title: Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.
abstract: Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m2. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required. The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes.
  
  
  
  Design: Multicentre randomised, controlled trial.
  
  
  
  Women with a singleton, live gestation between 10+0-20+0weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0and 20+0weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group. All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach. Primary Study Outcome: infant birth weight >4000 grams.
  
  
  
  524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed).
  
  
  
  This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.
  
  
  
  Australian and New Zealand Clinical Trials Registry ACTRN12612001277831 , prospectively registered 10thof December, 2012.
authors.affiliation: Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia. jodie.dodd@adelaide.edu.au.|Department of Perinatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia. jodie.dodd@adelaide.edu.au.|Discipline of Obstetrics & Gynaecology, and Robinson Institute, Women's & Children's Hospital, The University of Adelaide, 72 King William Road, North Adelaide, South Australia, 5006, Australia. jodie.dodd@adelaide.edu.au.
authors.forename: Jodie M
authors.initials: JM
authors.lastname: Dodd
authors.affiliation: Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.|Department of Obstetrics & Gynaecology, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Grivell
authors.affiliation: Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Deussen
authors.affiliation: Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.|Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
authors.forename: Gustaaf
authors.initials: G
authors.lastname: Dekker
authors.affiliation: The University of Adelaide, School of Public Health, Adelaide, South Australia, Australia.
authors.forename: Jennie
authors.initials: J
authors.lastname: Louise
authors.affiliation: Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.|Department of Perinatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Hague
mesh_terms: D000328:Adult; D001724:Birth Weight; D003376:Counseling / Q000379:methods*; D004032:Diet / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007231:Infant, Newborn; D007333:Insulin Resistance; D008019:Life Style; D050498:Live Birth; D008687:Metformin / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D050177:Overweight / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D011295:Prenatal Care / Q000379:methods*; D015430:Weight Gain
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin