Clinical trial NCT05025852: The Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial
Official title: A Multi-centre Follow up Study of the Effect of In-utero Exposure to Metformin in 5-11 Year Old Offspring of Mothers in the MiTy Trial
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Mellitus, Type 2
Pregnancy in Diabetic
Child Obesity
Child Development
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Sunnybrook Research Institute
name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-08-27
Enrollment: 220
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Offspring of women with type 2 diabetes who participated in the MiTy trial will be recruited for participation.

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Body Mass Index (BMI) z-score
timeFrame: 5-11 years of age
Secondary outcomes:
measure: Skinfold measurements
timeFrame: 5-11 years of age
measure: Sum of skinfold measurements:
timeFrame: 5-11 years of age
measure: Triceps skinfolds z-scores
timeFrame: 5-11 years of age
measure: Ratio of the central to peripheral skinfold ratio
timeFrame: 5-11 years of age
measure: Overweight and obesity status
timeFrame: 5-11 years of age
measure: Waist circumference
timeFrame: 5-11 years of age
measure: Waist to height ratio
timeFrame: 5-11 years of age
measure: Growth trajectory
timeFrame: 5-11 years of age
measure: Fat mass
timeFrame: 5-11 years of age
measure: Percentage of body fat
timeFrame: 5-11 years of age
measure: Measures of insulin resistance and metabolic syndrome
timeFrame: 5-11 years of age
measure: Neurocognitive development
timeFrame: 5-11 years of age
measure: Neurocognitive development
timeFrame: 5-11 years of age
measure: Neurocognitive development
timeFrame: 5-11 years of age
Other outcomes:
Locations:
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Misericordiae
state: Queensland
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Children's Health Research Institute of Manitoba (CHRIM)
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: St Joseph's Health Care
state: Ontario
city: Scarborough
country: Canada
facility: The Scarborough Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montréal
country: Canada
facility: Hospital Maisonneuve-Rosemont
state: Quebec
city: Quebec City
country: Canada
facility: Chuq-Chul
state: Quebec
Study officials:
affiliation: Mount Sinai Hospital, Toronto, ON, Canada
name: Denice Feig, MD
role: PRINCIPAL_INVESTIGATOR
References: