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Early-Life Nutrition Interventions and Associated Long-Term Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Early-life nutrition interventions can have lifelong cardiometabolic benefits. Most evidence on this topic is derived from observational studies. We evaluated the association of randomized controlled nutritional trials in early life and long-term cardiometabolic outcomes. Through literature search of PubMed, CABI Global Health, Embase, and Cochrane, with manual reference check and weekly alert from PubMed, we identified 8312 records, and included 53 records from 40 cohorts in 21 countries. The total number of participants was 33,551. Interventions were initiated as early as conception, and the longest until 7 y (except 1 study from infancy to 20 y). The cohorts were followed up for between 3 and 73 y. We identified 7 types of interventions (protein-energy supplements, long-chain PUFAs, single micronutrient, multiple micronutrients, infant and young child feeding, dietary counseling, and other) and 4 categories of cardiometabolic outcomes (biomarkers, cardiovascular, body size and composition, and subclinical/clinical outcomes). Most findings were null. Fasting glucose concentration was 0.04 mmol/L lower (95% CI: -0.05, -0.02 mmol/L; I2 = 0%) in the intervention groups than in the control groups (15 studies). BMI (kg/m2) was 0.20 higher (95% CI: 0.12, 0.28; I2 = 54%) in the intervention groups than control groups (14 studies). No significant effect was observed for total cholesterol (12 studies) or blood pressure (17 studies). Ongoing and personalized dietary counseling was associated with lower glucose and cholesterol, better endothelial function, and reduced risk of metabolic syndrome. The timing of intervention mattered, with earlier initiation conferring greater benefit (improved lipid profile and marginally lower glucose concentration) based on 2 studies. In sum, glucose concentration was lower following early-life nutrition interventions, but there is a risk of unintended consequences, including higher BMI. Maternal and child nutrition interventions must be evidence-based and tailored to each population to promote long-term cardiometabolic health.

SUBMITTER: He S

PROVIDER: S-EPMC8009753 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSevere acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences.MethodsWe extracted genomic DNA from muscle biopsies obtained from adult survivors of kwashiorkor (n=21) or marasmus (n=23) and compared epigenetic profiles (CpG methylation) between the two groups using the Infinium® 450K BeadChip array.FindingsWe found significant differences in methylation of CpG sites from 63 genes in skeletal muscle DNA. Gene ontology studies showed significant differential methylation of genes in immune, body composition, metabolic, musculoskeletal growth, neuronal function and cardiovascular pathways, pathways compatible with the differences in the pathophysiology of adult survivors of SAM.InterpretationThese findings suggest persistent developmental influences on adult physiology in survivors of SAM. Since children who develop marasmus have lower birth weights and after rehabilitation have different intermediary metabolism, these studies provide further support for persistent developmentally-induced phenomena mediated by epigenetic processes affecting both the infant response to acute malnutrition and later life consequences.FundingSupported by a Grant from the Bill and Melinda Gates Foundation (Global Health OPP1066846), Grand Challenge "Discover New Ways to Achieve Healthy Growth."Evidence before this studyPrevious research has shown that infants who develop either kwashiorkor or marasmus in response to SAM differ in birth weight and subsequently have different metabolic patterns in both infancy and adulthood.Added value of this studyThis study demonstrates epigenetic differences in the skeletal muscle of adult survivors of marasmus versus kwashiorkor and these differences are in genes that may underlie the longer-term consequences.Implications of all the available evidenceThese data are compatible with the different clinical responses to SAM arising from developmentally-induced epigenetic changes laid down largely before birth and provide evidence for the predictive adaptive response model operating in human development.

Project description:BackgroundMobile health (mHealth) interventions can increase physical activity (PA); however, their long-term impact is not well understood.ObjectiveThe primary aim of this study is to understand the immediate and long-term effects of mHealth interventions on PA. The secondary aim is to explore potential effect moderators.MethodsWe performed this study according to the Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, the Cochrane Library, SCOPUS, and PsycINFO in July 2020. Eligible studies included randomized controlled trials of mHealth interventions targeting PA as a primary outcome in adults. Eligible outcome measures were walking, moderate-to-vigorous physical activity (MVPA), total physical activity (TPA), and energy expenditure. Where reported, we extracted data for 3 time points (ie, end of intervention, follow-up ≤6 months, and follow-up >6 months). To explore effect moderators, we performed subgroup analyses by population, intervention design, and control group type. Results were summarized using random effects meta-analysis. Risk of bias was assessed using the Cochrane Collaboration tool.ResultsOf the 2828 identified studies, 117 were included. These studies reported on 21,118 participants with a mean age of 52.03 (SD 14.14) years, of whom 58.99% (n=12,459) were female. mHealth interventions significantly increased PA across all the 4 outcome measures at the end of intervention (walking standardized mean difference [SMD] 0.46, 95% CI 0.36-0.55; P<.001; MVPA SMD 0.28, 95% CI 0.21-0.35; P<.001; TPA SMD 0.34, 95% CI 0.20-0.47; P<.001; energy expenditure SMD 0.44, 95% CI 0.13-0.75; P=.01). Only 33 studies reported short-term follow-up measurements, and 8 studies reported long-term follow-up measurements in addition to end-of-intervention results. In the short term, effects were sustained for walking (SMD 0.26, 95% CI 0.09-0.42; P=.002), MVPA (SMD 0.20, 95% CI 0.05-0.35; P=.008), and TPA (SMD 0.53, 95% CI 0.13-0.93; P=.009). In the long term, effects were also sustained for walking (SMD 0.25, 95% CI 0.10-0.39; P=.001) and MVPA (SMD 0.19, 95% CI 0.11-0.27; P<.001). We found the study population to be an effect moderator, with higher effect scores in sick and at-risk populations. PA was increased both in scalable and nonscalable mHealth intervention designs and regardless of the control group type. The risk of bias was rated high in 80.3% (94/117) of the studies. Heterogeneity was significant, resulting in low to very low quality of evidence.ConclusionsmHealth interventions can foster small to moderate increases in PA. The effects are maintained long term; however, the effect size decreases over time. The results encourage using mHealth interventions in at-risk and sick populations and support the use of scalable mHealth intervention designs to affordably reach large populations. However, given the low evidence quality, further methodologically rigorous studies are warranted to evaluate the long-term effects.

Project description:BackgroundNeoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.MethodsWe obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).FindingsPatients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45).InterpretationTumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.FundingCancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.

Project description:BackgroundTransition into menopause is associated with an increased risk of cardiovascular disease (CVD). However, it is unclear whether the association exists between premature menopause (defined as age at menopause 40 years) or early menopause (defined as age at menopause 40-45 years) and CVD or cardiovascular risk factors. The aim of this review was to comprehensively evaluate and meta-analyze the most reliable evidence about the relationship between menopausal age and the risk of long-term cardiometabolic disease.MethodsA comprehensive literature search of the PubMed, Web of Science, and Embase databases from inception to October 1, 2022, for titles and abstracts with a restriction to English language papers led to the discovery of the studies. Data are expressed as the Hazard Ratio (HR) with 95% confidence intervals (CI). The degree of heterogeneity was measured using the I-square (I 2) index.Results921,517 participants from 20 cohort studies published between 1998 and 2022 were considered. Compared to women with menopause at age >45 years, women with premature menopause (PM) or early menopause (EM) had a higher risks of type 2 diabetes (RR: 1.32, 95% CI: 1.08-1.62; RR: 1.11, 95% CI: 0.91-1.36, respectively), hyperlipidemia (RR: 1.21, 95% CI: 1.05-1.39; RR: 1.17, 95% CI: 1.02-1.33, respectively), coronary heart disease (RR: 1.52, 95% CI: 1.22-1.91; RR: 1.19, 95% CI: 1.07-1.32, respectively), stroke (RR: 1.27, 95% CI: 1.02-1.58; RR: 1.13, 95% CI: 0.97-1.32, respectively) and total cardiovascular event (RR: 1.36, 95% CI: 1.16-1.60; RR: 1.14, 95% CI: 0.97-1.35, respectively). No difference was found for hypertension in PM or EM women (RR: 0.98, 95% CI: 0.89-1.07; RR: 0.97, 95% CI: 0.91-1.04, respectively). Additionally, we also found that PM women, but not EM women, were linked with an increased risk of ischemic and hemorrhagic stroke. However, this is not in line with the conclusion that both PM and EM had a higher risk of total stroke.ConclusionWomen with PM or EM have a higher risk of developing long-term CVD, compared to women with menopause at age >45 years. Therefore, we recommend early lifestyle interventions (e.g., maintaining a healthy lifestyle) and medical treatments (e.g., timely initiation of menopausal hormone therapy) to decrease the risk of cardiometabolic disease in early or premature menopausal women.Systematic review registrationPROSPERO, identifier CRD42022378750.

Project description:BackgroundAdolescents in low- and middle-income countries in need of mental health care often do not receive it due to stigma, cost, and lack of mental health professionals. Culturally appropriate, brief, and low-cost interventions delivered by lay-providers can help overcome these barriers and appear effective at reducing symptoms of depression and anxiety until several months post-intervention. However, little is known about whether these interventions may have long-term effects on health, mental health, social, or academic outcomes.MethodsThree previous randomized controlled trials of the Shamiri intervention, a 4-week, group-delivered, lay-provider-led intervention, have been conducted in Kenyan high schools. Shamiri teaches positively focused intervention elements (i.e., growth mindset and strategies for growth, gratitude, and value affirmation) to target symptoms of depression and anxiety and to improve academic performance and social relationships, by fostering character strengths. In this long-term follow-up study, we will test whether these mental health, academic, social, and character-strength outcomes, along with related health outcomes (e.g., sleep quality, heart-rate variability and activity level measured via wearables, HIV risk behaviors, alcohol and substance use), differ between the intervention and control group at 3-4-year follow-up. For primary analyses (Nanticipated = 432), youths who participated in the three previous trials will be contacted again to assess whether outcomes at 3-4-year-follow-up differ for those in the Shamiri Intervention group compared to those in the study-skills active control group. Multi-level models will be used to model trajectories over time of primary outcomes and secondary outcomes that were collected in previous trials. For outcomes only collected at 3-4-year follow-up, tests of location difference (e.g., t-tests) will be used to assess group differences in metric outcomes and difference tests (e.g., odds ratios) will be used to assess differences in categorical outcomes. Finally, standardized effect sizes will be used to compare groups on all measures.DiscussionThis follow-up study of participants from three randomized controlled trials of the Shamiri intervention will provide evidence bearing on the long-term and health and mental health effects of brief, lay-provider-delivered character strength interventions for youth in low- and middle-income countries.Trial registrationPACTR Trial ID: PACTR202201600200783 . Approved on January 21, 2022.

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Early-Life Nutrition Interventions and Associated Long-Term Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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