The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn.

The birth process induces fetal stress. Stress has profound effects on the immune system, also by acting on the trafficking of leukocytes, a process in which adhesion and chemotaxis are primordial and critical events for the development of effective antimicrobial defenses. The newborn is rapidly challenged by a microflora at the epithelia linings and therefore depending on early, innate immunity onset. The objective of the study was to investigate the immune response in cord blood from newborns in relation to different degrees of fetal stress, with focus on neutrophil chemotaxis. We analyzed in vitro transmigration ability of neutrophils and their CD11b expression, measured total white blood count (WBC) and the major leukocyte populations, interleukin (IL)-8, interferon (IFN)-gamma, and soluble E-Selectin, as well as relevant immuno-modulating hormones in infants born at term after Cesarean section prior to the start of labor (n = 55), normal vaginal delivery (n = 87), and assisted delivery (n = 26). Arterial pH and lactate were used as stress markers. We found that spontaneous and IL-8-induced transmigration ability of neutrophils from newborns after normal delivery was significantly higher compared with that of neutrophils from Cesarean section or from adults. With a progressive increase in fetal stress, there were significant elevations in total WBC, in particular neutrophils and monocytes, as well as an enhanced IL-8 and soluble E-Selectin level. Assisted delivery, associated with the highest degree of fetal stress in addition had an enhanced lymphocyte and monocytes count as well as an increased IFN-gamma level. There were significant direct correlations between neutrophils and monocytes, respectively, with cortisol, beta-endorphin, and prolactin. Interferon-gamma was directly related to dopamine, as well as to the lymphocyte and monocyte count. The setting of the HPA-axis at birth is a promoter of an alarm response and a surge of neuroendocrine immuno-modulating factors that enhances antimicrobial defenses of the newborn. We speculate that IL-8 induced by normal labor may be a priming factor for an increased neutrophil chemotaxis through the pre-activated endothelium of the fetus. Assisted delivery may trigger excessive recruitment of additional inflammatory cells and IFN-gamma release.

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.