problems and internalizing, externalizing and total behavioral problems at 4-4.5 years old, but not sleep duration. Mediation analyses supported that sleep problems (and not sleep duration) at 6 years old mediated the relationship between chronotype and socioemotional problems at 7 years old., Conclusions: Our findings suggest addressing sleep problems during early development may reduce socioemotional problems at school-age, especially among evening-chronotype children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YSC is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. All other authors involved in this study do not have any financial or non-financial conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Physical activity (PA), sedentary behavior (SB), and sleep are collectively referred to as 24-h movement behaviors, which may be linked to cognitive development in children. However, most of the evidence was based on cross-sectional studies and/or solely relied on parent-reported information on children's behaviors, and it remains uncertain whether all domains/contexts of PA and SB are similarly associated with executive function and academic achievement., Objective: We investigated the prospective associations of accelerometer-measured 24 h-movement behaviors and domain-specific PA and SB with executive function and academic achievement among school-aged children in Singapore., Methods: The Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort used a wrist-worn accelerometer (Actigraph-GT3x+) to measure 24 h-movement behaviors data at ages 5.5 and 8 years. Executive function and academic achievement were assessed using NEuroPSYchology (NEPSY) and Wechsler Individual Achievement Tests at ages 8.5 and 9-years, respectively. Compositional data analyses were conducted to explore the associations of 24 h-movement behavior with outcomes, and multiple linear regression models to examine the associations of domain-specific PA and SB with outcomes ( n  = 432)., Results: Among 432 children whose parents agreed to cognitive assessments (47% girls and 58% Chinese), the composition of 24 h-movement behaviors at ages 5.5 and 8 years was not associated with executive function and academic achievement. However, higher moderate-to-vigorous PA (MVPA) relative to remaining movement behaviors at age 5.5 years was associated with lower academic achievement [Mean difference (95% confidence interval): -0.367 (-0.726, -0.009) z-score], and reallocating MVPA time to sleep showed higher academic achievement scores [30 min from MVPA to sleep: 0.214 (0.023, 0.404) z-score]. Certain domains of PA and SB, notably organized PA/sports, outdoor play, and reading books were favorably associated with outcomes of interest, while indoor play and screen-viewing were unfavorably associated., Conclusion: The associations between movement behaviors and cognitive outcomes are multifaceted, influenced by specific domains of PA and SB. This study underscores the importance of participation in organized PA/sports, outdoor active play, and reading books, while ensuring adequate sleep and limiting screen viewing, to enhance cognitive outcomes. These findings underscore the need for further research into time-use trade-offs. Such studies could have major implications for revising current guidelines or strategies aimed at promoting healthier 24 h-movement behaviors in children., Study Registration: https://clinicaltrials.gov/, NCT01174875., Competing Interests: KMG receiving reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG and S-YC report being part of an academic consortium that has received research funding from Abbott Nutrition, Nestle and Danone. No other disclosures were reported. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Padmapriya, Bernard, Tan, Chu, Goh, Tan, Shek, Chong, Tan, Chan, Yap, Godfrey, Lee, Meaney, Eriksson, Tan, Law and Müller-Riemenschneider.)

Allergic diseases such as asthma, atopic dermatitis, and food allergies are a burgeoning health challenge in the Asia-Pacific region. Compounding this, the region has become increasingly susceptible to the impacts of climate change. The region has weathered extreme precipitation, intense heat waves, and dust storms over the recent decades. While the effects of environmental and genetic factors on allergic diseases are well understood, prevailing gaps in understanding the complex interactions between climate change and these factors remain. We aim to provide insights into the various pathways by which climate change influences allergic diseases in the Asia-Pacific population. We outline practical steps that allergists can take to reduce the carbon footprint of their practice on both a systemic and patient-specific level. We recommend that allergists optimize disease control to reduce the resources required for each patient's care, which contributes to reducing greenhouse gas emissions. We encourage the responsible prescription of metered dose inhalers by promoting the switch to dry powder inhalers for certain patients, at each clinician's discretion. We also recommend the utilization of virtual consultations to reduce patient travel while ensuring that evidence-based guidelines for rational allergy management are closely adhered to. Finally, eliminating unnecessary testing and medications will also reduce greenhouse gas emissions in many areas of medical care., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase., Methods: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms., Results: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development., Conclusion: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yap Seng Chong reports a relationship with Abbott Nutrition that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Abbott Nutrition that includes: funding grants and speaking and lecture fees. Yap Seng Chong reports a relationship with Nestle that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Nestle that includes: funding grants and speaking and lecture fees. Yap Seng Chong reports a relationship with Danone that includes: funding grants and speaking and lecture fees. Keith M Godfrey reports a relationship with Danone that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5-12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Abstract: Climate change, particularly increasing temperature, changes in rainfall, extreme weather events and changes in vector ecology, impacts the transmission of many climate-sensitive infectious diseases. Asia is the world's most populous, rapidly evolving and diverse continent, and it is already experiencing the effects of climate change. Climate change intersects with population, sociodemographic and geographical factors, amplifying the public health impact of infectious diseases and potentially widening existing disparities. In this narrative review, we outline the evidence of the impact of climate change on infectious diseases of importance in Asia, including vector-borne diseases, food- and water-borne diseases, antimicrobial resistance and other infectious diseases. We also highlight the imperative need for strategic intersectoral collaboration at the national and global levels and for the health sector to implement adaptation and mitigation measures, including responsibility for its own greenhouse gas emissions., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes. Cord plasma samples collected at term delivery were analyzed using targeted liquid-chromatography tandem mass-spectrometry to determine the concentrations of 404 lipid species across 17 lipid classes. The birthweights were standardized for sex and gestational age by local references, and regression analyses were adjusted for the maternal age, BMI, parity, mode of delivery, insulin treatment, and fasting/2 h glucose, with a false discovery-corrected p < 0.05 considered significant. Ten lysophosphatidylcholines (LPCs) and two lysophosphatidylethanolamines were positively associated with the birthweight percentiles, while twenty-four triacylglycerols were negatively associated with the birthweight percentiles. The topmost associated lipid was LPC 20:2 [21.28 (95%CI 12.70, 29.87) percentile increase in the standardized birthweight with each SD-unit increase in log 10 -transformed concentration]. Within these same regression models, maternal glycemia did not significantly associate with the birthweight percentiles. Specific fetal circulating lysophospholipids and triacylglycerols associate with birthweight independently of maternal glycemia, but a causal relationship remains to be established.

Background: Promoting active, balanced lifestyles among children may be an important approach to optimising their health-related quality of life (HRQoL). However, the relationships between children's movement behaviours and HRQoL remain unclear., Methods: We examined the associations between movement behaviours (sleep, inactivity, light and moderate-to-vigorous intensity physical activity) assessed using accelerometers at ages 8 and 10 years and self-reported HRQoL scores (overall, and physical and emotional well-being, self-esteem, relationship with family and friends, and school functioning domains) at age 10 years among 370 children in a local birth cohort using compositional isotemporal substitution techniques., Findings: Cross-sectionally, light and moderate-to-vigorous intensity physical activities were associated with better self-esteem (β = 15.94 [2.71, 29.18]) and relationship with friends (β = 10.28 [3.81, 16.74]) scores respectively. Prospectively, inactivity was associated with lower overall HRQoL (β = -10.00 [-19.13, -0.87]), relationship with friends (β = -16.41 [-31.60, -1.23]) and school functioning (β = -15.30 [-29.16, -1.44]) scores, while sleep showed a positive trend with overall HRQoL (β = 10.76 [-1.09, 22.61]) and school functioning (β = 17.12 [-0.87, 35.10]) scores. Children's movement behaviours were not associated with their physical and emotional well-being, or relationship with family scores. The isotemporal substitution analyses suggest that increasing time spent in physical activity and/or sleep at the expense of inactivity may benefit children's HRQoL., Interpretation: Our findings suggest that sleep and physical activity may be associated with better HRQoL, with the inverse for inactivity. However, the relationship between children's movement behaviours and HRQoL is complex and warrants further research., Funding: Singapore National Research Foundation, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research., Competing Interests: KMG reports being part of an academic consortium that has received research funding from Nestle Research, unrelated to the present manuscript. JYB is supported by a grant from the Agence Nationale de la Recherche (ANR) (iSCAN project, ANR-20-CE36-0001)., (© 2023 The Author(s).)

Study Objectives: Spatial working memory (SWM) capacity subserves complex cognitive functions, yet it is unclear whether individual diurnal preferences and time-of-day influence SWM in preschool children. The main and interaction effects of chronotype and time-of-day on SWM and SWM differences in preschoolers with different chronotypes within each time-of-day group will be examined., Methods: We studied a subset of typically developing 4.5-year-olds taking part in a birth cohort study (n = 359). The Children's Chronotype Questionnaire categorized children into morning-, intermediate-, and evening-types. Using a computerized neuropsychological test (Cambridge Neuropsychological Test Automated Battery), SWM was determined from the total number of between-search errors (ie, between search-total errors) and Strategy scores. Higher between search-total errors or lower Strategy scores indicated worse SWM. Time-of-day was categorized into late morning (10:00 am to 11:59 am), afternoon (12:00 pm to 3:59 pm), and late afternoon (4:00 pm to 6:30 pm). In a subsample (n = 199), caregiver-reported chronotype was validated using actigraphy-measured sleep midpoint., Results: After controlling for ethnicity, no significant main and interaction effects of chronotype and time-of-day on between search-total errors and Strategy scores were seen (all P > .05). However, evening-types outperformed morning-types (ie, lower mean between search-total errors) in the late afternoon ( P = .013) but not in the late morning and afternoon (all P > .05). Actigraphy data in the subsample confirmed that evening-types had later sleep midpoints during weekdays and weekends ( P < .001)., Conclusions: Since evening-type preschoolers had better SWM in the late afternoon compared to morning-type preschoolers, this gives insights into optimal learning opportunities in early childhood education., Citation: Abdul Jafar NK, Tham EKH, Eng DZH, et al. Chronotype and time-of-day effects on spatial working memory in preschool children. J Clin Sleep Med . 2023;19(10):1717-1726., (© 2023 American Academy of Sleep Medicine.)

Background: Childhood wheezing is a 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) persistent 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the associations between infants' dietary nutrient trajectories and subsequent neurodevelopment during childhood in the Growing Up in Singapore Towards healthy Outcomes study., Methods: One-day food records were collected at ages 6, 9 and 12 months, whilst Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intelligence Test-2 were conducted at ages 24 and 54 months respectively. Nutrient trajectories were constructed using multi-level mixed modelling and associations with neurodevelopment (24 months: n = 484; 54 months: n = 444) were examined using adjusted multivariable linear regression., Results: At age 24 months, higher protein intake (at 6 months) and increasing rate of intake (from 6 to 12 months) were associated with higher fine motor score [β = 0.17 SD (95% CI 0.03, 0.31) and 0.62 SD (0.10, 1.14) respectively]. Higher fat intake was associated with higher receptive language score [0.04 SD (0.003, 0.07)], but increasing rate of intake was associated with lower expressive language [- 0.20 SD (- 0.39, - 0.01)] and fine motor [- 0.29 SD (- 0.48, - 0.10)] scores. Higher carbohydrate intake was associated with lower gross motor score [- 0.07 SD (- 0.14, - 0.005)], but increasing rate of intake was associated with higher receptive language [0.44 SD (0.08, 0.81)] and fine motor [0.56 SD (0.18, 0.93)] scores. Increasing rate of dietary fibre intake was associated with higher fine motor scores [0.63 SD (0.16, 1.10)]. No significant associations were observed with neurodevelopment at 54 months., Conclusion: Our findings provide greater understanding of how nutrition over time could have varying effects on child neurodevelopment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Poor sleep quality may elevate cortisol levels and affect prenatal mental health through altered HPA axis functioning. This study aims to examine whether subjective sleep quality during preconception moderates the association between preconception hair cortisol levels and mental health from preconception to pregnancy trimesters., Methods: Women from a prospective cohort study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI) questionnaires during preconception (T0) and at each pregnancy trimesters (T1, T2, and T3). We analyzed 266 of these women who conceived and had fully completed measures at preconception for hair cortisol, sleep quality and either EPDS or STAI-state. Changes in EPDS and STAI-state scores were derived (i.e., T1-T0, T2-T0, T3-T0). Johnson-Neyman technique identified PSQI scores with significant moderation of cortisol on mental health., Results: After adjusting for potential covariates, there was a significant positive correlation between preconception hair cortisol levels and depressive symptom at the second trimester (r s (144) = 0.22, p = 0.008), but not the first and third trimesters (all p s  > 0.05). The positive association between preconception hair cortisol and change in depressive symptoms between third trimester and preconception was significant only among women with poor preconception sleep quality (PSQI ≥ 7)., Limitations: Sleep quality and prenatal mood were derived from self-reported questionnaires, which may be more susceptible to bias., Conclusions: The positive association between preconception hair cortisol and change in prenatal depressive symptoms is significant among women who reported poor sleep quality during preconception. Improving preconception sleep quality can potentially mitigate the association between preconception hair cortisol and depressive symptoms during pregnancy., Competing Interests: Declaration of competing interest Peter D. Gluckman and Yap-Seng Chong is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. Michael J. Meaney is supported by the Hope for Depression Research Foundation and the Jacobs Foundation. The remaining authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum., Methods: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohort recruited 1032 women planning pregnancy. Participants completed questionnaires at preconception, 34 to 36 weeks gestation, and 12 months postpartum. Repeated-measures linear regression models were used to analyze changes in walking, moderate to vigorous PA (MVPA), screen time, and total sedentary time, and to identify sociodemographic/clinical correlates associated with these changes., Results: Of the 373 women who delivered singleton live births, 281 provided questionnaires for all time points. Walking time increased from preconception to late pregnancy but decreased postpartum (adjusted means [95% CI]: 454 [333-575], 542 [433-651], and 434 [320-547] min/wk, respectively). Vigorous-intensity PA and MVPA decreased from preconception to late pregnancy but increased postpartum (vigorous-intensity PA: 44 [11-76], 1 [-3-5], and 11 [4-19] min/wk, MVPA: 273 [174-372], 165 [95-234], and 226 [126-325] min/wk, respectively). Screen time and total sedentary time remained consistent from preconception to pregnancy but decreased postpartum (screen: 238 [199-277], 244 [211-277], and 162 [136-189] min/d, total: 552 [506-598], 555 [514-596], and 454 [410-498] min/d, respectively). Individual characteristics of ethnicity, body mass index, employment, parity, and self-rated general health significantly influenced women's activity patterns., Conclusion: During late pregnancy, walking time increased, while MVPA declined significantly, and partially returned to preconception levels postpartum. Sedentary time remained stable during pregnancy but decreased postpartum. The identified set of sociodemographic/clinical correlates underscores need for targeted strategies.

Background: Longitudinal assessment of the determinants of obesogenic growth trajectories in childhood can suggest appropriate developmental windows for intervention., Methods: Latent class growth mixture modelling was used to identify body mass index (BMI) z-score trajectories from birth to age 6 years in 994 children from a prospective mother-offspring cohort (Chinese, Indian and Malay ethnicities) based in Singapore. We evaluated the early-life determinants of the trajectories as well as their associations with cardiometabolic risk markers at age 6 years., Results: Five BMI z-score trajectory patterns were identified, three within the healthy weight range, alongside early-acceleration and late-acceleration obesogenic trajectories. The early-acceleration pattern was characterized by elevated fetal abdominal circumference growth velocity, BMI acceleration immediately after birth and crossing of the obesity threshold by age 2 years. The late-acceleration pattern had normal fetal growth and BMI acceleration after infancy, and approached the obesity threshold by age 6 years. Abdominal fat, liver fat, insulin resistance and odds of pre-hypertension/hypertension were elevated in both groups. Indian ethnicity, high pre-pregnancy BMI, high polygenic risk scores for obesity and shorter breastfeeding duration were common risk factors for both groups. Malay ethnicity and low maternal educational attainment were uniquely associated with early BMI acceleration, whereas nulliparity and obesogenic eating behaviours in early childhood were uniquely associated with late BMI acceleration., Conclusion: BMI acceleration starting immediately after birth or after infancy were both linked to early cardiometabolic alterations. The determinants of these trajectories may be useful for developing early risk stratification and intervention approaches to counteract metabolic adversities linked to childhood obesity., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Purpose: This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48-50 months., Methods: Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep durations were obtained at 3, 6, 9, 12, 18, 24 using the Brief Infant Sleep Questionnaire and 54 months using the Child Sleep Habits Questionnaire. Total, night and day sleep trajectories with varying durations (short, moderate, or long) and variability (consistent or variable; defined by standard errors) were identified. The cognitive school readiness test battery was administered when the children were between 48 and 50 months old. Both unadjusted adjusted analysis of variance models and adjusted analysis of covariance models (for confounders) were performed to assess associations between sleep trajectories and individual school readiness tests in the domains of language, numeracy, general cognition and memory., Results: In the unadjusted models, children with short variable total sleep trajectories had poorer performance on language tests compared to those with longer and more consistent trajectories. In both unadjusted and adjusted models, children with short variable night sleep trajectories had poorer numeracy knowledge compared to their counterparts with long consistent night sleep trajectories. There were no equivalent associations between sleep trajectories and school readiness performance for tests in the general cognition or memory domains. There were no significant findings for day sleep trajectories., Conclusion: Findings suggest that individual differences in longitudinal sleep duration patterns from as early as 3 months of age may be associated with language and numeracy aspects of school readiness at 48-50 months of age. This is important, as early school readiness, particularly the domains of language and mathematics, is a key predictor of subsequent academic achievement., Competing Interests: NS was employed by Société des Produits Nestlé SA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tham, Xu, Fu, Goh, Gluckman, Chong, Yap, Shek, Teoh, Gooley, Goh, Schneider, Meaney, Cai and Broekman.)

Background: Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors., Methods: LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26-28 weeks' pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits., Results: Around 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%)., Conclusions: We describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period., Trial Registration: ClinicalTrials.gov, NCT03531658., (© 2023. The Author(s).)

Study Objectives: Examine how different trajectories of reported sleep duration associate with early childhood cognition., Methods: Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children's Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived-each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively., Results: Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory., Conclusions: Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive., Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level., Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022., Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6)., Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment., Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year., Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.

Subfertility is a global problem affecting millions worldwide, with declining total fertility rates. Preconception dietary supplementation may improve fecundability, but the magnitude of impact remains unclear. This prospective cohort study aimed to examine the association of preconception micronutrient supplements with fecundability, measured by time to pregnancy (TTP). The study was conducted at KK Women's and Children's Hospital, Singapore, between February 2015 and October 2017, on 908 women aged 18-45 years old, who were trying to conceive and were enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). Baseline sociodemographic characteristics and supplement intake were collected through face-to-face interviews. The fecundability ratio (FR) was estimated using discrete-time proportional hazard modelling. Adjusting for potentially confounding variables, folic acid (FA) (FR 1.26, 95% confidence interval 1.03-1.56) and iodine (1.28, 1.00-1.65) supplement users had higher fecundability compared to non-users. Conversely, evening primrose oil supplement users had lower fecundability (0.56, 0.31-0.99) than non-users. In this study, preconception FA and iodine supplementation were associated with shortened TTP, while evening primrose oil use was associated with longer TTP. Nonetheless, the association between supplement use and the magnitude of fecundability changes will need to be further confirmed with well-designed randomised controlled trials.

Objective: To evaluate whether characterization of maternal and foetoplacental factors beyond birthweight can enable early identification of children at risk of developing prehypertension/hypertension., Methods: We recruited 693 mother-offspring dyads from the GUSTO prospective mother-offspring cohort. Prehypertension/hypertension at age 6 years was identified using the simplified paediatric threshold of 110/70 mmHg. We evaluated the associations of pregnancy complications (gestational diabetes, excessive/inadequate gestational weight gain, hypertensive disorders of pregnancy), foetal growth deceleration (decline in foetal abdominal circumference at least 0.67 standard deviations between second and third trimesters), high foetoplacental vascular resistance (third trimester umbilical artery systolic-to-diastolic ratio ≥90th centile), preterm birth, small-for-gestational age and neonatal kidney volumes with risk of prehypertension/hypertension at age 6 years, after adjusting for sex, ethnicity, maternal education and prepregnancy BMI., Results: Pregnancy complications, small-for-gestational age, preterm birth, and low neonatal kidney volume were not associated with an increased risk of prehypertension/hypertension at age 6 years. In contrast, foetal growth deceleration was associated with a 72% higher risk [risk ratio (RR) = 1.72, 95% confidence interval (CI) 1.18-2.52]. High foetoplacental vascular resistance was associated with a 58% higher risk (RR = 1.58, 95% CI 0.96-2.62). Having both these characteristics, relative to having neither, was associated with over two-fold higher risk (RR = 2.55, 95% CI 1.26-5.16). Over 85% of the foetuses with either of these characteristics were born appropriate or large for gestational age., Conclusion: Foetal growth deceleration and high foetoplacental vascular resistance may be helpful in prioritizing high-risk children for regular blood pressure monitoring and preventive interventions, across the birthweight spectrum., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling., (© 2022 Ogishi et al.)

COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Seventeen mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls; 34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant blood, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, as well as cytokine levels. The placentae were examined microscopically. The study is registered at clinicaltrials.gov under the identifier NCT04802278. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Thus, antenatal SARS-CoV-2 infection led to high plasma titers of virus-specific antibodies in infants postnatally. However, this waned within 3-6 months of life. Virus neutralization by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralization. Virus-specific IgA levels were variable among convalescent individuals' sera and breast milk. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. Four placentae presented signs of acute inflammation, particularly in the subchorionic region, marked by neutrophil infiltration even though > 50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Low, Tan, Ng, Ng, Shunmuganathan, Gupta, MacAry, Amin, Lee, Lian, Shek, Zhong and Wang.)

Objective: Screen time in early childhood has been associated with children's prosocial and behavioral skills; however, the directionality of this relationship is unclear. We aimed to determine the direction of the relationship between screen time, social skills, and nonsocial behavioral traits in young children., Methods: This was a population-based, prospective cohort study with data across 5 time points. We examined the reciprocal relationships between caregiver-reported children's screen time at 12, 18, 24, 36, and 54 months and social behaviors collected using the Infant-Toddler Social-Emotional Assessment at 12 months; the Quantitative Checklist for Autism at 18, 24, and 36 months; and the Social Responsiveness Scale at 54 months. Cross-lagged path models were used for analysis., Results: A multiple imputation data set and complete data from 229 participants were included in the analyses. Screen time at 12, 18, and 36 months predicted nonsocial behavioral traits at 54 months. Cross-lagged path models showed a clear direction from increased screen time at earlier time points to both poorer social skills and atypical behaviors at later time points (Akaike information criterion 18936.55, Bayesian information criterion 19210.73, root mean square error of approximation 0.037, and comparative fit index 0.943). Social skills or behavioral traits at a younger age did not predict later screen time at any of the time points., Conclusion: Screen time in early childhood has lagged influences on social skills and nonsocial behaviors; the reverse relationship is not found. Close monitoring of social behaviors may be warranted in the setting of excessive screen time during early childhood., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented., Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and peanut allergies in a general population of Singaporean children below 30 months of age., Methods: A total of 4,115 children from the general population who attended well-baby visits between 2011 and 2015 completed standardized questionnaires to elicit a convincing history of food allergy to estimate the population prevalence of food allergies., Results: The prevalence of a convincing history of cow's milk allergy was 0.51% (95% confidence interval [CI], 0.3-0.7), hen's egg allergy 1.43% (95% CI, 1.1-1.8), and peanut allergy 0.27% (95% CI, 0.12-0.42). Of the 15 of 59 children with a convincing history of hen's egg allergy who consented, 12 (80%) had corroborative positive skin prick tests., Conclusion: The prevalence of food allergy, in particular peanut allergy, in children below 2 years of age is lower in this South East Asian population than reported in Western cohorts. Further research should focus on deciphering differential risk factors for food allergy across different geographical locations., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

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)], 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)]., 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., (© 2022 The Authors.)

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Wong, Leung, Yang, Fok, Mak, Yao, Ma, Mao, Zhao, Liang, Singh, Barbouche, He, Jiang, Liew, Le, Muktiarti, Santos-Ocampo, Djidjik, Belaid, Ismail, Abdul Latiff, Lee, Chen, Liu, Jin, Wang, Chien, Yu, Raj, Raj, Vaughan, Urban, Berg, Eley, Lee, Isa, Ang, Lee, Yeoh, Shek, Quynh Le, Nguyen, Phan Nguyen Lien, Capulong, Mallillin, Villanueva, Camonayan, Vera, Casis-Hao, Lobo, Foronda, Binas, Boushaki, Kechout, Phongsamart, Wongwaree, Jiratchaya, Lao-Araya, Trakultivakorn, Suratannon, Jirapongsananuruk, Chantveerawong, Kamchaisatian, Chan, Koh, Wong, Fong, Thong, Latiff, Noh, Silva, Jouhadi, Al-Saad, Vignesh, Jindal, Rawat, Gupta, Suri, Yang, Au, Kwok, Chan, Hui, Chua, Duque, Cheong, Chong, Ho, Lee, Wong, Yang, Lee, Tu, Yang and Lau.)

Background: Existing modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information from children aged 10 years and older., Objective: This study evaluated the validity of MEDAL for assessing children's movement behaviors by comparing self-reported and accelerometer-measured time spent in movement behavior among children in Singapore aged 10-11 years., Methods: Funding for this study was obtained in October 2017, and data were collected between April and August 2020. Participants recorded their daily activities using MEDAL over 2 specified weekdays and 2 weekend days and wore an Actigraph accelerometer on their nondominant wrist throughout the study to objectively assess movement behaviors. Spearman correlation coefficient and intraclass correlation coefficient (ICC) were used to compare the accelerometer measurements and self-reports for each movement behavior. Bland-Altman plots were generated to investigate trends of bias in the self-reports., Results: Among the participants aged 10-11 years (29/49, 59% boys), we observed that children reported lower light physical activity (LPA) and higher moderate-to-vigorous physical activity (MVPA), inactivity, and night sleep than that measured by the accelerometer. There was a moderate-to-strong correlation between self-reported and accelerometer-measured MVPA (r=0.37; 95% CI 0.20-0.54), inactivity (r=0.36; 95% CI 0.18-0.54), and night sleep (r=0.58; 95% CI 0.43-0.74); the correlation for LPA was poor (r=0.19; 95% CI 0.02-0.36). Agreement was poor for all behaviors (MVPA: ICC=0.24, 95% CI 0.07-0.40; LPA: ICC=0.19, 95% CI 0.01-0.36; inactivity: ICC=0.29, 95% CI 0.11-0.44; night sleep: ICC=0.45, 95% CI 0.29-0.58). There was stronger correlation and agreement on weekdays for inactivity and night sleep; conversely, there was stronger correlation and agreement for MVPA and LPA on weekend days. Finally, based on Bland-Altman plots, we observed that with increasing MVPA, children tended to report higher MVPA than that measured by the accelerometer. There were no clear trends for the other behaviors., Conclusions: MEDAL may be used to assess the movement behaviors of children. Based on self-reports, the children are able to estimate their time spent in MVPA, inactivity, and night sleep although actual time spent in these behaviors may differ from accelerometer-derived estimates; self-reported LPA warrant cautious interpretation. Observable differences in reporting accuracy exist between weekdays and weekend days., (©Sarah Yi Xuan Tan, Airu Chia, Bee Choo Tai, Padmapriya Natarajan, Claire Marie Jie Lin Goh, Lynette P Shek, Seang Mei Saw, Mary Foong-Fong Chong, Falk Müller-Riemenschneider. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 24.06.2022.)

'Mixed Milk Feeding' (MMF), whereby infants are fed with both breastmilk and infant formula during the same period, is a common feeding practice. Despite its high prevalence, knowledge regarding MMF practices and their association with (health) outcomes is limited, potentially because MMF behaviours are highly variable and difficult to standardise longitudinally. In this paper, we applied a statistical clustering algorithm on individual infant feeding data collected over the first year of life from two clinical trials: 'TEMPO' ( n = 855) and 'Venus' ( n = 539); these studies were conducted in different years and world regions. In TEMPO, more than half of infants were MMF. Four distinct MMF clusters were identified: early exclusive formula feeding (32%), later exclusive formula feeding (25%), long-term MMF (21%), and mostly breastfeeding (22%). The same method applied to 'Venus' resulted in comparable clusters, building trust in the robustness of the cluster approach. These results demonstrate that distinct MMF patterns can be identified, which may be applicable to diverse populations. These insights could support the design of future research studying the impact of infant feeding patterns on health outcomes. To standardise this in future research, it is important to establish a unified definition of MMF.

Background: Obesity compromises metabolic health and female fertility, yet not all obese women are similar in metabolic status. The extent to which fecundability is influenced by the metabolic health status of women who are overweight or obese before conception is unknown., Objective: This study aimed to: (1) determine the metabolic health status, and (2) examine the association between metabolic health status and fecundability of overweight and obese women trying to conceive in the Singapore PREconception Study of long-Term maternal and child Outcomes cohort study., Study Design: We conducted a prospective preconception cohort study of Asian women (Chinese, Malay, and Indian) aged 18 to 45 years trying to conceive who were treated from 2015 to 2017 in KK Women's and Children's Hospital in Singapore (n=834). We defined women to have metabolically unhealthy status if they: (1) met 3 or more modified Joint Interim Statement metabolic syndrome criteria; or (2) had homeostasis model assessment-insulin resistance index ≥2.5. Body mass index was categorized as normal (18.5-22.9 kg/m 2 ), overweight (23-27.4 kg/m 2 ), or obese (≥27.5 kg/m 2 ) on the basis of cutoff points for Asian populations. Fecundability was measured by time to pregnancy in menstrual cycles within a year of enrolment. Discrete-time proportional hazards models were used to estimate fecundability odds ratios, with adjustment for confounders and accounting for left truncation and right censoring., Results: Of 232 overweight women, 28 (12.1%) and 25 (10.8%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Of 175 obese women, 54 (30.9%) and 93 (53.1%) were metabolically unhealthy by metabolic syndrome ≥3 criteria and homeostasis model assessment-insulin resistance ≥2.5, respectively. Compared with metabolically healthy normal-weight women, lower fecundability was observed in metabolically unhealthy overweight women on the basis of metabolic syndrome criteria (fecundability odds ratios, 0.38 [95% confidence interval, 0.15-0.92]) and homeostasis model assessment-insulin resistance (fecundability odds ratios, 0.68 [95% confidence interval, 0.33-1.39]), with metabolic syndrome criteria showing a stronger association. Metabolically unhealthy obese women showed lower fecundability than the healthy normal-weight reference group by both metabolic syndrome (fecundability odds ratios, 0.35; 95% confidence interval, 0.17-0.72) and homeostasis model assessment-insulin resistance criteria (fecundability odds ratios, 0.43; 95% confidence interval, 0.26-0.71). Reduced fecundability was not observed in overweight or obese women who showed healthy metabolic profiles by either definition., Conclusion: Overweight or obesity was not synonymous with having metabolic syndrome or insulin resistance. In our preconception cohort, metabolically unhealthy overweight and obese women showed reduced fecundability, unlike their counterparts who were metabolically healthy. These findings suggest that metabolic health status, rather than simply being overweight and obese per se, plays an important role in fecundability., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Background: Increasing 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., Methods: Maternal 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., Results: Among 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., Conclusion: Maternal 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., Competing Interests: KG has received reimbursement for speaking at conferences sponsored by Nestle. KG and YC are part of an academic consortium that has received research funding from Abbot Nutrition, Nestle and Danone. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lau, Kee, Yap, Tham, Chan, Goh, Teoh, Eriksson, Godfrey, Gluckman, Chong, Chan, Van Bever, Lee, Shek, Meaney and Loo.)

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., Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT01174875], identifier [NCT01174875]., Competing Interests: YSC and NK are part of an academic consortium that has received research funding from Abbot Nutrition, Nestle and Danone. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loo, Ooi, Ong, Ta, Lau, Tay, Yap, Chan, Tham, Goh, Van Bever, Teoh, Eriksson, Chong, Gluckman, Yap, Karnani, Xu, Tan, Tan, Lee, Kramer, Shek, Meaney and Broekman.)