Associations Between Maternal Insulin Resistance During Pregnancy and Children Inflammation at Birth and at 5 Years of Age

• In Event: Poster Session 06
  In Poster Session: PS 06 Topic - Biological Processes: Psychophysiology

Abstract

Background: Prenatal and neonatal inflammation has been associated with long-term outcomes in offspring, in both metabolic and psychiatric domains. The prenatal environment has the potential to influence the unborn child during a critical and sensitive window of brain development. Insulin resistance in women during pregnancy is a normal physiological response to derive nutrients to the fetus, but if excessive, it can lead to gestational diabetes mellitus. Insulin resistance is associated with maternal inflammation during pregnancy but it’s unclear whether this condition is also related to inflammation in offspring. Thus, the goal of this study is to assess the relationship between maternal insulin resistance during pregnancy and offspring inflammation at birth and at 5 years of age.
Methods: This study is based on 660 mother-child pairs enrolled in the Genetics of Glucose regulation in Gestation and Growth (Gen3G) study, a Canadian prospective pre-birth cohort. We collected maternal blood samples during pregnancy and measured metabolic markers between 24 and 30 weeks of gestation, including insulin and glucose levels (fasting, 1h and 2h during oral glucose tolerance test (OGTT)), which allowed us to derive homoeostasis model of assessment of insulin resistance (HOMA-IR) and the Matsuda Index. Child inflammation was assessed using tumor necrosis factor alpha (TNFα) concentrations in cord blood at birth and in blood at 5 years. We applied multivariable linear regression models to examine the associations between maternal metabolic markers in pregnancy and children’s TNFα levels at birth and at 5 years of age adjusted for maternal age, ethnicity, smoking status, family history of diabetes, parity, education level and body mass index (BMI).
Results: At enrolment in early pregnancy, mean (SD) age of women was 28.3 (4.3) years, 21% had a BMI over 30 kg/m2, 71% of women had a college degree, and 97% self-reported being white. Results of the regression models presented in Table 1 show that fasting insulin levels and HOMA-IR were negatively associated with TNFα levels at birth (B = -1.06, 95% CI [-1.89, -0.22] and -1.02, 95% CI [-1.82, -0.21], respectively) in fully adjusted models. We did not find persistence of these associations with TNFα measured at 5 years of age. We observed weak or null associations with individual glucose levels, post-load insulin levels, or Matsuda Index.
Conclusions: Contrary to our hypothesis, higher prenatal fasting insulin and HOMA-IR levels were associated with lower TNFα of offspring at birth, indicating that higher maternal insulin resistance is related to lower neonatal inflammation levels. Based on these findings, we speculate that the placenta has an important role in the maternal/offspring inflammatory regulation. Results of this study highlighted the need to deepen our understanding of the mechanisms linking exposure to insulin resistance and long-term child development.

Authors

• Sabrina Faleschini, Harvard Medical School
  Presenting Author

• Myriam Doyon, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
  Non-Presenting Author

• Mélina Arguin, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
  Non-Presenting Author

• Patrice Perron, Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada
  Non-Presenting Author

• Luigi Bouchard, Department of Biochemistry and Functional genomics, Université de Sherbrooke, Sherbrooke, QC, Canada
  Non-Presenting Author

• Marie-France Hivert, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
  Non-Presenting Author