248-OR: MiTy Kids: Follow-Up of Offspring Exposed to Metformin In-Utero in Mothers with Type 2 Diabetes in the MiTy Trial
Authors: FEIG DENICE , SANCHEZ J. JOHANNA , MURPHY KELLIE , ASZTALOS ELIZABETH , ZINMAN BERNARD , SIMMONS DAVID , HAQQ ANDREA , FANTUS IVAN G. , LIPSCOMBE LORRAINE , ARMSON ANTHONY , BARRETT JON F.R. , DONOVAN LOIS E. , KARANICOLAS PAUL , KLEIN GAIL , TOBIN SIOBHAN , MANGOFF KATHRYN , TOMLINSON GEORGE , HAMILTON JILL 
Published: May 2022

Background: Offspring of mothers with T2D are at increased risk of obesity and diabetes. In the MiTy trial [pregnant T2D randomized to metformin vs. placebo], infants exposed to metformin were lighter, had lower fat-mass and risk of large-for-gestational-age, but at higher risk of small-for-gestational-age. There are questions on the long-term effects of in-utero exposure to metformin on offspring of women with T2D.
Aim: To examine adiposity in children of women with T2D, with and without exposure to metformin, up to 24 months.
Methods: We included infants of women who participated in MiTy. Anthropometric measurements were made at 3, 6, 12, 18 and 24 months of age. At 24 months, t-tests and linear regression were used to estimate differences in BMI z-score and sum of skinfolds by metformin group, adjusted for confounders. Comparisons over time used longitudinal models, with fractional polynomials for growth trajectories.
Results: Of the 465 eligible children from MiTy, 283 (60.8%) participated in MiTy Kids. At 24 months, there was no difference in BMI z-score (0·84±1·52 in metformin vs. 0·91±1·38 in placebo (p=0.72)) or sum of skinfolds (23·0±5·2 in metformin vs. 23·8±5·3 in placebo (p=0.31)) between groups. There was no difference in BMI trajectory by treatment overall but in males, treatment had significantly different trajectories (p=0.048) ; the metformin BMI was higher from 8 to 24 months. At 24 months, reduced sleep time (p=0.0125) and increased screen time (p=0.0549) were associated with increased BMI z-score. Offspring of women with T2D were approximately 1 SD heavier than the WHO reference population.
Conclusion: Offspring of women with T2D with and without exposure to metformin in-utero had similar anthropometrics overall. In males, metformin led to higher BMI growth trajectory between 8 and 24 months. Future follow-up is needed to see if these findings continue.

Disclosure
D.Feig: Advisory Panel; Novo Nordisk, Research Support; Apotex. A.Armson: None. J.F.R.Barrett: None. L.E.Donovan: Other Relationship; Dexcom, Inc., Inner Analytics, Medtronic, Tandem Diabetes Care, Inc. P.Karanicolas: Research Support; Baxter. G.Klein: None. S.Tobin: None. K.Mangoff: None. G.Tomlinson: None. J.Hamilton: Advisory Panel; Novo Nordisk Canada Inc., Research Support; Mead Johnson & Company, LLC. J.Sanchez: None. K.Murphy: None. E.Asztalos: None. B.Zinman: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi K.K. D.Simmons: Other Relationship; Elsevier, Research Support; Abbott, Hitachi, Ltd., Novo Nordisk, Speaker's Bureau; Sanofi. A.Haqq: None. I.G.Fantus: None. L.Lipscombe: n/a.

Funding
Canadian Health Institute for Research