Douglas McMillan

Part 11: Neonatal Resuscitation 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

2010;126;e1319-e1344; originally published online Oct 18, 2010; Pediatrics COLLABORATORS CHAPTER Sithembiso Velaphi and on behalf of the NEONATAL RESUSCITATION Sam Richmond, Wendy M. Simon, Nalini Singhal, Edgardo Szyld, Masanori Tamura, Chameides, Jay P. Goldsmith, Ruth Guinsburg, Mary Fran Hazinski, Colin Morley, Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Dianne L. Atkins, Leon Recommendations Resuscitation and Emergency Cardiovascular Care Science With Treatment Neonatal Resuscitation: 2010 International Consensus on Cardiopulmonary http://www.pediatrics.org/cgi/content/full/126/5/e1319 located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Grove Village, Illinois, 60007. Copyright

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis

OBJECTIVE To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

A multicenter study on the clinical outcome of chorioamnionitis in preterm infants

OBJECTIVE The purpose of this study was to examine the effects of clinical maternal chorioamnionitis on morbidity and mortality rates among infants who are at < 33 weeks of gestation, adjusted for patient characteristics that included admission neonatal illness severity (Score for Neonatal Acute Physiology, version II; SNAP-II). STUDY DESIGN With multivariate logistic regression analysis, prospectively collected hospital outcomes from the Canadian Neonatal Network of singleton infants with birth gestational age of < 33 weeks and clinical chorioamnionitis were compared retrospectively with nonexposed infants. RESULTS Of 3094 infants, 477 infants (15.4%) who were exposed to clinical chorioamnionitis had significantly higher admission SNAP-II scores. Bivariate analysis revealed that the neonatal mortality rate was increased significantly in the chorioamnionitis group (10.6% vs 6.1%). Multivariate regression analysis with adjustment for illness severity indicated that chorioamnionitis was associated with an increased risk of early sepsis (odds ratio, 5.54; 95% confidence interval, 2.87-10.69) and severe intraventricular hemorrhage (odds ratio, 1.62; 95% confidence interval, 1.17-2.24) but not neonatal death. CONCLUSION Preterm infants who are exposed to clinical chorioamnionitis have an increased risk of early-onset sepsis and severe intraventricular hemorrhage.

Canadian Pediatric Surgical Network: a population-based pediatric surgery network and database for analyzing surgical birth defects. The first 100 cases of gastroschisis

PURPOSE Outcomes studies for gastroschisis are constrained by small numbers, prolonged accrual, and nonstandardized data collection. The aim of this study is to create a national pediatric surgical network and database for gastroschisis (GS) that tracks cases from diagnosis to hospital discharge. METHODS The 16-center network serves a population of 32 million. Gastroschisis cases are ascertained at prenatal diagnosis. Perinatal data include maternal risk and fetal ultrasound variables, delivery plan and outcome, a postnatal bowel injury score, intended and actual surgical treatment, and neonatal outcomes. Institutional review board-approved data collection conforms to regional privacy legislation. Deidentified data are centralized and accessible for research through the network steering committee. RESULTS To date, 114 cases of pre- and/or postnatal gastroschisis have been uploaded. Of 106 live-born infants (40 [38%] by cesarean delivery), 100 had complete records, and overall survival to discharge was 96%, with a mean survivor length of stay (LOS) of 46 days. Infants treated with attempted urgent closure (61%) had significantly shorter LOS (42 vs 57 days; P = .048) but comparable LOS compared with those treated with silos and delayed closure. Fetal bowel dilation 18 mm or greater did not predict a difference in outcome. CONCLUSION Population-based databases allow rapid case accrual and enable studies that should aid in the identification of optimal perinatal treatment.

Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?

Objective:To compare risk-adjusted changes in outcomes of preterm infants <29 weeks gestation born in 1996 to 1997 with those born in 2006 to 2007.Study Design:Observational retrospective comparison of data from 15 units that participated in the Canadian Neonatal Network during 1996 to 1997 and 2006 to 2007 was performed. Rates of mortality and common neonatal morbidities were compared after adjustment for confounders.Result:Data on 1897 infants in 1996 to 1997 and 1866 infants in 2006 to 2007 were analyzed. A higher proportion of patients in the later cohort received antenatal steroids and had lower acuity of illness on admission. Unadjusted analyses revealed reduction in mortality (unadjusted odds ratio (UAOR): 0.83, 95% confidence interval (CI): 0.63, 0.98), severe retinopathy (UAOR: 0.68, 95% CI: 0.50 to 0.92), but increase in bronchopulmonary dysplasia (UAOR: 1.61, 95% CI: 1.39 to 1.86) and patent ductus arteriosus (UAOR: 1.22, 95% CI: 1.07 to 1.39). Adjusted analyses revealed increases in the later cohort for bronchopulmonary dysplasia (adjusted odds ratio (AOR): 1.88, 95% CI: 1.60 to 2.20) and severe neurological injury (AOR: 1.49, 95% CI: 1.22 to 1.80). However, the ascertainment methods for neurological findings and ductus arteriosus differed between the two time periods.Conclusion:Improvements in prenatal care has resulted in improvement in the quality of care, as reflected by reduced severity of illness and mortality. However, after adjustment of prenatal factors, no improvement in any of the outcomes was observed and on the contrary bronchopulmonary dysplasia increased. There is need for identification and application of postnatal strategies to improve outcomes of extreme preterm infants.

Research priorities to reduce global mortality from newborn infections by 2015.

Background: Newborn infections are responsible for approximately one-third of the estimated 4.0 million neonatal deaths that occur globally every year. Appropriately targeted research is required to guide investment in effective interventions, especially in low resource settings. Setting global priorities for research to address neonatal infections is essential and urgent. Methods: The Department of Child and Adolescent Health and Development of the World Health Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative (CHNRI) priority-setting methodology to identify and stimulate research most likely to reduce global newborn infection-related mortality by 2015. Technical experts were invited by WHO/CAH to systematically list and then use standard methods to score research questions according to their likelihood to (i) be answered in an ethical way, (ii) lead to (or improve) effective interventions, (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden reduction, and (v) have an equitable effect in the population. The scores were then weighted according to the values provided by a wide group of stakeholders from the global research priority-setting network. Findings: On a 100-point scale, the final priority scores for 69 research questions ranged from 39 to 83. Most of the 15 research questions that received the highest scores were in the domain of health systems and policy research to address barriers affecting existing cost-effective interventions. The priority questions focused on promotion of home care practices to prevent newborn infections and approaches to increase coverage and quality of management of newborn infections in health facilities as well as in the community. While community-based intervention research is receiving some current investment, rigorous evaluation and cost analysis is almost entirely lacking for research on facility-based interventions and quality improvement. Interpretation: Given the lack of progress in improving newborn survival despite the existence of effective interventions, it is not surprising that of the top ranked research priorities in this article the majority are in the domain of health systems and policy research. We urge funding agencies and investigators to invest in these research priorities to accelerate reduction of neonatal deaths, particularly those due to infections.

Evaluation of the effectiveness of the standardized neonatal resuscitation program.

OBJECTIVE: To determine if health care personnel trained in the Neonatal Resuscitation Program (NRP) used the NRP guidelines in the resuscitation of newborn babies. To determine differences between self-reporting and documentation of resuscitation in medical records.STUDY DESIGN: Using a validated questionnaire, individuals participating in resuscitation of newborns voluntarily phoned and answered questions on an Interactive Voice Response (IVR) system. The study was undertaken in level II hospitals in Southern Alberta with 7500 deliveries per year.RESULTS: Of the 5155 babies delivered during the study, 16% required resuscitation (bag and mask ventilation 10.6%, intubation for meconium or intermittent positive pressure ventilation, IPPV, 3.6%, cardiac massage, CM, 0.3%, epinephrine 0.1%, naloxone 6.9%). Of babies whose interventions could be assessed, bag and mask was correct in 99%, endotracheal intubation for IPPV in 100%, and CM in 100%. Only 75% of babies had meconium managed correctly and 92% had naloxone administered according to guidelines. There were more instances where IVR (48) reported a procedure, which was not charted versus charted and not reported by IVR (21). Educational needs identified by IVR included skills of resuscitation and NRP indications for management.CONCLUSION: Bag and mask ventilation and intubation for neonatal resuscitation are more common than previously reported. Management of the meconium-stained baby and use of naloxone require further education. Compared to charts, use of IVR system allows more complete documentation with rationale of interventions and identification of continuing educational needs.

Variations in rates of nosocomial infection among Canadian neonatal intensive care units may be practice-related

BackgroundNosocomial infection (NI), particularly with positive blood or cerebrospinal fluid bacterial cultures, is a major cause of morbidity in neonatal intensive care units (NICUs). Rates of NI appear to vary substantially between NICUs. The aim of this study was to determine risk factors for NI, as well as the risk-adjusted variations in NI rates among Canadian NICUs.MethodsFrom January 1996 to October 1997, data on demographics, intervention, illness severity and NI rates were submitted from 17 Canadian NICUs. Infants admitted at <4 days of age were included. NI was defined as a positive blood or cerebrospinal fluid culture after > 48 hrs in hospital.Results765 (23.5%) of 3253 infants <1500 g and 328 (2.5%) of 13228 infants ≥1500 g developed at least one episode of NI. Over 95% of episodes were due to nosocomial bacteremia. Major morbidity was more common amongst those with NI versus those without. Mortality was more strongly associated with NI versus those without for infants ≥1500 g, but not for infants <1500 g. Multiple logistic regression analysis showed that for infants <1500 g, risk factors for NI included gestation <29 weeks, outborn status, increased acuity on day 1, mechanical ventilation and parenteral nutrition. When NICUs were compared for babies <1500 g, the odds ratios for NI ranged from 0.2 (95% confidence interval [CI] 0.1 to 0.4) to 8.6 (95% CI 4.1 to 18.2) when compared to a reference site. This trend persisted after adjustment for risk factors, and was also found in larger babies.ConclusionRates of nosocomial infection in Canadian NICUs vary considerably, even after adjustment for known risk factors. The implication is that this variation is due to differences in clinical practices and therefore may be amenable to interventions that alter practice.

Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials☆☆☆★

Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.

Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study

Background: We previously demonstrated improvement in bronchopulmonary dysplasia and nosocomial infection among preterm infants at 12 neonatal units using the Evidence-based Practice for Improving Quality (EPIQ). In the current study, we assessed the association of Canada-wide implementation of EPIQ with mortality and morbidity among preterm infants less than 29 weeks gestational age. Methods: This prospective cohort study included 6026 infants admitted to 25 Canadian units between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n = 1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of training and planning, EPIQ was implemented over 3 years. Our primary outcome was a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis and nosocomial infection. We compared outcomes for baseline and year 3 using multivariable analyses. Results: In adjusted analyses comparing baseline with year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60, 95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52 to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82) were significantly reduced. The composite outcome was lower among infants born at 26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI 0.44 to 1.20). Interpretation: EPIQ methodology was generalizable within Canada and was associated with significantly lower likelihood of the composite outcome, severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants born at 26 to 28 weeks gestational age benefited the most.