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Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes
  1. Trecia A Wouldes1,
  2. Malcolm Battin2,
  3. Suzette Coat3,
  4. Elaine C Rush4,
  5. William M Hague5,
  6. Janet A Rowan6
  1. 1Department of Psychological Medicine, Faculty of Medical and Health Sciences, Auckland, New Zealand
  2. 2New Born Services, Auckland City Hospital, Auckland, New Zealand
  3. 3Robinson Research Institute, The University of Adelaide, North Adelaide, South Australia
  4. 4Centre for Child Health Research, Auckland University of Technology, Auckland, New Zealand
  5. 5Department of Obstetrics, Women and Children's Hospital, University of Adelaide, North Adelaide, South Australia
  6. 6Department of Obstetrics, National Women's Health, Auckland City Hospital, Auckland, New Zealand
  1. Correspondence to Professor Trecia A Wouldes, Department of Psychological Medicine, Faculty of Medical and Health Sciences, Private Bag 92019, Auckland 1142, New Zealand; t.wouldes{at}


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.

Design 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.

Trial registration number ACTRN 12605000311651.

  • Neurodevelopment
  • Outcomes research
  • Gestational Diabetes Mellitus
  • Metformin

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  • Contributors All authors contributed to the design of the MiG TOFU study. TAW, MB and SC designed the neurodevelopmental follow-up. TAW and MB analysed and interpreted the data with JAR. TAW wrote a first draft of the manuscript, and all co-authors critically evaluated and suggested revisions to the manuscript and approved the final submission.

  • Funding This study was supported by funding from the Health Research Council, New Zealand; the Auckland Medical Research Foundation; the Evelyn Bond Trust, Auckland; and the National Health and Medical Research Council, Australia.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethical approval for the study was obtained at each site.

  • Provenance and peer review Not commissioned; externally peer reviewed.