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

Mount Sinai Hospital, Canada

Status: Enrolling

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

Study type: Observational

Funder types: Other

Identifiers

NCT05025852

CTO 3632

Details and patient eligibility

About

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.

Enrollment: 220 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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).

Trial design

220 participants in 2 patient groups

Metformin exposed in utero

Description:

Offspring of mothers who were exposed to metformin during pregnancy in the MiTy trial.

Placebo exposed in utero

Description:

Offspring of mothers who were not exposed to metformin during pregnancy in the MiTy trial.