Insulin-like growth factor binding protein-1 and interleukin-6 are markers of fetal stress during parturition at term gestation

OBJECTIVE: Maintaining an adequate blood glucose level is essential for neuron integrity. The increased energy demand imposed on the fetus by the birth process in combination with a limited glucose production capacity therefore threatens brain function. It is logical to presume that mechanisms increasing glucose mobilization as well as decreasing peripheral glucose utilization has evolved to preserve brain function, even after complicated deliveries. DESIGN: We studied umbilical cord levels of hormones involved in acute glucose regulation as well as insulin-like growth factor-I (IGF-I), modulating factors insulin-like growth factor binding protein (IGFBP)-1 and -3 as well as interleukin-6 (IL-6) in 149 infants born after different degrees of birth stress. We measured glucose, insulin, IGF-I, IGFBP-1, IGFBP-3, glucagon, growth hormone (GH), prolactin, adrenocorticotropin (ACTH), cortisol and IL-6 in umbilical cord blood of infants born at term gestation after: A) elective Cesarean-section (n = 37), B) normal delivery (n = 87) or C) complicated delivery (n = 25). All infants were of normal birth weight for gestational age. Arterial pH and lactate as well as S-100B, a marker of neuronal damage, were used as stress variables. RESULTS: With increasing fetal stress, we found significant and generally progressive elevations in glucose, IGFBP-1, IL-6, ACTH, cortisol, glucagon, GH, prolactin and lactate. This was accompanied by significant decreases of IGF-I, insulin and arterial pH. S-100B and IGFBP-3 levels did not differ between groups. IGFBP-1 showed a significant positive correlation to IL-6 and lactate and a significant negative correlation to both IGF-I and arterial pH. CONCLUSIONS: Increasing stress and energy demands during birth are accompanied by increasing fetal levels of glucose-mobilizing hormones in combination with depressed levels of insulin and IGF-I, despite increasing blood glucose. Furthermore, IGFBP-1 and IL-6 increase steeply, presumably aimed at diminishing insulin-like activity of IGF-I, thereby reducing peripheral glucose utilization. We believe that IGFBP-1 and IL-6 deserve evaluation as potential intrapartum indicators of fetuses at risk for asphyxia.