A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

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.

Tracking of dietary patterns between pregnancy and 6 years post-pregnancy in a multiethnic Asian cohort: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.

PURPOSE: Few studies have described adherence to dietary patterns over time in women of childbearing age. This study aims to describe, examine the stability and changes in dietary patterns between pregnancy and 6 years post-pregnancy and the sociodemographic and lifestyle factors influencing the adherence over time. METHODS: During pregnancy and at 6 years post-pregnancy, 24-h recalls and food frequency questionnaires were collected, respectively, from 709 women. Data on sociodemographic and lifestyle factors were collected via questionnaires. Dietary patterns were identified using principal component analysis and stability assessed using Pearson's correlation coefficients (r) and Cohen's weighted kappa (κ). Associations with sociodemographic characteristics were assessed by multiple logistic regression. RESULTS: The 'Fruits, Vegetables and Legumes' (FVL) and 'Seafood, Noodle, Soup' (SNS) patterns were identified at both time points, with low correlation for the dietary pattern z scores (r 0.2 and 0.3, respectively) and modest agreement in tertile assignment, suggesting poor stability. An 'unhealthy' pattern was only observed at 6 years post-pregnancy. Women who showed increased adherence to FVL pattern had higher educational attainment and exhibited healthy lifestyle behaviours. Women who had gestational diabetes during pregnancy were less likely to decrease adherence to FVL pattern over time. Women who adhered more closely to the 'unhealthy' pattern at 6 years post-pregnancy tended to be younger, of Malay ethnicity, had lower socioeconomic status, were less physically active and had additional pregnancies. CONCLUSIONS: Dietary habits of women became less healthy during the transition from pregnancy to 6 years post-pregnancy. However, results should be interpreted with caution due to the different dietary assessment tools used at the two time points.

Role of maternal tryptophan metabolism in allergic diseases in the offspring.

BACKGROUND: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development. OBJECTIVE: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization. METHODS: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method. RESULTS: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.

Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort.

BACKGROUND: Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS: The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. RESULTS: Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. CONCLUSIONS: We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.

Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema.

BACKGROUND: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. METHODS: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. RESULTS: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. CONCLUSION: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

Naturally occurring circadian rhythm and sleep duration are related to executive functions in early adulthood.

Experimental sleep deprivation studies suggest that insufficient sleep and circadian misalignment associates with poorer executive function. It is not known whether this association translates to naturally occurring sleep patterns. A total of 512 of full-term-born members of the Arvo Ylppö Longitudinal Study [mean age = 25.3, standard deviation (SD) = 0.65] (44.3% men) wore actigraphs to define sleep duration, its irregularity and circadian rhythm (sleep mid-point) during a 1-week period (mean 6.9 nights, SD = 1.7). Performance-based executive function was assessed with the Trail-Making Test, Conners' Continuous Performance Test and Stroop. The self-rated adult version of Behavior Rating Inventory of Executive Function was used to assess trait-like executive function. We found that performance-based and self-reported trait-like executive function correlated only modestly (all correlations ≤0.17). Shorter sleep duration associated with more commission errors. Later circadian rhythm associated with poorer trait-like executive function, as indicated by the Brief Metacognitive Index and the Behavior Regulation Index. Those belonging to the group with the most irregular sleep duration performed slower than others in the Trail-Making Test Part A. All associations were adjusted for sex, age, socioeconomic status and body mass index. In conclusion, naturally occurring insufficient sleep and later circadian rhythm showed modest associations with poorer executive function. Shorter habitual sleep duration was associated with lower scores of performance-based tests of executive function, and later circadian rhythm was associated mainly with poorer trait-like executive function characteristics. Our findings suggest additionally that sleep duration and circadian rhythm associate with different domains of executive function, and there are no additive effects between the two.

A holistic lifestyle mobile health intervention for the prevention of type 2 diabetes and common mental disorders in Asian women with a history of gestational diabetes: a randomised control trial with 3-year follow-up protocol.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are 12-fold more likely to develop type 2 diabetes (T2D) 4-6 years after delivery than women without GDM. Similarly, GDM is associated with the development of common mental disorders (CMDs) (e.g. anxiety and depression). Evidence shows that holistic lifestyle interventions focusing on physical activity (PA), dietary intake, sleep, and mental well-being strategies can prevent T2D and CMDs. This study aims to assess the effectiveness of a holistic lifestyle mobile health intervention (mHealth) with post-GDM women in preventing T2D and CMDs in a community setting in Singapore. METHODS: The study consists of a 1-year randomised controlled trial (RCT) with a 3-year follow-up period. Post-GDM women with no current diabetes diagnosis and not planning to become pregnant will be eligible for the study. In addition, participants will complete mental well-being questionnaires (e.g. depression, anxiety, sleep) and their child's socio-emotional and cognitive development. The participants will be randomised to either Group 1 (Intervention) or Group 2 (comparison). The intervention group will receive the "LVL UP App", a smartphone-based, conversational agent-delivered holistic lifestyle intervention focused on three pillars: Move More (PA), Eat Well (Diet), and Stress Less (mental wellbeing). The intervention consists of health literacy and psychoeducational coaching sessions, daily "Life Hacks" (healthy activity suggestions), slow-paced breathing exercises, a step tracker (including brisk steps), a low-burden food diary, and a journaling tool. Women from both groups will be provided with an Oura ring for tracking physical activity, sleep, and heart rate variability (a proxy for stress), and the "HAPPY App", a mHealth app which provides health promotion information about PA, diet, sleep, and mental wellbeing, as well as display body mass index, blood pressure, and results from the oral glucose tolerance tests. Short-term aggregate effects will be assessed at 26/27 weeks (midpoint) and a 1-year visit, followed by a 2, 3, and 4-year follow-up period. DISCUSSION: High rates of progression of T2D and CMDs in women with post-GDM suggest an urgent need to promote a healthy lifestyle, including diet, PA, sleep, and mental well-being. Preventive interventions through a holistic, healthy lifestyle may be the solution, considering the inextricable relationship between physical and psychological health. We expect that holistic lifestyle mHealth may effectively support behavioural changes among women with a history of GDM to prevent T2D and CMDs. TRIAL STATUS: The protocol study was approved by the National Healthcare Group in Singapore, Domain Specific Review Board (DSRB) [2023/00178]; June 2023. Recruitment began on October 18, 2023. TRIAL REGISTRATION: ClinicalTrials.gov NCT05949957. The first submission date is June 08, 2023.

A holistic approach to preventing type 2 diabetes in Asian women with a history of gestational diabetes mellitus: a feasibility study and pilot randomized controlled trial.

Background: Gestational Diabetes Mellitus (GDM) exposes women to future risk of Type 2 Diabetes. Previous studies focused on diet and physical activity, less emphasis was given to tackle intertwined risk factors such as sleep and stress. Knowledge remains scarce in multi-ethnic Asian communities. This study explored the: (1) feasibility of a holistic digital intervention on improving diet, physical activity (PA), sleep and stress of Asian women with a history of GDM, and (2) preliminary efficacy of the holistic intervention on women's physical and mental well-being via a pilot randomized controlled trial. Methods: Female volunteers with a history of GDM but without pre-existing diabetes were recruited from multi-ethnic Singaporean community. Each eligible woman was given a self-monitoring opportunity using Oura Ring that provided daily feedback on step counts, PA, sleep and bedtime heart rate. Intervention group additionally received personalized recommendations aimed to reinforce healthy behaviors holistically (diet, PA, sleep and stress). Dietary intake was evaluated by a research dietitian, while step counts, PA, sleep and bedtime heart rate were evaluated by health coaches based on Oura Ring data. Perceived physical and mental health and well-being were self-reported. Clinical outcomes included glycemic status determined by HbA1c and OGTT tests, body mass index, blood pressures and lipid profile. Results: Of 196 women from the community, 72 women completed diabetes screening, 61 women were eligible and 56 women completed the study. The 56 completers had mean age of 35.8 ± 3.7 years, predominantly Chinese, majority had their first GDM diagnosed at least 2 years ago and had two GDM-affected pregnancies. After intervention period, more women in the Intervention group achieved at least 8,000 steps/day and had at least 6 hours of sleep per night. Noticeable reduction of added sugar in their food and beverages were observed after the dietary intervention. Changes in body weight and mental well-being were observed but group differences were not statistically significant. Conclusions: The holistic approach appeared feasible for personalizing lifestyle recommendations to promote physical and mental well-being among women with a history of GDM. Larger studies with sufficient assessment timepoints and follow-up duration are warranted to improve the evaluation of intervention effects on clinical outcomes. Clinical trial registration number: https://clinicaltrials.gov/show/NCT05512871, NCT05512871.

Physical discipline as a normative childhood experience in Singapore.

BACKGROUND: The cultural normativeness theory posits that specific parenting behaviors can be interpreted as displays of appropriate parenting in contexts where they are deemed normative. Previous studies suggest high acceptance of physical discipline in Singapore, where strict parenting could be interpreted as care for the child. However, there is a lack of studies on the local prevalence and implications of physical discipline. This study aimed to investigate the prevalence of Singaporean children experiencing parental physical discipline, longitudinal changes in this prevalence, and how exposure to physical discipline relates to children's evaluation of their parents' parenting. METHODS: Participants were 710 children with parental reports of physical discipline at one or more assessments at ages 4.5, 6, 9, and 11 years in the Growing Up in Singapore Towards healthy Outcomes birth cohort study. Parental reports of physical discipline were obtained using the Parenting Styles and Dimensions Questionnaire or the Alabama Parenting Questionnaire across the four assessments. Child reports of their parents' care and control were obtained using the Parental Bonding Instrument for Children at the age 9 assessment. Prevalence was specified as being exposed to at least one physical discipline at any frequency. A generalized linear mixed model was performed to examine whether children's age predicted their exposure to physical discipline. Linear regression analyses were conducted to investigate whether children's exposure to physical discipline predicted their evaluation of their parents' parenting. RESULTS: The prevalence of children experiencing at least one physical discipline was above 80% at all ages. There was a decrease in this prevalence from age 4.5 to 11 years (B = - 0.14, SE = 0.01, OR = 0.87, p < 0.001). The more frequent the paternal physical discipline children were exposed to, the more likely they were to report lower levels of care (B = - 1.74, SE = 0.66, p = 0.03) and higher levels of denial of psychological autonomy by fathers (B = 1.05, SE = 0.45, p = 0.04). Maternal physical discipline was not significantly associated with children's evaluation of their mothers' parenting (ps ≥ 0.53). CONCLUSIONS: Physical discipline was a common experience among our Singaporean sample, consistent with the notion that strict parenting could be regarded as a form of care. However, exposure to physical discipline did not translate to children reporting their parents as caring, with paternal physical discipline being negatively associated with children's evaluations of paternal care.

Resistance Training Increases White Matter Density in Frail Elderly Women.

We aimed to investigate the effects of maternal obesity on brain structure and metabolism in frail women, and their reversibility in response to exercise. We recruited 37 frail elderly women (20 offspring of lean/normal-weight mothers (OLM) and 17 offspring of obese/overweight mothers (OOM)) and nine non-frail controls to undergo magnetic resonance and diffusion tensor imaging (DTI), positron emission tomography with Fluorine-18-fluorodeoxyglucose (PET), and cognitive function tests (CERAD). Frail women were studied before and after a 4-month resistance training, and controls were studied once. White matter (WM) density (voxel-based morphometry) was higher in OLM than in OOM subjects. Exercise increased WM density in both OLM and OOM in the cerebellum in superior parietal regions in OLM and in cuneal and precuneal regions in OOM. OLM gained more WM density than OOM in response to intervention. No significant results were found from the Freesurfer analysis, nor from PET or DTI images. Exercise has an impact on brain morphology and cognition in elderly frail women.

Cross-sectional and prospective associations between children's 24-h time use and their health-related quality of life: a compositional isotemporal substitution approach.

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 (ß = 15.94 [2.71, 29.18]) and relationship with friends (ß = 10.28 [3.81, 16.74]) scores respectively. Prospectively, inactivity was associated with lower overall HRQoL (ß = -10.00 [-19.13, -0.87]), relationship with friends (ß = -16.41 [-31.60, -1.23]) and school functioning (ß = -15.30 [-29.16, -1.44]) scores, while sleep showed a positive trend with overall HRQoL (ß = 10.76 [-1.09, 22.61]) and school functioning (ß = 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.

Sensitive LC-MS/MS method for the temporal profiling of bile acids, fatty acids and branched-chain alpha-keto acids in maternal plasma during pregnancy and cord blood plasma at delivery.

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

Associations Between Maternal Distress During Early Life Periods and Offspring Respiratory Infections and Allergic Outcomes.

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.

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children.

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].

Birth weight modifies the association between a healthy Nordic diet and office blood pressure in old age.

A healthy diet reduces risk for high blood pressure. A small body size at birth increases risk for high blood pressure. Our aim was to study whether birth weight modifies the association between a healthy Nordic diet, characterized by high intake of Nordic vegetables, fruits, and berries, whole-grain rye, oat, and barley, and rapeseed oil, and blood pressure. Finnish men and women (n = 960) born in 1934-1944 attended clinical visits including clinical measurements, and questionnaires in 2001-2004 and 2011-2013. Linear regression was applied to investigate the interactions between birth weight and Nordic diet (measured by the Baltic sea diet score (BSDS)) on blood pressure change during the 10-year follow-up. Baseline Nordic diet and birth weight showed a significant interaction on systolic blood pressure (SBP) (p = 0.02), and pulse pressure (PP) (p < 0.01) over a 10-year follow-up. In the lowest birth weight category (women < 2951 g, men < 3061 g), predicted SBP decreased across BSDS thirds (lowest (T1): 155 mmHg, highest (T3): 145 mmHg, p for linearity = 0.01) as did predicted PP (T1: 71 mmHg, T3: 63 mmHg, p < 0.01). In the middle birth weight category, predicted SBP increased across BSDS thirds (T1: 151 mmHg, T3: 155 mmHg, p = 0.02) as did predicted PP (T1: 67 mmHg, T3: 71 mmHg, p < 0.01). In the highest birth weight category, no associations were found. Higher adherence to a healthy Nordic diet was associated with lower SBP and PP in individuals with low birth weight but with higher SBP and PP in those with average birth weight.

Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach.

Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (-0.5 SD [95% CI: -0.7, -0.2]), lighter (-0.6 SD [-0.9, -0.3]) and have lower skinfold thicknesses (e.g. -14% [-24%, -3%] suprailiac), and blood pressure (-3 mmHg [-6, -0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.