Michael J. Kenny

Mortality and Neonatal Morbidity Among Infants 501 to 1500 Grams From 2000 to 2009

OBJECTIVE: To identify changes in mortality and neonatal morbidities for infants with birth weight 501 to 1500 g born from 2000 to 2009. METHODS: There were 355 806 infants weighing 501 to 1500 g who were born in 2000–2009. Mortality during initial hospitalization and major neonatal morbidity in survivors (early and late infection, chronic lung disease, necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, and periventricular leukomalacia) were assessed by using data from 669 North American hospitals in the Vermont Oxford Network. RESULTS: From 2000 to 2009, mortality for infants weighing 501 to 1500 g decreased from 14.3% to 12.4% (difference, −1.9%; 95% confidence interval, −2.3% to −1.5%). Major morbidity in survivors decreased from 46.4% to 41.4% (difference, −4.9%; 95% confidence interval, −5.6% to −4.2%). In 2009, mortality ranged from 36.6% for infants 501 to 750 g to 3.5% for infants 1251 to 1500 g, whereas major morbidity in survivors ranged from 82.7% to 18.7%. In 2009, 49.2% of all very low birth weight infants and 89.2% of infants 501 to 750 g either died or survived with a major neonatal morbidity. CONCLUSIONS: Mortality and major neonatal morbidity in survivors decreased for infants with birth weight 501 to 1500 g between 2000 and 2009. However, at the end of the decade, a high proportion of these infants still either died or survived after experiencing ≥1 major neonatal morbidity known to be associated with both short- and long-term adverse consequences.

Mortality of necrotizing enterocolitis expressed by birth weight categories

PURPOSE Low birth weight is the most important risk factor for developing necrotizing enterocolitis (NEC). We aimed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC. METHODS Five hundred eleven centers belonging to the Vermont Oxford Network prospectively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006. The primary outcome variable was in-hospital mortality. RESULTS Birth weight was divided into 4 categories by 250-g increments. The NEC risk (P < .001) and mortality (P < .001) decreased with higher birth weight category. Necrotizing enterocolitis was associated with a significant odds ratio for death for each category (P < .001). Across groups, the odds ratio for NEC mortality increased with higher birth weight category (category 1 = 1.6 vs category 4 = 9.9; P < .001). CONCLUSION The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category. Although the risk and absolute mortality of NEC decrease with higher birth weight, the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight. These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers.

Nurse Staffing and NICU Infection Rates

IMPORTANCE There are substantial shortfalls in nurse staffing in US neonatal intensive care units (NICUs) relative to national guidelines. These are associated with higher rates of nosocomial infections among infants with very low birth weights. OBJECTIVE To study the adequacy of NICU nurse staffing in the United States using national guidelines and analyze its association with infant outcomes. DESIGN Retrospective cohort study. Data for 2008 were collected by web survey of staff nurses. Data for 2009 were collected for 4 shifts in 4 calendar quarters (3 in 2009 and 1 in 2010). SETTING Sixty-seven US NICUs from the Vermont Oxford Network, a national voluntary network of hospital NICUs. PARTICIPANTS All inborn very low-birth-weight (VLBW) infants, with a NICU stay of at least 3 days, discharged from the NICUs in 2008 (n = 5771) and 2009 (n = 5630). All staff-registered nurses with infant assignments. EXPOSURES We measured nurse understaffing relative to acuity-based guidelines using 2008 survey data (4046 nurses and 10 394 infant assignments) and data for 4 complete shifts (3645 nurses and 8804 infant assignments) in 2009-2010. MAIN OUTCOMES AND MEASURES An infection in blood or cerebrospinal fluid culture occurring more than 3 days after birth among VLBW inborn infants. The hypothesis was formulated prior to data collection. RESULTS Hospitals understaffed 31% of their NICU infants and 68% of high-acuity infants relative to guidelines. To meet minimum staffing guidelines on average would require an additional 0.11 of a nurse per infant overall and 0.34 of a nurse per high-acuity infant. Very low-birth-weight infant infection rates were 16.4% in 2008 and 13.9% in 2009. A 1 standard deviation-higher understaffing level (SD, 0.11 in 2008 and 0.08 in 2009) was associated with adjusted odds ratios of 1.39 (95% CI, 1.19-1.62; P < .001) in 2008 and 1.40 (95% CI, 1.19-1.65; P < .001) in 2009. CONCLUSIONS AND RELEVANCE Substantial NICU nurse understaffing relative to national guidelines is widespread. Understaffing is associated with an increased risk for VLBW nosocomial infection. Hospital administrators and NICU managers should assess their staffing decisions to devote needed nursing care to critically ill infants.

Mortality and Management of Surgical Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Prospective Cohort Study

BACKGROUND Necrotizing enterocolitis (NEC) is a leading cause of death in very low birth weight (VLBW) neonates. The overall mortality of NEC is well documented. However, those requiring surgery appear to have increased mortality compared with those managed medically. The objective of this study was to establish national birth-weight-based benchmarks for the mortality of surgical NEC and describe the use and mortality of laparotomy vs peritoneal drainage. STUDY DESIGN There were 655 US centers that prospectively evaluated 188,703 VLBW neonates (401 to 1,500 g) between 2006 and 2010. Survival was defined as living in-hospital at 1-year or hospital discharge. RESULTS There were 17,159 (9%) patients who had NEC, with mortality of 28%; 8,224 patients did not receive operations (medical NEC, mortality 21%) and 8,935 were operated on (mortality 35%). On multivariable regression, lower birth weight, laparotomy, and peritoneal drainage were independent predictors of mortality (p < 0.0001). In surgical NEC, a plateau mortality of around 30% persisted despite birth weights >750 g; medical NEC mortality fell consistently with increasing birth weight. For example, in neonates weighing 1,251 to 1,500 g, mortality was 27% in surgical vs 6% in medical NEC (odds ratio [OR] 6.10, 95% CI 4.58 to 8.12). Of those treated surgically, 6,131 (69%) underwent laparotomy only (mortality 31%), 1,283 received peritoneal drainage and a laparotomy (mortality 34%), and 1,521 had peritoneal drainage alone (mortality 50%). CONCLUSIONS Fifty-two percent of VLBW neonates with NEC underwent surgery, which was accompanied by a substantial increase in mortality. Regardless of birth weight, surgical NEC showed a plateau in mortality at approximately 30%. Laparotomy was the more frequent method of treatment (69%) and of those managed by drainage, 46% also had a laparotomy. The laparotomy alone and drainage with laparotomy groups had similar mortalities, while the drainage alone treatment cohort was associated with the highest mortality.

Misuse of and dependence on over-the-counter nicotine gum in a volunteer sample

To estimate the amount of misuse of and dependence on nicotine gum in an over-the-counter (OTC) setting, we conducted two telephone surveys of smokers recruited by newspaper ads. Study 1 surveyed 266 U.S. ever-smokers using OTC gum to determine the percentage who used the gum for noncessation reasons or used gum and cigarettes concurrently. In Study 1, 6% initially purchased nicotine gum to reduce smoking and 1% to avoid smoking restrictions. At the time of interview, 35% chewed gum and smoked cigarettes concurrently with a mean of six cigarettes per day and 15 mg/day of nicotine from gum. Among long-term users (>/=90 days), 20% attributed their use to addiction. To determine what proportion of those reporting addiction would meet DSM-IV or ICD-10 criteria for dependence, Study 2 surveyed 100 current and ex-smokers who reported addiction to OTC nicotine gum. In these gum users, 66% met DSM-IV and 74% met ICD-10 criteria for dependence. Combining the results of Studies 1 and 2 with other data suggests very few gum users develop dependence on the gum. We conclude (a) very few people use nicotine gum for noncessation reasons, (b) concurrent use of gum and cigarettes is common but involves a small number of cigarettes and pieces of gum per day, and (c) the incidence of dependence on OTC nicotine gum is very small.

Obstetric and Neonatal Care Practices for Infants 501 to 1500 g From 2000 to 2009

OBJECTIVE: To identify changes in clinical practices for infants with birth weights of 501 to 1500 g born from 2000 to 2009. METHODS: We used prospectively collected registry data for 355 806 infants born from 2000 to 2009 and cared for at 669 North American hospitals in the Vermont Oxford Network. Main outcome measures included obstetric and neonatal practices, including cesarean delivery, antenatal steroids, delivery room interventions, respiratory practices, neuroimaging, retinal exams, and feeding at discharge. RESULTS: Significant changes in many obstetric, delivery room, and neonatal practices occurred from 2000 to 2009. Use of surfactant treatment in the delivery room increased overall (adjusted difference [AD] 17.0%; 95% confidence interval [CI] 16.4% to 17.6%), as did less-invasive methods of respiratory support, such as nasal continuous positive airway pressure (AD 9.9%; 95% CI 9.1% to 10.6%). Use of any ventilation (AD –7.5%; 95% CI –8.0% to –6.9%) and steroids for chronic lung disease (AD –15.3%; 95% CI –15.8% to –14.8%) decreased significantly overall. Most of the changes in respiratory care were observed within each of 4 birth weight strata (501–750 g, 751–1000 g, 1001–1250 g, 1251–1500 g). CONCLUSIONS: Many obstetric and neonatal care practices used in the management of infants 501 to 1500 g changed between 2000 and 2009. In particular, less-invasive approaches to respiratory support increased.

Distribution of and Mortality From Serious Congenital Heart Disease in Very Low Birth Weight Infants

OBJECTIVE: To characterize serious congenital heart disease in very low birth weight (VLBW) infants (born at <1500 g or a gestational age of 22–29 weeks) in a large, international database. PATIENTS AND METHODS: We analyzed a database of 99 786 VLBW infants born or treated at 703 NICUs between calendar years 2006 and 2007. We defined serious congenital heart disease as 1 of 14 specific lesions or any other structural congenital heart disease that required surgical or medical treatment by initial hospital discharge or by the age of 1 year. We reviewed records for all infants with cardiac diagnoses and other genetic syndromes and associations to determine which had serious congenital heart disease. We excluded nonstructural disease as well as isolated and untreated atrial or ventricular septal defects. We determined the frequency of serious congenital heart disease, compared overall mortality rates of those with and without serious congenital heart disease, and determined the distribution of specific lesions and mortality for each diagnosis. RESULTS: Of 99 786 VLBW infants studied, 893 had serious congenital heart disease (8.9 per 1000). The most common lesions were tetralogy of Fallot (n = 166 [18.6% of those with serious congenital heart disease]), aortic coarctation (n = 103 [11.5%]), complete atrioventricular canal (n = 81 [9.1%]), pulmonary atresia (n = 73 [8.2%]), and double-outlet right ventricle (n = 68 [7.6%]). The mortality rate of those with serious congenital heart disease was 44%, compared with 12.7% in those without serious congenital heart disease (P < .0001). CONCLUSIONS: Serious congenital heart disease is probably more frequent in VLBW infants treated in NICUs than in the general live-born population, and the distribution reflects lesions associated with extracardiac malformations. VLBW infants with serious congenital heart disease have higher a mortality rate than those without, independent of other risk factors.

Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry

BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. OBJECTIVES: To identify antecedents in a large registry of infants who had NE. METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of ≥36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of ≤3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of ≥37.5°C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained.

The Vermont oxford neonatal encephalopathy registry: Rationale, methods, and initial results

BackgroundIn 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care.MethodsEligible infants were ≥ 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of ≤ 3, or receiving HT. Infants with central nervous system birth defects were excluded.ResultsFrom 2006–2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of ≤ 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived.ConclusionsThe VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice.

Neuroimaging in the Evaluation of Neonatal Encephalopathy

BACKGROUND AND OBJECTIVE: Computed tomography (CT) is still used for neuroimaging of infants with known or suspected neurologic disorders. Alternative neuroimaging options that do not expose the immature brain to radiation include MRI and cranial ultrasound. We aim to characterize and compare the use and findings of neuroimaging modalities, especially CT, in infants with neonatal encephalopathy. METHODS: The Vermont Oxford Network Neonatal Encephalopathy Registry enrolled 4171 infants (≥36 weeks’ gestation or treated with therapeutic hypothermia) between 2006 and 2010 who were diagnosed with encephalopathy in the first 3 days of life. Demographic, perinatal, and medical conditions were recorded, along with treatments, comorbidities, and outcomes. The modality, timing, and results of neuroimaging were also collected. RESULTS: CT scans were performed on 933 of 4107 (22.7%) infants, and 100 of 921 (10.9%) of those received multiple CT scans. Compared with MRI, CT provided less detailed evaluation of cerebral injury in areas of prognostic significance, but was more sensitive than cranial ultrasound for hemorrhage and deep brain structural abnormalities. CONCLUSIONS: CT is commonly used for neuroimaging in newborn infants with neonatal encephalopathy despite concerns over potential harm from radiation exposure. The diagnostic performance of CT is inferior to MRI in identifying neonatal brain injury. Our data suggest that using cranial ultrasound for screening, followed by MRI would be more appropriate than CT at any stage to evaluate infants with neonatal encephalopathy.