Title: Diet and physical activity in pregnancy to prevent gestational diabetes: Individual Participant Data (IPD) meta-analysis on the differential effects of interventions with economic evaluation
Funder: Department of Health and Social Care

Abstract: WHAT IS THE PROBLEM?_x000D_ _x000D_ During pregnancy between 8-24% of women develop ‘gestational diabetes’. This is a condition where women are noticed to have high blood sugar levels for the first time in pregnancy. Mothers with gestational diabetes are at high risk of developing raised blood pressure, having caesarean section and suffering stillbirths. Their babies are at risk of being large for gestation resulting in difficult birth, and are prone to complications that often require admission to the baby unit. Moreover, half of the 40,000 women who are diagnosed with gestational diabetes each year will go on to develop type 2 diabetes within 5-10 years. Type 2 diabetes costs the NHS £14 billion pounds each year. _x000D_ _x000D_ But the risks of developing gestational diabetes is not the same for all women. Mothers with obesity are twice more likely to be diagnosed with gestational diabetes than normal weight mothers, ethnic minority women three to eight times more than Caucasian women, and those from low socioeconomic background twice more than others. _x000D_ _x000D_ WHAT IS NEEDED?_x000D_ _x000D_ Studies have suggested that following a healthy diet and physical activity in pregnancy may prevent gestational diabetes. But there is no definitive evidence to support this. Specifically, we do not know if all women benefit equally or if the benefit varies between women according to their individual characteristics. _x000D_ _x000D_ In order to ensure beneficial interventions are offered to women in the NHS, we also need to identify the type of intervention and delivery method that is most effective for women in preventing gestational diabetes alongside their associated costs._x000D_ _x000D_ WHAT DO WE PLAN TO DO?_x000D_ _x000D_ We have already established an International Weight Management in Pregnancy collaborative network (i-WIP) with 40 researchers from 16 countries. Through the network, we have access to the individual anonymised data of women who have participated in studies on diet and physical activity in pregnancy (24,766 women, 58 studies). We have mapped the details of these interventions such as the type of intervention, how often and who delivered it, and in what setting for all studies. We will combine the data from all these individual women using a method of analysis known as Individual Participant Data (IPD) meta-analysis. This will allow us to make specific evidence-based recommendations about what diet and physical activity in pregnancy will benefit whom (all or specific groups) and by how much in preventing gestational diabetes. _x000D_ _x000D_ HOW HAVE WE INVOLVED PATIENTS AND PUBLIC?_x000D_ _x000D_ Many of our patient and public involvement (PPI) advisory group members have experienced gestational diabetes. They also have one or more of the risk factors that we plan to study such as obesity, ethnic minority background, varied age and number of babies, and different socioeconomic backgrounds. Our discussions with them have particularly shaped the primary outcomes. This study was also felt to be particularly important by mothers because of the scale and potential long-term impact._x000D_ _x000D_ WHAT WILL HAPPEN WHEN THE STUDY IS FINISHED?_x000D_ _x000D_ We will use our new knowledge to inform future guidelines in this field. To ensure our findings have maximum impact will engage with key individuals in Public Health England, Diabetes UK, British Nutrition Foundation, NHS providers, relevant clinicians and PPI members to facilitate integration of beneficial lifestyle interventions.

Lay abstract: BACKGROUND_x000D_ _x000D_ Mothers with gestational diabetes (glucose intolerance diagnosed for the first time in pregnancy) are at high risk of complications in pregnancy, and of type 2 diabetes in the long term. Diet and physical activity interventions have the potential to prevent gestational diabetes. However, numerous trials (> 60) and aggregate meta-analyses (>10) have not led to clear implementable recommendations due to variations in population, interventions and outcomes. Evidence synthesis using the individual participant data (IPD) can address these the limitations._x000D_ _x000D_ AIM_x000D_ _x000D_ To determine using IPD meta-analysis, whether diet and physical activity-based interventions prevent gestational diabetes, and its complications, in all or in specific groups of women, and identify the costs and components of effective interventions through our NIHR-funded i-WIP (International Weight Management in Pregnancy) database._x000D_ _x000D_ OBJECTIVES_x000D_ _x000D_ Primary _x000D_ To assess the_x000D_ 1. overall effects across all interventions, and according to each type (diet, physical activity, mixed), on gestational diabetes as defined by NICE (National Institute of Health and Care Excellence) and by any criteria_x000D_ 2. differential effects on subgroups based on maternal body mass index (BMI), age, parity, ethnicity, and socioeconomic status_x000D_ _x000D_ Secondary _x000D_ To evaluate_x000D_ 3. the effects of interventions on critically important offspring and maternal outcomes _x000D_ 4. variation in effects by intervention components_x000D_ 5. the effects on gestational diabetes diagnosed using specific criteria_x000D_ 6. the cost-effectiveness of interventions _x000D_ _x000D_ METHODS_x000D_ _x000D_ IDENTIFICATION OF NEW TRIALS AND DATA ACQUISITION_x000D_ We already have standardised relevant IPD of 37 trials (17,106 women, 16 countries) in our i-WIP database. A further 21 trials (7,660 women) have agreed to share IPD and are in the process of transferring the data. _x000D_ _x000D_ QUALITY ASSESSMENT AND DATA HARMONISATION_x000D_ We will add new studies and variables to the existing i-WIP database, assess study quality, harmonise new data, and extract data on the diagnostic blood glucose values, intervention components, and outcomes._x000D_ _x000D_ DATA SYNTHESIS_x000D_ We will perform 1-stage and 2-stage random effect IPD meta-analyses to obtain the pooled intervention effect for primary and secondary outcomes. We will examine whether maternal characteristics (covariate values) modify effect by extending the meta-analysis framework to summarise treatment-covariate interaction terms. Our cost effectiveness analysis will be primarily based on outcomes for a hypothetical cohort of 10,000 pregnant women derived from the IPD meta-analysis. A secondary analysis will compare costs and outcomes for subgroups of women. _x000D_ _x000D_ SAMPLE SIZE_x000D_ _x000D_ Of the 27,538 women (71 studies) with eligible data, we have a sample size of 24,766 women (58 studies shared/agreed IPD). This provides us with 90% or higher power to detect any interactions between overall effects and most subgroups for a 30% reduction in odds of gestational diabetes; for a 25% reduction in gestational diabetes our IPD sample size accrued so far has over 80%, and around 75-80% for most other subgroups._x000D_ _x000D_ TIMELINE_x000D_ _x000D_ 18 months _x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION_x000D_ _x000D_ We will liaise with NHS England Directors, UK Chief Medical Officers, NICE Guideline leads, NHS providers, local authorities, Charities and patient groups to enable implementation of findings into practice. We plan to disseminate via journals, conferences, blogs, social media.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;3.3 NUTRITION AND CHEMOPREVENTION
Health categories: METABOLIC AND ENDOCRINE;REPRODUCTIVE HEALTH AND CHILDBIRTH