MiTy Tykes: The Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial
Study Details
Study Description
Brief Summary
The incidence of diabetes in pregnancy is rising, with rates of 1 in 7 pregnancies globally. Metformin is used for type 2 diabetes (T2DM) outside of pregnancy and is now increasingly prescribed during pregnancy. There are some concerns as metformin crosses the placenta and effects on offspring exposed during pregnancy are unknown. Animal and human evidence indicate that metformin may create an atypical in-utero environment similar to under-nutrition which has been associated with adult obesity. This is supported by studies in children of mothers treated with metformin in other populations where an increase in childhood obesity was found at 4-9 years of age. We now have evidence from the MiTy trial, that offspring of metformin-exposed women with T2DM have less large infants and are less adipose at birth, but are also more likely to be small for gestational age (SGA). These effects could lead to benefit or harm in the long-term. Offspring of MiTy mothers are currently being followed up to 2 years. Given that long-term effects may not be evident until 5 years of age, it is imperative to follow these children longer.
Goals/Research Aims:To determine whether in-utero exposure to metformin, in offspring of women with T2DM, is beneficial or harmful in the long-term.
Research Questions: 1. In offspring of women with T2DM, how does treatment with metformin during pregnancy affect a) adiposity b) growth over time c) metabolic syndrome d) cognitive and behavioral measures:2. What factors predict altered childhood adiposity and insulin resistance in these offspring?
Primary Outcome: Body mass index (BMI) z-score.
Secondary Outcomes: 1) other measures of adiposity (i.e. skinfolds, 2) growth over time 3) measures of insulin resistance 4) adipocytokines 5)neurodevelopment
Expected Outcomes Given these increasing concerns, this study will inform the best treatment for pregnant mothers with diabetes by studying the long-term outcomes of children exposed to metformin during pregnancy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Metformin exposed in utero Offspring of mothers who were exposed to metformin during pregnancy in the MiTy trial. |
|
| Placebo exposed in utero Offspring of mothers who were not exposed to metformin during pregnancy in the MiTy trial. |
Outcome Measures
Primary Outcome Measures
- Body Mass Index (BMI) z-score [5-11 years of age]
Using WHO or other appropriate growth charts
Secondary Outcome Measures
- Skinfold measurements [5-11 years of age]
triceps, subscapular and suprailiac skinfold thicknesses
- Sum of skinfold measurements: [5-11 years of age]
sum of triceps, subscapular and suprailiac skinfold thicknesses
- Triceps skinfolds z-scores [5-11 years of age]
Using WHO or other appropriate growth charts
- Ratio of the central to peripheral skinfold ratio [5-11 years of age]
ratio of the central (suprailiac) to peripheral (triceps) skinfold ratio;
- Overweight and obesity status [5-11 years of age]
Defined using WHO or other appropriate growth charts
- Waist circumference [5-11 years of age]
Waist circumference measurement
- Waist to height ratio [5-11 years of age]
Waist and height measurements
- Growth trajectory [5-11 years of age]
Longitudinal growth outcomes will be assessed using adiposity measurements from the MiTy trial (newborns) and at 3, 6, 12, 18 and 24 months from the MiTy Kids trial, to ages 5-11 years in the MiTy Tykes trial.
- Fat mass [5-11 years of age]
Using the Tanita SC-240 bioimpedance analyzer (BIA)
- Percentage of body fat [5-11 years of age]
Using the Tanita SC-240 bioimpedance analyzer (BIA)
- Measures of insulin resistance and metabolic syndrome [5-11 years of age]
The following measurements combined will contribute to the assessment of insulin resistance and metabolic syndrome: fasting glucose, fasting insulin, fasting insulin-to-glucose ratio, and the HOMA-IR, serum levels of leptin, adiponectin and lipids
- Neurocognitive development [5-11 years of age]
Attention Deficit Hyperactivity Disorder (ADHD)-5 Rating scale
- Neurocognitive development [5-11 years of age]
Children's Communication Checklist (CCC-2)
- Neurocognitive development [5-11 years of age]
Social Responsiveness Scale (SRS-2)
Eligibility Criteria
Criteria
Inclusion Criteria:
- Liveborn offspring of women who participated, are participating or will participate, in the MiTy Kids study.
Exclusion Criteria:
- Offspring with major congenital anomalies that would affect growth or development (these children have already been excluded from MiTy Kids).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mount Sinai Hospital | Toronto | Ontario | Canada |
Sponsors and Collaborators
- Mount Sinai Hospital, Canada
- Sunnybrook Research Institute
- Canadian Institutes of Health Research (CIHR)
Investigators
- Principal Investigator: Denice Feig, MD, Mount Sinai Hospital, Toronto, ON, Canada
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CTO 3632