Codesign and Launch of 'On the Ball': An Inclusive Community-Based 'Testicular Awareness' Campaign.

INTRODUCTION: Increased awareness of testicular diseases can lead to early diagnosis. Evidence suggests that men's awareness of testicular diseases is low, with many expressing their willingness to delay help-seeking for symptoms of concern. The risk of testicular diseases is higher in gender and sexual minority groups. In this study, we discuss the codesign, refinement and launch of 'On the Ball', an inclusive community-based 'testicular awareness' campaign. METHODS: The World Café participatory research methodology was used. Individuals from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, policymakers, media/marketing experts and graphic designers were recruited. Participants were handed a brief for 'On the Ball', which was designed based on feedback from a previous World Café workshop. They were assigned to three tables. Participants rotated tables at random for three 20-min rounds of conversations. Each table had a facilitator who focussed on one element of the campaign brief. Data were collected using audio recorders and in writing and were analysed thematically. RESULTS: Thirteen individuals participated in the workshop. The following themes emerged from the data: (i) campaign identity, (ii) campaign delivery and (iii) campaign impact. Participants recommended enhancements to the campaign logo, slogan, social media posts and poster. They suggested delivering the campaign online via social media and offline using various print and broadcast media. Participants recommended targeting areas with a large number of men such as workplaces. To help measure the impact of the campaign, participants proposed capturing social media analytics and tracking statistics relating to testicular diseases. Recommendations were used to refine the 'On the Ball' campaign and launch it in a university. In total, 411 students engaged with the various elements of the campaign during the soft launch. CONCLUSIONS: 'On the Ball' campaign visuals ought to be inclusive. Online and offline campaign delivery is warranted to reach out to a wider cohort. Campaign impact can be captured using social media analytics as well as measuring clinical outcomes relating to testicular diseases. Future research is needed to implement the campaign online and offline, explore its impact and evaluate its feasibility, acceptability, cost and effect on promoting testicular awareness. PATIENT OR PUBLIC CONTRIBUTION: The 'On the Ball' campaign was codesigned and refined with members of Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policymakers, media and marketing experts and graphic designers using the World Café participatory research methodology.

Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity.

This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.

Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95 % CI: -39, -27), Asian (% difference = -43; 95 % CI: -51, -35) and other non-White (% difference = -26; 95 % CI: -35, -14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

General practitioners' experiences of providing lifestyle advice to patients with depression: A qualitative focus group study.

OBJECTIVE: Depression is an increasingly common mental health disorder in the UK, managed predominantly in the community by GPs. Emerging evidence suggests lifestyle medicine is a key component in the management of depression. We aimed to explore GPs' experiences, attitudes, and challenges to providing lifestyle advice to patients with depression. METHOD: Focus groups were conducted virtually with UK GPs (May-July 2022). A topic guide facilitated the discussion and included questions on experiences, current practices, competence, challenges, and service provision. Data were analysed using template analysis. RESULTS: 'Supporting Effective Conversations'; 'Willing, but Blocked from Establishing Relational Care'; 'Working Towards Patient Empowerment'; and 'Control Over the Prognosis' were all elements of how individualised lifestyle advice was key to the management of depression. Establishing a doctor-patient relationship by building trust and rapport was fundamental to having effective conversations about lifestyle behaviours. Empowering patients to make positive lifestyle changes required tailoring advice using a patient-centred approach. Confidence varied across participants, depending on education, experience, type of patient, and severity of depression. CONCLUSIONS: GPs play an important role in managing depression using lifestyle medicine and a patient-centred approach. Organisational and educational changes are necessary to facilitate GPs in providing optimal care to patients with depression.

Interventions in preconception and pregnant women at risk of gestational diabetes; a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. OBJECTIVE: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. METHODS: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. RESULTS: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference - 0.03, 95% CI 0.06, - 0.01; I2 58.69%), inositol (risk difference - 0.19, 95% CI 0.33, - 0.06; I2 92.19%), and vitamin D supplements (risk difference - 0.16, 95% CI 0.25, - 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference - 0.16, 95% CI 0.25, - 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference - 0.17, 95% CI 0.22, - 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. CONCLUSIONS: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted.

Promoting 'testicular awareness': Co-design of an inclusive campaign using the World Café Methodology.

INTRODUCTION: Testicular cancer is the most common cancer in men aged 15-44 years in many countries. Most men with testicular cancer present with a lump. Testicular symptoms are more likely to occur secondary to benign diseases like epididymo-orchitis, a common sexually transmitted infection. Gender and sexual minorities are at an increased risk of testicular diseases and health disparities. The aim of this study was to co-design an inclusive community-based campaign to promote testicular awareness. METHODS: This study uses the World Café methodology. Participation was sought from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers. Participants engaged in three rounds of conversations to co-design the campaign. Data were collected using drawing sheets, artefact cards, sticky notes, coloured markers and a voice recorder. Deductive thematic analysis was conducted. RESULTS: Seventeen individuals participated in the study. Six themes emerged from the analysis as follows: (i) online communication; (ii) offline communication; (iii) behavioural targeting and education; (iv) campaign frequency and reach; (v) demographic segmentation; and (vi) campaign identity. The use of social media for campaign delivery featured strongly in all conversations. Participants also recommended offline communication using posters and radio/television advertisements to scale up the campaign and achieve wider reach. Advertisements to overcome embarrassment surrounding testicular health were particularly recommended. Participants emphasised that campaign delivery must be dynamic whilst ensuring that the health-promoting messages are not diluted or lost. They stressed the importance of being inclusive and tailoring the campaign to different age groups, gender identities and sexual orientations. CONCLUSIONS: Study recommendations will be used to design and deliver the campaign. Future research will be needed to evaluate the feasibility, acceptability, cost and effect of the campaign on promoting testicular awareness and early detection of testicular diseases. PATIENT OR PUBLIC CONTRIBUTION: A participatory research approach was used to co-design the campaign with members of Lesbian, Gay, Bisexual, Transgender and Queer+ (LGBTQ+) friendly organisations, LGBTQ+ student bodies, LGBTQ+ staff networks, LGBTQ+ sports clubs, men's health organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers.

Maternal Obesity and Patterns in Postnatal Diet, Physical Activity and Weight among a Highly Deprived Population in the UK: The GLOWING Pilot Trial.

Preconception obesity is associated with adverse pregnancy outcomes and deprivation. The postnatal period provides an opportunity for preconception intervention. There is a lack of published postnatal behaviour and weight data to inform intervention needs. Secondary analysis of the GLOWING study explored postnatal diet, physical activity (PA) and weight among women living with obesity in deprivation. Thirty-nine women completed food frequency and PA questionnaires and provided weight measurement(s) between 3-12 months postnatal. Women's diet and PA fell short of national guidelines, especially for fruit/vegetables (median 1.6-2.0 portions/day) and oily fish (0-4 g/day). PA was predominantly light intensity. Patterns in weight change across time points indicated postnatal weight loss compared with 1st (median -0.8 to -2.3 kg) and 3rd-trimester weights (-9.0 to -11.6 kg). Weight loss was higher among women without excessive gestational weight gain (GWG) (-2.7 to -9.7 kg) than those with excessive GWG (2.3 to -1.8 kg), resulting in postnatal weight measurements lower than their 1st trimester. These pilot data suggest preconception interventions should commence in pregnancy with a focus on GWG, and postnatal women need early support to achieve guideline-recommendations for diet and PA. Further research in a larger population could inform preconception intervention strategies to tackle inequalities in maternal obesity and subsequent pregnancy outcomes.

Family members' perspectives of hope when supporting a relative experiencing mental health problems.

Current research views hope as a process that plays a positive role in the recovery of individuals with mental health problems. However, little attention has been given to the role of hope in the lives of their families. We aimed to address that gap. We deployed a qualitative descriptive design and carried out individual interviews with nine family members who supported a relative with mental health problems. A cross-comparison of the data generated three major themes: understandings of hope; factors that diminish hope and factors that nurture hope. The participants viewed hope as a positive and productive feeling or attitude that was life-affirming, and empowering. They also associated it with behaviours and dispositions such as attentiveness and empathy and the possibility of a return to a more stable and 'normal' life. The participants experienced hope as initially eroded when their relative was first diagnosed and institutionalized. Hope was further diminished due to the poor communication practices of some mental health professionals and the stress of the caring role itself. On the other hand, hope was nurtured through the support of other family members, friends, neighbours and peers. Acquiring knowledge and understanding about the relative's state of mental health nurtured hope and enabled the participants to have a more meaningful role in their recovery process. Practices of self-care such as independent activities and counselling also strengthened hope and some mental health professionals played a positive role in supporting these. Most striking about the reports of many of the participants was their assertion of their abiding love for their relative. Their account of their ability to see beyond the illness of their relative was an insight that we did not find in other accounts of the experiences of family members. We highlight the need for family members to have timely access to relevant information about their relatives' illness. We conclude that hope is relational at its core because of the interplay of intrapersonal, interpersonal and social factors that diminish or nurture it over time. Specifically, we propose that friends, neighbours and peer support groups as key actors in nurturing the hope of both family members and their relatives.

Interventions to enhance pre-pregnancy care for women with type 2 diabetes: A systematic review of the literature.

AIMS: The aim of the study was to examine the content and impact of interventions that have been used to increase the uptake of pre-pregnancy care for women with type 2 diabetes, and their impact on maternal and fetal outcomes. METHODS: A systematic search of multiple databases was conducted in November 2021, and updated July 2022, to identify studies assessing interventions to enhance pre-pregnancy care for women with type 2 diabetes. Over 10% of articles were screened by two reviewers at title and abstract phase, after which all selected full-text articles were screened by two reviewers. Quality assessment was conducted using the Critical Appraisal Skills Programme checklist for cohort studies. Meta-analysis was not possible due to study heterogeneity; therefore, narrative synthesis was conducted. RESULTS: Four eligible cohort studies were identified. The conclusions able to be drawn by this review were limited as women with type 2 diabetes (n = 800) were in the minority in all four studies (35%-40%) and none of the interventions were exclusively tailored for them. The uptake of pre-pregnancy care was lower in women with type 2 diabetes (8%-10%) compared with other participant groups in the studies. Pregnancy preparation indicators generally improved among all groups exposed to pre-pregnancy care, with varying impact on pregnancy outcomes. CONCLUSIONS: This review demonstrates that previous interventions have had a limited impact on pre-pregnancy care uptake in women with type 2 diabetes. Future studies should focus on tailored interventions for improving pre-pregnancy care for women with type 2 diabetes, particularly those from ethnic minorities and living in poorer communities.

Effects of Non-Essential "Toxic" Trace Elements on Pregnancy Outcomes: A Narrative Overview of Recent Literature Syntheses.

Adverse pregnancy outcomes and their complications cause increased maternal and neonatal morbidity and mortality and contribute considerably to the global burden of disease. In the last two decades, numerous narrative and systematic reviews have emerged assessing non-essential, potentially harmful, trace element exposure as a potential risk factor. This narrative review summarizes the recent literature covering associations between exposure to cadmium, lead, arsenic, and mercury and pregnancy outcomes and highlights common limitations of existing evidence that may hinder decision-making within public health. Several initial scoping searches informed our review, and we searched PubMed (latest date July 2022) for the literature published within the last five years reporting on cadmium, lead, arsenic, or mercury and pre-eclampsia, preterm birth, or prenatal growth. Pre-eclampsia may be associated with cadmium and strongly associated with lead exposure, and exposure to these metals may increase risk of preterm birth. Many reviews have observed cadmium to be negatively associated with birth weight. Additionally, lead and arsenic exposure may be negatively associated with birth weight, with arsenic exposure also adversely affecting birth length and head circumference. These findings should be interpreted with caution due to the limitations of the reviews summarized in this paper, including high heterogeneity due to different exposure assessment methods, study designs, and timing of sampling. Other common limitations were the low quality of the included studies, differences in confounding variables, the low number of studies, and small sample sizes.

Longitudinal dietary trajectories from pregnancy to 3 years post delivery in women with obesity: relationships with adiposity.

OBJECTIVE: The study aim was to examine the relationships between longitudinal dietary trajectories from early pregnancy to 3 years post delivery and adiposity measures in women with obesity. METHODS: The diets of 1208 women with obesity in the UPBEAT (UK Pregnancy Better Eating and Activity Trial) study were assessed using a food frequency questionnaire (FFQ) at 15+0 to 18+6 weeks' gestation (baseline), 27+0 to 28+6 weeks' gestation, and 34+0 to 36+0 weeks' gestation, as well as 6 months and 3 years post delivery. Using factor analysis of the baseline FFQ data, four dietary patterns were identified: fruit & vegetable, African/Caribbean, processed, and snacking. The baseline scoring system was applied to the FFQ data at the four subsequent time points. Group-based trajectory modeling was used to extract longitudinal dietary pattern trajectories. Using adjusted regression, associations between dietary trajectories and log-transformed/standardized adiposity measures (BMI and waist and mid-upper arm circumferences) at 3 years post delivery were examined. RESULTS: Two trajectories were found to best describe the data for the four individual dietary patterns; these were characterized as high and low adherence. A high adherence to the processed pattern was associated with a higher BMI (ß = 0.38 [95% CI: 0.06-0.69]) and higher waist (ß = 0.35 [0.03-0.67]) and mid-upper arm circumferences (ß = 0.36 [0.04-0.67]) at 3 years post delivery. CONCLUSIONS: In women with obesity, a processed dietary pattern across pregnancy and 3 years post delivery is associated with higher adiposity.

The physical-mental health interface in the preconception period: analysis of 131 182 women planning pregnancy in the UK.

OBJECTIVE: The physical and mental health of women prior to conception can have a significant impact on pregnancy and child outcomes. Given the rising burden of non-communicable diseases, the aim was to explore the relation between mental health, physical health and health behaviour in women planning a pregnancy. METHODS: Cross-sectional analysis of responses from 131 182 women to a preconception health digital education tool, providing data on physical and mental health and health behaviour. Logistic regression was used to explore associations between mental health and physical health variables. RESULTS: Physical health conditions were reported by 13.1% and mental health conditions by 17.8%. There was evidence for an association between self-reported physical and mental health conditions (odds ratio [OR] 2.22, 95% CI 2.14-2.3). Those with a mental health condition were less likely to engage with healthy behaviour at preconception such as folate supplementation (OR 0.89, 95% CI 0.86-0.92) and consumption of the recommended amount of fruit and vegetables (OR 0.77, 95% CI 0.74-0.79). They were more likely to be physically inactive (OR 1.14, 95% CI 1.11-1.18), smoke tobacco (OR 1.72, 95% CI 1.66-1.78) and use illicit substances (OR 2.4, 95% CI 2.25-2.55). CONCLUSIONS: Greater recognition of mental and physical comorbidities is needed and closer integration of physical and mental healthcare in the preconception period, which could support people to optimise their health during this time and improve long-term outcomes.

Pre-pregnancy health of women with pre-existing diabetes or previous gestational diabetes: Analysis of pregnancy risk factors and behavioural data from a digital tool.

AIMS: To examine health behaviours and risk factors in women with pre-existing diabetes or previous gestational diabetes mellitus who are planning pregnancy. METHODS: Health behaviour, risk factor and demographic data obtained from a digital pregnancy planning advisory tool (Tommy's charity UK) were analysed. Descriptive statistical analysis was performed, stratified by diabetes type. RESULTS: Data from 84,359 women, including 668 with type 1 diabetes, 707 with type 2 diabetes and 1785 with previous gestational diabetes obtained over a 12-month period (September 2019-September 2020) were analysed. 65%, 95%CI (61,68%) of women with type 2 diabetes and 46%, 95%CI (43,48%) with previous gestational diabetes were obese (BMI ≥30 kg/m2 ), compared with 26%, 95%CI (26,26%) without diabetes. Use of folic acid supplements was low; 41%, 95%CI (40,41%) of women without diabetes and 42%, 95%CI (40,45%) with previous gestational diabetes reported taking folic acid (any dose) while 47%, 95%CI (43.50%) women with type 1 diabetes and 44%, 95%CI (40,47%) women with type 2 diabetes respectively reported taking the recommended dose (5 mg). More women with type 1 diabetes and type 2 diabetes reported smoking (20%, 95%CI [17,23%] and 23%, 95%CI [20,26%] respectively) and taking illicit/recreational drugs (7%, 95%CI [6,10%] and 9%, 95% CI [7,11%]) compared to women without diabetes (smoking 17%, 95% CI [16,17%], drug use 5%, 95%CI [5,5%]). Alcohol consumption, low levels of physical activity and of fruit and vegetable intake were also evident. CONCLUSIONS: This study highlights the potential of online pregnancy planning advisory tools to reach high-risk women and emphasises the need to improve pre-pregnancy care for women with pre-existing diabetes and previous gestational diabetes, many of whom are actively seeking advice. It is also the first to describe pre-pregnancy health behaviours in women with previous gestational diabetes.

'People still want a face and that's where we can fill in': a qualitative study of community pharmacists' experiences of providing healthcare advice about preconception and pregnancy.

OBJECTIVES: This study aimed to explore community pharmacists' practices and attitudes towards the provision of healthcare advice regarding preconception and pregnancy. METHODS: A qualitative focus group study was conducted virtually with community pharmacists around urban areas of London in October 2021. A topic guide was utilised to cover pharmacy practice, barriers and confidence in counselling women, education and training and thoughts on how to improve preconception and pregnancy health services. Focus groups were transcribed and analysed using thematic analysis. KEY FINDINGS: Eleven community pharmacists participated. Three themes were identified: 'Community Driven Needs'; 'Needs of Community Pharmacists'; 'Shared Needs and Understanding' which were related through a central organising concept of 'Unmet Needs in Pharmacy-led Preconception and Pregnancy Care'. Community pharmacists are frequently consulted by women before and during pregnancy, however, a discord was uncovered between current pharmacy practice and the needs of the community. A clear need was identified for the incorporation of risk minimisation counselling focusing on smoking, alcohol intake and drug use. Education and organisational factors were reported as challenges to providing advice. CONCLUSIONS: Community pharmacists can play a pivotal role in providing information and support to women before and during pregnancy. Our findings suggest integration of community pharmacy-led structured counselling may be a useful public health strategy to optimise pregnancy health. Our work highlights educational and organisational barriers which hinder the ability of pharmacists to promote preconception and pregnancy health. These must be addressed, and we provide recommendations for change to both policy and practice.

"There's very little that you can do other than refer them to the doctor if you think they've got postnatal depression": Scoping the potential for perinatal mental health care by community pharmacists.

BACKGROUND: Twenty percent of women in the UK develop perinatal mental health (PMH) problems, which have widespread effects on maternal and child health. Community pharmacists are ideally placed to identify PMH problems and refer to other trained healthcare professionals. OBJECTIVE: This study explored community pharmacists' attitudes, current counselling practices, and barriers to providing mental health advice to perinatal women. METHODS: A qualitative focus group study was performed virtually with community pharmacists (n = 11), working in urban settings across London. A topic guide was used to cover current counselling practice, barriers to and confidence in counselling women, and thoughts on potential pharmacist-led perinatal mental health services. The focus groups were recorded, transcribed, and analysed using thematic analysis. RESULTS: Three themes were identified: Doing Mental Health Care; Willing, but Unable; and Introspection and reflection, which were related through a central organising concept of 'Perinatal mental health care as a new frontier for community pharmacy'. It was found that while community pharmacists provide mental health advice to perinatal women and their partners, they lacked confidence, which was related to a lack of knowledge and inadequate training opportunities. Organisational barriers were identified including a lack of a formal referral pathway to existing mental health services and other trained healthcare professionals. Perceptions of opportunities and recommendations for service improvement and change were also garnered. CONCLUSION: This study demonstrates community pharmacists have a potential role within community mental healthcare in identification of PMH problems and providing appropriate advice and support. Upskilling community pharmacists in mental health should be considered to increase knowledge and confidence while formal referral pathways to other trained healthcare professionals and existing services should be established and made available to pharmacists.

Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Pre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia. METHODS: A systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women. RESULTS: Twenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, -0.15 (-0.27, -0.03, I2 = 83.4%)), and vitamin D (risk difference, -0.09 (-0.17, -0.02, I2 = 0.0%)) supplementation. CONCLUSION: Our findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women.

Metabolic Profiling of Pregnant Women with Obesity: An Exploratory Study in Women at Greater Risk of Gestational Diabetes.

Gestational diabetes mellitus (GDM) is one of the most prevalent obstetric conditions, particularly among women with obesity. Pathways to hyperglycaemia remain obscure and a better understanding of the pathophysiology would facilitate early detection and targeted intervention. Among obese women from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we aimed to compare metabolic profiles early and mid-pregnancy in women identified as high-risk of developing GDM, stratified by GDM diagnosis. Using a GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c, 231 women were identified as being at higher-risk, of whom 119 women developed GDM. Analyte data (nuclear magnetic resonance and conventional) were compared between higher-risk women who developed GDM and those who did not at timepoint 1 (15+0−18+6 weeks) and at timepoint 2 (23+2−30+0 weeks). The adjusted regression analyses revealed some differences in the early second trimester between those who developed GDM and those who did not, including lower adiponectin and glutamine concentrations, and higher C-peptide concentrations (FDR-adjusted p < 0.005, < 0.05, < 0.05 respectively). More differences were evident at the time of GDM diagnosis (timepoint 2) including greater impairment in ß-cell function (as assessed by HOMA2-%B), an increase in the glycolysis-intermediate pyruvate (FDR-adjusted p < 0.001, < 0.05 respectively) and differing lipid profiles. The liver function marker γ-glutamyl transferase was higher at both timepoints (FDR-adjusted p < 0.05). This exploratory study underlines the difficulty in early prediction of GDM development in high-risk women but adds to the evidence that among pregnant women with obesity, insulin secretory dysfunction may be an important discriminator for those who develop GDM.

Longitudinal phenotyping of maternal antenatal depression in obese pregnant women supports multiple-hit hypothesis for fetal brain development, a secondary analysis of the UPBEAT study.

Background: Maternal antenatal depression is associated with offspring psychological disorders, but obesity is also widely implicated in maternal depression and neurodevelopment. In pregnant women with obesity we explored interrelationships between antenatal depressive symptom trajectories and multiple exposures implicated in fetal neurodevelopment which could explain these associations, as a prelude to exploring associations with infant mental health. Methods: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) recruited multi-ethnic pregnant women with obesity (BMI >= 30kg/m2) between March 2009 and June 2014 from 8 UK sites and 1369 were included to model longitudinal antenatal depressive symptoms from Edinburgh Postnatal Depression Scale (EPDS) scores using Latent Class Growth Analysis. Classes were compared on maternal baseline demography, biomarkers of metabolism, inflammation and placental function, infection, diet and by pregnancy and birth outcomes. Odds ratios, mean differences and 95% Confidence Intervals were calculated using robust auxiliary modelling techniques. Findings: The chosen model produced four classes: "Not Depressed" (n=575 [42%], "reference"), "Mild" (n=523 [37·5%]), "Moderate" (n=219 [16%]) and "Severe" (n=62 [4·5%]) symptom trajectories. Socio-economic deprivation and ethnic diversity were greater in Severe and Moderate classes. Dietary glycaemic load and saturated fat intake were higher in Severe and Moderate classes (at 17 and 27 weeks). Higher Interleukin-6, glycoprotein acetyls (17 weeks), glucose (34 weeks) and lower placental growth factor (PlGF, 17 and 27 weeks) was found in the Severe class. PlGF was lower in the Moderate class (27 weeks). Infection was least likely in the Not Depressed class across gestation. Risks of preterm birth were associated with Severe depressive symptoms (aOR 3·05[1·11 to 8·36]). Interpretation: Comprehensive phenotyping exposes important fetal exposures implicated in adverse neurodevelopment, differing by depression class. This study expands substantially on causal models of suboptimal fetal neurodevelopment and offers potential new targets for intervention in obese pregnant women. Funding: JNS was funded by a PhD studentship from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. UPBEAT was supported by the European Union's 7th Framework Programme (FP7/2007-2013), project EarlyNutrition; grant agreement no. 289346 and the National Institute for Health Research (NIHR) (UK) Programme Grants for Applied Research Programme (RP-0407-10452), Medical Research Council UK Project Grant (MR/L002477/1). Support was also provided by the Chief Scientist Office Scotland, Guy's and St Thomas' Charity and Tommy's Charity (Registered charity no. 1060508). LP and SLW are funded by Tommy's Charity.

Association between maternal adiposity measures and infant health outcomes: A systematic review and meta-analysis.

Maternal obesity increases risks of adverse fetal and infant outcomes. Guidelines use body mass index to diagnose maternal obesity. Evidence suggests body fat distribution might better predict individual risk, but there is a lack of robust evidence during pregnancy. We explored associations between maternal adiposity and infant health. Searches included six databases, references, citations, and contacting authors. Screening and quality assessment were carried out by two authors independently. Random effects meta-analysis and narrative synthesis were conducted. We included 34 studies (n = 40,143 pregnancies). Meta-analysis showed a significant association between maternal fat-free mass and birthweight (average effect [AE] 18.07 g, 95%CI 12.75, 23.38) but not fat mass (AE 8.76 g, 95%CI -4.84, 22.36). Women with macrosomic infants had higher waist circumference than controls (mean difference 4.93 cm, 95% confidence interval [CI] 1.05, 8.82). There was no significant association between subcutaneous fat and large for gestational age (odds ratio 1.06 95% CI 0.91, 1.25). Waist-to-hip ratio, neck circumference, skinfolds, and visceral fat were significantly associated with several infant outcomes including small for gestational age, preterm delivery, neonatal morbidity, and mortality, although meta-analysis was not possible for these variables. Our findings suggest that some measures of maternal adiposity may be useful for risk prediction of infant outcomes. Individual participant data meta-analysis could overcome some limitations in our ability to pool published data.

Association between maternal adiposity measures and adverse maternal outcomes of pregnancy: Systematic review and meta-analysis.

Maternal obesity increases pregnancy-related risks. Women with a body mass index (BMI) ≥ 30 kg/m2 are considered to be at risk and should receive additional care, although approximately half will have uncomplicated pregnancies. This systematic review aimed to identify early pregnancy measures of adiposity associated with adverse maternal health outcomes. Searches included six databases, reference lists, citations, and contacting authors. Screening and quality assessment were carried out by two authors independently. Random effects meta-analysis and narrative synthesis were conducted. Seventy studies were included with a pooled sample of 89,588 women. Meta-analysis showed significantly increased odds of gestational diabetes mellitus (GDM) with higher waist circumference (WC) categories (1.40, 95% confidence interval [CI] 1.04, 1.88) and per unit increase in WC (1.31, 95% CI 1.03, 1.67). Women with GDM had higher WC than controls (mean difference [MD] 6.18 cm, 95% CI 3.92, 8.44). WC was significantly associated with hypertensive disorders, delivery-related outcomes, metabolic syndrome, and composite pregnancy outcomes. Waist to hip ratio was significantly associated with GDM, hypertensive disorders, and delivery-related outcomes. Fat mass, neck circumference, skinfolds, and visceral fat were significantly associated with adverse outcomes, although limited data were available. Our findings identify the need to explore how useful adiposity measures are at predicting risk in pregnancy, compared with BMI, to direct care to women with the greatest need.