Noninvasive optical monitoring of cerebral hemodynamics in a preclinical model of neonatal intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) is a common complication in premature infants and is associated with white matter injury and long-term neurodevelopmental disabilities. Standard diagnostic tools such as cranial ultrasound and MRI are widely used in both preclinical drug development and clinical practice to detect IVH. However, these methods only provide endpoint assessments of blood accumulation and lack real-time information about dynamic changes in ventricular blood flow.

Bacteria - derived short chain fatty acids restore sympathoadrenal responsiveness to hypoglycemia after antibiotic-induced gut microbiota depletion.

The microbiome co-evolved with their mammalian host over thousands of years. This commensal relationship serves a pivotal role in various metabolic, physiological, and immunological processes. Recently we discovered impaired adrenal catecholamine stress responses in germ-free mice suggesting developmental modification of the reflex arc or absence of an ongoing microbiome signal.

Implementing a Hospital-Based Safe Sleep Program for Newborns and Infants.

Background: An unsafe sleep environment remains the leading contributor to unexpected infant death.

Purpose: To determine the effectiveness of a quality improvement initiative developed to create a hospital-based safe sleep environment for all newborns and infants.

Methods: A multidisciplinary team from the well-baby nursery (WBN) and neonatal intensive care unit (NICU) of a 149-bed academic, quaternary care, regional referral center developed and implemented safe sleep environments within the hospital for all prior to discharge.

Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.

Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions.

Presence of neonatal intensive care services at birth hospital and early intervention enrollment in infants ≤1500 g.

Objectives To determine whether the receipt of therapeutic services of very-low-birth-weight (VLBW; ≤1500 g) neonates inadvertently delivered at community Level 2 and 3 neonatal intensive care units (NICUs) compared with those born at a well-baby nursery (WBN; Level 1) differed. Methods This is a retrospective study of neonates who were born at Level 1 (WBN), 2, 3, and 4 NICUs and discharged from a Level 4 hospital (n = 529). All infants were evaluated at the Regional Neonatal Follow-up Program at 12 ± 1 months corrected gestational age (CA) and assessed for use of therapeutic services including: early intervention (EI), occupational therapy (OT), physical therapy (PT), speech therapy (ST), and special education (SE).

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.

Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age.

Postnatal glucocorticoid-induced hypomyelination, gliosis, and neurologic deficits are dose-dependent, preparation-specific, and reversible.

Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear.

Partial blockade of nicotinic acetylcholine receptors improves the counterregulatory response to hypoglycemia in recurrently hypoglycemic rats.

Recurrent exposure to hypoglycemia can impair the normal counterregulatory hormonal responses that guard against hypoglycemia, leading to hypoglycemia unawareness. This pathological condition known as hypoglycemia-associated autonomic failure (HAAF) is the main adverse consequence that prevents individuals with type 1 diabetes mellitus from attaining the long-term health benefits of tight glycemic control. The underlying molecular mechanisms responsible for the progressive loss of the epinephrine response to subsequent bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown.

Thyroid hormone supplementation in preterm infants born before 28 weeks gestational age and neurodevelopmental outcome at age 36 months.

Background: Thyroid hormones are required for normal brain maturation, and neonatal plasma thyroid hormone concentrations are low in infants less than 28 weeks gestation. It is not known whether treatment of such infants with thyroid hormone improves neurodevelopmental outcome.

Methods: At three years corrected age, mental, motor, and neurological development was assessed in infants born at less than 28 weeks gestational age who had participated in a phase 1 trial of differing doses and modes of administration of thyroid hormone.

Hemophagocytic lymphohistiocytosis associated with necrotizing enterocolitis in premature newborns.

Hemophagocytic lymphohistiocytosis (HLH) is a systemic disease resulting from the excessive release of inflammatory cytokines by macrophages under prolonged antigenic stimulation. If untreated, it leads to multiorgan failure and death. Necrotizing enterocolitis (NEC) has not previously been associated with HLH.

Stability of thyroid hormones during continuous infusion.

We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2-8°C (36-46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point.

Neuroprotection in a rabbit model of intraventricular haemorrhage by cyclooxygenase-2, prostanoid receptor-1 or tumour necrosis factor-alpha inhibition.

Intraventricular haemorrhage is a major complication of prematurity that results in neurological dysfunctions, including cerebral palsy and cognitive deficits. No therapeutic options are currently available to limit the catastrophic brain damage initiated by the development of intraventricular haemorrhage. As intraventricular haemorrhage leads to an inflammatory response, we asked whether cyclooxygenase-2, its derivative prostaglandin E2, prostanoid receptors and pro-inflammatory cytokines were elevated in intraventricular haemorrhage; whether their suppression would confer neuroprotection; and determined how cyclooxygenase-2 and cytokines were mechanistically-linked.

Delivery of gastroschisis patients before 37 weeks of gestation is associated with increased morbidities.

Background: Despite advances in the care of neonates with gastroschisis, patients present with significant morbidities. Preterm delivery of neonates with gastroschisis is often advocated to avoid the intestinal damage that may be sustained with prolonged exposure to amniotic fluid. However, preterm delivery may impose additional morbidities to this disease process.

Oxidative-nitrosative stress in a rabbit pup model of germinal matrix hemorrhage: role of NAD(P)H oxidase.

Background And Purpose: Germinal matrix hemorrhage-intraventricular hemorrhage is the most common neurological problem of premature infants. Despite this, mechanisms of brain injury from intraventricular hemorrhage are elusive. We hypothesized that germinal matrix hemorrhage-intraventricular hemorrhage, by induction of NAD(P)H oxidases, might cause oxidative/nitrosative stress contributing to brain injuries and that NAD(P)H oxidase inhibition could offer neuroprotection.

Outbreak of Acinetobacter infection in extremely low birth weight neonates.

Objective: We describe the first outbreak of multiple drug-resistant Acinetobacter baumannii (MDR-Ab) in a neonatal intensive care unit in the United States.

Design/methods: MDR-Ab was identified in the blood of a 24-week gestation, 7-day-old extremely low birth weight neonate. Multiple samplings of surveillance surface cultures were performed on exposed and nonexposed neonates.

Outbreak of parainfluenza virus type 3 in a neonatal intensive care unit.

Parainfluenza virus (PIV) causes > 30% of all acute respiratory infections in infants and children and is second only to respiratory syncytial virus as a cause of lower respiratory tract infection. However in the neonatal intensive care unit (NICU), PIV outbreaks are highly uncommon. This case report describes an outbreak of 3 cases of PIV type 3 in a regional NICU.

Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal matrix hemorrhage.

Background And Purpose: Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common neurological problem of premature infants and has enormous financial and social impact. Despite this, there is no standardized animal model of IVH depicting acute brain injuries.

Methods: We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries.

Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone.

Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature-laminin, fibronectin, collagen IV, and perlecan-provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen.

Toward improving mucosal barrier defenses: rhG-CSF plus IgG antibody.

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens.

Addressing the "New" NEC: Part I: rediscovering the basics.

Epithelial cell functions ultimately define the ability of the extremely low birth weight human fetus to survive outside of the uterus. These specialized epithelial cell capacities manage all human interactions with the ex utero world including: (i) lung mechanics, surface chemistry and gas exchange, (ii) renal tubular balance of fluid and electrolytes, (iii) barrier functions of the intestine and skin for keeping bacteria out and water in, plus enabling intestinal digestion, as well as (iv) maintaining an intact neuroepithelium lining of the ventricles of the brain and retina. In Part I of this two part review, the authors describe why the gut barrier is a clinically relevant model system for studying the complex interplay between innate and adaptive immunity, dendritic &epithelial cell interactions, intraepithelial lymphocytes, M-cells, as well as the gut associated lymphoid tissues where colonization after birth, clinician feeding practices, use of antibiotics as well as exposure to prebiotics, probiotics and maternal vaginal flora all program the neonate for a life-time of immune competence distinguishing "self" from foreign antigens.

Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates.

The purpose of this study was to determine an association between packed red blood cell (PRBC) transfusions for anemia and necrotizing enterocolitis (NEC) in a subset of stable, growing, premature neonates. As part of a survey of current clinical practices over a 17-month period from June 1999 to October 2000, a chart review was performed to determine the relationship between elective PRBC transfusions and the occurrence of NEC. Demographic data were tabulated and compared between the NEC patients with a prior history of immediate blood transfusion (within 48 hours of onset of symptoms) and those NEC patients without a prior history of immediate blood transfusion.