Objective To characterize the implementation of hypothermia for neonatal hypoxic ischemic encephalopathy (HIE) in a population-based cohort. Study design Using the California Perinatal Quality Care ...Collaborative and California Perinatal Transport System linked 2010-2012 datasets, we categorized infants ≥36 weeks' gestation with HIE as receiving hypothermia or normothermia. Sociodemographic and clinical factors were compared, and multivariable logistic regression was used to determine factors associated with hypothermia therapy. Results There were 238 reported encephalopathy cases in 2010, 280 in 2011, and 311 in 2012. Hypothermia therapy use in newborns with HIE increased from 59% to 73% across the study period, mainly occurring in newborns with mild or moderate encephalopathy. A total of 36 centers provided hypothermia and cared for 94% of infants, with the remaining 6% being cared for at one of 25 other centers. Of the centers providing hypothermia, 12 centers performed hypothermia therapy to more than 20 patients during the 3-year study period, and 24 centers cared for <20 patients receiving hypothermia. In-hospital mortality was 13%, which primarily was associated with the severity of encephalopathy. Conclusions Our findings highlight an opportunity to explore practice-site variation and to develop quality improvement interventions to assure consistent evidence-based care of term infants with HIE and appropriate application of hypothermia therapy for eligible newborns.
Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the Eunice Kennedy ...Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of ≥1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9). Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population.
Abstract The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition ...of the 2 randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure.
Objective To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants. Study design This was a prospective pilot RCT of ...infants 23-0/7 to 26-6/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo). Results Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. A total of 161 infants (44%) were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study because of the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin. Conclusions This pilot RCT was not feasible because of low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.
In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. ...Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group ( P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. Trial registration ClinicalTrials.gov : NCT01913340.
Abstract Extracorporeal membrane oxygenation (ECMO) continues to be an important rescue therapy for newborns with a variety of causes of cardio-respiratory failure unresponsive to high-frequency ...ventilation, surfactant replacement, and inhaled nitric oxide. There are approximately 800 neonatal respiratory ECMO cases reported annually to the Extracorporeal Life Support Organization; venoarterial ECMO has been used in approximately 72% with a cumulative survival of 71% and venovenous has been used in 28% with a survival of 84%. Congenital diaphragmatic hernia is now the most common indication for ECMO. This article reviews the development of the two types of extracorporeal support, venoarterial and venovenous ECMO, and discusses the advantages of each method, the current selection criteria, the procedure, and the clinical management of neonates on ECMO.
Objective To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS). Study design Retrospective analysis of ...VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the National Institute of Child Health and Human Development Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hours of birth (EOS) or >72 hours (LOS) and antimicrobial therapy for ≥5 days or death <5 days while receiving therapy. Regression models were used to assess risk of death or LOS by 120 days and LOS by 120 days among survivors to discharge or 120 days, adjusting for gestational age and other covariates. Results Of 34 396 infants studied, 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120 days did not differ overall for infants with EOS compared with those without EOS risk ratio (RR): 0.99 (0.89-1.09) but was reduced in infants born at <25 weeks gestation RR: 0.87 (0.76-0.99), P = .048. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS RR: 0.88 (0.75-1.02), but LOS risk was reduced in infants with birth weight 401-750 g who had EOS RR: 0.80 (0.64-0.99), P = .047. Conclusions Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function.
Objective To assess interobserver reliability between 2 central readers of cranial ultrasound scanning (CUS) and accuracy of local, compared with central, interpretations. Study design The study was ...a retrospective analysis of CUS data from the National Institute of Child Health and Human Development (NICHD) trial of inhaled nitric oxide for premature infants. Interobserver reliability of 2 central readers was assessed with kappa or weighted kappa. Accuracy of local, compared with central, interpretations was assessed by using sensitivity and specificity. Results CUS from 326 infants had both central reader and local interpretations. Central reader agreement for grade 3/4 intraventricular hemorrhage (IVH), grade 3/4 IVH or periventricular leukomalacia (PVL), grade of IVH, and degree of ventriculomegaly was very good (kappa = 0.84, 0.81, 0.79, and 0.75, respectively). Agreement was poor for lower grade IVH and for PVL alone. Local interpretations were highly accurate for grade 3/4 IVH or PVL (sensitivity, 87%-90%; specificity, 92%-93%), but sensitivity was poor-to-fair for grade 1/2 IVH (48%-68%) and PVL (20%-44%). Conclusions Our findings demonstrate reliability and accuracy of highly unfavorable CUS findings, but suggest caution when interpreting mild to moderate IVH or white matter injury.
Objective To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) ...infants. Study design A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables. Results Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19). Conclusion ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors.
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.
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