J. Perinat. Med. 2014; 42(6): 705–709

Alexandra Almanzar Morel*, Sean M. Bailey, Gerry Shaw, Pradeep Mally and Sunil P. Malhotra

Measurement of novel biomarkers of neuronal injury and cerebral oxygenation after routine vaginal delivery versus cesarean section in term infants Abstract Aims: It remains unclear if mode of delivery can have any impact on the neonatal brain. Our aim was to determine in term newborns any differences based on mode of delivery in either neuronal injury biomarkers, phosphorylated axonal neurofilament heavy chain (pNF-H) and ubiquitin C-terminal hydrolase (UCHL1), or brain oxygenation values, regional cerebral tissue oxygen saturation (CrSO2) and cerebral fractional tissue oxygen extraction (CFOE). Methods: An Institutional Review Board approved prospective observational pilot study of well newborns. Serum pNF-H and UCHL1 levels were measured on the day following delivery. CrSO2 values along with CFOE values were also measured using near-infrared spectroscopy (NIRS) and pulse oximetry. Results: There were 22 subjects, 15 born vaginally and seven born by cesarean section. No difference was found in mean pNF-H (107.9 ± 54.3  pg/mL vs. 120.2 ± 43.3 pg/mL, P = 0.66) or mean UCHL1 (4.0 ± 3.5  pg/mL vs. 3.0 ± 2.2 pg/ mL, P = 0.68). No difference was found in mean CrSO2 (80.8 ± 5.3% vs. 80.8 ± 5.6%, P = 0.99) or mean CFOE (0.17 ± 0.06 vs. 0.15 ± 0.08, P = 0.51). Conclusions: We found no difference in neuronal injury markers between term neonates born vaginally compared to those born by cesarean section. From a neurologic standpoint, this supports current obstetric practice *Corresponding author: Alexandra Almanzar Morel, Division of Neonatology, Department of Pediatrics, New York University School of Medicine, NYU Langone Medical Center/Bellevue Hospital, 462 First Avenue, 8th floor, Room 8W31, New York, NY 10016, USA, E-mail: [email protected] Sean M. Bailey and Pradeep Mally: Division of Neonatology, Department of Pediatrics, New York University School of Medicine, New York, NY, USA Gerry Shaw: Department of Neuroscience, University of Florida, College of Medicine, Gainesville, FL, USA and EnCor Biotechnology Inc. Gainesville, FL, USA Sunil P. Malhotra: Division of Pediatric and Adult Congenital Cardiac Surgery, Department of Cardiothoracic Surgery, New York University School of Medicine, New York, NY, USA

guidelines that emphasize vaginal birth as the preferred delivery method whenever possible. Keywords: Cerebral fractional oxygen extraction; d ­ elivery mode; near-infrared spectroscopy; neuronal injury biomarkers; phosphorylated axonal neurofilament heavy chain; regional cerebral tissue oxygen saturation; ubiquitin C-terminal hydrolase. DOI 10.1515/jpm-2014-0274 Received April 23, 2014. Accepted July 23, 2014. Previously published online September 13, 2014.

Introduction The exact impact, if any, that mode of delivery may have on the neonatal brain and the circulatory adaptation during the first days of life remains unclear. Although felt to cause no harm, the compression and decompression of the skull at the moment of birth may affect cerebral blood flow in vaginally delivered infants [5]. Arterial oxygen saturation (SpO2) undergoes tremendous changes during transition from the fetus to newborn [12]. Simply, the process of the head going through the birth canal can theoretically have some impact on the infant brain. Additionally, during vaginal delivery, many catecholamines are released and they act to constrict the peripheral vessels and increase cerebral blood flow [11]. Recently discovered novel neuronal biomarkers are being studied as a way to rapidly determine if brain injury exists in newborn infants and the extent of such injury. Phosphorylated axonal neurofilament heavy chain (pNF-H) is concentrated in white matter brain regions, and ubiquitin C-terminal hydrolase (UCHL1), found in neuronal cell bodies and concentrated in cortices, are two brain injury biomarkers that can be measured in the serum [1, 6, 9]. They have previously been found useful in establishing if brain injury has occurred and the level of injury in infants, children, and adult patients [15].

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706      Almanzar et al., Neuronal injury markers and delivery mode Cerebral regional tissue oxygen saturation (CrSO2) can be monitored with near-infrared spectroscopy (NIRS) and it provides clinicians with live-time information about brain tissue blood perfusion and brain oxygen status [22]. Cerebral fractional oxygen extraction (CFOE) can be calculated using CrSO2 values and SpO2 values to determine how much oxygen is being extracted from hemoglobin as it passes through the brain tissue. These values have been shown to be markers of brain injury in infants with hypoxic-ischemic encephalopathy [7]. An effective biomarker should have a high correlation with short-term and long-term outcomes. Both UCHL1 and pNF-H demonstrate this potential. Both are expressed only in neurons and they may reflect brain injury more accurately than other inflammatory markers [14]. First determining normal range values for these neuronal injury biomarkers is important. These serum markers can be a clinically relevant tool providing information to clinicians about the degree of the initial brain injury an infant may have suffered. They can also provide prognostic information for clinicians and parents in regards to patients with processes that can have an effect on the neonatal brain, such as patients with HIE or congenital cardiac disease [7]. Both serum biomarkers and non-invasive monitoring of brain tissue oxygenation are being further explored as new ways to detect injury in the neonatal brain, the most vulnerable organ system in an infant. These methods are beginning to be found clinically useful. Normal values of pNF-H and UCHL1, however, have yet to be fully established in neonates. Normal brain tissue oxygenation values are being established, and CrSO2 and CFOE values associated with neurologic injury have been well established based on research in infants with congenital cardiac disease [4]. We suspected that there could possibly be a difference in neuronal biomarkers and cerebral oxygen delivery and extraction in term infants based on mode of delivery alone. Therefore, a study examining these parameters in a prospective observational model was conducted.

Patients and methods Study design We conducted an Institutional Review Board approved (NYU IRB S12-01870) prospective observational pilot study of term infants in the newborn nursery. Potential subjects were identified based on inclusion and exclusion criteria and parental consent was obtained before each subject was enrolled. On the second day of life of each subject, 1  mL of blood was obtained during a nursery visit. At this same visit, CrSO2 was monitored by placing a NIRS cerebral sensor

on the left forehead with the medial edge of the sensor 1  cm from midline and the inferior edge 1 cm above the brow line. This site was chosen as NIRS is used in this manner in our own clinical practice based on prior literature [2]. NIRS measurements were taken for 1 h at 30 s intervals. Pulse oximetry was also obtained continuously and simultaneously. All monitoring was conducted in the patient’s room while in their bassinette.

Subjects Healthy term infants (37–42 weeks of gestational age) who were born at the New York University Langone Medical Center (New York, NY, USA) and admitted to the well baby nursery were eligible to participate in this study. Infants with known genetic conditions, congenital defects, or a birth weight  

Measurement of novel biomarkers of neuronal injury and cerebral oxygenation after routine vaginal delivery versus cesarean section in term infants.

It remains unclear if mode of delivery can have any impact on the neonatal brain. Our aim was to determine in term newborns any differences based on m...
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