Childhood Transitions Between Weight Status Categories: Evidence from the UK Millennium Cohort Study.

BACKGROUND: Assessing the cost-effectiveness of interventions targeting childhood excess weight requires estimates of the hazards of transitioning between weight status categories. Current estimates are based on studies characterized by insufficient sample sizes, a lack of national representativeness, and untested assumptions. OBJECTIVES: We sought to (1) estimate transition probabilities and hazard ratios for transitioning between childhood weight status categories, (2) test the validity of the underlying assumption in the literature that transitions between childhood bodyweight categories are time-homogeneous, (3) account for complex sampling procedures when deriving nationally representative transition estimates, and (4) explore the impact of child, maternal, and sociodemographic characteristics. METHODS: We applied a multistate transition modeling approach accounting for complex survey design to UK Millennium Cohort Study (MCS) data to predict transition probabilities and hazard ratios for weight status movements for children aged 3-17. Surveys were conducted at ages 3 (wave 2 in 2004), 5 (wave 3 in 2006), 7 (wave 4 in 2008), 11 (wave 5 in 2012), 14 (wave 6 in 2015), and 17 (wave 7 in 2018) years. We derived datasets that included repeated body mass index measurements across waves after excluding multiple births and children with missing or implausible bodyweight records. To account for the stratified cluster sample design of the MCS, we incorporated survey weights and jackknife replicates of survey weights. Using a validation dataset from the MCS, we tested the validity of our models. Finally, we estimated the relationships between state transitions and child, maternal, and sociodemographic factors. RESULTS: The datasets for our primary analysis consisted of 10,399 children for waves 2-3, 10,729 for waves 3-4, 9685 for waves 4-5, 8593 for waves 5-6, and 7085 for waves 6-7. All datasets consisted of roughly equal splits of boys and girls. Under the assumption of time-heterogeneous transition rates (our base-case model), younger children (ages 3-5 and 5-7 years) had significantly higher annual transition probabilities of moving from healthy weight to overweight (0.033, 95% confidence interval [CI] 0.026-0.041, and 0.027, 95% CI 0.021-0.033, respectively) compared to older children (0.015, 95% CI 0.012-0.018, at ages 7-11; 0.018, 95% CI 0.013-0.023, at ages 11-14; and 0.018, 95% CI 0.013-0.025 at ages 14-17 years). However, the resolution of unhealthy weight was more strongly age-dependent than transitions from healthy weight to non-healthy weight states. Transition hazards differed by child, maternal, and sociodemographic factors. CONCLUSIONS: Our models generated estimates of bodyweight status transitions in a representative UK childhood population. Compared to our scenario models (i.e., time-homogeneous transition rates), our base-case model fits the observed data best, indicating a non-time-homogeneous pattern in transitions between bodyweight categories during childhood. Transition hazards varied significantly by age and across subpopulations, suggesting that conducting subgroup-specific cost-effectiveness analyses of childhood weight management interventions will optimize decision-making.

Association of gestational diabetes with long-term risk of premature mortality, and cardiovascular outcomes and risk factors: A retrospective cohort analysis in the UK Biobank.

AIM: To investigate the association of gestational diabetes mellitus (GDM) with premature mortality and cardiovascular (CVD) outcomes and risk factors. MATERIALS AND METHODS: Parous women recruited to the UK Biobank cohort during 2006-2010 were followed up from their first delivery until 31 October 2021. The data were linked to Hospital Episode Statistics and mortality registries. Multivariate Cox proportional hazard models investigated associations of GDM with all-cause mortality, CVD, diabetes, hypertension and dyslipidaemia. RESULTS: The maximum total analysis time at risk and under observation was 9 694 090 person-years. Among 220 726 women, 1225 self-reported or had a recorded diagnosis of GDM. After adjusting for confounders and behavioural factors, GDM was associated with increased risk for premature mortality [hazard ratio (HR): 1.44, 95% confidence interval (CI): 1.12-1.86], particularly CVD-related death (HR: 2.38, 95% CI: 1.63-3.48), as well as incident total CVD (HR: 1.50, 95% CI: 1.30-1.74), non-fatal CVD (HR: 1.41, 95% CI: 1.20-1.65), diabetes (HR: 14.37, 95% CI: 13.51-15.27), hypertension (HR: 1.49, 95% CI: 1.38-1.60), and dyslipidaemia (HR: 1.30, 95% CI: 1.22-1.39). The total CVD risk was greater in women with GDM who did not later develop diabetes than in those with GDM and diabetes. CONCLUSIONS: Women with GDM are at increased risk of premature death and have increased CV risk, emphasizing the importance of interventions to prevent GDM. If GDM develops, the diagnosis represents an opportunity for future surveillance and intervention to reduce CVD risk factors, prevent CVD and improve long-term health.

REduced-Carbohydrate intervention for managing Obesity and Reduction of gestational Diabetes (RECORD): A randomized controlled feasibility trial.

AIM: To test the feasibility and acceptability of a reduced-carbohydrate dietary program, intended to reduce the risk of gestational diabetes. MATERIALS AND METHODS: Fifty-one pregnant women at <20 weeks' gestation, with body mass index ≥30 kg/m2 , and a normal baseline oral glucose tolerance test (OGTT), were randomized 2:1 to an intervention or control group and followed-up until delivery. The dietary intervention aimed at providing 130-150 g carbohydrate/day. Feasibility outcomes assessed at 24-28 weeks' gestation, included adoption of the reduced-carbohydrate diet by the intervention group, and retention of all participants, assessed by completion of a second OGTT. Changes in glycemia, weight gain and dietary intake, and the maternal and neonatal outcomes were also assessed. Participants were interviewed about their experience of the intervention and the study. RESULTS: Forty-nine of 51 participants attended the follow-up OGTT, a retention rate of 96% (95% confidence interval [CI] 86.8%-98.9%). In the intervention group, carbohydrate intake at follow-up was 190.4 (95% CI 162.5-215.6) g/day, a reduction of -24.6 (95% CI -51.5-2.4) g/day from baseline. Potentially favourable effects of the intervention on glucose control, weight gain and blood pressure were observed, but the study was not powered to detect significant differences in these. Participants found the intervention acceptable, and were content with the study processes, but some reported barriers to sustained adherence, mainly pertaining to competing priorities. CONCLUSIONS: Retention was high, suggesting the study processes are feasible, but the carbohydrate reduction in the intervention group was small, and did not meet progression criteria, limiting the likelihood of achieving the desired goal to prevent gestational diabetes. TRIAL REGISTRATION NUMBER: ISRCTN16235884.

Dietary interventions in pregnancy for the prevention of gestational diabetes: a literature review.

The aim of this review is to provide an overview of dietary interventions delivered during pregnancy for the prevention of gestational diabetes mellitus (GDM). GDM increases the risk of adverse pregnancy and neonatal outcomes, and also increases future cardiometabolic risks for both the mother and the offspring. Carrying or gaining excessive weight during pregnancy increases the risk of developing GDM, and several clinical trials in women with overweight or obesity have tested whether interventions aimed at limiting gestational weight gain (GWG) could help prevent GDM. Most dietary interventions have provided general healthy eating guidelines, while some had a specific focus, such as low glycaemic index, increased fibre intake, reducing saturated fat or a Mediterranean-style diet. Although trials have generally been successful in attenuating GWG, the majority have been unable to reduce GDM risk, which suggests that limiting GWG may not be sufficient in itself to prevent GDM. The trials which have shown effectiveness in GDM prevention have included intensive face-to-face dietetic support, and/or provision of key foods to participants, but it is unclear whether these strategies could be delivered in routine practice. The mechanism behind the effectiveness of some interventions over others remains unclear. Dietary modifications from early stages of pregnancy seem to be key, but the optimum dietary composition is unknown. Future research should focus on designing acceptable and scalable dietary interventions to be tested early in pregnancy in women at risk of GDM.

Binge Eating (BE) and Obesity: Brain Activity and Psychological Measures before and after Roux-En-Y Gastric Bypass (RYGB).

Brain activity in response to food cues following Roux-En-Y Gastric Bypass (RYGB) in binge eating (BE) or non-binge eating (NB) individuals is understudied. Here, 15 RYGB (8 BE; 7 NB) and 13 no treatment (NT) (7 BE; 6 NB) women with obesity underwent fMRI imaging while viewing high and low energy density food (HEF and LEF, respectively) and non-food (NF) visual cues. A region of interest (ROI) analysis compared BE participants to NB participants in those undergoing RYGB surgery pre-surgery and 4 months post. Results were corrected for multiple comparisons using liberal (p < 0.006 uncorrected) and stringent (p < 0.05 FDR corrected) thresholds. Four months following RYGB (vs. no treatment (NT) control), both BE and NB participants showed greater reductions in blood oxygen level-dependent (BOLD) signals (a proxy of local brain activity) in the dorsomedial prefrontal cortex in response to HEF (vs. LEF) cues (p < 0.006). BE (vs. NB) participants showed greater increases in the precuneus (p < 0.006) and thalamic regions (p < 0.05 corrected) to food (vs. NF). For RYGB (vs. NT) participants, BE participants, but not NB participants, showed lower BOLD signal in the middle occipital gyrus (p < 0.006), whilst NB participants, but not BE participants, showed lower signal in inferior frontal gyrus (p < 0.006) in response to HEF (vs. LEF). Results suggest distinct neural mechanisms of RGYB in BE and may help lead to improved clinical treatments.

A systematic review of economic evaluations of interventions targeting childhood overweight and obesity.

This systematic review critically appraised and synthesized evidence from economic evaluations of interventions targeting childhood excess weight. We conducted systematic searches in 11 databases from inception to April 19, 2023. Studies were eligible if they evaluated interventions targeting children up to 18 years and the study intervention(s) targeted childhood excess weight or sought to improve diet or physical activity, regardless of the type of economic evaluation or the underpinning study design. We synthesized evidence using narrative synthesis methods. One-hundred fifty-one studies met the eligibility criteria and were classified into three groups based on the intervention approach: prevention-only (13 studies), prevention and treatment (100 studies), and treatment-only (38 studies). The predominant setting and study design differed considerably between the three groups of studies. However, compared with usual care, most interventions were deemed cost-effective. The study participants' ages, sex, and socioeconomic status were crucial to intervention cost-effectiveness. Interventions whose effects were projected beyond childhood, such as bariatric surgery, lower protein infant formula, and home-based general practitioner consultations, tended to be cost-effective. However, cost-effectiveness was sensitive to the assumptions underlying the persistence and intensity of such effects. Our findings can inform future recommendations on the conduct of economic evaluations of interventions targeting childhood overweight and obesity, as well as practice and policy recommendations.

Use of Cognitive and Behavioral Strategies During a Weight Loss Program: A Secondary Analysis of the Doctor Referral of Overweight People to Low-Energy Total Diet Replacement Treatment (DROPLET) Trial.

BACKGROUND: Achieving a sustained energy deficit is essential for weight loss, but the cognitive and behavioral strategies that support this goal are unclear. OBJECTIVE: The goal of this study was to investigate the number and type of cognitive and behavioral strategies used by participants who were enrolled in a 1-year weight loss trial and to explore associations between strategies and magnitude of weight loss at 3 months and 1 year. DESIGN: The study is a secondary post-hoc exploratory analysis of data collected as part of the Doctor Referral of Overweight People to Low-Energy total diet replacement Treatment (DROPLET), a randomized controlled trial conducted in general practices in England, United Kingdom, between January 2016 and August 2017. PARTICIPANTS/SETTING: This study involved 164 participants from both intervention and control groups of the DROPLET trial who completed the Oxford Food and Behaviours (OxFAB) questionnaire to assess the use of 115 strategies grouped into 21 domains used to manage their weight. INTERVENTIONS: Participants were randomized to either a behavioral weight loss program involving 8 weeks total diet replacement (TDR) and 4 weeks of food reintroduction or a program delivered by a medical practice nurse over a 3-month period (usual care [UC]). MAIN OUTCOME MEASURES: Weight was objectively measured at baseline, 3 months, and 1 year. Cognitive and behavioral strategies used to support weight loss were assessed using the OxFAB questionnaire at 3 months. STATISTICAL ANALYSIS PERFORMED: Exploratory factor analysis was used to generate data-driven patterns of strategy use, and a linear mixed-effects model was used to examine associations between use of these patterns and weight change. RESULTS: No evidence was found of a difference in the number of strategies (mean difference, 2.41; 95% confidence interval [CI], -0.83, 5.65) or the number of domains used (mean difference, -0.23; 95% CI, -0.69, 0.23) between the TDR group and the UC group. The number of strategies was not associated with weight loss at either 3 months (-0.02 kg; 95% CI, -0.11, 0.06) or 1 year (-0.05 kg; 95% CI, -0.14, 0.02). Similarly, the number of domains used was not associated with weight loss at 3 months (-0.02 kg; 95% CI, -0.53, 0.49) or 1 year (-0.07 kg; 95% CI, -0.60, 0.46). Factor analysis identified four coherent patterns of strategy use, identified as Physical Activity, Motivation, Planned Eating, and Food Purchasing patterns. Greater use of strategies in the Food Purchasing (-2.6 kg; 95% CI, -4.42, -0.71) and Planned Eating patterns (-3.20 kg; 95% CI, -4.94, -1.46) was associated with greater weight loss at 1 year. CONCLUSIONS: The number of cognitive and behavioral strategies or domains used does not appear to influence weight loss, but the types of strategy appear of greater importance. Supporting people to adopt strategies linked to planned eating and food purchasing may aid long-term weight loss.

Clinical guidelines for the management of weight during pregnancy: a qualitative evidence synthesis of practice recommendations across NHS Trusts in England.

BACKGROUND: Women who enter pregnancy with a Body Mass Index above 30 kg/m2 face an increased risk of complications during pregnancy and birth. National and local practice recommendations in the UK exist to guide healthcare professionals in supporting women to manage their weight. Despite this, women report inconsistent and confusing advice and healthcare professionals report a lack of confidence and skill in providing evidence-based guidance. A qualitative evidence synthesis was conducted to examine how local clinical guidelines interpret national recommendations to deliver weight management care to people who are pregnant or in the postnatal period. METHODS: A qualitative evidence synthesis of local NHS clinical practice guidelines in England was conducted. National Institute for Health and Care Excellence and Royal College of Obstetricians and Gynaecologists guidelines for weight management during pregnancy constructed the framework used for thematic synthesis. Data was interpreted within the embedded discourse of risk and the synthesis was informed by the Birth Territory Theory of Fahy and Parrat. RESULTS: A representative sample of twenty-eight NHS Trusts provided guidelines that included weight management care recommendations. Local recommendations were largely reflective of national guidance. Consistent recommendations included obtaining a weight at booking and informing women of the risks associated with being obese during pregnancy. There was variation in the adoption of routine weighing practices and referral pathways were ambiguous. Three interpretive themes were constructed, exposing a disconnect between the risk dominated discourse evident in the local guidelines and the individualised, partnership approach emphasised in national level maternity policy. CONCLUSIONS: Local NHS weight management guidelines are rooted in a medical model rather than the model advocated in national maternity policy that promotes a partnership approach to care. This synthesis exposes the challenges faced by healthcare professionals and the experiences of pregnant women who are in receipt of weight management care. Future research should target the tools utilised by maternity care providers to achieve weight management care that harnesses a partnership approach empowering pregnant and postnatal people in their journey through motherhood.

Evidence of lifestyle interventions in a pregnant population with chronic hypertension and/or pre-existing diabetes: A systematic review and narrative synthesis.

BACKGROUND: Pregnant people with chronic hypertension, pre-existing diabetes or both are at high risk of developing cardiovascular disease. Lifestyle interventions play an important role in disease management in non-pregnant populations. AIM: To review the existing evidence of randomised controlled trials (RCTs) that examine lifestyle interventions in pregnant people with chronic hypertension and/or pre-existing diabetes. METHODS: A systematic review and narrative synthesis was conducted. Five electronic databases were searched from inception to April 2021 for RCTs evaluating antenatal lifestyle interventions in people with chronic hypertension and/or pre-existing diabetes with outcomes to include weight or blood pressure change. RESULTS: Nine randomised controlled trials including 7438 pregnant women were eligible. Eight studies were mixed pregnant populations that included women with chronic hypertension and/or pre-existing diabetes. One study included only pregnant women with pre-existing diabetes. Intervention characteristics and procedures varied and targeted diet, physical activity and/or gestational weight. All studies reported weight and one study reported blood pressure change. Outcome data were frequently unavailable for the subset of women of interest, including subgroup data on important pregnancy and birth complications. Eligibility criteria were often ambiguous and baseline data on chronic hypertension was often omitted. CONCLUSION: A lack of primary interventional trials examining the effect of lifestyle interventions on weight and blood pressure outcomes in pregnant populations with chronic hypertension and/or pre-existing diabetes was evident. Lifestyle modification has the potential to alter disease progression. Future trials should address the ambiguity and frequent exclusion of these important populations.

Development and testing of a reduced carbohydrate intervention for the management of obesity and reduction of gestational diabetes (RECORD): protocol for a feasibility randomised controlled trial.

INTRODUCTION: Previous trials of dietary interventions to prevent gestational diabetes mellitus (GDM) have yielded only limited success. Low-carbohydrate diets have shown promise for the treatment of type 2 diabetes, but there is no evidence to support their use in pregnancy. The aim of this study is to explore the feasibility of a moderately reduced-carbohydrate dietary intervention delivered from mid-pregnancy alongside routine antenatal care. METHODS AND ANALYSIS: This is a feasibility randomised controlled trial (RCT) with embedded qualitative study. Sixty women who are pregnant <20 weeks' gestation, with body mass index ≥30 kg/m2 at their antenatal booking appointment, will be randomised 2:1 intervention or control (usual care) and followed up until delivery. The intervention is a moderately reduced-carbohydrate diet (~130-150 g total carbohydrate/day), designed to be delivered alongside routine antenatal appointments. Primary outcomes are measures of adoption of the diet and retention of participants. Secondary outcomes include incidence of GDM, change in markers of glycaemic control, gestational weight gain, total carbohydrate and energy intake. Process outcomes will examine resources and management issues. Exploratory outcomes include further dietary changes, quality of life, maternal and neonatal outcomes, and qualitative measures. ETHICS AND DISSEMINATION: This trial was reviewed and approved by the South-Central Oxford B Research Ethics Committee NHS National Research Ethics Committee and the Health Research Authority (Reference: 20/SC/0442). The study results will inform whether to progress to a full-scale RCT to test the clinical effectiveness of the RECORD programme to prevent GDM in women at high risk. The findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN16235884.

Study protocol: use of a smartphone application to support the implementation of a complex physical activity intervention (+Stay Active) in women with gestational diabetes mellitus-protocol for a non-randomised feasibility study.

INTRODUCTION: Physical activity (PA) interventions have a promising role in the management of gestational diabetes mellitus (GDM). Digital technologies can support PA at scale and remotely. The protocol describes a study designed to determine the feasibility and acceptability of a complex intervention; known as +Stay Active. +Stay Active combines motivational interviewing with a bespoke behaviour change informed smartphone application (Stay-Active) to augment PA levels in women with GDM. METHODS AND ANALYSIS: This is a non-randomised feasibility study using a mixed methods approach. Participants will be recruited from the GDM antenatal clinic at the Women Centre, John Radcliffe Hospital, Oxford. Following baseline assessments (visit 1) including self-reported and device determined PA assessment (wearing a wrist accelerometer), women will be invited to participate in an online motivational interview, then download and use the Stay-Active app (Android or iOS) (visit 2). Women will have access to Stay-Active until 36 weeks gestation, when engagement and PA levels will be reassessed (visit 3). The target sample size is 60 women. Primary outcomes are recruitment and retention rates, compliance and assessment of participant engagement and acceptability with the intervention. Secondary outcomes are assessment of blood glucose control, self-reported and device determined assessment of PA, usage and structured feedback of participant's attitudes to +Stay Active, assessment of health costs and description of maternal and neonatal outcomes. This study will provide key insights into this complex intervention regarding engagement in smartphone technology and the wearing of accelerometers. These data will inform the development of a randomised controlled trial with refinements to intervention implementation. ETHICS AND DISSEMINATION: The study has received a favourable opinion from South Central-Hampshire B Research Ethics Committee; REC reference: 20/SC/0342. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, conferences and seminar presentations. TRIAL REGISTRATION NUMBER: ISRCTN11366562.

Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study.

BACKGROUND: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England. METHODS: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m2) after vaccination. FINDINGS: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. INTERPRETATION: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (<18·5 kg/m2), in whom uptake is lower and vaccine effectiveness seems to be reduced. Strategies to achieve and maintain a healthy weight should be prioritised at the population level, which could help reduce the burden of COVID-19 disease. FUNDING: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.

Setting the top 10 priorities for obesity and weight-related research (POWeR): a stakeholder priority setting process.

OBJECTIVES: To identify and prioritise the most impactful, unanswered questions for obesity and weight-related research. DESIGN: Prioritisation exercise of research questions using online surveys and an independently facilitated workshop. SETTING: Online/virtual. PARTICIPANTS: We involved members of the public including people living with obesity, researchers, healthcare professionals and policy-makers in all stages of this study. PRIMARY OUTCOME MEASURES: Top 10 research questions to be prioritised in future obesity and weight-related research. RESULTS: Survey 1 produced 941 questions, from 278 respondents. Of these, 49 questions held satisfactory evidence in the scientific literature and 149 were out of scope. The remaining 743 questions were, where necessary, amalgamated and rephrased, into a list of 149 unique and unanswered questions. In the second survey, 405 respondents ranked the questions in order of importance. During the workshop, a subset of 38 survey respondents and stakeholders, agreed a final list of 10 priority research questions through small and large group consultation and consensus. The top 10 priority research questions covered: the role of the obesogenic environment; effective weight loss and maintenance strategies; prevention in children; effective prevention and treatment policies; the role of the food industry; access to and affordability of a healthy diet; sociocultural factors associated with weight; the biology of appetite and food intake; and long-term health modelling for obesity. CONCLUSIONS: This systematic and transparent process identified 149 unique and unanswered questions in the field of obesity and weight-related research culminating in a consensus among relevant stakeholders on 10 research priorities. Targeted research funding in these areas of top priority would lead to needed and impactful knowledge generation for the field of obesity and weight regulation and thereby improve population health.

Health Economic Aspects of Childhood Excess Weight: A Structured Review.

An economic perspective is crucial to understand the broad consequences of childhood excess weight (CEW). These can manifest in the form of elevated health care and societal costs, impaired health status, or inefficiencies in the allocation of resources targeted at its prevention, management, or treatment. Although existing systematic reviews provide summaries of distinct economic research strands covering CEW, they have a restricted focus that overlooks relevant evidence. The overarching aim of this structured review was to update and enhance recent key reviews of four strands of economic evidence in this area, namely, (1) economic costs associated with CEW, (2) health utilities associated with CEW, (3) economic evaluations of interventions targeting CEW, and (4) economic determinants and broader consequences of CEW. Our de novo searches identified six additional studies for the first research strand, five studies for the second, thirty-one for the third, and two for the fourth. Most studies were conducted in a small number of high-income countries. Our review highlights knowledge gaps across all the research strands. Evidence from this structured review can act as data input into future economic evaluations in this area and highlights areas where future economic research should be targeted.

Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe COVID-19 outcomes: observational study and Mendelian randomisation analysis.

BACKGROUND: Higher body mass index (BMI) and metabolic consequences of excess weight are associated with increased risk of severe COVID-19, though their mediating pathway is unclear. METHODS: A prospective cohort study included 435,504 UK Biobank participants. A two-sample Mendelian randomisation (MR) study used the COVID-19 Host Genetics Initiative in 1.6 million participants. We examined associations of total adiposity, body composition, fat distribution and metabolic consequences of excess weight, particularly type 2 diabetes, with incidence and severity of COVID-19, assessed by test positivity, hospital admission, intensive care unit (ICU) admission and death. RESULTS: BMI and body fat were associated with COVID-19 in the observational and MR analyses but muscle mass was not. The observational study suggested the association with central fat distribution was stronger than for BMI, but there was little evidence from the MR analyses than this was causal. There was evidence that strong associations of metabolic consequences with COVID-19 outcomes in observational but not MR analyses. Type 2 diabetes was strongly associated with COVID-19 in observational but not MR analyses. In adjusted models, the observational analysis showed that the association of BMI with COVID-19 diminished, while central fat distribution and metabolic consequences of excess weight remained strongly associated. In contrast, MR showed the reverse, with only BMI retaining a direct effect on COVID-19. CONCLUSIONS: Excess total adiposity is probably casually associated with severe COVID-19. Mendelian randomisation data do not support causality for the observed associations of central fat distribution or metabolic consequences of excess adiposity with COVID-19.

Replacing meat with alternative plant-based products (RE-MAP): a randomized controlled trial of a multicomponent behavioral intervention to reduce meat consumption.

BACKGROUND: Reducing meat consumption could protect the environment and human health. OBJECTIVES: We tested the impact of a behavioral intervention to reduce meat consumption. METHODS: Adult volunteers who regularly consumed meat were recruited from the general public and randomized 1:1 to an intervention or control condition. The intervention comprised free meat substitutes for 4 weeks, information about the benefits of eating less meat, success stories, and recipes. The control group received no intervention or advice on dietary change. The primary outcome was daily meat consumption after 4 weeks, assessed by a 7-day food diary, and repeated after 8 weeks as a secondary outcome. Other secondary and exploratory outcomes included the consumption of meat substitutes, cardiovascular risk factors, psychosocial variables related to meat consumption, and the nutritional composition of the diet. We also estimated the intervention's environmental impact. We evaluated the intervention using generalized linear mixed-effects models. RESULTS: Between June 2018 and October 2019, 115 participants were randomized. The baseline meat consumption values were 134 g/d in the control group and 130 g/d in the intervention group. Relative to the control condition, the intervention reduced meat consumption at 4 weeks by 63 g/d (95% CI: 44-82; P < 0.0001; n = 114) and at 8 weeks by 39 g/d (95% CI: 16-62; P = 0.0009; n = 113), adjusting for sex and baseline consumption. The intervention significantly increased the consumption of meat substitutes without changing the intakes of other principal food groups. The intervention increased intentions, positive attitudes, perceived control, and subjective norms of eating a low-meat diet and using meat substitutes, and decreased attachment to meat. At 8 weeks, 55% of intervention recipients identified as meat eaters, compared to 89% of participants in the control group. CONCLUSIONS: A behavioral program involving free meat substitutes can reduce meat intake and change psychosocial constructs consistent with a sustained reduction in meat intake.

Testing the short-term effectiveness of primary care referral to online weight loss programmes: A randomised controlled trial.

Guidelines ask health professionals to offer brief advice to encourage weight loss for people living with obesity. We tested whether referral to one of three online programmes could lead to successful weight loss. A total of 528 participants aged ≥18 years with a body mass index of ≥30 kg/m2 were invited via a letter from their GP. Participants were randomised to one of three online weight loss programmes (NHS Weight Loss Plan, Rosemary Online or Slimming World Online) or to a control group receiving no intervention. Participants self-reported weight at baseline and 8 weeks. The primary outcome was weight change in each of the active intervention groups compared with control. We also compared the proportion of participants losing ≥5% or ≥10% of body weight. For Rosemary, Online mean weight loss was modestly greater than control (-1.5 kg [95% confidence interval (CI) -2.3 to -0.6]) and more than three times as many participants in this group lost ≥5% (relative risk [RR] = 3.64, 95% CI: 1.63-8.1). For Slimming World, mean weight loss was not significantly different from control (-0.8 kg [95%CI -1.7 to 0.1]), twice as many participants lost ≥5% (RR = 2.70, 1.17-6.23). There was no significant difference in weight loss for participants using the NHS Weight Loss Plan (-0.4 kg, [95% CI -1.3 to 0.5]), or the proportion losing ≥5% (RR = 2.09, 0.87-5.01). Only one of three online weight loss programmes was superior to no intervention and the effect size modest among participants living with obesity.

Extended follow-up of a short total diet replacement programme: results of the Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET) randomised controlled trial at 3 years.

OBJECTIVES: To test the long-term effectiveness of a total diet replacement programme (TDR) for routine treatment of obesity in a primary care setting. METHODS: This study was a pragmatic, two-arm, parallel-group, open-label, individually randomised controlled trial in adults with obesity. The outcomes were change in weight and biomarkers of diabetes and cardiovascular disease risk from baseline to 3 years, analysed as intention-to-treat with mixed effects models. INTERVENTIONS: The intervention was TDR for 8 weeks, followed by food-reintroduction over 4 weeks. Behavioural support was provided weekly for 8 weeks, bi-weekly for the next 4 weeks, then monthly for 3 months after which no further support was provided. The usual care (UC) group received dietary advice and behavioural support from a practice nurse for up to 3 months. RESULTS: Outcome measures were collected from 179 (66%) participants. Compared with baseline, at 3 years the TDR group lost -6.2 kg (SD 9.1) and usual care -2.7 kg (SD 7.7); adjusted mean difference -3.3 kg (95% CI: -5.2, -1.5), p < 0.0001. Regain from programme end (6 months) to 3 years was greater in TDR group +8.9 kg (SD 9.4) than UC + 1.2, (SD 9.1); adjusted mean difference +6.9 kg (95% CI 4.2, 9.5) P < 0.001. At 3 years TDR led to greater reductions than UC in diastolic blood pressure (mean difference -3.3 mmHg (95% CI:-6.2; -0.4) P = 0.024), and systolic blood pressure (mean differences -3.7 mmHg (95% CI: -7.4; 0.1) P = 0.057). There was no evidence of differences between groups in the change from baseline to 3 years HbA1c (-1.9 mmol/mol (95% CI: -0.7; 4.5; P = 0.15), LDL cholesterol concentrations (0.2 mmol/L (95% CI -0.3, 0.7) P = 0.39), cardiovascular risk score (QRISK2) (-0.37 (95% CI -0.96; 0.22); P = 0.22). CONCLUSIONS: Treatment of people with obesity with a TDR programme compared with support from a practice nurse leads to greater weight loss which persists to at least 3 years, but there was only evidence of sustained improvements in BP and not in other aspects of cardiometabolic risk.

Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study.

BACKGROUND: Obesity is a major risk factor for adverse outcomes after infection with SARS-CoV-2. We aimed to examine this association, including interactions with demographic and behavioural characteristics, type 2 diabetes, and other health conditions. METHODS: In this prospective, community-based, cohort study, we used de-identified patient-level data from the QResearch database of general practices in England, UK. We extracted data for patients aged 20 years and older who were registered at a practice eligible for inclusion in the QResearch database between Jan 24, 2020 (date of the first recorded infection in the UK) and April 30, 2020, and with available data on BMI. Data extracted included demographic, clinical, clinical values linked with Public Health England's database of positive SARS-CoV-2 test results, and death certificates from the Office of National Statistics. Outcomes, as a proxy measure of severe COVID-19, were admission to hospital, admission to an intensive care unit (ICU), and death due to COVID-19. We used Cox proportional hazard models to estimate the risk of severe COVID-19, sequentially adjusting for demographic characteristics, behavioural factors, and comorbidities. FINDINGS: Among 6 910 695 eligible individuals (mean BMI 26·78 kg/m2 [SD 5·59]), 13 503 (0·20%) were admitted to hospital, 1601 (0·02%) to an ICU, and 5479 (0·08%) died after a positive test for SARS-CoV-2. We found J-shaped associations between BMI and admission to hospital due to COVID-19 (adjusted hazard ratio [HR] per kg/m2 from the nadir at BMI of 23 kg/m2 of 1·05 [95% CI 1·05-1·05]) and death (1·04 [1·04-1·05]), and a linear association across the whole BMI range with ICU admission (1·10 [1·09-1·10]). We found a significant interaction between BMI and age and ethnicity, with higher HR per kg/m2 above BMI 23 kg/m2 for younger people (adjusted HR per kg/m2 above BMI 23 kg/m2 for hospital admission 1·09 [95% CI 1·08-1·10] in 20-39 years age group vs 80-100 years group 1·01 [1·00-1·02]) and Black people than White people (1·07 [1·06-1·08] vs 1·04 [1·04-1·05]). The risk of admission to hospital and ICU due to COVID-19 associated with unit increase in BMI was slightly lower in people with type 2 diabetes, hypertension, and cardiovascular disease than in those without these morbidities. INTERPRETATION: At a BMI of more than 23 kg/m2, we found a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which is not attributable to excess risks of related diseases. The relative risk due to increasing BMI is particularly notable people younger than 40 years and of Black ethnicity. FUNDING: NIHR Oxford Biomedical Research Centre.

Exploring women's thoughts on self-weighing during pregnancy: results of the Self-Weighing in Pregnancy: Experiences (SWIPE) study.

BACKGROUND: Excess gestational weight gain is common and an important risk factor for adverse pregnancy outcomes. Regular weighing can be used to assess and manage weight gain, but NICE guidelines do not recommend routine weighing during antenatal care. Trials that have tested the effectiveness of self-weighing to manage GWG have been unsuccesful in engaging women in regular self-weighing, although the reasons for lack of engagement are not fully understood. This study aimed to understand why this lack of engagement occurred by exploring the naturally occurring thoughts and feelings of pregnant women (9 to 15 weeks gestational age) who were asked to weigh themselves at home. METHODS: Twenty-five women were recruited to take part. Participants completed short questionnaires at their first-trimester and 20-week scans. After recruitment, participants were asked to weigh themselves at roughly the same time each week for 8 weeks. Whilst they weighed themselves they were asked to audio-record their current weight and describe any thoughts or feelings that occurred as they weighed themselves. These audio recordings were then sent to researchers using a secure messaging service. RESULTS: Most of the recruited women (56%) were unaware of guidelines for gestational weight gain, and only 40% could identify the ideal rate of GWG for their BMI group. Thematic analysis of the think-aloud recordings resulted in three main themes: "understanding weight gain in pregnancy", "taking action to prevent weight gain" and "reactions to self-weighing". Overall, there was a relatively positive response to self-weighing and some participants used self-weighing to reflect on the reasons for weight gain and plan actions they could take to avoid excess gain. Negative emotional responses tended to be related to a lack of guidance about what level of weight gain or loss was "healthy", or to other worries about the pregnancy. Of the women recruited who submitted at least one think aloud recording (n 10), 80% found self-weighing to be useful, and said they would likely continue to self-weigh at home. CONCLUSIONS: Women had complex emotions about self-weighing during pregnancy but overall found it useful, suggesting it could be encouraged as part of self-regulatory interventions to control GWG. Clear guidelines about appropriate gestational weight gain could help to reduce anxiety. TRIAL REGISTRATION: The study was prospectively registered with ISRCTN ISRCTN10035244 .