The Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial

Recruiting

• Conditions: Pregnancy in Diabetic; Child Development; Diabetes Mellitus, Type 2; Child Obesity

• Registration Number: NCT05025852
• Lead Sponsor: Mount Sinai Hospital, Canada

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-11
• Study First Submitted QC: 2021-08-23
• Study First Posted: 2021-08-27
• Study Start: 2022-05-11
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-11
• Last Update Posted: 2024-01-16
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• Liveborn offspring of women who participated in the MiTy trial.

Exclusion Criteria

• Offspring with major congenital anomalies that would affect growth or development (these children have already been excluded from MiTy Kids).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Body Mass Index (BMI) z-score	5-11 years of age	Using WHO or other appropriate growth charts

Secondary Outcome Measures

Name	Time	Method
Triceps skinfolds z-scores	5-11 years of age	Using WHO or other appropriate growth charts
Waist to height ratio	5-11 years of age	Waist and height measurements
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
Overweight and obesity status	5-11 years of age	Defined using WHO or other appropriate growth charts
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.
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	Social Responsiveness Scale (SRS-2)
Percentage of body fat	5-11 years of age	Using the Tanita SC-240 bioimpedance analyzer (BIA)
Waist circumference	5-11 years of age	Waist circumference measurement
Ratio of the central to peripheral skinfold ratio	5-11 years of age	ratio of the central (suprailiac) to peripheral (triceps) skinfold ratio;
Fat mass	5-11 years of age	Using the Tanita SC-240 bioimpedance analyzer (BIA)

Trial Locations

Locations (12)

Campbelltown Hospital; 🇦🇺 Campbelltown, New South Wales, Australia

Mater Misericordiae; 🇦🇺 Brisbane, Queensland, Australia

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

Stollery Children's Hospital; 🇨🇦 Edmonton, Alberta, Canada

British Columbia Children's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Children's Health Research Institute of Manitoba (CHRIM); 🇨🇦 Winnipeg, Manitoba, Canada

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

St Joseph's Health Care; 🇨🇦 London, Ontario, Canada

The Scarborough Hospital; 🇨🇦 Scarborough, Ontario, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

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