Association of Long-term Child Growth and Developmental Outcomes With Metformin vs Insulin Treatment for Gestational Diabetes

摘要

Gestational diabetes mellitus (GDM) is a common pregnancy complication, characterized by relative insulin deficiency and insulin resistance, leading to maternal hyperglycemia. Oral hypoglycemic agents, such as metformin, have emerged as an option for GDM management. However, because metformin crosses the placenta (unlike insulin), patients and clinicians are concerned with its potential long-term effect on child health. These researchers sought to evaluate the association of treating GDM with metformin vs insulin with child growth and development. The researchers performed a population-based cohort study of New Zealand women treated with metformin or insulin for GDM from 2005 to 2012 and their children. Using national health care data, they created a cohort of mothers and their children with data from maternity care, pharmaceutical dispensing, hospitalizations, demographic records, and the B4 School Check preschool health assessment. Women treated with metformin or insulin during pregnancy were included, whereas pregnancies with evidence of pregestational diabetes and deliveries after 2013 were excluded. The primary outcomes and measures were child growth (weight and height) and the Strengths and Difficulties Questionnaire (SDQ) scores for behavioral development. All outcomes were derived from the B4 School Check screening program. To estimate the association of child growth and psychosocial outcomes with metformin versus insulin treatment for GDM, linear and log-binomial regression with inverse probability of treatment weighting was used to estimate the association of child growth and psychosocial outcomes with metformin versus insulin treatment for GDM. The researchers identified 3928 pregnancies treated with metformin (n = 1996) or insulin (n = 1932). In both treatment groups, the mean (SD) maternal age was 32 (5) years. A large proportion of mothers treated with insulin identified as New Zealand European (n = 867 [44.9%]), whereas 576 mothers who were treated with metformin (28.9%) identified as New Zealand European. Approximately one-third of mothers who were treated with metformin (n = 639) identified as Asian. After adjustment, they observed no significant difference in weight for height z scores between children exposed to metformin compared with insulin (mean difference, -0.10; 95% confidence interval [CI], -0.20 to 0.01). The risk of being 85th percentile or greater for weight or height was similar between treatment groups (adjusted risk ratio, 0.92; 95% CI, 0.83-1.02). Mean SDQ scores were not meaningfully different between the treatment groups: children of metformin-treated mothers were not significantly more likely to have parent-reported SDQ scores of 14 or more (adjusted risk ratio, 1.13; 95% CI, 0.88-1.46) than those of insulin-treated mothers. The researchers found that there were no meaningful differences in growth or behavioral and emotional development between treatment groups. As this study compared the long-term outcomes among school-aged children long after maternal use of metformin or insulin treatment for GDM, the researchers hope that these data will inform patients and practitioners when deciding the long-term merits of metformin versus insulin when making treatment decisions.