An N. Massaro

Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants.

Objective:Preliminary studies suggested an association between red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) in premature neonates. An advantageous effect of withholding feeds during transfusion has never been studied. We aimed, first, to determine whether preterm infants who developed NEC were more likely to be transfused in the 48 to 72 h before the diagnosis of NEC; second, to test if a strict policy of withholding feeds during transfusion would decrease the incidence of transfusion-associated NEC.Study Design:The study was conducted in two phases. Phase 1: a retrospective case–control study of premature low-birth weight (<32 weeks and <2500 g) infants who developed NEC over a 6-year period. Phase 2: a comparison study of the incidence of NEC during the 18-months preceding, and the 18 months following the change of practice to withholding feeds during RBC transfusion.Result:In the case–control study (25 infants with NEC and 25 controls), more infants in the NEC group received transfusions in the 48 and 72 h preceding diagnosis (56 vs 20% within 48 h, P=0.019; and 64 vs 24% within 72 h, P=0.01). The total number of transfusions and age of RBCs were not different between the two groups. Implementing the policy of withholding feeds during transfusion was associated with a decrease in the incidence of NEC from 5.3 to 1.3% (P=0.047).Conclusion:Infants who developed NEC frequently received RBC transfusions in the 48 and 72 h preceding presentation of NEC. A strict policy of withholding feeds during transfusion may have a protective effect from NEC.

Is It Safer to Intubate Premature Infants in the Delivery Room

Objectives. Early nasal continuous positive airway pressure (ENCPAP) has recently emerged in neonatal units as an acceptable alternative to routine intubation and mandatory ventilation. The risks and benefits of ENCPAP have yet to be established. In this study, we aimed to examine variables that influenced the decision to initiate ENCPAP in the delivery room (DR). We also explored potential harmful effects of early intubation and examined whether unsuccessful ENCPAP attempts might subject infants to any unforeseen morbidity. Methods. All inborn very low birth weight (VLBW) infants admitted to the NICU since the implementation of the ENCPAP policy were included in this retrospective study. Infants were stratified initially into 2 cohorts according to whether they were intubated in the DR or began ENCPAP. Infants were then stratified into 4 groups according to the respiratory management during their first week of life. Infants in group 1 were supported with ENCPAP in the DR and continued to receive continuous positive airway pressure (CPAP) at least for the entire first week. Infants in group 2 began ENCPAP treatment in the DR but required intubation during the first week of life. Infants in group 3 were intubated in the DR but transitioned successfully to CPAP within the first 48 hours and were treated with CPAP for the first week of life or longer. Infants in group 4 were intubated in the DR and treated with intermittent mandatory ventilation for >48 hours. Univariate analyses compared different groups with the Wilcoxon nonparametric test, Kruskal-Wallis test, and analysis of variance. A multivariate regression model adjusted for differences in birth weights (BWs), gestational ages (GAs), race, and Apgar scores between the groups. Results. A total of 234 VLBW infants (weight of <1500 g) were admitted to the NICU during the period from August 1997 to December 2003. The mean BW was 977.1 ± 305.8 g, and the mean GA was 27.7 ± 2.7 weeks. The overall mortality rate was 11.1%, and the incidence of bronchopulmonary dysplasia among survivors was 17.4%. ENCPAP was implemented successfully in the DR for 151 (64.5%) infants, whereas 83 (35.5%) infants required intubation. Infants who required intubation had significantly lower GAs, BWs, and 1-minute Apgar scores. The use of ENCPAP in the DR increased significantly over time. The chance of successful maintenance with ENCPAP for >48 hours was not demonstrable at <24 weeks of gestation (10% success). Use of ENCPAP improved significantly by 25 weeks of gestation (45% success). Infants in group 1 required a shorter duration of oxygen use than did infants in group 3 (7.9 ± 18.3 vs 39 ± 32.7 days; regression coefficient [b] = 19 ± 5.3). None of the infants in group 1 developed intraventricular hemorrhage of grade III or IV or retinopathy of prematurity of stage 3 or 4. Infants in group 3 did not show improved outcomes, compared with group 1. Compared with group 4, infants in group 2 had a higher incidence of necrotizing enterocolitis (15.6% vs 7.3%; b = 2.5 ± 1.2). Conclusions. The success of ENCPAP improved with increased GA and with staff experience over time. Infants treated successfully with ENCPAP were unlikely to develop intraventricular hemorrhage of grade III or IV. Infants who experienced ENCPAP failure were at increased risk for the development of necrotizing enterocolitis. Infants who were intubated briefly in the DR were at increased risk for prolonged oxygen requirement. An individualized approach should be considered for respiratory support of VLBW infants.

Factors associated with adverse neurodevelopmental outcomes in infants with congenital heart disease

OBJECTIVE To review reported neurodevelopmental outcome data for patients with congenital heart disease, identify risk factors for adverse neurodevelopmental sequelae and summarize potential neuromonitoring strategies that have been described. METHODS A Medline search was performed utilizing combinations of the keywords congenital heart, cardiac, neurologic, neurodevelopment, neuromonitoring, quality of life, and outcome. All prospective and longitudinal follow-up studies of patients with congenital heart disease were included. Additionally, studies that examined neuroimaging, neuromonitoring, and clinical factors in relation to outcome were examined. Case reports and editorials were excluded. Additional references were retrieved from selected articles if the abstract described an evaluation of neurodevelopmental outcomes and/or predictors of outcome in patients with congenital heart disease. RESULTS Overall, patients with CHD have increased rates of neurodevelopmental impairments, although intelligence appears to be in the normal range. Preoperative risk stratification, intraoperative techniques, postoperative care, and neuromonitoring strategies may all contribute to ultimate long-term neurodevelopmental outcomes in patients with CHD postsurgical repair. CONCLUSIONS As advances in the medical and surgical management improves survival in patients with CHD, increasing knowledge about neurodevelopmental outcomes and the factors that affect them will provide for strategies to optimize long-term outcome in this high-risk population.

Impact of Congenital Heart Disease on Brain Development and Neurodevelopmental Outcome

Advances in cardiac surgical techniques and perioperative intensive care have led to improved survival in babies with congenital heart disease (CHD). While it is true that the majority of children with CHD today will survive, many will have impaired neurodevelopmental outcome across a wide spectrum of domains. While continuing to improve short-term morbidity and mortality is an important goal, recent and ongoing research has focused on defining the impact of CHD on brain development, minimizing postnatal brain injury, and improving long-term outcomes. This paper will review the impact that CHD has on the developing brain of the fetus and infant. Neurologic abnormalities detectable prior to surgery will be described. Potential etiologies of these findings will be discussed, including altered fetal intrauterine growth, cerebral blood flow and brain development, associated congenital brain abnormalities, and risk for postnatal brain injury. Finally, reported neurodevelopmental outcomes after surgical repair of CHD will be reviewed.

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

OBJECTIVE: To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. METHODS: In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7.00 or base deficit ≥15, or resuscitation at 10 minutes); and received hypothermia. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation. Two independent observers rated MRI brain injury severity by using an established scoring system. RESULTS: The mean age at first study drug was 16.5 hours (SD, 5.9). Neonatal deaths did not significantly differ between Epo and placebo groups (8% vs 19%, P = .42). Brain MRI at mean 5.1 days (SD, 2.3) showed a lower global brain injury score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epo-treated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05). CONCLUSIONS: High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.

Massage with kinesthetic stimulation improves weight gain in preterm infants

Objective:The aim of this study was to evaluate the effects of massage with or without kinesthetic stimulation on weight gain and length of hospital stay in the preterm infant.Study Design:A prospective randomized clinical trial was conducted evaluating the effects of massage with or without kinesthetic stimulation (KS) on weight gain and length of stay (LOS) in medically stable premature (<1500 g and/or ⩽32 weeks gestational age) neonates. Infants were randomized either to receive no intervention (control), massage therapy alone (massage), or massage therapy with KS (M/KS). Linear regression analysis was performed to evaluate differences in the primary outcomes between the groups after controlling for covariates. Post hoc analysis with stratification by birthweight (BW> and <1000 g) was also performed.Result:A total of 60 premature infants were recruited for this study; 20 infants in each group. Average daily weight gain and LOS were similar between the groups after controlling for covariates. For infants with BW>1000 g, average daily weight gain was increased in the intervention groups compared to control. This effect was mainly attributable to the M/KS group.Conclusion:Massage with KS is a relatively simple and inexpensive intervention that can improve weight gain in selected preterm infants. Length of hospital stay is not impacted by massage with or without KS. Further studies are needed to evaluate the effect of massage in the extremely low BW(<1000 g) infant.

Neuroimaging and neurodevelopmental outcome of premature infants.

Preterm birth is associated with variable degrees of brain injury and adverse neurodevelopmental outcomes. Neuroimaging has been investigated as a predictor of outcome in this population. Head ultrasound allows for rapid bedside evaluation of the neonatal brain for early intraventricular hemorrhage surveillance and later detection of periventricular leukomalacia. Computed tomography can provide excellent views for bones, hemorrhage, extra-axial space, and the ventricles but is rarely used for prognostic purposes. Magnetic resonance imaging allows for high-resolution images of brain structures, differentiation of white and gray matter, visualization of the brain stem and posterior fossa, and getting additional physiological information with specialized sequences. Though controversial, the use of magnetic resonance imaging, at term equivalent, as a predictor of later outcome in preterm infants has been increasing and has been advocated by some as a standard practice. In this article, we review and contrast the use of these various imaging modalities in predicting neurodevelopmental outcome of premature infants.

Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: A pilot study

Objectives: To determine if candidate biomarkers, ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein, are elevated in neonates with hypoxic ischemic encephalopathy who die or have severe MRI injury compared with surviving infants with minimal or no injury on brain MRI. Design: Prospective observational study. Setting: Level IIIC outborn neonatal ICU in a free-standing children’s hospital. Patients: Term newborns with moderate-to-severe hypoxic ischemic encephalopathy referred for therapeutic hypothermia Interventions: Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. MRI was performed in surviving infants at target 7–10 days of life and was scored by a pediatric neuroradiologist masked to biomarker and clinical data. Measurements and Main Results: Serial biomarker levels were determined in 20 hypoxic ischemic encephalopathy patients. Ubiquitin carboxyl-terminal esterase L1 was higher at initiation and 72 hours of cooling, while glial fibrillary acidic protein was higher at 24 and 72 hours in babies with adverse outcome compared with those with favorable outcome. Conclusions: This preliminary data support further studies to evaluate ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein as immediate biomarkers of cerebral injury severity in newborns with hypoxic ischemic encephalopathy.

Brain Perfusion in Encephalopathic Newborns after Therapeutic Hypothermia

BACKGROUND AND PURPOSE: Cerebral perfusion patterns in neonates with HIE after therapeutic hypothermia have not been well described. The objectives of this study were to compare global and regional perfusion between infants with HIE and neonate controls and to relate measures of cerebral perfusion to brain injury on conventional MR imaging in neonates with HIE. MATERIALS AND METHODS: Term encephalopathic neonates meeting criteria for hypothermia between June 2011 and January 2012 were enrolled in this prospective observational study. MR imaging-ASL was performed in the second week of life. Comparisons were made with data from neonate controls who underwent the same imaging protocol. NIRS measures of cerebral oxygenation during and immediately after hypothermia were also evaluated in a subset of patients. Secondary analyses were performed to assess cerebral perfusion and oxygenation differences by pattern of injury on qualitative MR imaging interpretation. RESULTS: We enrolled 18 infants with HIE and 18 control infants. Mean global CBF and regional CBF in the basal ganglia, thalamus, and anterior white matter were higher in cases compared with controls. Infants with HIE with injury on MR imaging, however, had lower CBF (significant in the thalamus) compared with those with normal MR imaging. Decreased FTOE by NIRS further differentiated patients with HIE with injury on MR imaging. CONCLUSIONS: Disturbed cerebral perfusion is observed in the second week of life in some babies with HIE despite treatment with hypothermia. Infants with HIE with injury on MR imaging have lower regional CBF in the thalamus compared with those without injury, possibly representing pseudonormalization of CBF and low metabolic demand after progression to irreversible brain injury.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group

Objective:To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes.Study Design:This is a descriptive study evaluating the data collected prospectively in the Children’s Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children’s hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks’ gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010–July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge.Result:High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%.Conclusion:Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.