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1.
JAMA Netw Open ; 6(9): e2334889, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37733345

RESUMO

Importance: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. Objective: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. Design, Setting, and Participants: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Interventions: Near-infrared spectroscopy monitoring of Csat and Msat. Main Outcomes and Measures: Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. Results: A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03). Conclusions and Relevance: In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia. Trial Registration: ClinicalTrials.gov Identifier: NCT01702805.


Assuntos
Recém-Nascido Prematuro , Espectroscopia de Luz Próxima ao Infravermelho , Recém-Nascido , Criança , Lactente , Humanos , Masculino , Adulto , Feminino , Peso ao Nascer , Transfusão de Sangue , Idade Gestacional
2.
J Pediatr ; 263: 113638, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37517646

RESUMO

OBJECTIVE: To characterize phosphatidylcholine (PC) molecular species in serial gastric aspirates as biomarkers for lung maturity, delivery of aerosolized surfactant (AS), and need for intubation. METHODS: In a phase II clinical trial of aerosolized surfactant in preterm neonates with respiratory distress syndrome receiving noninvasive ventilation, infants received a maximum of 2 doses of nebulized beractant. Gastric aspirates were collected before and after each dose and were analyzed for PCs using liquid chromatography mass spectrometry. RESULTS: Of 149 infants enrolled, gastric aspirates were obtained before (n = 91) and after (n = 94) dose 1, and before (n = 56) and after (n = 57) dose 2 of nebulized beractant. The mean ± SD values of birthweight, gestational age, and age at collection of baseline gastric aspirate were 1.7 ± 0.6 kg, 31.7 ± 2.8 weeks, and 5.5 ± 1.7 hours, respectively. The most abundant PC in beractant and gastric aspirates was PC(16:0/16:0). Advancing gestational age and number of antenatal corticosteroid doses predicted increased gastric aspirate PC(16:0/16:0), whereas maternal diabetes predicted a decrease. Several PCs increased significantly (P < .05) after nebulized beractant, consistent with effective aerosol delivery. Infants who received intubation within 72 hours of birth were more likely to have lower PC(16:0/16:0) levels in baseline gastric aspirates compared with those who did not (P = .024). CONCLUSIONS: PC molecular species in gastric aspirates of preterm neonates are potentially novel and precise biomarkers to assess lung maturity, aerosol delivery, and need for endotracheal intubation.


Assuntos
Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Gravidez , Recém-Nascido , Lactente , Humanos , Feminino , Tensoativos/uso terapêutico , Fosfatidilcolinas/uso terapêutico , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Lipoproteínas , Biomarcadores , Aerossóis e Gotículas Respiratórios
3.
Pediatr Pulmonol ; 58(7): 1982-1992, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37098830

RESUMO

BACKGROUND AND OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth, resulting in significant morbidity and mortality. Recent studies have suggested that microRNA (miRNA) dysregulation is involved in the pathogenesis of BPD and may serve as biomarkers for early detection. We conducted a directed search for dysregulated miRNAs in lung and heart autopsy samples of infants with histologic BPD. METHODS: We used archived lung and heart samples from BPD (13 lung, 6 heart) and control (24 lung, 5 heart) subjects. To measure miRNA expression, RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue specimens then reverse-transcribed, labeled, and hybridized to miRNA microarrays. The microarrays were scanned, and data were quantile normalized. Statistical analysis with a moderated t-test and control of the false discovery rate (5%) was used to compare normalized miRNA expression values between clinical categories. RESULTS: With our set of 48 samples, 43 miRNAs had a significant difference in expression comparing BPD to non-BPD controls. Among the most statistically significant miRNAs, miR-378b, miRNA-184, miRNA-3667-5p, miRNA-3976, miRNA-4646-5p, and miRNA-7846-3p were all consistently upregulated in both the heart and lung tissues of BPD subjects. The cellular pathway predicted to be most affected by these miRNAs is the Hippo signaling pathway. CONCLUSIONS: This study identifies miRNAs that are similarly dysregulated in postmortem lung and heart samples in subjects with histologic BPD. These miRNAs may contribute to the pathogenesis of BPD, have potential as biomarkers, and may provide insight to novel approaches for diagnosis and treatment.


Assuntos
Displasia Broncopulmonar , MicroRNAs , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Lactente , MicroRNAs/genética , MicroRNAs/metabolismo , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/metabolismo , Pulmão/metabolismo , Biomarcadores/metabolismo
4.
Pediatrics ; 150(3)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045299

RESUMO

Through this policy statement, the American Academy of Pediatrics advocates that all health care insurers adopt consistent medical necessity definitions that reflect the needs of infants, children, adolescents, and young adults (hereafter noted as "children") as a function of developmental, epidemiologic, dependency, demographic, and cost-related factors that change over the pediatric continuum and that differ from adults. Optimally, the scope of benefits defined in health care contracts should address the complete spectrum of health care needs of children and families, but in reality, many plans offer a limited scope of benefits for children. Even if a proposed intervention falls within the scope of benefits or is not specifically excluded from coverage, the health plan may still deny the intervention. In such cases, contractual language may allow an appeal to succeed if the provider demonstrates medical necessity. With the assistance of experienced pediatric physicians and other providers with pediatric expertise, health care payers and agencies should clearly detail the processes that define, evaluate, and determine medical necessity and through which providers may appeal decisions. A basic requirement for any medical necessity process is the consideration of input from the physician(s) caring for a pediatric patient for whom a medical necessity determination is necessary.


Assuntos
Contratos , Idioma , Adolescente , Criança , Humanos , Lactente , Estados Unidos
5.
Early Hum Dev ; 171: 105612, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35797784

RESUMO

Bronchopulmonary Dysplasia (BPD), the commonest complication of prematurity, is defined by treatment with oxygen for ≥28 days. Pulmonary hypertension (PH) often coexists with BPD and is associated with increased mortality. In 42 autopsies, histological changes of BPD and PH were demonstrated in 25 % and 65 % respectively of preterm infants <28 days of age, highlighting the need for early diagnosis and treatment.


Assuntos
Displasia Broncopulmonar , Hipertensão Pulmonar , Doenças do Prematuro , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Idade Gestacional , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro
6.
Pediatr Clin North Am ; 68(5): 1055-1070, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34538298

RESUMO

COVID-19 has afflicted the health of children and women across all age groups. Since the outbreak of the pandemic in December 2019, various epidemiologic, immunologic, clinical, and pharmaceutical studies have been conducted to understand its infectious characteristics, pathogenesis, and clinical profile. COVID-19 affects pregnant women more seriously than nonpregnant women, endangering the health of the newborn. Changes have been implemented to guidelines for antenatal care of pregnant women, delivery, and newborn care. We highlight the current trends of clinical care in pregnant women and newborns during the COVID-19 pandemic.


Assuntos
COVID-19/diagnóstico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Resultado da Gravidez/epidemiologia , Cuidado Pré-Natal/métodos , COVID-19/transmissão , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Gravidez
8.
Pediatr Dev Pathol ; 24(5): 430-437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048316

RESUMO

OBJECTIVE: Correlation of BPD with placental pathology is important for clarification of the multifactorial pathogenesis of BPD; however, previous reports have yielded varying results. We report placental findings in no/mild BPD compared to moderate/severe BPD, and with and without pulmonary hypertension (PH). METHODS: Eligible infants were 230/7-276/7 weeks gestational age. BPD was defined by the need for oxygen at ≥28 days with severity based on need for respiratory support at ≥36 weeks. Acute and chronic inflammatory placental lesions and lesions of maternal and fetal vascular malperfusion were examined. RESULTS: Of 246 eligible infants, 146 (59%) developed moderate/severe BPD. Thirty-four (23%) infants developed PH, all but 1 being in the moderate/severe BPD group. Chronic deciduitis (32% vs 16%, P = .003), chronic chorioamnionitis (23% vs 12%, P = .014), and ≥ 2 chronic inflammatory lesions (13% vs 3%, P = .007) were more frequent in the moderate/severe BPD group. Development of PH was associated with placental villous lesions of maternal vascular malperfusion (30% vs 15%, P = .047). CONCLUSIONS: The association of chronic inflammatory placental lesions with BPD severity has not been previously reported. This supports the injury responsible for BPD as beginning before birth in some neonates, possibly related to cytokines associated with these chronic inflammatory lesions.


Assuntos
Displasia Broncopulmonar/etiologia , Lactente Extremamente Prematuro , Doenças Placentárias/fisiopatologia , Placenta/patologia , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Recém-Nascido , Modelos Logísticos , Masculino , Gravidade do Paciente , Placenta/irrigação sanguínea , Placenta/fisiopatologia , Doenças Placentárias/patologia , Gravidez , Estudos Retrospectivos
10.
Pulm Pharmacol Ther ; 66: 101986, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33338661

RESUMO

PURPOSE: There is increasing research into novel techniques of administering surfactant to preterm infants (PTIs) with respiratory distress syndrome (RDS) receiving non-invasive respiratory support (NIRS). Although aerosolized surfactant (AS) is promising in PTIs receiving NIRS, the optimal surfactant dose and formulation, drug-device combination and patient profile is not known. The objective of this randomized clinical trial was to investigate the feasibility, safety, efficacy and impact of four dosing schedules of AS using two nebulizers in PTIs with RDS stratified by gestational age (GA). METHODS: PTIs with RDS receiving pre-defined NIRS for ≤8 h were assigned to 4 A S dosing schedules and 2 nebulizers within three GA strata (I = 240/7-286/7, II = 290/7-326/7, III = 330/7-366/7 weeks). There was no contemporaneous control group; at the recommendation of the Data Monitoring Committee, data was collected retrospectively for control infants. RESULTS: Of 149 subjects that received AS, the median age at initiation of the 1st dose and duration was 5.5 and 2.4 h respectively. There were 29 infants in stratum I, and 60 each in strata II and III. Of infants <32 weeks GA, 94% received caffeine prior to AS. Fifteen infants (10%) required intubation within 72 h; the rates were not significantly different between GA strata, dosing schedules and nebulizers for infants who received aerosolized surfactant. Compared to retrospective controls, infants who received AS were less likely to need intubation within 72 h in both the intention-to-treat (32% vs. 11%) and the per-protocol (22% vs. 10%) analyses (p < 0.05) with GA stratum specific differences. AS was well tolerated by infants and clinical caregivers. Commonest adverse events included surfactant reflux from nose and mouth (18%), desaturations (11%), and increased secretions (7%). CONCLUSIONS: We have demonstrated the feasibility, absence of serious adverse events and short-term efficacy of four dosing schedules of AS in the largest Phase II clinical trial of PTIs 24-36 weeks' GA with RDS receiving NIRS (ClinicalTrials.gov NCT02294630). The commonest adverse events noted were surfactant reflux and desaturations; no serious adverse effects were observed. Infants who received AS were less likely to receive intubation within 72 h compared to historical controls. AS is a promising new therapy for PTIs with RDS.


Assuntos
Produtos Biológicos , Síndrome do Desconforto Respiratório do Recém-Nascido , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Estudos Retrospectivos
11.
Pediatr Neonatol ; 61(3): 290-299, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32217025

RESUMO

BACKGROUND: Bronchopulmonary Dysplasia (BPD) is the commonest morbidity in extremely preterm infants (PTIs). Risk factors for BPD have been described in the era before the widespread availability of non-invasive ventilation (NIV) in the delivery room (DR). The objective of this study is to identify risk factors for Moderate/Severe BPD in an era of widespread availability of NIV in the DR. METHODS: Detailed antenatal and postnatal data were abstracted for PTIs, 230/7-276/7 weeks GA. Multivariate logistic regression and classification and regression tree analyses (CART) identified predictors for the primary outcome of Moderate/Severe BPD. RESULTS: Of 263 eligible infants, 59% had Moderate/Severe BPD. Moderate/Severe BPD was significantly associated with birthweight, gender, DR intubation and surfactant compared to No/Mild BPD. Of infants not intubated in the DR, 40% with No/Mild BPD and 80% with Moderate/Severe BPD received intubation by 48 hours (p < 0.05). Infants with Moderate/Severe BPD received longer duration of oxygen and mechanical (MV). On logistic regression, birthweight, gender, oxygen concentration, cumulative duration of oxygen and MV, surfactant, and blood transfusions predicted Moderate/Severe BPD. Both CART analysis and logistic regression showed duration of oxygen and MV to be the most important predictors for Moderate/Severe BPD. CONCLUSIONS: In an era of increasing availability of NIV in the DR, lower birthweight, male gender, surfactant treatment, blood transfusions and respiratory support in the first 2-3 weeks after birth predict Moderate/Severe BPD with high sensitivity and specificity. The majority of these infants received intubation within 48 hours of birth (97%). These data suggest that early failures of NIV represent opportunities for improvement of NIV techniques and of non-invasive surfactant to avoid intubation in the first 48 hours. Furthermore, these risk factors may allow earlier identification of infants most likely to benefit from interventions to prevent or decrease severity of BPD.


Assuntos
Displasia Broncopulmonar/etiologia , Adulto , Peso ao Nascer , Displasia Broncopulmonar/prevenção & controle , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Modelos Logísticos , Masculino , Ventilação não Invasiva , Gravidez , Surfactantes Pulmonares/uso terapêutico , Fatores de Risco
12.
Early Hum Dev ; 134: 19-25, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31121339

RESUMO

BACKGROUND: Treating respiratory distress syndrome (RDS) with intratracheal surfactant requires endotracheal intubation and mechanical ventilation, (MV) with their attendant risks. Use of non-invasive respiratory support in the delivery room averts the need for MV but delays surfactant administration. OBJECTIVE: We hypothesized that aerosolized surfactant is feasible and safe in infants 240/7-366/7 weeks gestational age (GA) with RDS, receiving non-invasive respiratory support. DESIGN/METHODS: In an unblinded Phase I study, sequentially enrolled infants with RDS stratified by GA received increasing doses (100 or 200 mg/kg of phospholipid) and dilutions (12.5 or 8.3 mg/ml) of surfactant using a jet nebulizer. Infants were monitored clinically and with cerebral oximetry. RESULTS: Seventeen infants were enrolled. Age at start of first dose and dose duration were 4.9 (3.4-10.1) and 2.1 (1.0-2.8) hours respectively. Two infants in the lowest GA stratum (240/7-286/7) required intubation within 2 h after the first dose. Fifteen infants completed the study; 13 received two doses. Infants tolerated the aerosol treatment well. No other significant adverse events were identified. Parental permission for cerebral oximetry was obtained in 16 infants. In the two infants who later exited the study, values prior to start of aerosolized surfactant were lower compared to 14 infants who completed the study (p = 0.0835), increased after start of study intervention (p = 0.0105) and decreased after intubation (p = 0.0003). CONCLUSIONS: We have demonstrated the feasibility and safety of aerosolized surfactant in preterm infants receiving non-invasive respiratory support. The treatment was well tolerated by infants and clinical caregivers.


Assuntos
Administração por Inalação , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Masculino , Nebulizadores e Vaporizadores , Surfactantes Pulmonares/efeitos adversos , Surfactantes Pulmonares/uso terapêutico
14.
Paediatr Drugs ; 21(1): 47-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30484072

RESUMO

OBJECTIVES: Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs). STUDY DESIGN: Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). RESULTS: Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27-2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94-4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08-23.56, p = 0.044). Results based on HRs were similar. CONCLUSIONS: Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling.


Assuntos
Analgésicos Opioides/efeitos adversos , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Fentanila/efeitos adversos , Unidades de Terapia Intensiva Pediátrica , Uso Off-Label , Administração Intravenosa , Administração Oral , Adolescente , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Medicamentos sob Prescrição , Estudos Prospectivos , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
15.
J Pediatr ; 196: 45-51.e3, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29502880

RESUMO

OBJECTIVE: To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS: We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial. RESULTS: Among 303 infants with HIE from these 2 studies, 67 (22%) had PPHN and 236 (78%) did not. We compared infants with PPHN with those without PPHN. The proportion of patients treated with therapeutic hypothermia was similar in PPHN and no-PPHN groups (66% vs 65%). Medication use during resuscitation (58% vs 44%), acidosis after birth (pH: 7.0 ± 0.2 vs 7.1 ± 0.2), severe HIE (43% vs 28%), meconium aspiration syndrome (39% vs 7%), pulmonary hemorrhage (12% vs 3%), culture-positive sepsis (12% vs 3%), systemic hypotension (65% vs 28%), inhaled nitric oxide therapy (64% vs 3%), and extracorporeal membrane oxygenation (12% vs 0%) were more common in the PPHN group. Length of stay (26 ± 21 vs 16 ± 14 days) and mortality (27% vs 16%) were higher in the PPHN group. CONCLUSIONS: PPHN is common among infants with moderate/severe HIE and is associated with severe encephalopathy, lung disease, sepsis, systemic hypotension, and increased mortality. The prevalence of PPHN was not different between those infants receiving therapeutic hypothermia at 33.5°C in these 2 trials (44/197 = 22%) compared with infants receiving normothermia in the induced hypothermia trial (23/106 = 22%).


Assuntos
Asfixia Neonatal/terapia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Acidose , Comorbidade , Interpretação Estatística de Dados , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipóxia-Isquemia Encefálica/complicações , Recém-Nascido , Tempo de Internação , Masculino , Idade Materna , Síndrome de Aspiração de Mecônio/complicações , Síndrome de Aspiração de Mecônio/diagnóstico , Síndrome de Aspiração de Mecônio/terapia
16.
Arch Dis Child Fetal Neonatal Ed ; 102(5): F439-F445, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28283553

RESUMO

OBJECTIVE: To identify genetic variants associated with sepsis (early-onset and late-onset) using a genome-wide association (GWA) analysis in a cohort of extremely premature infants. STUDY DESIGN: Previously generated GWA data from the Neonatal Research Network's anonymised genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole-genome-amplified DNA was genotyped for 1.2 million single-nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. p Values and false discovery rates (FDRs) were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10-5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. RESULTS: Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10-8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram-positive sepsis), RALA, IMMP2L (Gram-negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram-negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and interleukin-1-associated receptor kinase 2 (p values<0.001 and FDR<20%). CONCLUSIONS: No SNPs met genome-wide significance in this cohort of extremely low birthweight infants; however, areas of potential association and pathways meriting further study were identified.


Assuntos
Estudo de Associação Genômica Ampla , Lactente Extremamente Prematuro , Polimorfismo de Nucleotídeo Único , Sepse/genética , Transportadores de Cassetes de Ligação de ATP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Estudos de Coortes , Endopeptidases/genética , Feminino , Fatores de Transcrição Forkhead/genética , Proteínas Ativadoras de GTPase/genética , Genótipo , Humanos , Recém-Nascido , Canais Iônicos/genética , Masculino , Proteínas dos Microfilamentos/genética , Sepse/microbiologia
17.
J Matern Fetal Neonatal Med ; 29(5): 737-44, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25731658

RESUMO

BACKGROUND AND OBJECTIVES: Many observational studies reporting a temporal association between red cell transfusions (RBCTs) and necrotizing enterocolitis (NEC) in preterm infants fail to take into account RBCTs in infants without NEC. The objective of this study was to investigate the association between RBCTs and NEC in an analytical retrospective cohort study with minimization of selection and measurement bias and controlling for clinical covariates. METHODS: Inborn preterm infants [23-32 weeks gestational age (GA)] without major congenital anomalies were eligible. Association of RBCT and modified Bell's Stage ≥2A NEC was explored using bivariate analyses and verified using multivariable Cox regression. RESULTS: Of 627 eligible infants, 305 neither received RBCT nor developed NEC and 12 developed NEC prior to RBCT. Of 310 infants with RBCT, 27 developed NEC. Compared to infants without NEC, infants with NEC received significantly lower number of RBCTs before diagnosis of NEC (p = 0.000). On multivariable Cox regression controlling for clinical covariates, dichotomous RBCT exposure was associated with 60% reduced hazard for NEC. CONCLUSIONS: RBCT exposure was associated with decreased hazards for NEC in preterm infants in this study; factors previously reported to be associated with NEC remained statistically significant predictors.


Assuntos
Anemia Neonatal/terapia , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Transfusão de Eritrócitos/estatística & dados numéricos , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/terapia , Adulto , Anemia Neonatal/complicações , Anemia Neonatal/epidemiologia , Enterocolite Necrosante/etiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
18.
Semin Fetal Neonatal Med ; 20(3): 164-72, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25934116

RESUMO

Near-infrared spectroscopy (NIRS) offers non-invasive, in-vivo, real-time monitoring of tissue oxygenation. Changes in regional tissue oxygenation as detected by NIRS may reflect the delicate balance between oxygen delivery and consumption. Originally used predominantly to assess cerebral oxygenation and perfusion perioperatively during cardiac and neurosurgery, and following head trauma, NIRS has gained widespread popularity in many clinical settings in all age groups including neonates. However, more studies are required to establish the ability of NIRS monitoring to improve patient outcomes, especially in neonates. This review provides a comprehensive description of the use of NIRS in neonates.


Assuntos
Encéfalo/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Recém-Nascido , Monitorização Fisiológica , Oximetria/instrumentação , Oximetria/métodos , Oxigênio/análise
19.
Am J Perinatol ; 32(10): 973-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25730135

RESUMO

OBJECTIVE: The aim of this study is to determine whether the cystic periventricular leukomalacia (cPVL) detection rate differs between imaging studies performed at different time points. DESIGN: We retrospectively reviewed the prospectively collected data of 31,708 infants from the NICHD Neonatal Research Network. Inclusion criteria were infants < 1,000 g birth weight or < 29 weeks' gestational age who had cranial imaging performed using both early criterion (cranial ultrasound [CUS] < 28 days chronological age) and late criterion (CUS, magnetic resonance imaging, or computed tomography closest to 36 weeks postmenstrual age [PMA]). We compared the frequency of cPVL diagnosed by early and late criteria. RESULTS: About 664 (5.2%) of the 12,739 infants who met inclusion criteria had cPVL using either early or late criteria; 569 using the late criterion, 250 using the early criterion, and 155 patients at both times. About 95 (14.3%) of 664 cPVL cases seen on early imaging were no longer visible on repeat screening closest to 36 weeks PMA. Such disappearance of cPVL was more common in infants < 26 weeks' gestation versus infants of 26 to 28 weeks' gestation (18.5 vs. 11.5%; p = 0.013). CONCLUSIONS: Cranial imaging at both < 28 days chronological age and closest to 36 weeks PMA improves cPVL detection, especially for more premature infants.


Assuntos
Encéfalo/patologia , Leucomalácia Periventricular/diagnóstico , Encéfalo/diagnóstico por imagem , Ecoencefalografia , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética , Triagem Neonatal , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
20.
Am J Obstet Gynecol ; 212(1): 94.e1-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25046806

RESUMO

OBJECTIVE: Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. STUDY DESIGN: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. RESULTS: We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group. CONCLUSION: Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups.


Assuntos
Cardiopatias/induzido quimicamente , Doenças do Prematuro/induzido quimicamente , Sulfato de Magnésio/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtornos Respiratórios/induzido quimicamente , Doença Aguda , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Estudos Retrospectivos , Adulto Jovem
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