Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study.
ABSTRACT: 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.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.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).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.
Project description:Importance:Severe morbidity in very preterm infants is associated with profound clinical implications on development and life-course health. However, studies of racial/ethnic disparities in severe neonatal morbidities are scant and suggest that these disparities are modest or null, which may be an underestimation resulting from the analytic approach used. Objective:To estimate racial/ethnic differences in severe morbidities among very preterm infants. Design, Setting, and Participants:This population-based retrospective cohort study was conducted in New York City, New York, using linked birth certificate, mortality data, and hospital discharge data from January 1, 2010, through December 31, 2014. Infants born before 24 weeks' gestation, with congenital anomalies, and with missing data were excluded. Racial/ethnic disparities in very preterm birth morbidities were estimated through 2 approaches, conventional analysis and fetuses-at-risk analysis. The conventional analysis used log-binomial regression to estimate the relative risk of 4 severe neonatal morbidities for the racial/ethnic groups. For the fetuses-at-risk analysis, Cox proportional hazards regression with death as competing risk was used to estimate subhazard ratios associating race/ethnicity with each outcome. Estimates were adjusted for sociodemographic factors and maternal morbidities. Data were analyzed from September 5, 2017, to May 21, 2018. Main Outcomes and Measures:Four morbidity outcomes were defined using International Classification of Diseases, Ninth Revision, diagnosis and procedure codes: necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, and retinopathy of prematurity. Results:In total, 582 297 infants were included in this study. Of these infants, 285 006 were female (48.9%) and 297 291 were male (51.0%). Using the conventional approach in the very preterm birth subcohort, black compared with white infants had an increased risk of only bronchopulmonary dysplasia (adjusted risk ratio [aRR], 1.34; 95% CI, 1.09-1.64) and a borderline increased risk of necrotizing enterocolitis (aRR, 1.39; 95% CI, 1.00-1.93). Hispanic infants had a borderline increased risk of necrotizing enterocolitis (aRR, 1.39; 95% CI, 0.98-1.96), and Asian infants had an increased risk of retinopathy of prematurity (aRR, 1.85; 95% CI, 1.15-2.97). In the fetuses-at-risk analysis, black infants had a 4.40 times higher rate of necrotizing enterocolitis (95% CI, 2.98-6.51), a 2.73 times higher rate of intraventricular hemorrhage (95% CI, 1.63-4.57), a 4.43 times higher rate of bronchopulmonary dysplasia (95% CI, 2.88-6.81), and a 2.98 times higher rate of retinopathy of prematurity (95% CI, 2.01-4.40). Hispanic infants had an approximately 2 times higher rate for all outcomes, and Asian infants had increased risk only for retinopathy of prematurity (adjusted hazard ratio, 2.43; 95% CI, 1.43-4.11). Conclusions and Relevance:In this study, racial/ethnic disparities in neonatal morbidities among very preterm infants appear to be sizable, but may have been underestimated in previous studies, and may have implications for the future. Understanding these racial/ethnic disparities is important, as they may contribute to inequalities in health and development later in the child's life.
Project description:Objectives: To describe the rates and variability of mortality and morbidity of preterm infants born in China. Methods: This prospective cohort study included infants born at <34 weeks' gestation and admitted to 25 NICUs within 7 days of birth between May 1st, 2015 and April 30th, 2016. Infants were followed until death or NICU discharge. The primary outcome was a composite of mortality or any major morbidity (sepsis, necrotizing enterocolitis, intraventricular/periventricular leukomalacia, retinopathy of prematurity, and bronchopulmonary dysplasia) in infants who received complete care following medical advice. Secondary outcomes included rate of discharge against medical advice, mortality and individual morbidities. Results: Of the 8,065 infants, 6,852 (85%) received complete care and 1,213 (15%) were discharged against medical advice. Among infants who received complete care, the rate of the composite outcome was 27% (1,827/6,852), mortality 4% (248/6,852), sepsis 14% (990/6,852), necrotizing enterocolitis 3% (191/6,550), intraventricular hemorrhage/periventricular leukomalacia 7% (422/6,307), retinopathy of prematurity 2% (67/3,349), and bronchopulmonary dysplasia 9% (616/6,852). There were significant variations between NICUs for all outcomes. Conclusions: Discharged against medical advice, mortality, and morbidity rates for preterm infants <34 weeks' gestation are high in China with significant variations between NICUs.
Project description:Importance:There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective:To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants:Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures:Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures:The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results:A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance:In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.
Project description:To determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs).A multi-center interrupted time series analysis.44 German NICUs with routine use of dual-strain probiotics on neonatal ward level.Preterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014.Routine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level.Incidences of NEC, overall mortality, mortality following NEC and nosocomial BSI.Data from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38-0.62), overall mortality (HR = 0.60, 95% CI = 0.44-0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26-0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81-0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g.In order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards.
Project description:<h4>Importance</h4>Observational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation.<h4>Objective</h4>Evaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes.<h4>Design, setting, and participants</h4>This retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs.<h4>Exposure</h4>Surgical ligation vs medical management.<h4>Main outcomes and measures</h4>The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders.<h4>Results</h4>Of 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813  grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21).<h4>Conclusions and relevance</h4>Patent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.
Project description:OBJECTIVE:To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. STUDY DESIGN:This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. RESULTS:There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. CONCLUSIONS:Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.
Project description:IMPORTANCE:Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. OBJECTIVE:To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS:This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N?=?361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS:Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES:The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes-defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18 to 22 months corrected age. RESULTS:Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%-22%) vs 21% in the placebo group (95% CI, 15%-28%; odds ratio, 0.73 [95% CI, 0.43-1.23]; P?=?.24; treatment difference, -5% [95% CI, -13% to 3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%-6%]) vs the placebo group (9% [95% CI, 5%-14%]; P?=?.02; treatment difference, -6% [95% CI, -11% to -1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole, 31% [95% CI, 21%-41%] vs placebo, 27% [95% CI, 18%-37%]; P?=?.60; treatment difference, 4% [95% CI, -10% to 17%]). CONCLUSIONS AND RELEVANCE:Among infants with a birth weight of less than 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely low-birth-weight infants. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00734539.
Project description:OBJECTIVE:A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain injury, and severe retinopathy of prematurity) strongly predict the risk of death or neurosensory impairment in extremely low birth weight infants who survive to 36 weeks' postmenstrual age. Neonatal infection has also been linked with later impairment. We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome. METHODS:We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks' postmenstrual age. Culture-proven sepsis, meningitis, and stage II or III necrotizing enterocolitis were recorded prospectively. We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia, brain injury, and severe retinopathy. Poor outcome at 18 months of age was death or survival with 1 or more of the following: cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. RESULTS:There were 414 (44%) infants with at least 1 episode of infection or necrotizing enterocolitis. Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model. The odds ratio associated with infection or necrotizing enterocolitis in this model was 50% smaller than the odds ratio associated with each count of the other 3 neonatal morbidities. Meningitis was rare and occurred in 22 (2.3%) of 944 infants. CONCLUSIONS:In this cohort of extremely low birth weight infants who survived to 36 weeks' postmenstrual age, neonatal infection increased the risk of a late death or survival with neurosensory impairment. However, infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia, brain injury, and severe retinopathy.
Project description:Importance:Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective:To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants:All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures:Delivery at 22-26 weeks' gestational age. Main Outcomes and Measures:The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results:During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008). Conclusions and Relevance:Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.
Project description:Importance:Substantial quality improvements in neonatal care have occurred over the past decade yet racial and ethnic disparities in morbidity and mortality remain. It is uncertain whether disparate patterns of care by race and ethnicity contribute to disparities in neonatal outcomes. Objectives:To examine differences in neonatal morbidity and mortality rates among non-Hispanic black (black), Hispanic, and non-Hispanic white (white) very preterm infants and to determine whether these differences are explained by site of delivery. Design, Setting, and Participants:Population-based retrospective cohort study of 7177 nonanomalous infants born between 24 and 31 completed gestational weeks in 39 New York City hospitals using linked 2010 to 2014 New York City discharge abstract and birth certificate data sets. Mixed-effects logistic regression with a random hospital-specific intercept was used to generate risk-adjusted neonatal morbidity and mortality rates for very preterm infants in each hospital. Hospitals were ranked using this measure, and differences in the distribution of black, Hispanic, and white very preterm births were assessed among these hospitals. The statistical analysis was performed in 2016-2017. Exposure:Race/ethnicity. Main Outcomes and Measures:Composite of mortality (neonatal or in-hospital up to 1 year) or severe neonatal morbidity (bronchopulmonary dysplasia, severe necrotizing enterocolitis, retinopathy of prematurity stage 3 or greater, or intraventricular hemorrhage grade 3 or greater). Results:Among 7177 very preterm births (VPTBs), morbidity and mortality occurred in 2011 (28%) and was higher among black (893 [32.2%]) and Hispanic (610 [28.1%]) than white (319 [22.5%]) VPTBs (2-tailed P?<?.001). The risk-standardized morbidity and mortality rate was twice as great for VPTB infants born in hospitals in the highest morbidity and mortality tertile (0.40; 95% CI, 0.38-0.41) as for those born in the lowest morbidity and mortality tertile (0.16; 95% CI, 0.14-0.18). Black (1204 of 2775 [43.4%]) and Hispanic (746 of 2168 [34.4%]) VPTB infants were more likely than white (325 of 1418 [22.9%]) VPTB infants to be born in hospitals in the highest morbidity and mortality tertile (2-tailed P?<?.001; black-white difference, 20%; 95% CI, 18%-23% and Hispanic-white difference, 11%; 95% CI, 9%-14%). The largest proportion of the explained disparities can be attributed to differences in infant health risks among black, Hispanic, and white VPTB infants. However, 40% (95% CI, 30%-50%) of the black-white disparity and 30% (95% CI, 10%-49%) of the Hispanic-white disparity was explained by birth hospital. Conclusions and Relevance:Black and Hispanic VPTB infants are more likely to be born at hospitals with higher risk-adjusted neonatal morbidity and mortality rates, and these differences contribute to excess morbidity and mortality among black and Hispanic infants.