Maternal Obesity and Excessive Gestational Weight Gain Alter the Maternal-Fetal Insulin-Like Growth Factor Axis

      Obesity and excessive gestational weight gain (GWG) increase risk of fetal overgrowth and tracking of excess weight throughout life. The physiological mechanisms underlying these associations are incomplete yet the IGF axis has garnered attention for its role in glycemic control and fetal growth. This overview examines the effects of obesity and excessive GWG on IGF axis protein expression patterns in mother-infant dyads. Fasting serum samples from 12 control and 12 obese (BMI ≥30 kg/m2 ) pregnant women were obtained prior to, and the corresponding umbilical cord blood, immediately following elective C-section. We examined IGF axis protein expression and hormone concentrations in both maternal and cord blood and then assessed GWG between groups by comparing those who met [(ADHERE group) i.e., gained in accordance to Institute of Medicine (IOM) GWG recommendations] and those who exceeded [(EXCEED group) i.e., those who exceeded IOM GWG recommendations)]. Elevated maternal insulin (p=0.03) and leptin (p<0.01) levels were observed in obese gravidas. After adjustment, maternal HOMA-IR positively correlated with both maternal BMI and leptin levels (p<0.01). Umbilical cord blood levels of IGF binding protein-3 (IGFBP-3) were directly related to fetal-placental weight ratio (p<0.01) and showed an inverse trend to maternal HOMA-IR (p=0.03). However, in cord serum from obese mothers IGFBP-4 expression was attenuated when compared to controls (p<0.05). With respect to GWG, elevated maternal leptin (p≤0.05) concentrations were observed in gravidas who exceeded recommendations. However, there were greater numbers of obese women in the EXCEED group (p<0.05). After adjustment, maternal leptin was positively correlated with maternal HOMA-IR score and excessive GWG (p<0.01). However, serum IGFBP-3 expression in the EXCEED mothers was greater than that in the ADHERE group (p≤0.05). Our findings suggest that obesity and GWG affect maternal-fetal growth signals during pregnancy.