Oxidative Stress and Indicators of Brain Damage Following Pediatric Heart Surgery.

Pediatric cardiac surgery induces an increased oxidative stress (OS) response. Increased OS is associated with poor neurologic outcomes in neonatal populations with similar patterns of brain injury. We investigated OS and brain injury in infants undergoing heart surgery. Patients 6 months or younger, undergoing cardiac surgery with or without cardiopulmonary bypass (CPB), were included in this prospective, observational study. Patients were divided into infant (30 days−6 months) and neonatal (<30 days) groups for analysis. Urine OS biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) was quantified pre-surgery and at 0 and 24 h post-surgery. A serum brain damage biomarker S100B protein was also measured pre-surgery and at 0 and 72 h post-surgery. Amplitude-integrated electroencephalography during surgery was analyzed. Neuropsychological evaluation using the Bayley III or Vineland test was performed in all patients at 24 months of age. Sixty-two patients were included, 44 of whom underwent follow-up neurologic evaluation. 8-iso-PGF2α and S100B levels were increased after surgery. Postoperative levels of S100B were positively correlated with 8-iso-PGF2α levels 24 h after surgery (rho = 0.5224; p = 0.0261). There was also a correlation between immediate post-surgery levels of 8-iso-PGF2α and intra-surgery seizure burden (rho = 0.4285, p = 0.0205). Patients with an abnormal neurological evaluation had increased levels of S100B 72 h after surgery (p = 0.048). 8-iso-PGF2α levels 24 h after surgery were also related to abnormal neurologic outcomes. Levels of 8-iso-PGF2α following pediatric cardiac surgery are associated with several indicators of brain injury including brain damage biomarkers, intra-operative seizures, and abnormal neurological evaluation at follow-up, suggesting the importance of oxidative stress response in the origin of brain damage in this population.

Oxidative stress response in children undergoing cardiac surgery: Utility of the clearance of isoprostanes.

INTRODUCTION: Cardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of their organs and antioxidant systems as well as the induction of OS in cardio-pulmonary bypass (CPB) surgery may have an important impact on outcomes. The purpose of this study was to describe the OS response, measured by urinary free 8-iso-PGF2α, in infants undergoing CS and to evaluate the relationship between OS response and post-operative clinical outcomes. METHODS: Infants with congenital heart disease undergoing CS with or without CPB were eligible for enrollment. Children were classified as neonates (<30 days) or infants (30 days-6 months) based on the age at surgery. Perioperative continuous non-invasive neuromonitoring included amplitude-integrated electroencephalogram and cerebral regional oxygen saturation measured with near-infrared spectroscopy. Urine 8-iso-PGF2α levels were measured before, immediately post-, and 24-hours post-surgery, and the 8-iso-PGF2 clearance was calculated. RESULTS: Sixty-two patients (60% neonates) were included. Urine 8-iso-PGF2α levels 24 hours after surgery (8.04 [6.4-10.3] ng/mg Cr) were higher than pre-operative levels (5.7 [4.65-7.58] ng/mg Cr) (p<0.001). Those patients with a severe degree of cyanosis caused by Transposition of the Great Arteries (TGA) had the highest post-operative 8-iso-PGF2α levels. Patients with intra-operative seizures had higher post-operative 8-iso-PGF2α levels. 8-iso-PGF2α clearance at 24 hours post-surgery was different between newborns and infant patients, and it was inversely correlated with days of mechanical ventilation (p = 0.05), ICU LOS (p = 0.05) and VIS score at 24 hours (p = 0.036). CONCLUSIONS: Children undergoing CS, particularly neonatal patients, experience a significant post-operative OS response that might play an important role in postoperative morbidity. TGA patients undergoing arterial switch operations demonstrate the highest post-operative OS response. Rapid clearance of isoprostanes, which occurs more frequently in older patients with more mature antioxidant systems, might be associated with better clinical outcomes.

Drug testing in biological samples vs. maternal surveys for the detection of substance use during whole pregnancy.

BACKGROUND: Early diagnosis of nicotine, ethanol and drug use during pregnancy is critical in order to provide adequate care. Current screening procedures show limitations in terms of reliability and short windows of detection. OBJECTIVES: To investigate the prevalence and identify biomarkers of substance use and changes in substance use during pregnancy. To compare drug testing results in different types of biological samples (maternal hair, meconium, placenta, umbilical-cord) with self-reported data. PARTICIPANTS AND SETTING: Prospective cohort study using data from pregnant women and their newborns. METHODS: Biological matrices were collected at birth and analyzed by liquid chromatography tandem mass spectrometry. A paper survey was provided to determine substance use habits. RESULTS: 867 mother-newborn pairs were included. According to the analysis of biological samples, 29.1% cases were positive for one or more substances (13.6% nicotine, 8.4% ethanol, 8.3% cocaine, 6.4% cannabis, 5.7% opioids). The profile of the substance-using mother was a single woman, <28 years-old, with no higher education and unemployed. Segmental maternal hair analysis showed a decrease in tobacco, cannabis and cocaine use throughout pregnancy (p < 0.001). The level of concordance between results from interviews and from biological analyses was weak for opioids, cocaine, and cannabis (kappa coefficient < 0.40). Maternal hair detected the highest number of cases, followed by meconium and by placenta and/or umbilical-cord. CONCLUSIONS: Maternal survey was not a reliable screening technique. Analysis of maternal hair detected the highest number of cases with the broadest detection window (whole pregnancy).

Risk stratification models for congenital heart surgery in children: Comparative single-center study.

OBJECTIVE: Three scores have been proposed to stratify the risk of mortality for each cardiac surgical procedure: The RACHS-1, the Aristotle Basic Complexity (ABC), and the STS-EACTS complexity scoring model. The aim was to compare the ability to predict mortality and morbidity of the three scores applied to a specific population. DESIGN: Retrospective, descriptive study. SETTING: Pediatric and neonatal intensive care units in a referral hospital. PATIENTS: Children under 18 years admitted to the intensive care unit after surgery. INTERVENTIONS: None. OUTCOME MEASURES: Demographic, clinical, and surgical data were assessed. Morbidity was considered as prolonged length of stay (LOS > 75 percentile), high respiratory (>72 hours of mechanical ventilation), and high hemodynamic support (inotropic support >20). RESULTS: One thousand and thirty-seven patients were included, in which 205 were newborns (18%). The category 2 was the most frequent in the three scores: In RACHS-1, ABC, 44.9%, and STS-EACTS, 40.8%. Newborns presented significant higher categories. Children required cardiopulmonary bypass in more occasions (P < .001) but the times of bypass and aortic cross-clamp were significantly higher in newborns (P < .001 and P = .016). Thirty-two patients died (2.8%). A quarter of patients had a prolonged LOS, 17%, a high respiratory support, and 7.1%, a high hemodynamic support. RACHS-1 (AUC 0.760) and STS-EACTS (AUC 0.763) were more powerful for predicting mortality and STS-EACTS for predicting prolonged LOS (AUC 0.733) and the need for high respiratory support (AUC 0.742). CONCLUSIONS: STS-EACTS seems to stratify better risk of mortality, prolonged LOS, and need for respiratory support after surgery.

Availability of Donor Milk for Very Preterm Infants Decreased the Risk of Necrotizing Enterocolitis without Adversely Impacting Growth or Rates of Breastfeeding.

Human milk contains non-nutritional factors that promote intestinal maturation and protect against infectious and inflammatory conditions. In the Neonatal Intensive Care Unit (NICU) setting, donor milk (DM) is recommended when availability of own mother's milk (OMM) is not enough. Our aim was to compare the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm infants (VPI) after the introduction of DM. Growth and breastfeeding rates were examined as secondary outcomes. Single center, observational and retrospective cohort study comparing 227 VPI admitted to our neonatal unit before (Group 1, n = 99) and after (Group 2, n = 128) DM introduction. Enteral nutrition was started earlier after DM availability (2.6 ± 1.1 vs. 2.1 ± 1 days, p = 0.001). Incidence of NEC decreased in group 2 (9.1% vs. 3.4%, p = 0.055), especially in those born between 28 and 32 weeks (5.4 vs. 0.0%, p = 0.044). Surgical NEC was also less frequent. Suffering NEC was 4 times more likely in group 1 (multivariate analysis). Availability of DM did not impact breastfeeding rates or preterm growth. Our findings support the protective role of DM against NEC, particularly in non-extreme VPI, a group less frequently included in clinical guidelines and research studies on the use of DM.