The Effectiveness of a Lactobacilli-Based Probiotic Food Supplement on Bone Mineral Density and Bone Metabolism in Australian Early Postmenopausal Women: Protocol for a Double-Blind Randomized Placebo-Controlled Trial.

Osteoporosis affects one in three women over the age of 50 and results in fragility fractures. Oestrogen deficiency during and after menopause exacerbates bone loss, accounting for higher prevalence of fragility fractures in women. The gut microbiota (GM) has been proposed as a key regulator of bone health, as it performs vital functions such as immune regulation and biosynthesis of vitamins. Therefore, GM modulation via probiotic supplementation has been proposed as a target for potential therapeutic intervention to reduce bone loss. While promising results have been observed in mouse model studies, translation into human trials is limited. Here, we present the study protocol for a double-blind randomized controlled trial that aims to examine the effectiveness of three lactobacilli strains on volumetric bone mineral density (vBMD), trabecular, and cortical microstructure, as measured using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The trial will randomize 124 healthy early postmenopausal women (up to 8 years from menopause) to receive either probiotic or placebo administered once daily for 12 months. Secondary outcomes will investigate the probiotics' effects on areal BMD and specific mechanistic biomarkers, including bone metabolism and inflammatory markers. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12621000810819).

Associations between household food environment and daily intake of regular and diet soft drinks per BMI status of European children: Feel4Diabetes Study.

The objective of this study was to investigate how the availability of food in the household environment is associated with a daily intake of regular and diet soft drinks in European children, considering BMI status. This cross-sectional study utilised baseline data from 12 211 schoolchildren participating in the Feel4Diabetes European lifestyle modification intervention. Sociodemographics, soft drink intake and household food availability data were collected using parent-completed questionnaires. Anthropometry was recorded, and children were classified into BMI categories according to the International Obesity Task Force cut-offs. In the multivariate logistic regression analysis controlled for children's sex, mother's BMI, and educational level, frequent household availability of fruit juice (sugar added), regular soft drinks and salty snacks compared to less frequent were positively associated with daily regular soft drink intake in children, regardless of BMI group (ORs range 1.59-6.69). Conversely, frequent availability of fruit juice (no added sugar) was inversely related to regular soft drink intake in both BMI groups, as was the availability of fresh fruit in the overweight/obesity group, and the availability of diet soft drinks in the underweight/normal-weight (ORs range 0.31-0.54). In conclusion, habitual household availability of selected energy-dense foods/beverages was positively associated with a daily intake of regular soft drinks in European children, regardless of BMI status. Contrastingly, household availability of fresh fruit, fruit juice (no added sugar) and diet soft drinks were inversely associated with regular soft drink intake. Programmes focusing on reducing children's soft drink intake should consider reducing the availability of sugar-added beverages in the household food environment and encouraging water consumption, as a practical, healthier alternative suggestion.

The Association of Maternal Weight Status throughout the Life-Course with the Development of Childhood Obesity: A Secondary Analysis of the Healthy Growth Study Data.

Maternal weight-status at various time-points may influence child obesity development, however the most critical time-point remains unidentified. We used data from the Healthy Growth Study, a cross-sectional study of 2666 Greek schoolchildren aged 9-13 years, exploring associations between childhood obesity and maternal weight-status at pre-pregnancy, during pregnancy/gestational weight gain, and at the child's pre-adolescence. Logistic regression analyses examined associations between maternal weight-status being "below" or "above" the recommended cut-off points (WHO BMI thresholds or IOM cut-off points), at the three time-points, individually or combined into weight-status trajectory groups to determine the strongest associations with child obesity in pre-adolescence. Adjusted models found significant associations and the highest odds ratios [95% Confidence Intervals] for mothers affected by obesity before pregnancy (4.16 [2.47, 7.02]), those with excessive gestational weight gain during pregnancy (1.50 [1.08, 2.08]), and those affected by obesity at their child's pre-adolescence (3.3 [2.29, 4.87]). When combining these weight-status groups, mothers who were above-above-below (3.24 [1.10, 9.55]), and above-above-above (3.07 [1.95, 4.85]) the healthy weight recommendation-based thresholds in each time-point, had a three-fold higher likelihood of child obesity, compared to the below-below-below trajectory group. Maternal obesity across all examined time-points was significantly associated with childhood obesity. Effective childhood obesity preventive initiatives should commence at pre-conception, targeting maternal weight throughout the life-course and childhood developmental stages.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Effectiveness of Technology-Enabled, Low Carbohydrate Dietary Interventions, in the Prevention or Treatment of Type 2 Diabetes Mellitus in Adults: A Systematic Literature Review of Randomised Controlled and Non-Randomised Trials.

Evidence suggests that low carbohydrate dietary (LCD) approaches can improve glycaemic control and may result in type 2 diabetes mellitus (T2DM) remission. This systematic literature review (SLR) aimed to assess the effectiveness of technology-enabled LCD interventions in the management of people with prediabetes or T2DM. Data sources included Medline, Embase, CINAHL, and Web of Science. Randomised (RCTs) or non-randomised (non-RCTs) controlled trials investigating the effect of technology-enabled LCDs (<130 g/day) or very low carbohydrate diets (VLCDs < 50 g/day) on glycosylated haemoglobin A1c (HbA1c) for at least three months and published in English between 2009 and 2023 were included. Risk of bias assessment, data extraction, and synthesis were conducted using standard tools and procedures. Six studies (two RCTs and four non-RCTs, total sample, n = 1519) were identified and included in the SLR. Two studies examining LCDs reported significant reductions in mean HbA1c (0.4% and -1.2%) and weight loss (-3.8 kg and -7.5 kg) at one year. Three studies examining VLCDs reported significant reductions in mean HbA1c (-0.8% to -1.3%) and weight loss (-12 kg to -14 kg) up to two years. Technology-enabled LCD or VLCD interventions can be a novel approach in helping people with prediabetes or T2DM self-manage their condition and possibly achieve remission. However, further research is required to determine the sustainability, effectiveness, and safety of this approach.

Cost effectiveness review of text messaging, smartphone application, and website interventions targeting T2DM or hypertension.

Digital health interventions have been shown to be clinically-effective for type 2 diabetes mellitus (T2DM) and hypertension prevention and treatment. This study synthesizes and compares the cost-effectiveness of text-messaging, smartphone application, and websites by searching CINAHL, Cochrane Central, Embase, Medline and PsycInfo for full economic or cost-minimisation studies of digital health interventions in adults with or at risk of T2DM and/or hypertension. Costs and health effects are synthesised narratively. Study quality appraisal using the Consensus on Health Economic Criteria (CHEC) list results in recommendations for future health economic evaluations of digital health interventions. Of 3056 records identified, 14 studies are included (7 studies applied text-messaging, 4 employed smartphone applications, and 5 used websites). Ten studies are cost-utility analyses: incremental cost-utility ratios (ICUR) vary from dominant to €75,233/quality-adjusted life year (QALY), with a median of €3840/QALY (interquartile range €16,179). One study finds no QALY difference. None of the three digital health intervention modes is associated with substantially better cost-effectiveness. Interventions are consistently cost-effective in populations with (pre)T2DM but not in populations with hypertension. Mean quality score is 63.0% (standard deviation 13.7%). Substandard application of time horizon, sensitivity analysis, and subgroup analysis next to transparency concerns (regarding competing alternatives, perspective, and costing) downgrades quality of evidence. In conclusion, smartphone application, text-messaging, and website-based interventions are cost-effective without substantial differences between the different delivery modes. Future health economic studies should increase transparency, conduct sufficient sensitivity analyses, and appraise the ICUR more critically in light of a reasoned willingness-to-pay threshold.Registration: PROSPERO (CRD42021247845).

Role of parenting practices and digital media on beverage intake in European schoolchildren of different weight status. Feel4Diabetes-study.

OBJECTIVES: Halting the rise in childhood obesity is an ongoing challenge in Europe. Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption has become common practice at home and during family meals. The objective of this study was to investigate associations of parenting practices and home digital media availability with beverage intake in European schoolchildren of different weight groups. METHODS: Cross-sectional data were derived from six countries taking part in the multicentered Feel4Diabetes-study. Anthropometric data were measured for 12 030 schoolchildren (n = 6097 girls; median age = 8.1 y). Details on sociodemographic characteristics, beverage intake, food parenting practices, and home availability of digital media were collated from questionnaires. The outcomes, daily SSB and ASB intakes, were included as dependent variables in multivariable regression models that provided odds ratios reflecting their association with parenting practices and digital media (exposures), after stratifying for children's weight status (underweight or normal versus overweight or obese). RESULTS: After controlling for children's sex, region, maternal body mass index, and education, the multivariate model found that in both body mass index groups, permissive parenting practices, such as rewarding and allowing consumption of unhealthy foods "very often or often," as compared with "rarely or never," were associated with a high daily intake of SSBs and ASBs in children, while parents "watching television together with their child," rewarding with screen time, and availability of television in children's rooms increased the likelihood of both beverages in the underweight or normal-weight group. CONCLUSIONS: Modification of permissive parenting practices and removal of television from children's rooms could effectively reduce SSB intake and curb the ongoing threat of child obesity in Europe.

Parental BMI and country classification by Gross National Income are stronger determinants of prospective BMI deterioration compared to perinatal risk factors at pre-adolescence: Feel4Diabetes Study.

OBJECTIVES: This study aimed to evaluate all known risk factors, from perinatal to adolescence and identify those predominantly related with prospective BMI deterioration. METHODS: Prospective data analysis from the European Feel4Diabetes-study involving 12,211 children from six countries. Details on perinatal and sociodemographic characteristics were collected by parental self-reported questionnaires. Children's anthropometric data were measured by research personnel. Associations between risk factors and children's BMI deterioration (i.e increase) from baseline (mean age 8.2 ± 0.98 years) to the 2-year follow-up (10.3 ± 1.0 years) were explored by applying logistic regression analyses. RESULTS: Univariate analysis revealed that all known risk factors for early overweight/obesity development, remained dominant in prospective BMI deterioration. When multivariate analysis was applied including additional variables such as parents' current BMI status, family socio-demographic characteristics and country economic classification based on Gross National Income, most perinatal risk factors were no longer significant. Multivariate analysis revealed that pre-pregnancy maternal overweight/obesity (OR, 95%CI: 2.71, 1.67-4.38), early introduction of solid foods (2.54, 1.21-5.31), parental current BMI status (3.53, 2.17-5.72) and country economic classification (low income: 4.67, 2.20-9.93; under austerity measures: 6.78, 3.18-14.48) were the only parameters associated with higher odds for children's BMI deterioration from the study baseline to 2-year follow-up after adjusting for children's gender. CONCLUSIONS: The most predominant risk factors influencing children's prospective BMI deterioration were parental BMI and country economic classification as compared to perinatal. These findings should guide public health initiatives aiming to tackle the childhood obesity epidemic and social inequalities on a European level.

Overweight and Obesity: The Interplay of Eating Habits and Physical Activity.

The prevalence of overweight and obesity has been steadily increasing over the last 50 years, with worldwide obesity rates tripling since 1975, thus reaching pandemic proportions [...].

Effectiveness of a Digitally Delivered Continuous Care Intervention (Defeat Diabetes) on Type 2 Diabetes Outcomes: A 12-Month Single-Arm, Pre-Post Intervention Study.

Low-carbohydrate dietary approaches can lead to improvements in blood glucose levels and weight loss, as well as a reduction and/or cessation in medication use in people with type 2 diabetes (T2D). Recent technological advances have led to the development of health-related applications (apps), including a high proportion dedicated to the management of diabetes. The Defeat Diabetes Program is a smartphone- and web-based app that provides guidance on a low-carbohydrate dietary approach for T2D and was designed to be used in conjunction with standard care in the medical management of T2D. The primary aim of this protocol is to provide the rationale and design of a single-arm 12-month pre-post intervention clinical trial using the Defeat Diabetes Program in an Australian community-based cohort of people with T2D who were referred by their general practitioner (GP). The study seeks to engage the GP community to help demonstrate whether the results of using a low-carbohydrate dietary approach for T2D can be achieved by the Defeat Diabetes Program in their patients. This protocol describes (1) the rationale for the selection of primary and secondary outcome measures, (2) the sampling procedures and methodological steps used to identify eligible participants and collect data, and (3) the approach followed to involve and educate GPs to support the trial.

The Impact of Infant Feeding Regimen on Cow's Milk Protein Allergy, Atopic Dermatitis and Growth in High-Risk Infants during the First 6 Months of Life: The Allergy Reduction Trial.

The development of early-onset cow's milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow's milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants (p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow's milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula (p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis.

Likelihood of obesity in early and late childhood based on growth trajectory during infancy.

BACKGROUND: Childhood obesity rates have reached epidemic levels with Mediterranean countries reporting among the highest numbers globally. Evidence suggests early life factors, including infant growth rate, increase the likelihood of obesity later in childhood. However, optimal rates of infant growth associated with lower odds of future obesity still remain undetermined. The study aim was to determine the optimal infant growth rate associated with a lower likelihood of childhood overweight and obesity. METHODS: Perinatal and anthropometric data collected from 1778 Greek preschool (2-5 years old) and 2294 Greek preadolescent (10-12 years old) children participating in the ToyBox and the Healthy Growth Study (HGS) respectively, was combined for examination. Logistic regression models and receiver operating curves were used to determine the association between infant growth rate and development of childhood overweight and obesity, as well as optimal infant growth rate, respectively. RESULTS: Rapid weight gain during the first 6 months of life was positively associated with overweight and obesity in preadolescent children (OR:1.36, 95% CI: 1.13-1.63). Optimal cut-off points for several infancy growth rate indices (i.e., WAZ, WLZ, HAZ, BAZ) associated with a lower likelihood of overweight and obesity in preschool years and preadolescence were also identified. CONCLUSIONS: The current findings could possibly set the basis for healthcare professionals and families to better monitor, assess, and control infant growth rates, thus providing another obesity prevention strategy from early life. These findings, however, and the recommended optimal cut-offs need to be confirmed through further prospective research.

The Emerging Prevalence of Obesity within Families in Europe and its Associations with Family Socio-Demographic Characteristics and Lifestyle Factors; A Cross-Sectional Analysis of Baseline Data from the Feel4Diabetes Study.

The Feel4Diabetes study is a type 2 diabetes prevention program that recruited 12,193 children [age: 8.20 (±1.01) years] and their parents from six European countries. The current work used pre-intervention data collected from 9576 children-parents pairs, to develop a novel family obesity variable and to examine its associations with family sociodemographic and lifestyle characteristics. Family obesity, defined as the presence of obesity in at least two family members, had a prevalence of 6.6%. Countries under austerity measures (Greece and Spain) displayed higher prevalence (7.6%), compared to low-income (Bulgaria and Hungary: 7%) and high-income countries (Belgium and Finland: 4.5%). Family obesity odds were significantly lower when mothers (OR: 0.42 [95% CI: 0.32, 0.55]) or fathers (0.72 [95% CI: 0.57, 0.92]) had higher education, mothers were fully (0.67 [95% CI: 0.56, 0.81]) or partially employed (0.60 [95% CI: 0.45, 0.81]), families consumed breakfast more often (0.94 [95% CI: 0.91 0.96]), more portions of vegetables (0.90 [95% CI: 0.86, 0.95]), fruits (0.96 [95% CI: 0.92, 0.99]) and wholegrain cereals (0.72 [95% CI: 0.62, 0.83]), and for more physically active families (0.96 [95% CI: 0.93, 0.98]). Family obesity odds increased when mothers were older (1.50 [95% CI: 1.18, 1.91]), with the consumption of savoury snacks (1.11 [95% CI: 1.05, 1.17]), and increased screen time (1.05 [95% CI: 1.01, 1.09]). Clinicians should familiarise themselves with the risk factors for family obesity and choose interventions that target the whole family. Future research should explore the causal basis of the reported associations to facilitate devising tailored family-based interventions for obesity prevention.

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.

AIMS: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. METHODS AND RESULTS: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. CONCLUSION: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Effectiveness, reach, uptake, and feasibility of digital health interventions for adults with hypertension: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Digital health interventions are effective for hypertension self-management, but a comparison of the effectiveness and implementation of the different modes of interventions is not currently available. This study aimed to compare the effectiveness of SMS, smartphone application, and website interventions on improving blood pressure in adults with hypertension, and to report on their reach, uptake, and feasibility. METHODS: In this systematic review and meta-analysis we searched CINAHL Complete, Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, and APA PsycInfo on May 25, 2022, for randomised controlled trials (RCTs) published in English from Jan 1, 2009, that examined the effectiveness of digital health interventions on reducing blood pressure in adults with hypertension. Screening was carried out using Covidence, and data were extracted following Cochrane's guidelines. The primary endpoint was change in the mean of systolic blood pressure. Risk of bias was assessed with Cochrane Risk of Bias 2. Data on systolic and diastolic blood pressure reduction were synthesised in a meta-analysis, and data on reach, uptake and feasibility were summarised narratively. Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to evaluate the level of evidence. The study was registered with PROSPERO CRD42021247845. FINDINGS: Of the 3235 records identified, 29 RCTs from 13 regions (n=7592 participants) were included in the systematic review, and 28 of these RCTs (n=7092 participants) were included in the meta-analysis. 11 studies used SMS as the primary mode of delivery of the digital health intervention, 13 used smartphone applications, and five used websites. Overall, digital health intervention group participants had a -3·62 mm Hg (95% CI -5·22 to -2·02) greater reduction in systolic blood pressure, and a -2·45 mm Hg (-3·83 to -1·07) greater reduction in diastolic blood pressure, compared with control group participants. No statistically significant differences between the three different modes of delivery were observed for both the systolic (p=0·73) and the diastolic blood pressure (p=0·80) outcomes. Smartphone application interventions had a statistically significant reduction in diastolic blood pressure (-2·45 mm Hg [-4·15 to -0·74]); however, there were no statistically significant reductions for SMS interventions (-1·80 mm Hg [-4·60 to 1·00]) or website interventions (-3·43 mm Hg [-7·24 to 0·38]). Due to the considerable heterogeneity between included studies and the high risk of bias in some, the level of evidence was assigned a low overall score. Interventions were more effective among people with greater severity of hypertension at baseline. SMS interventions reported higher reach and smartphone application studies reported higher uptake, but differences were not statistically significant. INTERPRETATION: SMS, smartphone application, and website interventions were associated with statistically and clinically significant systolic and diastolic blood pressure reductions, compared with usual care, regardless of the mode of delivery of the intervention. This conclusion is tempered by the considerable heterogeneity of included studies and the high risk of bias in most. Future studies need to describe in detail the mediators and moderators of the effectiveness and implementation of these interventions, to both further improve their effectiveness as well as increase their reach, uptake, and feasibility. FUNDING: European Union's Horizon 2020 Research and Innovation Programme.

Effectiveness, reach, uptake, and feasibility of digital health interventions for adults with type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Digital health interventions have shown promising results for the management of type 2 diabetes, but a comparison of the effectiveness and implementation of the different modes is not currently available. Therefore, this study aimed to compare the effectiveness of SMS, smartphone application, and website-based interventions on improving glycaemia in adults with type 2 diabetes and report on their reach, uptake, and feasibility. METHODS: In this systematic review and meta-analysis, we searched CINAHL, Cochrane Central, Embase, MEDLINE, and PsycInfo on May 25, 2022, for randomised controlled trials (RCTs) that examined the effectiveness of digital health interventions in reducing glycated haemoglobin A1c (HbA1c) in adults with type 2 diabetes, published in English from Jan 1, 2009. Screening was carried out using Covidence, and data were extracted following Cochrane's guidelines. The primary endpoint assessed was the change in the mean (and 95% CI) plasma concentration of HbA1c at 3 months or more. Cochrane risk of bias 2 was used to assess risk of bias. Data on reach, uptake, and feasibility were summarised narratively and data on HbA1c reduction were synthesised in a meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation criteria was used to evaluate the level of evidence. The study was registered with PROSPERO, CRD42021247845. FINDINGS: Of the 3236 records identified, 56 RCTs from 24 regions (n=11 486 participants), were included in the narrative synthesis, and 26 studies (n=4546 participants) in the meta-analysis. 20 studies used SMS as the primary mode of delivery of the digital health intervention, 25 used smartphone applications, and 11 implemented interventions via websites. Smartphone application interventions reported higher reach compared with SMS and website-based interventions, but website-based interventions reported higher uptake compared with SMS and smartphone application interventions. Effective interventions, in general, included people with greater severity of their condition at baseline (ie, higher HbA1c) and administration of a higher dose intensity of the intervention, such as more frequent use of smartphone applications. Overall, digital health intervention group participants had a -0·30 (95% CI -0·42 to -0·19) percentage point greater reduction in HbA1c, compared with control group participants. The difference in HbA1c reduction between groups was statistically significant when interventions were delivered through smartphone applications (-0·42% [-0·63 to -0·20]) and via SMS (-0·37% [-0·57 to -0·17]), but not when delivered via websites (-0·09% [-0·64 to 0·46]). Due to the considerable heterogeneity between included studies, the level of evidence was moderate overall. INTERPRETATION: Smartphone application and SMS interventions, but not website-based interventions, were associated with better glycaemic control. However, the studies' heterogeneity should be recognised. Considering that both smartphone application and SMS interventions are effective for diabetes management, clinicians should consider factors such as reach, uptake, patient preference, and context of the intervention when deciding on the mode of delivery of the intervention. Nine in ten people worldwide own a feature phone and can receive SMS and four in five people have access to a smartphone, with numerous smartphone applications being available for diabetes management. Clinicians should familiarise themselves with this modality of programme delivery and encourage people with type 2 diabetes to use evidence-based applications for improving their self-management of diabetes. Future research needs to describe in detail the mediators and moderators of the effectiveness and implementation of SMS and smartphone application interventions, such as the optimal dose, frequency, timing, user interface, and communication mode to both further improve their effectiveness and to increase their reach, uptake, and feasibility. FUNDING: EU's Horizon 2020 Research and Innovation Programme.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

The Effect of Maternal Overweight and Obesity Pre-Pregnancy and During Childhood in the Development of Obesity in Children and Adolescents: A Systematic Literature Review.

Maternal overweight/obesity has been associated with an increased risk of obesity in childhood. We investigated the effect of maternal overweight/obesity during pre-pregnancy and whether it is a stronger predictor of child obesity, compared to maternal overweight/obesity during childhood. Prospective or retrospective cohort studies published in English, reporting on obese children and adolescents (2-18 years), with overweight/obese mothers in either pre-pregnancy or during childhood were included. A search was conducted from 2012 to April 2022 in MEDLINE, Web of Science, CINAHL, and EMBASE, followed by screening, data extraction, quality assessment and narrative synthesis. Eleven eligible studies (9 prospective and 2 retrospective cohort studies; total sample, n = 27,505) were identified. Eight studies examined maternal overweight/obesity in pre-conception, presenting consistent positive associations with childhood obesity, three reported positive associations between childhood obesity and maternal overweight/obesity during childhood, and one presented positive associations between both maternal exposures. The narrative synthesis failed to identify which maternal exposure is the strongest predictor of childhood obesity, with studies reporting significant associations between maternal overweight/obesity and child obesity in both time points. Intervention programs aiming to reduce childhood obesity should focus on supporting women of childbearing age with weight management from preconception and throughout their life-course.

Nurturing children's development through healthy eating and active living: Time for policies to support effective interventions in the context of responsive emotional support and early learning.

Fostering the growth, development, health, and wellbeing of children is a global priority. The early childhood period presents a critical window to influence lifelong trajectories, however urgent multisectoral action is needed to ensure that families are adequately supported to nurture their children's growth and development. With a shared vision to give every child the best start in life, thus helping them reach their full developmental potential, we have formed the International Healthy Eating Active Living Matters (HEALing Matters) Alliance. Together, we form a global network of academics and practitioners working across child health and development, and who are dedicated to improving health equity for children and their families. Our goal is to ensure that all families are free from structural inequality and oppression and are empowered to nurture their children's growth and development through healthy eating and physical activity within the context of responsive emotional support, safety and security, and opportunities for early learning. To date, there have been disparate approaches to promoting these objectives across the health, community service, and education sectors. The crucial importance of our collective work is to bring these priorities for early childhood together through multisectoral interventions, and in so doing tackle head on siloed approaches. In this Policy paper, we draw upon extensive research and call for collective action to promote equity and foster positive developmental trajectories for all children. We call for the delivery of evidence-based programs, policies, and services that are co-designed to meet the needs of all children and families and address structural and systemic inequalities. Moving beyond the "what" is needed to foster the best start to life for all children, we provide recommendations of "how" we can do this. Such collective impact will facilitate intergenerational progression that builds human capital in future generations.

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.