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Original Investigation
December 3, 2018

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

Author Affiliations
  • 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill
  • 2National Institute of Health Innovation, University of Auckland, Auckland, New Zealand
  • 3Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill
  • 4Department of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand
JAMA Pediatr. Published online December 3, 2018. doi:10.1001/jamapediatrics.2018.4214
Key Points

Question  How do long-term child growth and development outcomes differ following prenatal exposure to metformin vs insulin when used for the treatment of gestational diabetes?

Findings  In this population-based cohort study, 3928 women treated with metformin or insulin for gestational diabetes in New Zealand were linked with their children’s preschool health assessments. We did not observe significant differences in child weight, weight for height, or body mass index in children of insulin-treated vs metformin-treated mothers, nor did we observe differences in results from behavioral assessments.

Meaning  Children of metformin-treated mothers were indistinguishable on growth and developmental assessments from those of insulin-treated mothers.

Abstract

Importance  Metformin is an emerging option for treating gestational diabetes (GDM). However, because metformin crosses the placenta, patients and clinicians are concerned with its long-term effect on child health.

Objective  To estimate the association of treating GDM with metformin vs insulin with child growth and development.

Design, Setting, and Participants  Population-based cohort study of New Zealand women treated with metformin or insulin for GDM from 2005 to 2012 and their children. This study linked national health care data to create a cohort of mothers and their children, including data from maternity care, pharmaceutical dispensing, hospitalizations, demographic records, and the B4 School Check (B4SC) preschool health assessment. Women treated pharmacologically with metformin or insulin during pregnancy were included. We excluded pregnancies with evidence of diabetes and deliveries prior to 2013. Liveborn infants were linked to their B4SC results. Data were analyzed between January 2017 and May 2018.

Exposures  Pharmacologic treatment for GDM with metformin or insulin, measured using pharmaceutical claims data.

Main Outcomes and Measures  Child growth (weight and height) and Strengths and Difficulties Questionnaire (SDQ) scores for behavioral development. All outcomes were derived from the B4SC screening program. 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 vs insulin treatment for GDM.

Results  In both treatment groups, the mean (SD) maternal age was 32 (5) years. A large proportion of mothers who were treated with insulin identified as New Zealand European (867 [44.9%]) while 756 mothers (28.9%) identified as New Zealand European. Approximately one-third of mothers who were treated with metformin (n = 639) identified as Asian. We identified 3928 pregnancies treated with metformin (n = 1996) or insulin (n = 1932). After adjustment, we observed no meaningful difference in weight for height z scores between children exposed to metformin compared with insulin (mean difference, –0.10; 95% CI, −0.20 to 0.01). Risk of being 85th percentile or greater for weight for 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.

Conclusions and Relevance  Our study compares long-term outcomes among school-aged children following maternal use of metformin vs insulin treatment for GDM. Children of metformin-treated mothers were indistinguishable on growth and developmental assessments from those of insulin-treated mothers. These results will help inform future GDM treatment guidelines.

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