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1.
Am J Perinatol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382299

RESUMO

OBJECTIVE: To compare short-term respiratory outcomes of three steroids (dexamethasone, hydrocortisone, and methylprednisolone) to facilitate extubation by improving respiratory status in preterm infants. STUDY DESIGN: This is a retrospective, single-center, cohort study of 98 intubated preterm infants ≤346/7 weeks' gestation, admitted to a 64-bed, level III neonatal intensive care unit at the Women & Children's Hospital of Buffalo, Buffalo, NY, between 2006 and 2012, who received a short course of low-dose steroids for lung disease after first week of life. RESULTS: Study infants received dexamethasone (34%), hydrocortisone (44%), or methylprednisolone (22%) based on clinical team preference. By day 7 after initiation of steroids, extubation occurred in 59, 44, and 41%, respectively, in infants on dexamethasone, hydrocortisone, and methylprednisolone (p = 0.3). The mean respiratory severity score (RSS = fraction of inspired oxygen × mean airway pressure), a quantitative measure of respiratory status, decreased by 44% for all infants and by 59% in the dexamethasone group by day 7. CONCLUSION: Steroids improved short-term respiratory outcomes in all infants (RSS and extubation); by day 7, dexamethasone treatment was associated with the greatest decrease in RSS. Additional prospective, randomized trials of short-course low-dose steroids are warranted to substantiate these findings to guide clinical decision making and in evaluating differential steroid effects on long-term neurodevelopmental outcomes.

2.
J Pediatr ; 208: 148-155.e3, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30857774

RESUMO

OBJECTIVE: To determine patterns of respiratory medications used in neonatal intensive care unit graduates. STUDY DESIGN: The Prematurity Respiratory Outcomes Program enrolled 835 babies <29 weeks of gestation in the first week. Of 751 survivors, 738 (98%) completed at least 1, and 85% completed all 4, postdischarge medication usage in-person/telephone parental questionnaires requested at 3, 6, 9, and 12 months of corrected age. Respiratory drug usage over the first year of life after in neonatal intensive care unit discharge was analyzed. RESULTS: During any given quarter, 66%-75% of the babies received no respiratory medication and 45% of the infants received no respiratory drug over the first year. The most common postdischarge medication was the inhaled bronchodilator albuterol; its use increased significantly from 13% to 31%. Diuretic usage decreased significantly from 11% to 2% over the first year. Systemic steroids (prednisone, most commonly) were used in approximately 5% of subjects in any one quarter. Inhaled steroids significantly increased over the first year from 9% to 14% at 12 months. Drug exposure changed significantly based on gestational age with 72% of babies born at 23-24 weeks receiving at least 1 respiratory medication but only 40% of babies born at 28 weeks. Overall, at some time in the first year, 55% of infants received at least 1 drug including an inhaled bronchodilator (45%), an inhaled steroid (22%), a systemic steroid (15%), or diuretic (12%). CONCLUSION: Many babies born at <29 weeks have no respiratory medication exposure postdischarge during the first year of life. Inhaled medications, including bronchodilators and steroids, increase over the first year.

3.
J Pediatr ; 207: 130-135.e2, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612812

RESUMO

OBJECTIVE: To use a large current prospective cohort of infants <29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants. STUDY DESIGN: The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at <29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth. RESULTS: Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P = .004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%). CONCLUSIONS: In this large cohort of recently born preterm infants at <29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.

4.
Dev Med Child Neurol ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30417338

RESUMO

AIM: Since cross-sectional trends of 8-year-old cerebral palsy (CP) birth prevalence based on record review were stable from 1985 to 2002 in Metropolitan Atlanta, we examined birth cohort trends using administrative data sets promptly. METHOD: Among 755 433 live births from 1996 to 2009 in South Carolina, 2080 received CP diagnosis by age 4 years from linked Medicaid claims with International Classification of Diseases, Ninth Revision codes 343.X (contributing 1061 [51%] unique cases), hospital discharge data (57 [3%] unique cases), and Department of Disabilities and Special Needs program (64 [3%] unique cases). Trends were assessed using negative binominal regression. RESULTS: Including 3.7 percent of cases who died before age 4 years, CP prevalence per 1000 live births decreased significantly from 3.6 in 1996 to 2.1 in 2006 (-3.0% average annual change; 95% confidence interval -4.4 to -1.6). The overall prevalence was 2.8 per 1000 live births, 46.0 per 1000 very-low-birthweight (VLBW) live births, and 53.0 per 1000 VLBW 1-year survivors. Disparities and downward trends persisted across subgroups with higher rates among non-Hispanic black infants than non-Hispanic white and among males compared to females. INTERPRETATION: Downward CP prevalence rates and persistent disparities remain in South Carolina. Further research should validate this methodology, including early deaths, and develop broad surveillance systems to inform clinical practices and etiology. WHAT THIS PAPER ADDS: Birth cohort cerebral palsy (CP) prevalence decreased in South Carolina from 1996 to 2009. CP prevalence was higher in very-low-birthweight infants, non-Hispanic blacks, and males. Three administrative data sets captured 2080 patients with CP in South Carolina. Medicaid claims contributed 51% of unique cases of CP to the cohort. CP diagnoses included 76 patients who died before age 4 years.

5.
J Pediatr Surg ; 53(6): 1187-1191, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29622398

RESUMO

BACKGROUND: For infants with necrotizing enterocolitis (NEC) treated nonoperatively, no consensus exists on the optimal fasting period prior to reintroducing feeds after NEC. We report our experience with early (<7days) and late (≥7days) refeeding in this population. METHODS: A chart review of infants with NEC born between 2006 and 2016 was performed. Data elements include demographics, comorbidities, day of diagnosis, Bell's stage, recurrence, strictures, length of stay and mortality, and were grouped into early and late refeeding. T-tests were used for means and chi-squared tests for distribution of proportions. Linear and logistic regressions were used to further evaluate the association of length of stay, stricture, recurrence, and death with time to refeeding. RESULTS: Of 228 NEC patients, 149(65%) were treated nonoperatively (Bell Stages I, IIA, IIB, IIIA). Eleven patients were excluded owing to never restarting feeds, largely secondary to early death. The early (n=40) and late refeeding (n=98) groups were not significantly different with regard to mean gestational age at birth, race, birth weight, day of life at NEC diagnosis, or cardiac disease. NEC Stage was significantly different (p<0.001). The late group had significantly more Stage IIB patients (p=.02), and the early group had more stage I patients (p=<0.01). After adjusting for Bell's stage, the odds of NEC recurrence, death, and the composite outcome of recurrence or stricture or death were not significantly different between early and late groups. CONCLUSIONS: No standardized guidelines exist for restarting enteral nutrition following medical NEC. In patients managed nonoperatively, early reintroduction of feeding was not significantly associated with increased NEC recurrence, mortality, or stricture. LEVEL OF EVIDENCE: Treatment Study - Level III.


Assuntos
Nutrição Enteral/métodos , Enterocolite Necrosante/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
7.
JCI Insight ; 3(4)2018 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-29467329

RESUMO

The inverse relationship between gestational age at birth and postviral respiratory morbidity suggests that infants born preterm (PT) may miss a critical developmental window of T cell maturation. Despite a continued increase in younger PT survivors with respiratory complications, we have limited understanding of normal human fetal T cell maturation, how ex utero development in premature infants may interrupt normal T cell development, and whether T cell development has an effect on infant outcomes. In our longitudinal cohort of 157 infants born between 23 and 42 weeks of gestation, we identified differences in T cells present at birth that were dependent on gestational age and differences in postnatal T cell development that predicted respiratory outcome at 1 year of age. We show that naive CD4+ T cells shift from a CD31-TNF-α+ bias in mid gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term born infants were at an over 3.5-fold higher risk for respiratory complications after NICU discharge. This study is the first to our knowledge to identify a pattern of normal functional T cell development in later gestation and to associate abnormal T cell development with health outcomes in infants.

8.
Anat Rec (Hoboken) ; 301(4): 717-726, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29281864

RESUMO

The outcomes of premature infants have improved greatly; however, the health risks in adulthood are still relatively unclear. Bronchopulmonary dysplasia (BPD) in premature infants is a major risk factor for alteration in lung function and predisposition to respiratory morbidity, and is associated with hyperoxia. The study explores the effect of neonatal hyperoxia on organ systems in adult mice. Newborn mouse litters were randomized to 85%O2 or room air (RA) on P3 for 12 days; mice were sacrificed at P3, P7, P15, 3 months and 9 months. Lungs were assessed by histopathology, radial alveolar count, mean linear intercept, and α-Smooth muscle actin immunohistochemistry. Aortic assessment included histology, wall thickness, elastin, and collagen content. Glomerular histology and nephron number were assessed in the kidneys. Hyperoxia-exposed mice had progressive alveolar simplification and poor weight gain over time. Greater thickness of pulmonary arterioles by 3 months and a higher Fulton index by 9 months suggest worsening pulmonary hypertension. Aortic wall thickness to lumen ratio was greater with a lower aortic elastin-to-collagen ratio suggesting long-term effects of neonatal hyperoxia. Hyperoxia-exposed mice at 9 months had smaller glomeruli as indicated by glomerular diameter and volume. Prolonged neonatal hyperoxia during the critical period of development induces irreversible lung damage, pulmonary hypertension and structural changes in the kidneys and aorta in adult mice. This could have implications for chronic adult diseases following exposure to high levels of oxygen in the newborn period. Anat Rec, 301:717-726, 2018. © 2017 Wiley Periodicals, Inc.

9.
Microbiome ; 5(1): 158, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29228972

RESUMO

BACKGROUND: Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. RESULTS: With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. CONCLUSION: The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Recém-Nascido Prematuro/crescimento & desenvolvimento , Mecônio/microbiologia , Estado Nutricional , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Aleitamento Materno , Estudos de Coortes , DNA Bacteriano , Feminino , Idade Gestacional , Humanos , Lactente , Saúde do Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Doenças do Prematuro/dietoterapia , Doenças do Prematuro/prevenção & controle , Masculino , RNA Ribossômico 16S , Análise de Sequência de DNA
10.
Physiol Rep ; 5(16)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28830981

RESUMO

Nuclear Factor I (Nfi) genes encode transcription factors essential for the development of organ systems including the lung. Nfib null mice die at birth with immature lungs. Nfib hemizygous mice have reduced lung maturation with decreased survival. We therefore hypothesized that these mice would be more sensitive to lung injury and would have lower survival to hyperoxia. Adult Nfib hemizygous mice and their wild-type (Wt) littermates were exposed to 100% O2 for 89, 80, 72 and 66 h for survival studies with lung outcome measurements at 66 h. Nfib hemizygous and Wt controls were also studied in RA at 66 h. Cell counts and cytokines were measured in bronchoalveolar lavage (BAL); lung sections examined by histopathology; lung angiogenic and oxidative stress gene expression assessed by real-time PCR Unexpectedly, Nfib hemizygous mice (0/14-0%) had significantly lower mortality compared to Wt mice (10/22-45%) at 80 h of hyperoxia (P < 0.003). LD50 was 80 h in the Wt group versus 89 h in the hemizygous group. There were no differences in BAL cell counts between the groups. Among the cytokines studied, MIP-2 was significantly lower in hemizygous mice exposed to hyperoxia. New vessel formation, edema, congestion, and alveolar hemorrhage were noted on histopathology at 72 and 80 h in wild-type mice. Nfib hemizygous lungs had significant downregulation of genes involved in redox signaling and inflammatory pathways. Adult Nfib hemizygous mice are relatively resistant to hyperoxia compared to wild-type littermates. Mechanisms contributing to this resistance are not clear; however, transcription factors such as Nfib may regulate cell survival and play a role in modulating postnatal lung development.


Assuntos
Hiperóxia/metabolismo , Pulmão/metabolismo , Fatores de Transcrição NFI/metabolismo , Animais , Quimiocina CXCL2/metabolismo , Citocinas/metabolismo , Hemizigoto , Hiperóxia/genética , Hiperóxia/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFI/genética , Estresse Oxidativo
11.
J Pediatr ; 186: 4-5, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28483065
12.
Pediatr Res ; 82(2): 349-355, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28288148

RESUMO

Background: At birth, the release of surfactant from alveolar type II cells (ATIIs) is stimulated by increased activity of the beta-adrenergic/adenylyl cyclase/cyclic 3'-5' adenosine monophosphate-signaling cascade. Atrial natriuretic peptide (ANP) stimulates surfactant secretion through natriuretic peptide receptor A (NPR-A). ANP inhibits adenylyl cyclase activity through its binding to NPR-C. We wished to further understand the role of the NPR-C in perinatal transition. Methods: We studied ATII expression of NPR-C in fetal and newborn sheep using immunohistochemistry, and surfactant secretion in isolated ATIIs by measuring 3[H] choline release into the media. Results: ANP induced surfactant secretion, and, at higher doses, it inhibits the stimulatory effect of the secretagogue terbutaline. ATII NPR-C expression decreased significantly after birth. Premature delivery also markedly decreased ANP and NPR-C in ATIIs. Co-incubation of terbutaline (10-4 M) with ANP (10-6 M) significantly decreased 3[H] choline release from isolated newborn ATII cells when compared with terbutaline alone; this inhibitory effect was mimicked by the specific NPR-C agonist, C-ANP (10-10 M). Conclusion: ANP may act as an important epithelial-derived inhibitor of surfactant release in the fetal lung, and downregulation of ANP and NPR-C following birth may sensitize ATII cells to the effects of circulating catecholamines, thus facilitating surfactant secretion.


Assuntos
Pulmão/metabolismo , Peptídeo Natriurético Tipo C/metabolismo , Ovinos/embriologia , Animais , Animais Recém-Nascidos , Imuno-Histoquímica , Toxina Pertussis/farmacologia , Surfactantes Pulmonares/metabolismo , Terbutalina/farmacologia
13.
J Pediatr ; 183: 19-25.e2, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28100402

RESUMO

OBJECTIVE: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control). STUDY DESIGN: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys). RESULTS: Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM. CONCLUSION: Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.


Assuntos
Recém-Nascido de Peso Extremamente Baixo ao Nascer , Óxido Nítrico/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Administração por Inalação , Fatores Etários , Displasia Broncopulmonar/prevenção & controle , Intervalos de Confiança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Medição de Risco , Taxa de Sobrevida , Fatores de Tempo
14.
Pediatr Res ; 81(1-2): 210-213, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27682969

RESUMO

Despite the many advances in neonatology, bronchopulmonary dysplasia (BPD) continues to be a frustrating disease of prematurity. BPD is a disease which is defined oddly by its treatment rather than its pathophysiology, leading to frequently changing nomenclature which has widespread implications on our ability to both understand and follow the progression of BPD. As various treatment modalities for BPD were developed and a larger number of extremely preterm infants survived, the "old" BPD based on lung injury from oxygen therapy and mechanical ventilation transitioned into a "new" BPD focused more on the interruption of normal development. However, the interruption of normal development does not solely apply to lung development. The effects of prematurity on vascular development cannot be overstated and pulmonary vascular disease has become the new frontier of BPD. As we begin to better understand the complex, multifactorial pathophysiology of BPD, it is necessary to again focus on appropriate, pathology-driven nomenclature that can effectively describe the multiple clinical phenotypes of BPD.


Assuntos
Displasia Broncopulmonar/história , Displasia Broncopulmonar/terapia , Animais , Biomarcadores/metabolismo , História do Século XX , História do Século XXI , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal , Pulmão/fisiopatologia , Oxigenoterapia , Fenótipo , Respiração Artificial , Resultado do Tratamento
15.
J Immunol Methods ; 437: 13-20, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27438473

RESUMO

RATIONALE: Emerging data suggest an important role for T lymphocytes in the pathogenesis of chronic lung disease in preterm infants. Comprehensive assessment of the lymphocyte transcriptome may identify biomarkers and mechanisms of disease. METHODS: Small volume peripheral blood samples were collected from premature infants enrolled with consent in the Prematurity and Respiratory Outcomes Program (PROP), at the time of discharge from the hospital. Blood samples were collected at two sites and shipped to a central laboratory for processing. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque gradient centrifugation and separated into individual lymphocyte cell types by fluorescence-activated cell sorting. Gating strategies were optimized to ensure reproducible recovery of highly purified lymphocyte populations over a multi-year recruitment period. RNA was isolated from sorted cells and characterized by high-throughput sequencing (RNASeq). RESULTS: Blood volumes averaged 2.5ml, and sufficient PBMCs were collected from 165 of the 246 samples obtained (67%) from the 277 recruited subjects to complete sorting and RNASeq analysis on the resulting sorted cells. The number of total lymphocytes per ml of blood in the neonatal subjects was approximately 4 million/ml. Total lymphocyte frequencies recovered following sort varied widely among subjects, as did the frequency of individual lymphocyte and NK cell sub-populations. RNA yield from sorted cells varied according to cell type, but RNA of sufficient quantity and quality was recovered to enable RNASeq. SUMMARY: Our results describe a validated procedure for the generation of genome-wide expression data from isolated lymphocyte sub-populations obtained from newborn blood.


Assuntos
Perfilação da Expressão Gênica/métodos , Linfócitos/fisiologia , Separação Celular , Centrifugação com Gradiente de Concentração , Estudos de Viabilidade , Ficoll , Citometria de Fluxo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Contagem de Linfócitos , Miniaturização
16.
Pediatr Pulmonol ; 51(11): 1131-1141, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27116319

RESUMO

BACKGROUND: Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. METHODS: Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. RESULTS: Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP-1, IL-12, INF-γ) and at 15 weeks (LTB4 , VEGF); Lipoxin-A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. CONCLUSIONS: Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. 2016;51:1131-1141. © 2016 Wiley Periodicals, Inc.


Assuntos
Hiperóxia/fisiopatologia , Pulmão/fisiopatologia , Pneumonia/fisiopatologia , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Quimiocina CCL2/metabolismo , Hiperóxia/complicações , Hiperóxia/metabolismo , Interleucina-12/metabolismo , Pulmão/metabolismo , Linfócitos/metabolismo , Cloreto de Metacolina , Camundongos , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Oxigênio , Pneumonia/etiologia , Pneumonia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
J Pediatr ; 168: 23-9.e4, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26500107

RESUMO

OBJECTIVE: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. RESULTS: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. CONCLUSION: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.


Assuntos
Displasia Broncopulmonar/etiologia , Óxido Nítrico/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Respiração Artificial/efeitos adversos , Administração por Inalação , Displasia Broncopulmonar/epidemiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso , Masculino , Óxido Nítrico/efeitos adversos , Surfactantes Pulmonares/efeitos adversos , Respiração Artificial/mortalidade , Taxa de Sobrevida , Estados Unidos
18.
Clin Immunol ; 161(2): 65-74, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26232733

RESUMO

Homeostatic T cell proliferation is more robust during human fetal development. In order to understand the relative effect of normal fetal homeostasis and perinatal exposures on CD8+ T cell behavior in PT infants, we characterized umbilical cord blood CD8+ T cells from infants born between 23-42weeks gestation. Subjects were recruited as part of the NHLBI-sponsored Prematurity and Respiratory Outcomes Program. Cord blood from PT infants had fewer naïve CD8+ T cells and lower regulatory CD31 expression on both naïve and effector, independent of prenatal exposures. CD8+ T cell in vitro effector function was greater at younger gestational ages, an effect that was exaggerated in infants with prior inflammatory exposures. These results suggest that CD8+ T cells earlier in gestation have loss of regulatory co-receptor CD31 and greater effector differentiation, which may place PT neonates at unique risk for CD8+ T cell-mediated inflammation and impaired T cell memory formation.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Recém-Nascido Prematuro/imunologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/imunologia , Proliferação de Células/fisiologia , Feminino , Sangue Fetal/imunologia , Homeostase/imunologia , Humanos , Memória Imunológica/imunologia , Recém-Nascido , Ativação Linfocitária/imunologia , Masculino , Gravidez
19.
Hum Immunol ; 76(5): 329-338, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25797206

RESUMO

BACKGROUND: Chorioamnionitis (CA) is associated with premature delivery and bronchopulmonary dysplasia (BPD). We hypothesize that preterm infants exposed to CA have reduced suppressive regulatory T cells (Treg) and increased non-regulatory T cell pro-inflammatory cytokines, increasing risk for BPD. OBJECTIVE: To evaluate cord blood CD4(+) T cell regulatory phenotype and pro-inflammatory cytokine production in CA and BPD groups. STUDY DESIGN: Cord blood mononuclear cells from infants (GA ⩽32 weeks), with or without placental histological evidence of CA (hChorio), were analyzed by flow cytometry. Clinical information was collected by retrospective chart review. Numbers of putative Treg (CD4(+)FoxP3(+)CD25(+)CD127Dim), CD4(+) non-Tregs, and CD4(+) T cell intracellular cytokine content following in vitro stimulation were compared with CA status and oxygen requirement at 36weeks postmenstrual age. RESULT: Absolute Treg numbers were not different in CA and non-CA exposed samples. However, the infants who developed BPD had a significant decrease in Treg and non-regulatory T cell numbers. Greater IL-6 production was observed in hCA group. CONCLUSION: A pro-inflammatory CD4(+) T cell status is noted in CA and BPD but the later disease is also associated with decrease in Tregs, suggesting that the development of BPD is marked by distinct inflammatory changes from those of CA exposed infants.


Assuntos
Displasia Broncopulmonar/imunologia , Corioamnionite/imunologia , Sangue Fetal/imunologia , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Nascimento Prematuro/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Antígenos CD4/metabolismo , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Recém-Nascido , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-6/genética , Gravidez
20.
Am J Perinatol ; 32(3): 225-32, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24968129

RESUMO

OBJECTIVE: Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. STUDY DESIGN: Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO. RESULTS: In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. CONCLUSION: Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development.


Assuntos
Displasia Broncopulmonar/prevenção & controle , GMP Cíclico/urina , Doenças do Prematuro/prevenção & controle , Óxido Nítrico/urina , Administração por Inalação , Biomarcadores/urina , Creatinina/urina , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Óxido Nítrico/administração & dosagem , Análise de Regressão , Respiração Artificial
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