First name
Bradley
Middle name
A
Last name
Yoder

Title

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies.

Year of Publication

2020

Number of Pages

e200593

Date Published

2020 May 04

ISSN Number

2168-6211

Abstract

<p><strong>Importance: </strong>Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies.</p>

<p><strong>Objective: </strong>To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants.</p>

<p><strong>Design, Setting, and Participants: </strong>This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020.</p>

<p><strong>Main Outcomes and Measures: </strong>Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death.</p>

<p><strong>Results: </strong>A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008).</p>

<p><strong>Conclusions and Relevance: </strong>In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.</p>

DOI

10.1001/jamapediatrics.2020.0593

Alternate Title

JAMA Pediatr

PMID

32364598

Title

The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants: An Evidence-Based Approach.

Year of Publication

2019

Date Published

2019 Apr 17

ISSN Number

1535-4970

Abstract

<p><strong>RATIONALE: </strong>Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, nor adequately predict childhood morbidity.</p>

<p><strong>OBJECTIVE: </strong>To determine which of 18 pre-specified, revised definitions of bronchopulmonary dysplasia, that variably define disease presence and severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks postmenstrual age, best predicts death or serious respiratory morbidity through 18-26 months corrected age.</p>

<p><strong>METHODS: </strong>We assessed infants born &lt;32 weeks' gestation between 2011-2015 at 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network.</p>

<p><strong>RESULTS: </strong>Of 2677 infants, 683 (26%) died or developed serious respiratory morbidity. The criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks postmenstrual age, irrespective of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n=773); grade 1, nasal cannula ≤2L/min (n=1038); grade 2, nasal cannula &gt;2L/min or non-invasive positive airway pressure (n=617); and grade 3, invasive mechanical ventilation (n=249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33%-79%) was observed for death or neurodevelopmental impairment.</p>

<p><strong>CONCLUSIONS: </strong>The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support at 36 weeks postmenstrual age, irrespective of supplemental oxygen use. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial License 4.0 (http://creativecommons.org/licenses/by-nc/4.0/).</p>

DOI

10.1164/rccm.201812-2348OC

Alternate Title

Am. J. Respir. Crit. Care Med.

PMID

30995069

Title

Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants.

Year of Publication

2018

Number of Pages

28-33.e5.

Date Published

2018 Mar

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVE: </strong>To test the hypothesis that significant positive end-expiratory pressure (PEEP) level variation exists between neonatal centers.</p>

<p><strong>STUDY DESIGN: </strong>We performed a secondary analysis cohort study of the Nasal Intermittent Positive-Pressure Ventilation trial. Our study population was extremely low birth weight infants requiring mechanical ventilation within 28 days of life. The exposure was neonatal center; 34 international centers participated in the trial. Subjects from centers with fewer than 5 eligible cases were excluded. The main outcome was the maximal PEEP level used during the first course of mechanical ventilation. Infant characteristics judged a priori to directly influence clinical PEEP level selection and all characteristics associated with PEEP at P &lt;.05 in bivariable analyses were included with and without center in multivariable linear regression models. Variation in PEEP level use between centers following adjustment for infant characteristics was assessed.</p>

<p><strong>RESULTS: </strong>A total of 278 extremely low birth weight infants from 17 centers were included. Maximal PEEP ranged from 3 to 9 cm H2O, mean = 5.7 (SD = 0.9). Significant variation between centers remained despite adjustment for infant characteristics (P &lt; .0001). Further, center alone explained a greater proportion of the PEEP level variation than all infant characteristics combined.</p>

<p><strong>CONCLUSIONS: </strong>Marked variation in PEEP levels for extremely low birth weight infants exists between neonatal centers. Research providing evidence-based guidance for this important aspect of respiratory care in preterm infants at high risk of lung injury is needed.</p>

<p><strong>TRIAL REGISTRATION: </strong>ClinicalTrials.govNCT00433212.</p>

DOI

10.1016/j.jpeds.2017.10.065

Alternate Title

J. Pediatr.

PMID

29275926

Title

Reliability of a Noninvasive Measure of V./Q. Mismatch for Bronchopulmonary Dysplasia.

Year of Publication

2015

Number of Pages

727-33

Date Published

2015 May

ISSN Number

2325-6621

Abstract

<p><strong>RATIONALE: </strong>Currently used definitions of bronchopulmonary dysplasia (BPD) lack a continuous measure of disease severity.</p>

<p><strong>OBJECTIVES: </strong>To determine if an indirect measure of V./Q. mismatch is reliable when simplified to facilitate more widespread use for grading disease severity in BPD at 36 weeks postmenstrual age.</p>

<p><strong>METHODS: </strong>We used prospectively collected data from 32 preterm infants undergoing an oxygen reduction test at 36 weeks postmenstrual age to perform a simplified indirect assessment of V./Q. mismatch for each infant. Independent raters applied the model, and interrater reliability for a quantitative measure of mismatch was measured by intraclass correlation coefficient. A receiver operating characteristic curve evaluated the impact of increasing degrees of V./Q. mismatch on diagnosing BPD as defined by oxygen reduction test failure.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>Concordance for the quantitative measure of V./Q. mismatch between independent raters improved from 0.72 (confidence interval [CI], 0.48-0.86) to 0.93 (CI, 0.87-0.96) after refinement of instructions for applying the simplified model. Higher degrees of mismatch were increasingly predictive of oxygen reduction test failure, with a receiver operating characteristic curve analysis area under the curve of 0.83 (CI, 0.68-0.99; P = 0.03).</p>

<p><strong>CONCLUSIONS: </strong>A simplified indirect measure of V./Q. mismatch for diagnosing and grading disease severity in BPD has high reliability and can be performed with data obtained during a standard oxygen reduction test. This should facilitate more widespread investigation of this model as a technique for characterizing BPD severity.</p>

DOI

10.1513/AnnalsATS.201410-462OC

Alternate Title

Ann Am Thorac Soc

PMID

25714998

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