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Dr. Nashita Patel On behalf of the UPBEAT Consortium Clinical Research Fellow to Professor Lucilla Poston

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Long term risk Neonatal Obstetric Maternal T2DM Maternal and childhood obesity Abnormal offspring glucose homeostasis SGA/LGA >NICU admission Birth injuries Infection > CS PPH VTE PET PIH GDM

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Strong association between maternal BMI and healthcare costs Mean costs 23% higher among overweight women Mean costs 37% higher among obese women UK: normal weight 3546; overweight 4244; obese 4717

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Re the IOM GUIDELINES * The recommendations were not validated by intervention studies. Without evidence from large-scale trials, it is not clear whether or not adhering to the recommended ranges lowers the risk of adverse outcomes for mothers and their babies.

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Adipose tissueAdiponectinGDMFetal Metabolic memory Macrosomia Offspring obesityOffspring insulin resistance TNF-, IL-6 Leptin IL-2, IL-12, IFN- IL-4, IL-5, IL-10, IL-13 Fetal hypothalamic neuro-peptides Fetal hypothalamus IL-2, IL-12, IFN- Glucose, Lipids, insulin Background

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2 year old Children of Diabetic Women Treated with Metformin Have Higher Skin Folds Thickness than Children of Mothers Treated with Insulin

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LIMIT trial; Dodd et al (BMJ 2014) The first lifestyle RCT powered for clinical outcomes 2152 Overweight and obese women Primary outcome: LGA Results: No significant difference in primary outcome Significant reduction (20%) in BW>4kg No reduction in GWG

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IG POP study Pilot trial of a slow digesting low GI supplement on blood glucose during an obese pregnancy Inform the design of a nutritional intervention RCT of dietary advice with LGI supplement in an obese pregnancy

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1.Significant reduction in post prandial glycaemia at breakfast & dinner 2.Significant reduction in overall daytime glucose vs. control and habitual diet 3.Significant reduction in nocturnal glucose vs. habitual diet

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* Complex intervention in 1546 obese women * Diet; Low Glycemic load, reduce saturated fat and free sugars * Exercise; Mild to moderate exercise * Primary Outcome: * Maternal: OGTT 28 weeks. (IADPSG criteria) * Neonatal; Delivery of Large for Gestational Age infant * (LGA >90 th Customised Centile ) * Secondary Outcomes: * Childhood adiposity at 6mths and 3 years

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18 Recruitment BMI >30kg/m 2 Randomisation 15 +0 -17 +6 weeks gestation All women Intervention arm Baseline Physical Activity (PA), Diet 28 weeks gestation OGTT, PA, Diet 36 weeks gestation PA, Diet 1:1 Health Trainer Interview Handbook Exercise DVD 8 weekly sessions (SMART goals) 1:1 Health Trainer Interview Handbook Exercise DVD 8 weekly sessions (SMART goals) Pregnancy outcome Childhood follow up

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PILOT ControlInterventionDifference (95% CI) p Total Energy Intake (MJ/d) Baseline7.53 (2.2)7.26 (2.29) 28 weeks7.71 (2.30)6.75(2.57)-0.94 (-1.72 to -0.18) 0.016 Dietary Glycemic Load (g/d) Baseline133 (48)129 (41)