Safety and efficacy of belantamab mafodotin with pembrolizumab in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles. RESULTS: Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed. CONCLUSIONS: The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www. CLINICALTRIALS: gov as NCT03848845.

Treatment patterns and outcomes in patients with metastatic synovial sarcoma in France, Germany, Italy, Spain and the UK.

Aim: Describing the treatment patterns, outcomes by line of treatment (LOT), and healthcare resource utilization (HCRU) in patients with metastatic synovial sarcoma (mSS). Patients & methods: In this descriptive, non-interventional, retrospective cohort study, physicians from five European countries reported on patients with recent pharmacological treatment for mSS. Results: Among 296 patients with mSS, 86.1, 38.9 and 8.4% received 1 LOT (1L), 2 LOTs (2L) and 3+ LOTs (L3+), respectively. Common regimens were doxorubicin/ifosfamide-based (37.4%) for 1L and trabectedin-based for 2L (29.7%). For 1L, median time to next treatment was 13.1 and 6.0 months for living and deceased patients, respectively. Median OS was 22.0, 6.0 and 4.9 months in all patients, 2L and 3L, respectively. HCRU data showed median one inpatient hospital admission, 3 days in hospital and four outpatient visits yearly. Conclusion: This large-scale study documents high unmet needs in patients previously treated for mSS and for more effective therapies.

Meta-analysis of pazopanib and trabectedin effectiveness in previously treated metastatic synovial sarcoma (second-line setting and beyond).

Background: This study examined the efficacy/effectiveness of pazopanib and trabectedin in previously treated metastatic synovial sarcoma (mSS). Materials & methods: A literature search identified studies (2002-2019) reporting outcomes of pazopanib and trabectedin in previously treated mSS, including median overall survival (mOS) and overall response rate (ORR). A meta-analysis was conducted and sensitivity analyses examined outcomes by agent (pazopanib/trabectedin), study type (clinical trial [CT] or real-world [RW]) and sample size. Results: Sixteen studies were included (pazopanib: n = 7; trabectedin: n = 9). Pooled mOS was 10.4 months and was consistent across agents and in RW and CT (pazopanib: 10.3; trabectedin: 10.4; CT: 10.8; RW: 9.9). ORR results were more variable (pooled ORR: 14.7%). ORR was consistently higher for RW (17.7%) than for CT (9.5%) and for pazopanib (18.9%) compared with trabectedin (12.3%). Conclusion: Poor outcomes across agents and settings highlight a need for novel treatments with improved efficacy. This study serves as a benchmark for efficacy estimates in this rare disease.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma. SS frequently spreads to other locations, referred to as metastatic SS (mSS) and is associated with a high death rate. Patients treated with first-line chemotherapy (1L setting), may need further lines of treatment (≥2L setting), which commonly involve the drugs pazopanib and trabectedin. This study assessed how well pazopanib and trabectedin work in people with ≥2L mSS, by examining both clinical trial (CT) and real-world (RW) studies. Overall, findings across 16 studies showed that mSS patients lived approximately 10 months after treatment with pazopanib or trabectedin in the ≥2L setting, and this was similar across both agents (10.3 months for pazopanib; 10.4 months for trabectedin) and between the CT (10.8 months) and the RW (9.9 months) settings. In terms of response to treatment, a higher percentage of people appeared to respond in RW settings (17.7%) than in CTs (9.5%), and to pazopanib (18.9%) compared with trabectedin (12.3%). These results show there is a need for better treatments for patients with previously treated mSS. These findings are useful benchmarks for the development of future treatment approaches for this rare disease.

The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial.

BACKGROUND: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women. METHODS: Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m2) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values. RESULTS: All very low-density lipoprotein (VLDL) particles increased by 1.5-3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1-2 SD, between 16 and 36 weeks' gestation. Triglycerides increased by 2-3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides. CONCLUSION: There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication. TRIAL REGISTRATION: UPBEAT was registered with Current Controlled Trials, ISRCTN89971375 , on July 23, 2008 (prior to recruitment).

Placental lipid droplet composition: Effect of a lifestyle intervention (UPBEAT) in obese pregnant women.

Maternal obesity is associated with adverse outcomes. Placental lipid droplets (LD) have been implicated in maternal-fetal lipid transfer but it is not known whether placental LD fat composition is modifiable. We evaluated the effects of a diet and physical activity intervention in obese pregnant women compared to routine antenatal care (UPBEAT study) on placental LD composition. LD were isolated by ultracentrifugation. Total FAs and phospholipids (phosphatidylcholines, PCs; sphingomyelins, SMs and lyso-phosphatidylcholines, Lyso-PCs) were analyzed by LC-MS/MS. Placenta MFSD2a expression was assessed by western blot. Placental LDs from obese women were comprised of predominantly saturated and monounsaturated FAs. TG and Chol composition was similar between intervention (n = 20) and control (n = 23) groups. PCs containing dihomo-ɣ-linolenic acid in LD were positively associated with gestational weight gain (P < 0.007), and lowered by the intervention. In the whole sample, PCs carrying DHA and arachidonic acid were inversely associated with placental weight. Placenta MFSD2a expression was associated with DHA cord blood metabolites and relationships were observed between LD lipids, especially DHA carrying species, and cord blood metabolites. We describe placenta LD composition for the first time and demonstrate modest, potentially beneficial effects of a lifestyle intervention on LD FAs in obese pregnant women.

Mode of infant feeding, eating behaviour and anthropometry in infants at 6-months of age born to obese women - a secondary analysis of the UPBEAT trial.

BACKGROUND: Maternal obesity and rapid infant weight gain have been associated with increased risk of obesity in childhood. Breastfeeding is suggested to be protective against childhood obesity, but no previous study has addressed the potential benefit of breastfeeding as a preventive method of childhood obesity amongst obese women. The primary aim of this study was to assess the relationship between mode of feeding and body composition, growth and eating behaviours in 6-month-old infants of obese women who participated in UPBEAT; a multi-centre randomised controlled trial comparing a lifestyle intervention of diet and physical activity to standard care during pregnancy. METHODS: Three hundred and fifty-three mother and infant pairs attended a 6-months postpartum follow-up visit, during which they completed the Baby-Eating Behaviour Questionnaire, a parent-reported psychometric measure of appetite traits. Measures of infant body composition were also undertaken. As there was no effect of the antenatal intervention on infant feeding and appetite the study was treated as a cohort. Using regression analyses, we examined relationships between: 1) mode of feeding and body composition and growth; 2) mode of feeding and eating behaviour and 3) eating behaviour and body composition. RESULTS: Formula fed infants of obese women in comparison to those exclusively breastfed, demonstrated higher weight z-scores (mean difference 0.26; 95% confidence interval 0.01 to 0.52), higher rate of weight gain (0.04; 0.00 to 0.07) and greater catch-up growth (2.48; 1.31 to 4.71). There was also a lower enjoyment of food (p = 0.002) amongst formula fed infants, following adjustment for confounders. Independent of the mode of feeding, a measure of infant appetite was associated with sum of skinfold thicknesses (ß 0.66; 95% CI 0.12 to 1.21), calculated body fat percentage (0.83; 0.15 to 1.52), weight z-scores (0.21; 0.06 to 0.36) and catch-up growth (odds ratio 1.98; 1.21 to 3.21). CONCLUSIONS: In obese women, exclusive breastfeeding was protective against increasing weight z-scores and trajectories of weight gain in their 6-month old infants. Measures of general appetite in early infancy were associated with measures of adiposity, weight and catch up growth independent of cord blood leptin concentrations and mode of early feeding.

Prediction of uncomplicated pregnancies in obese women: a prospective multicentre study.

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m2) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15+0 to 18+6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m2), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth.

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial.

BACKGROUND: Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. METHODS: In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks' gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). RESULTS: Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (-0.14; 95% CI -0.19, -0.08, P <0.0001) and Snacks (-0.24; 95% CI -0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes. CONCLUSIONS: In a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

Determining the consequences of maternal obesity for offspring health.

NEW FINDINGS: What is the topic of this review? Observational studies have highlighted the association of increasing maternal body mass index with offspring adiposity and the subsequent risk of cardiometabolic disorders in adulthood. The in utero environment has become a target for intervention in order to reduce the burden of obesity, despite the mechanistic pathways of this association remaining unclear. What advances does it highlight? This short review provides a critical appraisal of the recent literature, including biological pathways and strategies to address causal relationships. The global obesity epidemic has been causally linked to changes in diet and lifestyle. Observational data and animal studies have now highlighted associations between in utero environmental exposures and increased susceptibility to obesity and related cardiometabolic disorders in later life. Maternal body mass index has been reported to show an independent association with offspring adiposity from an early age and to play an important role in the predisposition to obesity and metabolic disease in later life. Thus, the in utero environment has been the focus of recent targeted interventions to improve public health. In this review, we summarize recent progress in this field, including the use of animal models to investigate mechanistic links between maternal obesity and offspring metabolic risk. We then assess the level of evidence and challenges in establishing causal inferences from present birth cohorts.

Dietary recommendations for obese pregnant women: current questions and controversies.

With the increasing prevalence of obesity, maternal obesity is now one of the most common high-risk obstetric conditions. Obesity and excessive gestational weight gain are important modifiable risk factors for maternal and neonatal morbidity and mortality. Maternal obesity, associated with neonatal adiposity and high birthweight, has been implicated in increased risk of childhood obesity. Considerable effort has been directed towards improving clinical outcomes by lifestyle change in pregnant obese women, but there is at present no evidence-based intervention of adequate efficacy which can be recommended. The focus has been on preventing excessive weight gain, but studies have lacked the power to address effects on clinical outcomes; therefore preventing clinical practice translation. Adequately powered intervention studies devised to reduce neonatal adiposity by improvement of maternal glucose homeostasis, are needed to inform the optimal dietary and/or physical activity regimen.

A complex intervention to improve pregnancy outcome in obese women; the UPBEAT randomised controlled trial.

BACKGROUND: Despite the widespread recognition that obesity in pregnant women is associated with adverse outcomes for mother and child, there is no intervention proven to reduce the risk of these complications. The primary aim of this randomised controlled trial is to assess in obese pregnant women, whether a complex behavioural intervention, based on changing diet (to foods with a lower glycemic index) and physical activity, will reduce the risk of gestational diabetes (GDM) and delivery of a large for gestational age (LGA) infant. A secondary aim is to determine whether the intervention lowers the long term risk of obesity in the offspring. METHODS/DESIGN: Multicentre randomised controlled trial comparing a behavioural intervention designed to improve glycemic control with standard antenatal care in obese pregnant women.Inclusion criteria; women with a BMI ≥30 kg/m2 and a singleton pregnancy between 15+0 weeks and 18+6 weeks' gestation. Exclusion criteria; pre-defined, pre-existing diseases and multiple pregnancy. Randomisation is on-line by a computer generated programme and is minimised by BMI category, maternal age, ethnicity, parity and centre. Intervention; this is delivered by a health trainer over 8 sessions. Based on control theory, with elements of social cognitive theory, the intervention is designed to improve maternal glycemic control. Women randomised to the control arm receive standard antenatal care until delivery according to local guidelines. All women have a 75 g oral glucose tolerance test at 27+0- 28+6 weeks' gestation.Primary outcome; Maternal: diagnosis of GDM, according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Neonatal; infant LGA defined as >90th customised birth weight centile.Sample size; 1546 women to provide 80% power to detect a 25% reduction in the incidence of GDM and a 30% reduction in infants large for gestational age. DISCUSSION: All aspects of this protocol have been evaluated in a pilot randomised controlled trial, with subsequent optimisation of the intervention. The findings of this trial will inform whether lifestyle mediated improvement of glycemic control in obese pregnant women can minimise the risk of pregnancy complications. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

GLU: a software package for analysing continuously measured glucose levels in epidemiology.

Continuous glucose monitors (CGM) record interstitial glucose levels 'continuously', producing a sequence of measurements for each participant (e.g. the average glucose level every 5 min over several days, both day and night). To analyse these data, researchers tend to derive summary variables such as the area under the curve (AUC), to then use in subsequent analyses. To date, a lack of consistency and transparency of precise definitions used for these summary variables has hindered interpretation, replication and comparison of results across studies. We present GLU, an open-source software package for deriving a consistent set of summary variables from CGM data. GLU performs quality control of each CGM sample (e.g. addressing missing data), derives a diverse set of summary variables (e.g. AUC and proportion of time spent in hypo-, normo- and hyper- glycaemic levels) covering six broad domains, and outputs these (with quality control information) to the user. GLU is implemented in R and is available on GitHub at https://github.com/MRCIEU/GLU. Git tag v0.2 corresponds to the version presented here.

The second generation of The Avon Longitudinal Study of Parents and Children (ALSPAC-G2): a cohort profile.

Background: The Avon Longitudinal Study of Parents and Children-Generation 2 (ALSPAC-G2) was set up to provide a unique multi-generational cohort. It builds on the existing ALSPAC resource, which recruited 14,541 pregnancies to women resident in the South West of England who were expected to deliver between 01/04/1991 and 31/12/1992. Those women and their partners (Generation 0; ALSPAC-G0) and their offspring (ALSPAC-G1) have been followed for the last 26 years. This profile describes recruitment and data collection on the next generation (ALSPAC-G2)-the grandchildren of ALSPAC-G0 and children of ALSPAC-G1. Recruitment: Recruitment began on the 6 th of June 2012 and we present details of recruitment and participants up to 30 th June 2018 (~6 years). We knew at the start of recruitment that some ALSPAC-G1 participants had already become parents and ALSPAC-G2 is an open cohort; we recruit at any age. We hope to continue recruiting until all ALSPAC-G1 participants have completed their families. Up to 30 th June 2018 we recruited 810 ALSPAC-G2 participants from 548 families. Of these 810, 389 (48%) were recruited during their mother's pregnancy, 287 (35%) before age 3 years, 104 (13%) between 3-6 years and 30 (4%) after 6 years. Over 70% of those invited to early pregnancy, late pregnancy, second week of life, 6-, 12- and 24-month assessments (whether for their recruitment, or a follow-up, visit) have attended, with attendance being over 60% for subsequent visits up to 7 years (to few are eligible for the 9- and 11-year assessments to analyse). Data collection: We collect a wide-range of social, lifestyle, clinical, anthropometric and biological data on all family members repeatedly. Biological samples include blood (including cord-blood), urine, meconium and faeces, and placental tissue. In subgroups detailed data collection, such as continuous glucose monitoring and videos of parent-child interactions, are being collected.

Cord Metabolic Profiles in Obese Pregnant Women: Insights Into Offspring Growth and Body Composition.

Context: Offspring exposed in utero to maternal obesity have an increased risk of later obesity; however, the underlying mechanisms remain unknown. Objective: To assess the effect of an antenatal lifestyle intervention in obese women on the offspring's cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Design: Randomized controlled trial and cohort study. Setting: The UK Pregnancies Better Eating and Activity Trial. Participants: Three hundred forty-four mother-offspring pairs. Intervention: Antenatal behavioral lifestyle (diet and physical activity) intervention. Main Outcome Measures: Targeted cord blood metabolic profile, including candidate hormone and metabolomic analyses. Results: The lifestyle intervention was not associated with change in the cord blood metabolic profile. Higher maternal glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (ß = 0.65; 95% confidence interval: 0.03 to 0.10) and 18.1 (0.52; 0.02 to 0.80), independent of the lifestyle intervention. A principal component of cord blood phosphatidylcholines and LPCs was associated with infant z scores of birth weight (0.04; 0.02 to 0.07) and weight at age 6 months (0.05; 0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Conclusions: Concentrations of LPCs and IGF-1 in cord blood are related to infant weight. These findings support the hypothesis that susceptibility to childhood obesity may be programmed in utero, but further investigation is required to establish whether these associations are causally related.

A Slow-Digesting, Low-Glycemic Load Nutritional Beverage Improves Glucose Tolerance in Obese Pregnant Women Without Gestational Diabetes.

BACKGROUND: Obesity is a risk factor for gestational diabetes (gestational diabetes). Low-glycemic index diets attenuate hyperglycemia. We designed a study to determine whether a slow-digesting, low-glycemic load (SD-LGL) beverage improves glucose tolerance in obese pregnant women without GDM. METHODS: This was a 3-arm comparison study comparing the effects of an SD-LGL nutritional beverage (glycemic load [GL] 730), an isocaloric control beverage (GL 1124), and habitual diet on glycemia in obese pregnant women. Sixteen women (mean body mass index 37 kg/m2) were recruited at 24-28 weeks to receive either the SD-LGL or eucaloric control beverage. This was consumed with breakfast and as a midafternoon snack over 2 days with a controlled diet. Following a 2-day washout period of habitual diet, women completed 2 days on the alternative beverage with controlled diet. A 10-h fast preceded each intervention phase. Twenty-four hour glucose was measured using continuous glucose monitoring. RESULTS: Consumption of the lower GL beverage was associated with improved measures of glycemia, compared with the control beverage and habitual diet at different time periods. Glucose estimates for control versus SD-LDL at 24 h (0.23 mmol/L [0.16 to 0.31], P < 0.001), daytime (0.26 mmol/L [0.18 to 0.34], P < 0.001), and nighttime (0.05 mmol/L [-0.01 to 0.11], P = 0.09). Postprandial glucose was lower after breakfast but not after dinner, compared with the control beverage (0.09 mmol/L [0.01 to 0.18], P = 0.03). CONCLUSION: A slow-digesting, low-glycemic nutritional beverage may facilitate improved glucose control in obese pregnant women. To address potential benefit for clinical outcomes, a randomized controlled trial is warranted.

Gestational diabetes modifies the association between PlGF in early pregnancy and preeclampsia in women with obesity.

OBJECTIVE: To identify clinical and biomarker risk factors for preeclampsia in women with obesity and to explore interactions with gestational diabetes, a condition associated with preeclampsia. STUDY DESIGN: In women with obesity (body mass index ≥ 30 kg/m2) from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we examined 8 clinical factors (socio-demographic characteristics, BMI, waist circumference and clinical variables) and 7 biomarkers (HDL cholesterol, hemoglobin A1c, adiponectin, interleukin-6, high sensitivity C-reactive protein, and placental growth factor (PlGF)) in the early second trimester for association with later development of preeclampsia using logistic regression. Factors were selected based on prior association with preeclampsia. Interaction with gestational diabetes was assessed. MAIN OUTCOME MEASURE: Preeclampsia. RESULTS: Prevalence of preeclampsia was 7.3% (59/824). Factors independently associated with preeclampsia were higher mean arterial blood pressure (Odds Ratio (OR) 2.22; 95% Confidence Interval (CI) 1.58-3.12, per 10 mmHg) and lower PlGF (OR 1.39; 95% CI 1.03-1.87, per each lower 1 log2). The association of PlGF with preeclampsia was present amongst obese women without gestational diabetes (OR 1.91; 95% CI 1.32-2.78), but not in those with GDM (OR 1.05; 95% CI 0.67-1.63), p = 0.04 for interaction. CONCLUSION: The relationship between PlGF and preeclampsia differed in women with obesity according to gestational diabetes status, which may suggest different mechanistic pathways to preeclampsia. Whilst replication is required in other populations, this study suggests that performance of prediction models for preeclampsia should be confirmed in pre-specified subgroups.

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

User engagement in the delivery and design of maternity services.

User engagement is defined as a mutual exchange of information between the patient and the health professional, which has shown to improve patient experience as well as outcomes. Engaging the patient is vital for the healthcare system to remain sustainable. The National Health Service has attempted to incorporate and enhance patient engagement in the delivery of maternity services for the last decade. The financial crisis, changing socio-demographic status, increase in birth rate and public expectations-engaging the patient to take responsibility of their own health has not been achieved. Through in-depth examinations of these barriers we are able to draw conclusions as to why current policies have failed and recommend potential solutions.