Oral Concurrent Session 7 - Diabetes
Oral Concurrent Sessions
Claire E. Jensen, MD, MSCR (she/her/hers)
Fellow
University of North Carolina
Chapel Hill, North Carolina, United States
Ashley N. Battarbee, MD, MSCR
Assistant Professor
Center for Women’s Reproductive Health, University of Alabama at Birmingham
Birmingham, Alabama, United States
Kim Boggess, MD
Professor
University of North Carolina
Chapel Hill, North Carolina, United States
Kjersti M. Aagaard, MD, PhD
Medical Director, HCA Healthcare and HCA Research Institute
Boston Children’s Hospital, Division of Fetal Medicine and Surgery, Boston, MA; HCA Healthcare and HCA Healthcare Research Institute, Nashville, TN; HCA Texas Maternal Fetal Medicine, Houston, TX; Baylor College of Medicine and Texas Children's Hospital, Houston, TX
Tomball, Texas, United States
Murine and primate models treated with maternal metformin exhibit fetal bioaccumulation, leading to reduced muscle and retroperitoneal fat mass with fetal growth restriction. In clinical trials, maternal metformin use during pregnancy results in smaller neonates with reduced LGA risk, alongside a variable increased risk for SGA births. We hypothesized that the observed decreased prevalence of LGA births with maternal metformin use during pregnancy results from reduced accumulation of fetal fat free mass (FFM, i.e., muscle accretion) rather than diminished adiposity.
Study Design:
Secondary analysis of a large multicenter RCT (MOMPOD) of metformin 1000mg BID vs. placebo in singleton pregnancies at 11-23 weeks with insulin-treated early diabetes or pre-existing T2DM. We included all participants who took ≥ 1 dose of study drug and had neonatal anthropometry. Multivariable linear regression estimated the association between metformin use and neonatal FFM and evaluated for effect modification by key covariates.
Results:
Of n=794 participants, 437 (55%) completed comprehensive neonatal anthropometry. They were demographically similar to the full cohort and balanced between treatment groups. Mean FFM was 2786 g (SD 408.15g, 86.2% of birth weight). FFM was 81.8g less in neonates exposed to metformin (95% CI -157.59, -4.56). The association between metformin exposure and FFM did not vary by neonatal sex, maternal race/ethnicity, pregestational diabetes diagnosis, nor excess maternal weight gain (Table 1). There was a trend toward effect modification by duration of exposure (Figure 1), indicating that the metformin-associated decline in muscle accretion increased with gestational age (p=0.21).
Conclusion:
Metformin is associated with lower neonatal muscle accretion, measured as FFM. Our finding of decreased FFM among metformin-exposed neonates adds to the mounting evidence raising concern for transplacental transfer and bioaccumulation in the fetus, which may restrict healthy physiologic growth patterns and potentially increase risk for adverse long-term cardiometabolic outcomes.
