Search

Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p 0.001).Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Author(s): Greenberg, Rachel G; Chowdhury, Dhuly; Hansen, Nellie I; Smith, P Brian; Stoll, Barbara J; Sanchez, Pablo J; Das, Abhik; Puopolo, Karen M; Mukhopadhyay, Sagori; Higgins, Rosemary D; Cotten, C Michael; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network | Abstract: BackgroundProlonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC.MethodsCohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression.ResultsA total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC.ConclusionsThe proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.

Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children. Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30’ later, evening). Results: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p

Prolonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC.Cohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression.A total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC.The proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.

BackgroundExtremely preterm infants (EPT

BACKGROUND: The goal was to identify cytokines associated with necrotizing enterocolitis (NEC). Based on our earlier reports of decreased tissue expression of transforming growth factor (TGF)-β, we hypothesized that infants with NEC also have low blood TGF-β levels. We further hypothesized that because fetal inflammation increases the risk of NEC, infants who develop NEC have elevated blood cytokine levels in early neonatal period.METHODS: Data on 104 extremely-low-birth-weight infants with NEC and 893 without NEC from 17 centers were analyzed. Clinical information was correlated with blood cytokine levels on postnatal day 1 (D1), D3, D7, D14, and D21.RESULTS: Male gender, non-Caucasian/non-African American ethnicity, sepsis, lower blood TGF-β and interleukin (IL)-2 levels, and higher IL-8 levels were associated with NEC. The NEC group had lower TGF-β levels than controls since D1. The diagnosis of NEC was associated with elevated IL-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1/CC-motif ligand-2, macrophage inflammatory protein-1β/CC-motif ligand-3, and C-reactive protein.CONCLUSION: Clinical characteristics, such as gender and ethnicity, and low blood TGF-β levels are associated with higher risk of NEC. Infants who developed NEC did not start with high blood levels of inflammatory cytokines, but these rose mainly after the onset of NEC.

Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic–ischemic encephalopathy (HIE). We conducted a cohort study of infants who survived HIE and had 18–22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/–, and e2/–. A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/–, and 14 (10%) were of the e2/– genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the e3/e3 genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29% among those with and without the e4 allele, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups. Disability was not associated with the APOE genotype in this cohort of HIE survivors.

The effect of birth location on hypothermia-related outcomes has not been rigorously examined in the literature. In this study, we determined whether birth location had an impact on the benefits of whole-body cooling to 33.5 °C for 72 h in term infants (n = 208) with hypoxic-ischemic encephalopathy (HIE) who participated in the Neonatal Research Network (NRN) randomized controlled trial.Heterogeneity by birth location was examined with respect to cooling treatment for the 18-mo primary outcomes (death, moderate disability, severe disability) and secondary outcomes (death, components of disability), and in-hospital organ dysfunction. Logistic regression models were used to generate adjusted odds ratios.Infants born at a location other than an NRN center (outborn) (n = 93) experienced significant delays in initiation of therapy (mean (SD): 5.5 (1.1) vs. 4.4 (1.2) h), lower baseline temperatures (36.6 (1.2) vs. 37.1 (0.9) °C), and more severe HIE (43 vs. 29%) than infants born in an NRN center (inborn) (n = 115). Maternal education12 y (50 vs. 14%) and African-American ethnicity (43 vs. 25%) were more common in the inborn group. When adjusted for NRN center and HIE severity, there were no significant differences in 18-mo outcomes or in-hospital organ dysfunction between inborn and outborn infants.Although limited by sample size and some differences in baseline characteristics, the study showed that birth location does not appear to modify the treatment effect of hypothermia after HIE.

Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS). In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined—FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0–1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3 and sepsis group was explored. Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-γ (IFN-γ), interleukin (IL)-10, IL-18, transforming growth factor–β (TGF-β), and tumor necrosis factor–α (TNF-α) (P < 0.05). Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β, and TNF-α in FS, BS, or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.

Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.

Case reports and observational studies continue to report adverse events from medical errors. However, despite considerable attention to patient safety in the popular media, this topic is not a regular component of medical education, and much research needs to be carried out to understand the causes, consequences, and prevention of healthcare-related adverse events during neonatal intensive care. To address the knowledge gaps and to formulate a research and educational agenda in neonatology, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invited a panel of experts to a workshop in August 2010. Patient safety issues discussed were: the reasons for errors, including systems design, working conditions, and worker fatigue; a need to develop a “culture” of patient safety; the role of electronic medical records, information technology, and simulators in reducing errors; error disclosure practices; medico-legal concerns; and educational needs. Specific neonatology-related topics discussed were: errors during resuscitation, mechanical ventilation, and performance of invasive procedures; medication errors including those associated with milk feedings; diagnostic errors; and misidentification of patients. This article provides an executive summary of the workshop.

Matrix metalloproteinases (MMP) and chemokines appear to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and β chemokine concentrations. The following analytes were measured on blood spots on days 1 and 3 of life, using luminex technology in 1059 infants (birth weights < 1000 grams) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (MIP 1α and β), and Regulated upon Activation, Normal T-cell Expressed and Secreted (RANTES). Infants administered O2 continually from 6 to 24 hours of life (n=729), when compared to those with < 6 hours exposure (n=330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p≤ 0.002). On day 3, MCP 1 was higher and RANTES lower among infants with early prolonged O2 exposure. After adjusting for covariates, prolonged early O2 exposure retained a statistically significant association with higher MCP 1 on day 3 (p=0.003). The consistent association between O2 exposure and MCP 1 among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted.

The National Institute of Child Health and Human Development and the Digestive Diseases Interagency Coordinating Committee held a workshop, chaired by Dr. W. Allan Walker, on July 10-11, 2006, to identify promising leads in necrotizing enterocolitis (NEC) research. The goals of the workshop were to identify new approaches to the prevention and treatment of NEC, to define basic and translational mechanisms of potential approaches to NEC, and to develop recommendations for clinical studies to reduce the incidence of NEC. Workshop participants implicated prematurity, introduction of enteral feedings, gastrointestinal bacterial colonization, gut motility, proinflammatory cytokines, impaired gut blood flow, and various neonatal complications in the pathogenesis of NEC. They concluded that a unifying hypothesis encompassing these pathogenetic factors is the uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants. The inflammatory cascade appears to offer multiple targets for interventions with a variety of anti-inflammatory agents, including human milk and probiotics. Because of the rapidity with which the inflammatory response gets out of control in infants with NEC, workshop participants agreed that searching for ways to prevent NEC will be more rewarding than trying to identify ways to treat the condition once it has become established.

Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury

The goal of this study was to determine whether an antiangiogenic agent, squalamine, given late during the evolution of oxygen-induced retinopathy (OIR) in the mouse, could improve retinal neovascularization. OIR was induced in neonatal C57BL6 mice and the neonates were treated s.c. with squalamine doses begun at various times after OIR induction. A system of retinal whole mounts and assessment of neovascular nuclei extending beyond the inner limiting membrane from animals reared under room air or OIR conditions and killed periodically from d 12 to 21 were used to assess retinopathy in squalamine-treated and untreated animals. OIR evolved after 75% oxygen exposure in neonatal mice with florid retinal neovascularization developing by d 14. Squalamine (single dose, 25 mg/kg s.c.) given on d 15 or 16, but not d 17, substantially improved retinal neovascularization in the mouse model of OIR. There was improvement seen in the degree of blood vessel tuft formation, blood vessel tortuosity, and central vasoconstriction with squalamine treatment at d 15 or 16. Single-dose squalamine at d 12 was effective at reducing subsequent development of retinal neovascularization at doses as low as 1 mg/kg. Squalamine is a very active inhibitor of OIR in mouse neonates at doses as low as 1 mg/kg given once. Further, squalamine given late in the course of OIR improves retinopathy by inducing regression of retinal neovessels and abrogating invasion of new vessels beyond the inner-limiting membrane of the retina.

Retinopathy of prematurity is a disease commonly affecting extremely premature babies. Indomethacin is widely used in the perinatal period. The goal of the present study was to test the hypothesis that indomethacin will improve retinopathy in a mouse model when administered during the period of injury (hyperoxia exposure) to the developing retinal vasculature. C57BL6 mice pups were exposed to 75% oxygen from postnatal d 7 through 12. Indomethacin was administered along with the oxygen exposure as a single subcutaneous dose of 0.5 mg/kg/d for 5 d. Animals were killed on postnatal d 17 through 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extraretinal nuclei by use of periodic acid-Schiff-stained retinal sections. Animals that received indomethacin during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score 5 (4.5, 6) compared with animals that received oxygen [8 (7.5, 10)]. Animals given indomethacin during hyperoxia exposure had a significantly lower extraretinal nuclei count per section (13.3 +/- 4.6) (mean +/- SD) compared with animals that were oxygen exposed (41.9 +/- 14.7). Indomethacin did not affect the normal development of the retinal vasculature or the growth of the animals. The data show that indomethacin improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development or growth of the animals.

Dexamethasone is widely used in the postnatal period. Its impact on retinopathy of prematurity (ROP) is extremely controversial; published studies have found a detrimental, protective, or no effect on ROP. The goal of this study was to test the hypothesis that use of dexamethasone during the injury phase (oxygen exposure) reduces the severity of oxygen-induced retinopathy (OIR) in a mouse model. C57BL6 mice pups were exposed to either room air or hyperoxia (75% FiO2) from postnatal d 7 through 12 (PN7-12) with or without dexamethasone (0.5 mg/kg/d s.c.) and killed on PN17-21. Retinopathy was assessed by a scoring system of retinal flat mount preparations and periodic acid-Schiff (PAS) staining of retinal sections. Pups exposed to dexamethasone and oxygen had a lower median retinopathy score of 5 (4,6) [median (25th, 75th quartile)] compared with animals exposed to oxygen alone with median score of 9 (6,10) with p < 0.001. PAS staining for extra retinal neovascularization in the dexamethasone and oxygen treated animals showed a significant reduction in number of nuclei extending beyond the inner limiting membrane when compared with oxygen exposed alone (p = 0.04). Animals treated with dexamethasone had decreased weight gain compared with control animals. Dexamethasone did not appear to affect the normal development of retinal vasculature as assessed by the scoring system when compared with control animals. Thus, dexamethasone decreases severity of OIR without having an adverse effect on normal retinal vascular development in the mouse model. We speculate that dexamethasone decreases the injury response that occurs during the hyperoxic phase, thus protecting the developing vasculature and improving the subsequent retinopathy.

Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia, and reduced severe retinopathy of prematurity in two randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed before efficacy trials.Infants born in 23-29 wk of gestation were randomized to a single intravenous (i.v.) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed-effects approach. Safety outcomes were recorded.A single-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age strata, and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance was 0.0679 l/kg/h, endogenous production was 2.67 mg/kg/h, and the half-life was 5.22 h when modeled without the covariates. During the first 12 h, renal inositol excretion quadrupled in the 120 mg/kg group, returning to near-baseline value after 48 h. There was no diuretic side effect. No significant differences in adverse events occurred among the three groups (P0.05).A single-compartment model accounting for endogenous production satisfactorily described the PK of i.v. inositol.

Prenatal cocaine exposure (PCE) is associated with blunted stress responsivity within the extrauterine environment. This study investigated the association between PCE and diurnal salivary cortisol levels in preadolescent children characterized by high biological and/or social risk (n = 725). Saliva samples were collected at their home. Analyses revealed no group differences in basal evening or morning cortisol levels; however, children with higher degrees of PCE exhibited blunted overnight increases in cortisol, controlling for additional risk factors. Race and caregiver depression were also associated with diurnal cortisol patterns. Although repeated PCE may contribute to alterations in the normal or expected stress response later in life, sociodemographic and environmental factors are likewise important in understanding hormone physiology, especially as more time elapses from the PCE. Anticipating the potential long-term medical, developmental, or behavioral effects of an altered ability to mount a normal protective cortisol stress response is essential in optimizing the outcomes of children with PCE.

To evaluate whether differences in early nutritional support provided to extremely premature infants mediate the effect of critical illness on later outcomes, we examined whether nutritional support provided to "more critically ill" infants differs from that provided to "less critically ill" infants during the initial weeks of life, and if, after controlling for critical illness, that difference is associated with growth and rates of adverse outcomes. One thousand three hundred sixty-six participants in the NICHD Neonatal Research Network parenteral glutamine supplementation randomized controlled trial who were alive on day of life 7 were stratified by whether they received mechanical ventilation for the first 7 d of life. Compared with more critically ill infants, less critically ill infants received significantly more total nutritional support during each of the first 3 wk of life, had significantly faster growth velocities, less moderate/severe bronchopulmonary dysplasia, less late-onset sepsis, less death, shorter hospital stays, and better neurodevelopmental outcomes at 18-22 mo corrected age. Rates of necrotizing enterocolitis were similar. Adjusted analyses using general linear and logistic regression modeling and a formal mediation framework demonstrated that the influence of critical illness on the risk of adverse outcomes was mediated by total daily energy intake during the first week of life.

Retinopathy of prematurity is a disorder of abnormal retinal vascular proliferation, and one hypothesis for its pathogenesis involves abnormal activity of angiogenic growth factors in the retina. One of these, acidic fibroblast growth factor, is found primarily in retina and brain tissues. Its mitogenic effect is greatly potentiated in vitro by heparin. Because retinopathy of prematurity occurs most often in premature infants who receive the greatest amount of heparin, we tested the hypothesis that heparin may adversely affect the retinopathy observed in kittens after hyperoxic (80% oxygen) exposure. Seventeen litters of kittens were randomly assigned to receive either saline or heparin s.c. injections from d 2 through recovery to 28 d of age; 65 h of high oxygen exposure was started on d 3 to induce a standard retinal injury in our model. There were no differences in the degree of retinopathy between the heparin-treated group [severity score 5.9 +/- 2.2 (mean +/- SD)], and the saline-treated group (severity score 7.1 +/- 1.7, p greater than 0.20, 80% power to detect a 2-point difference in score at alpha = 0.05). These findings do not support a concern that clinical doses of heparin potentiate retinopathy of prematurity.

Background: Post-asphyxial hypothermia is protective in experimental animals; however, there have been no RCT evaluating safety and effectiveness of whole body hypothermia in term infants with HIE.

BACKGROUND:Retinopathy of Prematurity (ROP) is a developmental vascular retinopathy of multifactorial origin including oxygen exposure, occuring in the incompletely vascularized retina of the premature infant, which may have devastating consequences. Indomethacin is widely used in the perinatal period, for tocolysis, prevention of cerebral hemorrhage, and for nonsurgical closure of the patent ductus arteriosus. Its impact on ROP is controversial, with published studies showing a worsening, no effect, or improvement in ROP. OBJECTIVE: To test the hypothesis that indomethacin administration during the hyperoxic injury phase reduces the severity of oxygen induced retinopathy (OIR) in the mouse model. METHODS: The mouse (C57BL6)model of OIR was used. Pups were exposed either to normoxia or hyperoxia (75% FiO2) from postnatal day 7 through 12(P7-P12) with or without indomethacin (0.5mg/kg/day SQ). Animals were sacrificed between P17-P21. The severity of OIR was assessed using a scoring system with fluorescein conjugated dextran angiography of the retinal vasculature. These findings were corroborrated using periodic acid Schiff(PAS) staining of retinal sections. Statistical significance was evaluated using the students t test. RESULTS: Pups exposed to indomethacin and oxygen had significantly lower retinopathy scores (5.6 ± 1.4)than animals exposed to oxygen alone (8.1 ± 2.1). There was also a statistically significant decrease in the severity of blood vessel tufts, extraretinal neovascularization, central vasoconstriction and plus disease, when compared to animals exposed to hyperoxia alone. PAS staining for extraretinal neovascularization in the indomethacin and hyperoxia group showed a significantly lower number of nuclei (11.8± 6.6) as compared to hyperoxia alone (38.4 ± 10.4) per retinal section. CONCLUSION: Indomethacin decreases the severity of OIR without having an adverse effect on the normal retinal vasculature development in the mouse model. We postulate a protective mechanism of indomethacin because of its inhibition of cyclooxygenase which may modulate the inflammatory response during the hyperoxic injury phase and improve OIR.

Purpose. The goal of this study was to determine if systemic calcium channel blockade in the mouse model of oxygen induced retinopathy during the period of vascular injury (hyperoxia) would modulate the resultant retinopathy. Methods. C57BL6 mice pups were placed in 75% oxygen from postnatal day 7 through 12 (Smith et. al., IVOS, 1994) to induce retinal neovascularization which is maximal at postnatal day 17-21. Mice pups received varying doses of diltiazem (0.05, 0.2, and 0.5 mg/kg/day) from day 7 to 12. Animals were sacrificed at day 17-21 and retinal neovascularization was assessed by quantification of extra retinal neovascular nuclei in retinal sections and by a retinal scoring system of whole mount preparations. Results. Animals who received 0.2 and 0.5 mg/kg/day of diltiazem concurrent with oxygen exposure had significantly lower degrees of retinopathy as assessed by the neovascular nuclei and the retinal scoring system (p

PURPOSE: To develop a scoring system for the mouse model of oxygen induced retinopathy based on examining retinal whole mount preparations.

BACKGROUND: Retinopathy of prematurity (ROP) is a significant complication in extremely low birth weight (ELBW) infants. ROP has been correlated with lower birth weight, earlier gestational age, and degree of respiratory illness. We undertook this study to assess the association of Candida sepsis with ROP in ELBW infants.

In order to assess risk factors associated with incidence and severity of Retinopathy of Prematurity (ROP), a consecutive sample of all infants born at an urban public hospital with birth weight < 1250 grams was enrolled beginning July 1991 through July 1995. Surviving infants received ophthalmologic screening in accordance with AAP recommendations. Information collected on each infant included birth weight, gestational age, sex, antenatal dexamethasone administration, and common complications of prematurity. Seventy three percent (63/87) of the infants were included in the analysis (22 infants died and 2 were transferred prior to ophthalmology screening examinations). Mean birth weight was 981 ± 179 grams; mean gestational age was 27.8 ± 2.4 weeks. Among infants receiving antenatal dexamethasone, 2/23 (8.7%) developed ROP ≥ stage 2. Infants who did not receive antenatal dexamethasone had a significantly greater incidence of ROP≥ stage 2 (14/40 or 35%), chi square = 4.0, p = 0.04. Other factors significantly associated with ROP ≥ stage 2 included birth weight, gestational age, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and patent ductus arteriosus (PDA). Antenatal dexamethasone administration was associated with a significantly decreased risk of ROP ≥ stage 2 by multiple logistic regression analysis, after controlling for birth weight, gestational age, RDS, BPD, and PDA (Adjusted Odds Ratio (AOR) = 0.14, 95% CI = 0.02, 0.93). The association was stronger (AOR = 0.02, 95% CI = 0.00, 0.76) when the analysis was restricted to infants of 24-28 weeks gestation (n= 36). This study demonstrates an association between antenatal dexamethasone administration and a decreased incidence of ROP ≥ stage 2 in an urban population. In addition to promoting lung maturation and decreasing the incidence of IVH, antenatal steroids may play a role in decreasing the severity of ROP.

Purpose: The goal of this study was to define the repertoire of integrin expression in the developing mouse retina, particularly vascular expression. Methods: Eyes from 17-21 day old C57BL mice were removed and embedded in OCT and frozen at -70°C. 12 μm sections were prepared and were successively incubated for 1 hour each as follows: PBS with 3%BSA, rat anti-mouse integrin or laminin monoclonal antibody or hamster anti-mouse αv, Texas-Red conjugated secondary antibody or FITC-conjugated for αv, and FITC-conjugated RCA-I lectin. Incubations included appropriate washings with PBS between steps. Double staining with the FITC-conjugated RCA-I lectin was performed for all of the above primary antibodies with the exception of that for αv. Sections were examined by fluorescent microscopy. Results: The expression of laminin in intraretinal vessels was demonstrated by the colocalization of RCA-I, which labels mouse vasculature, and laminin staining.α6 and β1 integrin subunits, which form the laminin receptor α6β1, also localized to intraretinal vessels. α6 staining was also seen in cells of the inner nuclear cell layer. The retinal vasculature had minimal β4 staining and lacked α2, α3, α5, and αv staining. α3 staining was seen in the outer synaptic layer.Conclusion: Intraretinal vessels in the developing mouse retina express laminin and the integrin laminin receptorsα6β1 and minimally α6β4. No vascular staining for the integrin subunits α2, α3,α5, or αv were demonstrated.