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.

Explainable Early Prediction of Gestational Diabetes Biomarkers by Combining Medical Background and Wearable Devices: A Pilot Study With a Cohort Group in South Africa.

This study aims to explore the potential of Internet of Things (IoT) devices and explainable Artificial Intelligence (AI) techniques in predicting biomarker values associated with GDM when measured 13-16 weeks prior to diagnosis. We developed a system that forecasts biomarkers such as LDL, HDL, triglycerides, cholesterol, HbA1c, and results from the Oral Glucose Tolerance Test (OGTT) including fasting glucose, 1-hour, and 2-hour post-load glucose values. These biomarker values are predicted based on sensory measurements collected around week 12 of pregnancy, including continuous glucose levels, short physical movement recordings, and medical background information. To the best of our knowledge, this is the first study to forecast GDM-associated biomarker values 13 to 16 weeks prior to the GDM screening test, using continuous glucose monitoring devices, a wristband for activity detection, and medical background data. We applied machine learning models, specifically Decision Tree and Random Forest Regressors, along with Coupled-Matrix Tensor Factorisation (CMTF) and Elastic Net techniques, examining all possible combinations of these methods across different data modalities. The results demonstrated good performance for most biomarkers. On average, the models achieved Mean Squared Error (MSE) between 0.29 and 0.42 and Mean Absolute Error (MAE) between 0.23 and 0.45 for biomarkers like HDL, LDL, cholesterol, and HbA1c. For the OGTT glucose values, the average MSE ranged from 0.95 to 2.44, and the average MAE ranged from 0.72 to 0.91. Additionally, the utilisation of CMTF with Alternating Least Squares technique yielded slightly better results (0.16 MSE and 0.07 MAE on average) compared to the well-known Elastic Net feature selection technique. While our study was conducted with a limited cohort in South Africa, our findings offer promising indications regarding the potential for predicting biomarker values in pregnant women through the integration of wearable devices and medical background data in the analysis. Nevertheless, further validation on a larger, more diverse cohort is imperative to substantiate these encouraging results.

Nicotinic acetylcholine receptor CHRNA5 is overexpressed in head and neck squamous cell carcinoma patients with a recent tobacco smoking history.

Tobacco smoking is a major driver of head and neck squamous cell carcinoma (HNSCC) occurrence, and previous studies have shed light on the precise molecular alterations in tobacco-related HNSCCs when compared to HNSCCs associated with other risk factors (ex: human papillomavirus/HPV status). In this study, we analyzed the gene expression differences in HNSCC cases with a recent smoking history and revealed that the nicotinic acetylcholine receptor CHRNA5 is differentially overexpressed in smoking-related HNSCCs. CHRNA5 overexpression in these HNSCCs corresponds with a worse prognosis and is inversely correlated with an immune expression signature commonly associated with better prognosis. From these results, our study highlights the potential role of the nicotine-activated CHRNA5 receptor in HNSCC progression and corresponds with other recent reports highlighting the potential role of nicotine induction in promoting cancer progression.

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.

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study.

OBJECTIVE: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. DESIGN: Retrospective multicentre cohort. SETTING: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. POPULATION: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). METHODS: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. MAIN OUTCOME MEASURES: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. RESULTS: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. CONCLUSIONS: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.

Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. METHODS: Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). RESULTS: A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. CONCLUSIONS: Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic.

How are fitness to practise processes applied in UK higher education institutions? - A systematic review.

AIM: This systematic review will establish how Fitness to Practise (FtP) processes are applied in UK Higher Education Institutions (HEI), in relation to both Health and Care Profession Council or Nursing and Midwifery Council approved programmes. BACKGROUND: Healthcare students are required to complete both practice and theory elements, in order to gain their degree and qualify as a healthcare practitioner such as a nurse. It is a requirement of UK HEIs which provide healthcare programmes, to provide evidence to the appropriate regulatory body that FtP policies and processes are in place, and that they review and manage any concerns in relation to a student's standard of practice. Regulatory bodies provide HEIs with strategic guidance on policy which can be interpreted and incorporated into existing policies; this means that there is no standard approach to the FtP process in HEI settings, allowing individual policies and procedures to exist. DESIGN: A systematic review, registered on PROSPERO (CRD42022291532 on the 21st January 2022). DATA SOURCES: Peer reviewed studies published in ten databases were used which included: Medline, Cochrane Library, PubMed, ScienceDirect, Education Source, PsycInfo and Cumulative Index of Nursing and Allied Health Literature (CINAHL) Complete. Citation searching also occurred. REVIEW METHODS: This systematic review utilised Preferred Reporting items for Systematic reviews and Meta-Analysis (PRISMA) techniques. The Critical Appraisal Skills Programme (CASP) checklists were used to appraise the quality of the research. RESULTS: In total twenty-five articles were retrieved including five papers that were finally selected for review. A thematic analysis identified three themes: a lack of identification of what FtP expectations are; the importance of collaborative working between Higher Education Institutions and practice; the inconsistencies with Higher Education Institution processes in managing FtP concerns. CONCLUSIONS: A lack of understanding of what FtP expectations are for students was identified. Collaborative working between Higher Education Institutions and practice is necessary to ensure healthcare students meet FtP requirements consistently in order to protect the public. Although HEIs FtP processes contain similar principles, it has been identified that there are inconsistencies in this process across universities in the UK. These differences include: what initiates the FtP process, to the outcomes. This could have an impact on patient care and safety, the need for review of national guidance, and potential amendments being required to the policies and procedures of both NHS Trusts and private organisations.

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.

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.

Towards Precision Medicine in Gestational Diabetes: Pathophysiology and Glycemic Patterns in Pregnant Women With Obesity.

AIMS: Precision medicine has revolutionized our understanding of type 1 diabetes and neonatal diabetes but has yet to improve insight into gestational diabetes mellitus (GDM), the most common obstetric complication and strongly linked to obesity. Here we explored if patterns of glycaemia (fasting, 1 hour, 2 hours) during the antenatal oral glucose tolerance test (OGTT), reflect distinct pathophysiological subtypes of GDM as defined by insulin secretion/sensitivity or lipid profiles. METHODS: 867 pregnant women with obesity (body mass index ≥ 30 kg/m2) from the UPBEAT trial (ISRCTN 89971375) were assessed for GDM at 28 weeks' gestation (75 g oral glucose tolerance test OGTT; World Health Organization criteria). Lipid profiling of the fasting plasma OGTT sample was undertaken using direct infusion mass spectrometry and analyzed by logistic/linear regression, with and without adjustment for confounders. Insulin secretion and sensitivity were characterized by homeostatic model assessment 2b and 2s, respectively. RESULTS: In women who developed GDM (n = 241), patterns of glycaemia were associated with distinct clinical and biochemical characteristics and changes to lipid abundance in the circulation. Severity of glucose derangement, rather than pattern of postload glycaemia, was most strongly related to insulin action and lipid abundance/profile. Unexpectedly, women with isolated postload hyperglycemia had comparable insulin secretion and sensitivity to euglycemic women, potentially indicative of a novel mechanistic pathway. CONCLUSIONS: Patterns of glycemia during the OGTT may contribute to a precision approach to GDM as assessed by differences in insulin resistance/secretion. Further research is indicated to determine if isolated postload hyperglycemia reflects a different mechanistic pathway for targeted management.

Rollout of Closed-Loop Technology to Pregnant Women with Type 1 Diabetes: Healthcare Professionals' Views About Potential Challenges and Solutions.

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed (n = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving (n = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

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.

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.

Gestational diabetes in women with obesity; an analysis of clinical history and simple clinical/anthropometric measures.

AIM: We assessed clinical risk factors, anthropometric measures of adiposity and weight gain to determine associations with development of GDM in a cohort of pregnant women with obesity. METHODS: This was a secondary analysis of the UPBEAT trial of a complex lifestyle intervention in pregnant women with obesity (ISRCTN89971375). Clinical risk factors, and measures of adiposity and weight were assessed in the early 2nd trimester (mean 17 +0 weeks), and adiposity and weight repeated in the early 3rd trimester (mean 27 +5 weeks'). RESULTS: Of the 1117 women (median BMI 35.0 kg/m2) with complete data, 25.8% (n = 304) developed GDM (IADPSG criteria, OGTT 24-28weeks). Using multivariable analysis, early clinical risk factors associated with later development of GDM included age (adj OR 1.06 per year; 95% CI 1.04-1.09), previous GDM (3.27; 1.34-7.93) and systolic blood pressure (per 10mmHg, 1.34; 1.18-1.53). Anthropometric measures positively associated with GDM included second trimester (mean 17+0 weeks) subscapular skinfold thickness, (per 5mm, 1.12; 1.05-1.21), and neck circumference (per cm, 1.11; 1.05-1.18). GDM was not associated with gestational weight gain, or changes in skinfolds thicknesses or circumferences between visits. CONCLUSIONS: In this cohort of women with obesity, we confirmed clinical risk factors for GDM, (age, systolic blood pressure) previously identified in heterogeneous weight women but add to these indices of adiposity which may provide a discriminatory approach to GDM risk assessment in this group. This study also underscores the need to focus on modifiable factors pre-pregnancy as an opportunity for GDM prevention, as targeting gestational weight gain and adiposity during pregnancy is likely to be less effective.

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.

The effects of repetition spacing on the illusory truth effect.

The illusory truth effect refers to the fact that repetition increases perceptions of truth. In these experiments, we examined whether the magnitude of the illusory truth effect varies based upon repetition spacing. In Experiment 1, participants read facts that repeated twice, with a lag of 0, 1, 2, 4, 8, 16, or 32 intervening facts. Participants later rated the truthfulness of these facts in addition to new facts. Here, we observed a spacing effect: Truth ratings were higher when repetitions were spaced (i.e., lags of 1 through 32) rather than massed (i.e., lag of 0). We also observed a lag effect that followed a quadratic pattern: Truth ratings increased up to a lag of 16, after which they decreased. In Experiment 2 we tested whether the spacing effect in truth ratings depends upon the number of repetitions. In Experiment 2a we used a small number of repetitions (2, 3, or 4) and short lag lengths (0, 1, or 2). In Experiment 2b, we increased the number of repetitions (2 or 10) and the lag lengths (0 or 10). In Experiment 2a there was an illusory truth effect, but its magnitude did not depend upon lag length or repetition number. However, in Experiment 2b the magnitude of the illusory truth effect increased as lag length and repetition number increased, but there was no interaction between these two factors. Together, these findings show that repetition is most likely to increase perceived truth when repetitions are spaced with a moderate number of intervening items.

Prevention of gestational diabetes in pregnant women with obesity: protocol for a pilot randomised controlled trial.

BACKGROUND: Obesity in pregnancy increases the risk of gestational diabetes mellitus (GDM) and associated adverse outcomes. Despite metabolic differences, all pregnant women with obesity are considered to have the same risk of developing GDM. Improved risk stratification is required to enable targeted intervention in women with obesity who would benefit the most. The aim of this study is to identify pregnant women with obesity at higher risk of developing GDM and, in a pilot randomised controlled trial (RCT), test feasibility and assess the efficacy of a lifestyle intervention and/or metformin to improve glycaemic control. METHODS: Women aged 18 years or older with a singleton pregnancy and body mass index (BMI) ≥ 30kg/m2 will be recruited from one maternity unit in London, UK. The risk of GDM will be assessed using a multivariable GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c. Women identified at a higher risk of developing GDM will be randomly allocated to one of two intervention groups (lifestyle advice with or without metformin) or standard antenatal care. The primary feasibility outcomes are study recruitment, retention rate and intervention adherence and to collect information needed for the sample size calculation for the definitive trial. A process evaluation will assess the acceptability of study processes and procedures to women. Secondary patient-centred outcomes include a reduction in mean glucose/24h of 0.5mmol/l as assessed by continuous glucose monitoring and changes in a targeted maternal metabolome, dietary intake and physical activity. A sample of 60 high-risk women is required. DISCUSSION: Early risk stratification of GDM in pregnant women with obesity and targeted intervention using lifestyle advice with or without metformin could improve glucose tolerance compared to standard antenatal care. The results from this feasibility study will inform a larger adequately powered RCT should the intervention show trends for potential effectiveness. TRIAL REGISTRATION: This study has been approved by the NHS Research Ethics Committee (UK IRAS integrated research application system; reference 18/LO/1500). EudraCT number 2018-000003-16 .