Maternal 24-h movement patterns across pregnancy and postpartum: The LIFE-Moms consortium.

Objective: Time spent among the 24-h movement behaviors (physical activity [PA], sleep, sedentary behavior [SB]) in the perinatal period is important for maternal and child health. We described changes to 24-h movement behaviors and behavior guideline attainment during pregnancy and postpartum and identified correlates of behavior changes. Methods: This secondary data analysis included the standard of care group (n = 439) from the U.S.-based Lifestyle Interventions For Expectant Moms (LIFE-Moms) consortium, including persons with overweight and obesity. Wrist-worn accelerometry was used to measure movement behaviors early (9-15 weeks) and late (35-36 weeks) pregnancy, and âˆ¼ 1-year postpartum. Sleep and moderate-to-vigorous PA (MVPA) were compared to adult and pregnancy-specific guidelines, respectively. SB was classified into quartiles. PA and SB context were quantified using questionnaires. Mixed models were used to examine changes in behaviors and guidelines and identify correlates. Results: Participants were 31.3 ± 3.5 years, 53.5 % were Black or Hispanic, and 45.1 % had overweight. Sleep duration decreased across time, but participants consistently met the guideline (range: 85.0-93.6 %). SB increased during pregnancy and decreased postpartum, while light PA and MVPA followed the inverse pattern. Participants met slightly fewer guidelines late pregnancy (1.2 ± 0.7 guidelines) but more postpartum (1.7 ± 0.8 guidelines) than early pregnancy (1.4 ± 0.8 guidelines). Black or Hispanic race/ethnicity, higher pregravid body mass index, and non-day work-shift (e.g., night-shift) were identified correlates of lower guideline adherence and varying PA and SB context. Conclusion: Perinatal interventions should consider strategies to prevent SB increase and sustain MVPA to promote guideline adherence.

The Impact of Obesity on Reproductive Health and Metabolism in Reproductive Age Females.

Obesity is a highly prevalent chronic disease that impacts over 40% of reproductive-aged females. The pathophysiology of obesity is complex and can be understood simply as a chronic energy imbalance whereby caloric intake exceeds caloric expenditure with energy surplus stored in adipose tissue. Obesity may be categorized into degrees of severity as well as different phenotypes based on metabolic health and underlying pathophysiology. Obesity and excess adiposity have a significant impact on fertility and reproductive health with direct effects on the hypothalamic-pituitary-ovarian axis, the ovary/oocyte, and the endometrium. There are significant adverse pregnancy outcomes related to obesity and together with excess weight gain prior to, during, and after pregnancy, can alter lifelong risk for metabolically unhealthy obesity. Given the high-prevalence and pervasive impact of obesity on reproductive health, there is a need for better and individualized care for reproductive-aged females that considers obesity phenotype, underlying pathophysiology, and effective and sustainable interventions to treat obesity and manage weight gain prior to, during, and after pregnancy.

Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. METHODS: Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics (who, what, when, where, and how). Subgroup analysis was performed by intervention characteristics. RESULTS: 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p-value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p-value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. CONCLUSIONS: Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don't impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.

The effect of any given intervention to prevent gestational diabetes (high blood sugar levels that arise during pregnancy) may depend on the way it is delivered (how, when, what, etc). This study reviewed published literature to investigate if the effects of interventions (diet, exercise, metformin, probiotics, myoinositol) to prevent gestational diabetes differ according to the way it is being delivered (e.g., online vs in-person, by health professionals or others, etc.). Exercise delivered to group settings, or those delivered at a healthcare facility worked better to prevent gestational diabetes. Although we did not observe any differences with other delivery characteristics (e.g., online vs in-person), it does not mean they are always equally effective, it is important to consider individual situations when prescribing or developing interventions.

An algorithm to simulate missing data for mixed meal tolerance test response curves.

BACKGROUND: Response curves formed by analyte concentrations measured at sampled time points after consuming a mixed meal are increasingly being used to characterize responses to differing diets. Unfortunately, owing to a variety of reasons, analyte concentrations for some of the time points may be missing. OBJECTIVES: This study aimed to develop an algorithm to estimate the missing values at sampled time points in the analyte response curve to a mixed meal tolerance test (MMTT). METHODS: We developed an algorithm to simulate the missing postprandial concentration values for an MMTT. The algorithm was developed to handle any number of missing values for 2 or less consecutive missing values. The algorithm was tested on MMTT response curve data for glucose and triglyceride measurements in data from 3 different studies with 2119 postprandial MMTT response curves. The algorithm was validated by removing concentration values that were not missing and replacing them with the algorithm simulated values. The AUC error between the actual curve and simulated curves were also calculated. A web-based application was developed to automatically simulate missing values for an uploaded MMTT data set. RESULTS: The algorithm was programmed in Python and the resulting web-based application and a video tutorial were provided. The validation indicated good agreement between actual and simulated values with error increasing for less frequently sampled time points. The study with the average minimum error of glucose concentrations was 6.2 ± 2.1 mg/dL and study with the average maximum error of glucose concentrations was 11.3 ± 4.7 mg/dL. Triglycerides had 16.1 ± 6.2 mg/dL average error. The AUC error was small ranging between 0.01% and 0.28%. CONCLUSIONS: The presented algorithm reconstructs postprandial response curves with estimations of values that are missing.

Healthful Eating Behaviors among Couples Contribute to Lower Gestational Weight Gain.

Through longitudinal analysis from the GLOWING cohort study, we examined the independent and joint relationships between couples' eating behaviors and gestational weight gain (GWG). Pregnant persons (n = 218) and their non-pregnant partners (n = 157) completed an Eating Inventory. GWG was calculated as gestation weight at 36 weeks minus that at 10 weeks. General linear models were used to examine the relationships between GWG and the pregnant persons, non-pregnant partners, and couples (n = 137; mean of pregnant persons and non-pregnant partners) cognitive restraint (range 0-21), dietary disinhibition (range 0-18), and perceived hunger (range 0-14), with higher scores reflecting poorer eating behaviors. The adjusted models included race/ethnicity, education, income, marital status, and age. The pregnant persons and their non-pregnant partners' cognitive restraint, dietary disinhibition, and perceived hunger scores were 9.8 ± 4.7, 4.8 ± 3.2, and 4.4 ± 2.5 and 6.6 ± 4.6, 5.4 ± 3.4, and 4.7 ± 3.2, respectively. Higher cognitive restraint scores among the pregnant persons and couples were positively associated with GWG (p ≤ 0.04 for both). Stratified analyses revealed this was significant for the pregnant persons with overweight (p ≤ 0.04). The non-pregnant partners' eating behaviors alone were not significantly associated with GWG (p ≥ 0.31 for all). The other explored relationships between GWG and the couples' eating behaviors were insignificant (p ≥ 0.12 for all). Among the pregnant persons and couples, reduced GWG may be achieved with higher levels of restrained eating. Involving non-pregnant partners in programs to optimize GWG may be beneficial.

Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis.

Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m2 ), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL) and a published DNA-methylation algorithm (DNAmTL). Intent-to-treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect-of-Treatment-on-the-Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12-month weight-loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24-months, leaving it unclear whether CR-related effects reflect long-term detriments to telomere fidelity, a hormesis-like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials.

Human Milk Components and the Infant Gut Microbiome at 6 Months: Understanding the Interconnected Relationship.

BACKGROUND: Human milk oligosaccharides have been shown to relate to the infant gut microbiome. However, the impact of other human milk components on infant gut bacterial colonization remains unexplored. OBJECTIVES: Our cross-sectional analysis aimed to investigate associations between human milk components (energy, macronutrients, free amino acids, inflammatory markers, and hormones) and infant gut microbiome diversity and composition (phylum, family, and genus) at 6 mo of age. METHODS: Human milk and infant stool samples were collected at 6 mo postpartum. The infant gut microbiome was profiled using 16S rRNA sequencing. Linear regression models were performed to examine associations, adjusting for pregravid BMI (kg/m2), delivery mode, duration of human milk feeding, and infant sex, with q < 0.2 considered significant. RESULTS: This analysis included a total of 54 mothers (100% exclusively feeding human milk) and infants (n = 28 male; 51.9%). Total energy in human milk showed a negative association with α-diversity measures (Chao1 and Shannon). Interleukin (IL)-8 in human milk was positively associated with Chao1 and observed operational taxonomic units. At the family level, human milk glutamine and serine levels showed a negative association with the abundance of Veillonellaceae, whereas isoleucine showed a positive association with Bacteroidaceae. Human milk IL-8 and IL-6 concentrations were positively associated with Bacteroidaceae abundance. IL-8 also had a positive relationship with Bifidobacteriaceae, whereas it had a negative relationship with Streptococcacea and Clostridiaceae. Human milk IL-8 was positively associated with the phylum Bacteroidetes, and negatively associated with Proteobacteria. At the genus level, human milk IL-8 exhibited a positive relationship with Bacteroides, whereas human milk isoleucine had a negative relationship with Bacteroides and Ruminococcus. Pregravid BMI and sex effects were observed. CONCLUSIONS: IL-8 in human milk could potentially prepare the infant's immune system to respond effectively to various microorganisms, potentially promoting the growth of beneficial gut bacteria and protecting against pathogens.

Influence of Food Security Status and Diet Quality on Maternal Gestational Weight Gain.

BACKGROUND: Recommended gestational weight gain (GWG) is crucial for health of women and their offspring. Food security status is hypothesized to influence diet quality and GWG. Therefore, we examined the relationship between diet quality and GWG by food security status. METHODS: Participants (n = 679) were enrolled in the Initial Vanguard Study of the National Children's Study. GWG was calculated as third trimester weight minus prepregnancy weight. Food security status and diet quality (Healthy Eating Index [HEI]-2015) were assessed using the Household Food Security Survey and a Diet History Questionnaire, respectively. General linear models evaluated the relationship between GWG and HEI-2015 by food security status. RESULTS: A greater proportion of women experienced food security (81.3%) compared with food insecurity (18.7%). In women with food security, GWG was negatively associated with HEI-2015 in women having overweight (r = -0.421, P = .003) and positively associated with HEI-2015 in women with inadequate GWG (r = 0.224, P = .019). Conversely, no significant relationships were found between GWG and HEI-2015 in women with food insecurity. DISCUSSION: Improved diet quality potentially lowers GWG in women with food security. However, in vulnerable populations, including women with food insecurity, improvements in diet quality may not effectively enhance GWG.

Proportion of caloric restriction-induced weight loss as skeletal muscle.

OBJECTIVE: This study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples. METHODS: The model development group included healthy nonexercising adults (n = 897) who had whole-body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26). RESULTS: A series of SM prediction models were developed in a sample of 415 males and 482 females. Model-predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model-predicted values. CONCLUSIONS: Nonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10-kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing.

Calorie restriction reduces biomarkers of cellular senescence in humans.

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA-IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA-sequencing data from a subset of participants, we observed a significant reduction in a senescence-focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health.

Co-designing a community lifestyle intervention program to reduce postpartum weight retention.

BACKGROUND: Postpartum weight retention is a major contributor to obesity in later life resulting in long-term health consequences in women. Postpartum lifestyle interventions are known to be effective in reducing postpartum weight retention and improving the overall health and wellbeing of mothers but have poor reach and engagement. This study describes the engagement of mothers with young children in the development of a theory- and evidence-based intervention to reduce postpartum weight retention. METHODS: A participatory design methodology with input from a community mothers' group, literature reviews and an expert advisory group was applied. Mothers who were members of 'Mothers of Preschoolers' (MOPS) were invited to participate in a focus group discussion and two co-design workshop sessions. RESULTS: Thirteen women participated in a focus group discussion and 12 women in each co-design workshop. We found that mothers valued having social support from their peers, practical support such as meal delivery, and learning opportunities that focus on the mother's health and wellbeing. The advisory group suggested leveraging the unique skills and prior experiences of mothers within the group and developing a curriculum that mothers can be trained to deliver. CONCLUSION: A program that emphasizes the strengths and value of mothers can increase their self-worth and self-confidence resulting in intrinsic motivation to improve lifestyle behaviours. An intervention designed to be implemented by MOPS for its members and incorporated into their regular sessions has the potential for feasibility and acceptability among mothers with young children. PATIENT OR PUBLIC CONTRIBUTION: Mothers with young children were part of the program planners and were involved in the design and conduct of this study and in the interpretation of the findings. A member of a community mothers' group recruited other mothers with young children within the group to participate in a series of sessions to discuss their experiences of the postpartum period and preferences for a lifestyle program. The mothers identified the behavioural outcomes and program goals for a postpartum lifestyle program and then generated the program ideas based on these.

Access, Interest, and Barriers to Incorporation of Birth Doula Care in the United States.

Doula care improves maternal care, yet barriers exist to incorporating doula care. The purpose of this study was to evaluate interest and barriers to doula care. Overall, 508 women, 26-35 years of age (54.5%), White/Caucasian (89.8%), and married (88.6%), completed this study. Most reported ≥1 previous birth (97.6%). Respondents would "feel comfortable" (73.2%) and "more confident" (54.9%) with doula care at birth, and 57.9% reported their provider would be supportive of doula care. Only 39.0% expressed benefits to doula care during pregnancy compared to 72.6% at birth and 68.1% during postpartum. Most would hire a doula if health insurance covered some of the costs. Despite the recognized benefits and support of doula care, cost-associated barriers exist to the incorporation of doula care.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

Impact of a Nutrient Formulation on Longitudinal Myelination, Cognition, and Behavior from Birth to 2 Years: A Randomized Clinical Trial.

Observation studies suggest differences in myelination in relation to differences in early life nutrition. This two-center randomized controlled trial investigates the effect of a 12-month nutritional intervention on longitudinal changes in myelination, cognition, and behavior. Eighty-one full-term, neurotypical infants were randomized into an investigational (N = 42) or a control group (N = 39), receiving higher versus lower levels of a blend of nutrients. Non-randomized breastfed infants (N = 108) served as a reference group. Main outcomes were myelination (MRI), neurodevelopment (Bayley-III), social-emotional development (ASQ:SE-2), infant and toddler behavior (IBQ-R and TBAQ), and infant sleep (BISQ) during the first 2 years of life. The full analysis set comprised N = 67 infants from the randomized groups, with 81 myelin-sensitive MRI sequences. Significantly higher myelination was observed in the investigational compared to the control group at 6, 12, 18, and 24 months of life, as well as significantly higher gray matter volume at 24 months, a reduced number of night awakenings at 6 months, increased day sleep at 12 months, and reduced social fearfulness at 24 months. The results suggest that brain development may be modifiable with brain- and age-relevant nutritional approaches in healthy infants and young children, which may be foundational for later learning outcomes.

Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.

The lifespan extension induced by 40% caloric restriction (CR) in rodents is accompanied by postponement of disease, preservation of function, and increased stress resistance. Whether CR elicits the same physiological and molecular responses in humans remains mostly unexplored. In the CALERIE study, 12% CR for 2 years in healthy humans induced minor losses of muscle mass (leg lean mass) without changes of muscle strength, but mechanisms for muscle quality preservation remained unclear. We performed high-depth RNA-Seq (387-618 million paired reads) on human vastus lateralis muscle biopsies collected from the CALERIE participants at baseline, 12- and 24-month follow-up from the 90 CALERIE participants randomized to CR and "ad libitum" control. Using linear mixed effect model, we identified protein-coding genes and splicing variants whose expression was significantly changed in the CR group compared to controls, including genes related to proteostasis, circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing/splicing, FOXO3 metabolism, apoptosis, and inflammation. Changes in some of these biological pathways mediated part of the positive effect of CR on muscle quality. Differentially expressed splicing variants were associated with change in pathways shown to be affected by CR in model organisms. Two years of sustained CR in humans positively affected skeletal muscle quality, and impacted gene expression and splicing profiles of biological pathways affected by CR in model organisms, suggesting that attainable levels of CR in a lifestyle intervention can benefit muscle health in humans.

Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis.

BACKGROUND: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. METHODS: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. RESULTS: From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. CONCLUSIONS: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

An individual's characteristics, such as medical, biochemical, social, and behavioural may affect their response to interventions aimed at preventing gestational diabetes, which occurs during pregnancy. Here, we evaluated the published literature on interventions such as diet, lifestyle, drug treatment and nutritional supplement and looked at which individual participant characteristics were associated with response to these interventions. Certain participant characteristics were associated with greater prevention of gestational diabetes through particular treatments. Some interventions were more effective when started prior to conception. Future studies should consider individual characteristics when assessing the effects of preventative measures.

"Weight loss is my goal and being healthy is my goal I can get over the hot flashes": a qualitative exploration of menopausal transition experiences and preferences for weight management among White women.

OBJECTIVES: A qualitative research study design was used to (1) describe experiences of White women during the menopausal transition, and (2) identify barriers and facilitators for participating in a lifestyle program targeting weight management. METHODS: Perimenopausal and postmenopausal White women who self-reported a desire to lose or maintain weight participated in focus groups. Women were queried about their past diet, exercise, and weight management practices; menopausal transition; and specific components and considerations for developing a lifestyle program for weight management. Thematic analysis was conducted on coded transcripts and four main themes emerged, each containing three to six subthemes. RESULTS: Twenty-eight White women (age 54 ± 3 y, body mass index 31.4 ± 9.5 kg/m 2 ) were enrolled. Overall, women felt menopause was a major life event that coincided with weight gain and frustrating body changes. Women already engaged in many different types of exercises and diets to lose weight. Women also talked to healthcare professionals about menopause but were disappointed in the support they received. Women were interested in a lifestyle program that included menopause-specific education, which focused on results beyond weight, which was flexible to their busy lifestyle, and which provided opportunities to build camaraderie among other women experiencing menopause. CONCLUSIONS: This cohort of White women were interested in receiving menopause information and improving their overall health as part of a lifestyle program targeting weight management during this transition. Building camaraderie with other women affected by menopause is important to women, as is creating a lifestyle program that is flexible with daily life.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/ MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

STUDY QUESTION: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? SUMMARY ANSWER: International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. WHAT IS KNOWN ALREADY: The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. STUDY DESIGN, SIZE, DURATION: The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. WIDER IMPLICATIONS OF THE FINDINGS: The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.