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Preterm neonates exposed to painful NICU procedures exhibit increased pain scores and alterations in oxygenation and heart rate. It is unclear whether these physiologic responses increase the risk of oxidative stress. Using a prospective study design, we examined the relationship between a tissue-damaging procedure (TDP, tape removal during discontinuation of an indwelling central arterial or venous catheter) and oxidative stress in 80 preterm neonates. Oxidative stress was quantified by measuring uric acid (UA) and malondialdehyde (MDA) concentration in plasma before and after neonates experienced a TDP (n=38) compared to those not experiencing any TDP (control group, n=42). Pain was measured before and during the TDP using the Premature Infant Pain Profile(PIPP). We found that pain scores were higher in the TDP group compared to the control group (median scores:11 and 5, respectively, P<0.001). UA significantly decreased over time in control neonates but remained stable in TDP neonates (132.76μM to 123.23μM vs.140.50μM to 138.9μM, P=0.002). MDA levels decreased over time in control neonates but increased in TDP neonates (2.07μM to 1.81μM vs. 2.07μM to 2.21μM, P=0.01). We found significant positive correlations between PIPP scores and MDA. Our data suggest a significant relationship between procedural pain and oxidative stress in preterm neonates.

Objective: Due to physiological and metabolic immaturity, prematurely born infants are at increased risk because of maternal separation in many neonatal intensive care units (NICUs). The stress induced from maternal–infant separation can lead to well-documented short-term physiologic instability and potentially lifelong neurological, sociological, or psychological sequelae. Based on previous studies of kangaroo mother care (KMC) that demonstrated improvement in physiologic parameters, we examined the impact of KMC on physiologic measures of stress (abdominal temperature, heart rate, oxygen saturation, perfusion index, near-infrared spectrometry), oxidative stress, and energy utilization/conservation in preterm infants. Methods: In this randomized, stratified study of premature neonates, we compared the effects on urinary concentrations of biomarkers of energy utilization and oxidative stress of 1 hr of KMC versus incubator care on Day 3 of life in intervention-group babies ( n = 26) and control-group babies ( n = 25), respectively. On Day 4, both groups received 1 hr of KMC. Urinary samples were collected 3 hr before and 3 hr after intervention/incubator care on both days. Energy utilization was assessed by measures of adenosine triphosphate (ATP) degradation (i.e., hypoxanthine, xanthine, and uric acid). Oxidative stress was assessed using urinary allantoin. Mixed-models analysis was used to assess differences in purine/allantoin. Results: Mean allantoin levels over Days 3 and 4 were significantly lower in the KMC group than in the control group ( p = .026). Conclusions: Results provide preliminary evidence that KMC reduces neonatal oxidative stress processes and that urinary allantoin could serve as an effective noninvasive marker for future studies.

Objective To examine the effects of sucrose on pain and biochemical markers of adenosine trisphosphate(ATP) degradation and oxidative stress in preterm neonates experiencing a clinically required heel lance. Study design Preterm neonates that met study criteria (n=131) were randomized into three groups: (1) control; (2) heel lance treated with placebo and non-nutritive sucking (NNS); and (3) heel lance treated with sucrose and NNS. Plasma markers of ATP degradation (hypoxanthine, xanthine and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured using the Premature Infant Pain Profile (PIPP). Data were analyzed using repeated measures ANOVA and Spearman rho. Results We found significant increases in plasma hypoxanthine and uric acid over time in neonates who received sucrose. We also found a significant negative correlation between plasma allantoin concentration and PIPP in a subgroup of neonates who received sucrose. Conclusion A single dose of oral sucrose, given before heel lance, significantly increased ATP utilization and oxidative stress in premature neonates. Because neonates are given multiple doses of sucrose per day, randomized trials are needed to examine the effect of repeated sucrose administration on ATP degradation, oxidative stress and cell injury.

Objective: The present study investigated the relationship between neurologic outcome and total circulating white blood cell (WBC) and absolute neutrophil counts (ANCs) in the first week of life in term infants with hypoxic-ischemic encephalopathy (HIE).Study design: Long-term neurologic outcome at 18 months was measured retrospectively in 30 term neonates with HIE using the Pediatric Cerebral Performance Category Scale (PCPCS) score with outcomes dichotomized as either good or poor. We then compared white blood cell and ANC levels during the first 4 days of life and magnetic resonance imaging (MRI) obtained within the first month life between the two PCPCS groups. MRI was quantified using a validated scoring system. Results:Neonates with good long-term outcomes had significantly lower MRI scores (indicating lesser injury) than neonates with poor outcomes. More importantly, neonates with poor outcomes had significantly higher WBC and ANC levels as early as12 h after birth and up to 96 h after birth compared to those with good outcomes. These data suggest that elevated peripheral neutrophil counts in the first 96 h of life may signal or predict adverse long-term outcome.Conclusions: Our findings suggest that elevated peripheral neutrophil counts in the first 96 h of life in term infants with HIE may contribute to abnormal neurodevelopmental outcome.