Regulation Of Maternal Fuel Supply And Neonatal Adiposity
Condition: Fetal Macrosomia; Gestational Diabetes
MeSH terms: Diabetes, Gestational; Fetal Macrosomia
Study type: Observational

Summary: 
      The purpose of this study is to determine whether unrecognized maternal hyperglycemia and
      postprandial lipemia early or late in gestation predicts excess neonatal adiposity.
    

Detailed description: 
      Mounting epidemiologic evidence suggests that maternal obesity and Gestational Diabetes
      Mellitus (GDM) independently influence size at birth and disease susceptibility later in
      life. A major gap in the understanding of fetal programming is the knowledge of whether and
      how exposure to excess maternal fuels in the absence of frank hyperglycemia impacts fetal fat
      accretion. The investigators hypothesis is that neonatal adiposity results from unrecognized
      maternal hyperglycemia and excess lipid availability in gestation, in part caused by
      excessive lipolysis in the white adipose tissue of obese women, some of whom will be
      subsequently diagnosed as having GDM. In Aim 1 the investigators will test the hypothesis
      that in obese women, some of whom will later be diagnosed with GDM, increased lipolysis and
      unrecognized hyperglycemia and hypertriglyceridemia occur earlier in gestation than in lean
      women, resulting in increased plasma non-esterified fatty acids (NEFA), glycerol,
      triglycerides (TGs), and glucose available for fetal metabolism. In Aim 2 the investigators
      will test the hypothesis that fetal adiposity by ultrasound and neonatal adiposity by
      Dual-energy X-ray Absorptiometry (DXA) are strongly correlated with excess lipid and glucose
      availability in obese mothers early in gestation, regardless of GDM status, and that fasting
      biomarkers of neonatal insulin sensitivity will correlate with neonatal adiposity. In Aim 3
      the investigators will test the hypothesis that the in-vitro suppression of lipolysis in
      white adipose tissue correlates with excess NEFA and TG availability in-vivo and is
      predictive of neonatal adiposity. The elucidation of specific derangements in both glucose
      and lipid metabolism and their timing in gestation in mothers who deliver infants with excess
      adiposity could challenge our current screening methods and entirely redirect our treatment
      to target the responsible maternal fuels. On a public health level, this research is
      instrumental to the investigators understanding of how an intrauterine environment may
      deliver excess glucose and/or lipids to the fetus and contribute to the genesis of the
      pediatric obesity epidemic. Such information may result in new treatment strategies in
      pregnant women to normalize fetal growth.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Lean (BMI 20-26 kg/m2)and Obese (BMI 30-38 kg/m2) pregnant women (age 18-35 yr) without
        chronic medical conditions or obstetric complications will be enrolled at 12-14 weeks
        gestation.
      
Keywords: Fetal programming; Fetal macrosomia; Fetal health; Gestational diabetes; Maternal health; Maternal obesity