Neurodevelopmental Outcome at 2 Years in Offspring of Women Randomised to Metformin or Insulin Treatment for Gestational Diabetes

Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with deficits in motor, social, or linguistic development in offspring. Diet modification and insulin, which does not cross the placenta, have been the mainstay of treatment for GDM. However, metformin has been identified as a potential alternative to insulin as it is directed at the pathophysiology of insulin resistance seen in GDM and has been found to have similar outcomes in comparison to women begun on insulin. The current study was conducted to examine the neurodevelopmental outcomes of offspring of women treated with metformin or insulin for GDM. Offspring of 211 women with GDM enrolled for the Metformin in Gestational Diabetes trial participated in this study. A total of 128 participants were from New Zealand, and 83 were from Australia. Sixty-four mothers from the New Zealand group and 44 mothers from the Australia group were treated with insulin, and 64 mothers from the New Zealand group and 39 mothers from the Australia group were treated with metformin. No differences were found between treatment groups within the New Zealand or Australian cohorts with regard to the primary outcomes of neurodevelopmental assessments. When stratified into New Zealand and Australia, cognitive (mental development index [MDI]) and motor (psychomotor development index [PDI]) quotients were the same for both metformin and insulin groups in both cohorts. No interaction between the sites was observed. Significant differences in MDI (mean, 85.2 [SD, 15.6] vs 100.3 [SD, 16.5]) and PDI (mean, 84.3 [SD, 14.3] vs 102.4 [SD, 15.2]) scores were seen between the New Zealand and Australian cohorts, respectively. It was also noted that significantly lower scores on both cognitive and motor development were reported in the New Zealand offspring as compared with the Australian offspring. Further analyses showed that maternal ethnicity (Pacific or Indian) or lifestyle factors were independently associated with low scores on the MDI. It was also observed that lower cognitive development was seen in children with a birth weight of greater than 4000 g. In parallel, children with occurrences of neonatal glucose values less than 2.6 mmol/L and offspring of mothers with higher glucose levels had poor motor development regardless of treatment. Ethnically diverse, yet well-matched sample of women from 2 different countries and the collection of environmental data at birth and at follow-up explaining differences between countries and within children add to this study, whereas the low follow-up rate from the original trial and the lower proportion of Polynesian children available at follow-up are a major limitation in this study. This study determined that no difference between the neurodevelopment of children at age 2 years was observed in children whose mothers were treated with metformin compared with children whose mothers received insulin during pregnancy to treat GDM. This indicates that using metformin, which can cross the placenta, for GDM did not affect the neurodevelopment of children at 2 years.