title: Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes.
abstract: OBJECTIVE
  Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is increasingly being treated with metformin that crosses the placenta rather than insulin, which does not. This study seeks to examine the neurodevelopment of offspring of women treated with metformin or insulin for GDM.
  
  
  METHODS
  We performed a prospective follow-up study of children whose mothers had been randomly assigned at 20-33 weeks gestation to treatment with metformin or insulin for GDM. Of the 211 children followed up at 2 years, 128 were from Auckland, New Zealand (64 metformin vs 64 insulin), and 83 from Adelaide, Australia (39 metformin vs 49 insulin). Neurodevelopment was examined with the Bayley Scales of Infant Development V.2 mental development index (MDI) and psychomotor development index (PDI). Clinical and demographic background characteristics were obtained at enrolment, birth and follow-up.
  
  
  RESULTS
  No significant differences were found between treatment groups in clinical or demographic characteristics. The MDI and PDI composite scores were tested with general linear models. No significant differences were found between metformin and insulin, respectively, in New Zealand (MDI, M=83.6 vs 86.9 and PDI, M=83.4 vs M=85.2) or Australia (MDI, M=102.5 vs M=98.4 and PDI, M=105.6 vs M=99.9) and no interactions observed. The differences in neurodevelopmental outcomes between the Auckland and Adelaide cohorts were explained by parental ethnicity, infant birth weight >4000 g, neonatal hypoglycaemia, maternal glycaemia and smoking in the household.
  
  
  CONCLUSIONS
  This study provides additional data supporting the safety of metformin in the treatment of GDM.
  
  
  BACKGROUND
  ACTRN 12605000311651.
authors.affiliation: Department of Psychological Medicine, Faculty of Medical and Health Sciences, Auckland, New Zealand.
authors.forename: Trecia A
authors.initials: TA
authors.lastname: Wouldes
authors.affiliation: New Born Services, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Battin
authors.affiliation: Robinson Research Institute, The University of Adelaide, North Adelaide, South Australia.
authors.forename: Suzette
authors.initials: S
authors.lastname: Coat
authors.affiliation: Centre for Child Health Research, Auckland University of Technology, Auckland, New Zealand.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Rush
authors.affiliation: Department of Obstetrics, Women and Children's Hospital, University of Adelaide, North Adelaide, South Australia.
authors.forename: William M
authors.initials: WM
authors.lastname: Hague
authors.affiliation: Department of Obstetrics, National Women's Health, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Rowan
keywords: Gestational Diabetes Mellitus; Metformin; Neurodevelopment; Outcomes research