Search

Vaginal birth prepares the fetus for postnatal life. It confers respiratory, cardiovascular and homeostatic advantages to the newborn infant compared with elective cesarean section, and is reported to provide neonatal analgesia. We hypothesize that infants born by vaginal delivery will show lower noxious-evoked brain activity a few hours after birth compared to those born by elective cesarean section. In the first few hours of neonatal life, we record electrophysiological measures of noxious-evoked brain activity following the application of a mildly noxious experimental stimulus in 41 infants born by either vaginal delivery or by elective cesarean section. We demonstrate that noxious-evoked brain activity is related to the mode of delivery and significantly lower in infants born by vaginal delivery compared with those born by elective cesarean section. Furthermore, we found that the magnitude of noxious-evoked brain activity is inversely correlated with fetal copeptin production, a surrogate marker of vasopressin, and dependent on the experience of birth-related distress. This suggests that nociceptive sensitivity in the first few hours of postnatal life is influenced by birth experience and endogenous hormonal production.

Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel, Switzerland; 6Department of Human Morphology and Biomedical Science, University of Milan, Milan, Italy; 7Research Department, B•R•A•H•M•S Biomarkers, Thermo Fisher Scientific, Hennigsdorf, Germany; 8Medical Intensive Care Unit, University Hospital Zürich, Zürich, Switzerland; 9Universidad Peruana Cayetano Heredia, Lima, Peru *These authors contributed equally to this work and share first authorship Background: A reduced oxygen supply puts patients at risk of tissue hypoxia, organ damage, and even death. In response, several changes are activated that allow for at least partial adaptation, thereby increasing the chances of survival. We aimed to investigate whether the arginine vasopressin marker, copeptin, can be used as a marker of the degree of acclimatization/adaptation in rats exposed to hypoxia. Methods: Sprague-Dawley rats were exposed to 10% oxygen for up to 48 hours. Arterial and right ventricular pressures were measured, and blood gas analysis was performed at set time points. Pulmonary changes were investigated by bronchoalveolar lavage, wet and dry weight measurements, and lung histology. Using a newly developed specific rat copeptin luminescence immunoassay, the regulation of vasopressin in response to hypoxia was studied, as was atrial natriuretic peptide (ANP) by detecting mid-regional proANP. Results: With a decreasing oxygen supply, the rats rapidly became cyanotic and inactive. Despite continued exposure to 10% oxygen, all animals recuperated within 16 hours and ultimately survived. Their systemic blood pressure fell with acute (5 minutes) hypoxia but was partially recovered over time. In contrast, right ventricular pressures increased with acute (5 minutes) hypoxia and normalized after 16 hours. No signs of pulmonary inflammation or edema were found despite prolonged hypoxia. Whereas copeptin levels increased significantly after acute (5 minutes) hypoxia and then returned to near baseline after 16 hours, mid-regional proANP levels were even further increased after 16 hours of exposure to hypoxia. Conclusion: Plasma copeptin is a sensitive marker of acute (5 minutes) exposure to severe hypoxia, and subsequent regulation can indicate recovery. Copeptin levels can therefore reflect clinical and physiological changes in response to hypoxia and indicate recovery from ongoing hypoxic exposure. Keywords: vasoactive peptides, hypoxia, copeptin, atrial natriuretic peptide, acclimatization, adaptation, critical illness

Copeptin is a stable by-product of arginine-vasopressin synthesis and reflects its secretion by the pituitary.The objective of the study was to investigate perinatal factors affecting copeptin concentrations in preterm infants at birth and at 3 d of life.This was a prospective cross-sectional study at two Swiss university hospitals.One hundred sixty-seven preterm infants were enrolled, 59 infants born between 24 and 31 wk gestational age, 50 infants between 32 and 34 wk, and 58 between 35 and 36 wk.Plasma copeptin concentrations, determined by a CT-proAVP-luminescence-immunoassay, were measured.Copeptin at birth was significantly higher in preterm infants born vaginally [median (range) 366 (1-2900) pmol/liter, n = 43] than those born by cesarean section [6.9 (2-1580), n = 124]. In infants born after cesarean without prior labor (n = 66), estimated fetal weight less than the fifth percentile, suspect fetal heart rate, compromised placental perfusion, and chorioamnionitis were each associated with significantly elevated cord copeptin. Copeptin at 3 d of life was not associated with cord blood copeptin but inversely related to gestational age (Rs = -0.6, P0.001) and birth weight (Rs -0.612, P0.001). Day 3 copeptin increased alongside the level of mechanical respiratory support.Copeptin is a highly sensitive marker of perinatal stress.