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Objective To increase preoperative identification of at-risk infants for severe Retinopathy of prematurity (ROP) to >95% by August 2016, with a secondary aim of reducing the number of infants with 100% intraoperative peripheral oxygen saturation (SpO2) during the same time. Study design Prospective quality improvement project centered on preterm surgical infants admitted to Primary Children's Hospital (n = 41). Preoperative ROP risk identification rates were analyzed using an annotated run chart, intraoperative SpO2 and laser intervention were compared using un-paired t test. Results Preoperative identification of ROP risk increased from 60 to 100% and no infant was exposed to 100% SpO2 intraoperatively during the study period. The incidence of laser intervention in this population decreased by 45% from 22 to 12% (p = 0.21). Conclusion Simplifying our preoperative handoff increased our rates of correct identification and communication ROP risk in preterm infants while decreasing exposure to 100% SpO2.

Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Neonates ≥36 weeks gestation and

Background: Retinopathy of prematurity (ROP) is a proliferative neovascular disorder and known complication of preterm birth. The disease occurs in two phases. Phase 1 (23-32w) is a vaso-obliterative phase. There is transition to the neovascular phase (phase II) around 32 weeks with complete vascular maturation around term. Many preterm infants undergo a surgical procedure prior to maturation of the retina. It is unknown how surgery affects retinal vascularization. We hypothesize that infants who undergo surgery will have increased risk of laser intervention. Methods: We performed a retrospective chart review …

Background: Retinopathy of Prematurity (ROP) is a proliferative neovascular disorder and known complication of preterm birth. In a recent analysis at our institution we found an eight fold increased risk for laser intervention for ROP among preterm infants who underwent surgery. Our objective was to reduce laser intervention in preterm infants undergoing surgery. With a specific aim of correctly identifying these patients preoperatively 95% of the time and secondary aim of reducing our intraoperative oxygen exposure in this population. Methods: We conducted a staged, multi-intervention quality improvement project. …

To assess the effect of massage on weight gain and body fat deposition in preterm infants.Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected.Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P .05). Female infants in the massage group had larger SSF increases than control female infants (P .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P .01) and was correlated to PI (r = 0.39, P .01).Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner.

Preterm delivery (

Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.

Improvements in neonatal intensive care during the last 20 years have increased the survival of the most immature newborns at 23 weeks from 0% to 65% at some centres, although rates vary widely among neonatal care centres. University of Utah, USA data show that each week in utero after week 23 raises survival by 6-9%, to 90% by 27-28 weeks and 95% by 33 weeks. Provision of care in specialised centres to provide high-risk obstetric and neonatal intensive care, prenatal treatment with corticosteroids, postnatal treatment with surfactant and nitric oxide, and improvements in respirators and equipment to care for extremely immature infants all contribute to these changes. The increased rate of survival for extremely premature newborns has not been accompanied by an increased rate of severe intraventricular haemorrhage or neurological impairment, such as cerebral palsy. Regardless, intraventricular haemorrhage remains a significant problem, especially if associated with post-haemorrhagic hydrocephalus, leading to long-term neurological impairment and decreased survival. Necrotising enterocolitis (NEC) is more common in premature than in term newborns and is the most frequent cause of short bowel syndrome in infancy. Survival after surgery for NEC has improved during the last two decades, but complications of nutritional support produce many long-term problems. Retinopathy of prematurity (ROP) remains a frequent cause of neurosensory impairment for extremely premature newborns. Laser photocoagulation for advanced ROP is more effective than cryotherapy for preventing retinal detachment and improving visual outcomes. Despite prenatal corticosteroid treatment and postnatal surfactant administration, many extremely premature newborns still develop bronchopulmonary dysplasia. Abnormal pulmonary function may persist into adulthood, but newer ventilators and management schemes appear to be reducing this long-term morbidity. Many changes in neonatal care occur each year, but carefully controlled outcome studies are needed to evaluate the effectiveness of these newer styles of neonatal intensive care.

Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia.Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics.Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf)) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was 26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P0.01).Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.

Premature birth is associated with increased adipose deposition after birth. Standard anthropometry (body weight, length, and head circumference) may not adequately assess fat deposition. Validated methods to assess adiposity are needed to optimize growth quality in preterm infants. The purpose of this study was to identify covariates of infant body fat. Air displacement plethysmography (ADP), standard anthropometry, and body circumferences were measured at hospital discharge in preterm (n = 28; 31–35 wk postmenstrual age (PMA)) and term (n = 28; 38–41 wks PMA) infants. Body weight, length, and head circumference were lower for preterm infants (P < 0.05) at hospital discharge compared with that of term infants. Despite smaller body size and younger PMA, preterm infant percent body fat (%BF) by ADP was 12.33 ± 4.15% vs. 9.64 ± 4.01% in term infants (P = 0.01). Mid-arm circumference (MAC) is a covariate of %BF in both preterm and term infants (adjusted R2 = 0.49; P < 0.001). In preterm infants alone, MAC accounted for 60.4% of the variability of percent body fat (%BF) by ADP (P < 0.01). Preterm infants have increased body fat deposition as they approach term-corrected age, and MAC is a reliable, low-cost measure for monitoring infant body fat deposition in preterm and term infants.

OBJECTIVES Previous studies in adults suggest that various types of physiologic stress appear to decrease phagocytic cell function. Adherence and chemotaxis of, and phagocytosis and bacterial killing by, neonatal neutrophils are altered compared with adult neutrophil function. Stresses encountered by the fetus and neonate, such as asphyxia, were hypothesized to further alter neonatal neutrophil function. To investigate the impact of asphyxia on systemic immunity, we developed a rat model of acute asphyxia and evaluated the effect of asphyxia on neutrophil number and function. DESIGN Prospective, laboratory study. SETTING Research laboratory. SUBJECTS Adult female Wistar rats. INTERVENTIONS Exposure to CO2 and cold stress. MEASUREMENTS AND MAIN RESULTS Arterial blood gas, blood glucose, neutrophil number, neutrophil-mediated, complement-dependent bacterial phagocytosis and killing were determined. After a 20-sec exposure to CO2 and cold stress (dry ice vapors), adult rats developed acute respiratory acidosis (pH 6.89 +/- 0.26, PaCO2 220 +/- 183 torr [29.3 +/- 24.3 kPa]), and mild hypoxia (60 +/- 20 torr [8.0 +/- 2.7 kPa]) followed by significant metabolic acidosis (base deficit = -12.0 +/- 1.5). Neutrophil number slowly increased and reached statistical significance by 72 hrs (5.0 +/- 1.5 x 10(3)/mm3) compared to controls (2.9 +/- 1.6 x 10(3)/mm3) (p = .03). Phagocytosis and killing of group B streptococci by neutrophils isolated immediately after asphyxia were significantly impaired (p = .03), and this decrease in function lasted for 24 hrs after asphyxia (p = .04), as measured by two different in vitro complement and antibody-mediated functional assays. CONCLUSIONS After brief exposure to CO2 and cold stress, rats developed an acute respiratory acidosis and subsequent metabolic acidosis similar to acute asphyxia. Neutrophil number did not increase until 72 hrs after asphyxia. However, neutrophil-mediated phagocytosis and killing of bacteria were immediately impaired. We speculate that asphyxia may increase the risk for sepsis secondary to altered neutrophil function.

Correction to: Journal of Perinatology advance online publication 26 April 2012; doi: 10.1038/jp.2012.47 Following the online publication of this article, the authors noted that Dr Beachy's name was misspelled. The complete and correct author names appear above.

SJL mice were injected intraperitoneally with adipocyte plasma membranes or with intrinsic membrane proteins obtained by extraction of plasma membranes with dimethylmaleic anhydride. Three days after the boost injection, the spleens were removed and fused with NS-1, a thioguanine-resistant myeloma cell line derived from P3X63 Ag8 (Balb/c). Following selection for hybrids with hypoxanthine, aminopterin, and thymidine, medium of the hybrid cells was tested for its ability to bind to the plasma membrane of the adipocyte and to stimulate the oxidation of D-(1-14C) glucose to 14CO2. Approximately 40% of the wells containing hybridomas derived from splenocytes of SJL mice immunized with plasma membranes produced immunoglobulin that bound to adipocyte plasma membranes. About 30% of these mimicked the ability of insulin to stimulate the oxidation of D-(1-14C) glucose to 14CO2 in adipocytes. Media from 51% of the wells containing hybridomas derived from splenocytes of SJL mice immunized with intrinsic membrane proteins produced immunoglobulin that bound to the plasma membrane and 48% of those stimulated glucose oxidation. The bioactivity of the hybrid cell media could be blocked by adsorption with intrinsic membrane proteins or by the removal of immunoglobulins using formalin-fixed Staphylococcus aureus. The hybrids generated in this study can be divided into three categories: (1) hybrids that secrete antibodies that can bind to plasma membranes and mimic insulin action of glucose transport; (2) hybrids that secrete antibodies that bind to plasma membranes but do not stimulate the oxidation of D-(1-14C) glucose to 14CO2; and (3) hybrids that produce no antimembrane antibodies. The data suggest that interaction of immunoglobulins with specific membrane proteins is essential in mimicking the action of insulin on glucose transport and oxidation in the rat adipocyte.