Group B Streptococcus Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

2022

1405-1415

10/2022

1537-6591

BACKGROUND: This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18-26 months.

METHODS: In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998-2016 at 22-28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants.

RESULTS: The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02-1.45]) and uninfected infants (1.44 [1.23-1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36-2.67]), compared with uninfected infants.

CONCLUSIONS: In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction.

CLINICAL TRIALS REGISTRATION: NCT00063063.

10.1093/cid/ciac222

Clin Infect Dis

35323895

Group B Streptococcal Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

2022

2022 Mar 22

1537-6591

<p><strong>BACKGROUND: </strong>Determine the incidence of GBS disease among extremely preterm infants and assess risk of death or neurodevelopmental impairment (NDI) at 18-26 months' corrected age.</p>

<p><strong>METHODS: </strong>Observational cohort study of infants enrolled in a multicenter registry. GBS disease incidence was assessed in infants born 1998-2016 at 22-28 weeks' gestation surviving &gt;12 hours. The composite outcome, death or NDI, was assessed in infants born 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood/CSF culture at ≤72 hours (early-onset disease, EOD) and &gt;72 hours (late-onset disease, LOD) after birth. The outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants using Poisson regression models.</p>

<p><strong>RESULTS: </strong>Incidence of GBS EOD (2.70/1000 births [95% CI: 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk (aRR, 95% CI) of death/NDI was higher among GBS EOD cases compared to infants with other infections (1.22, [1.02-1.45]) and uninfected infants (1.44, [1.23-1.69]). Death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving &gt;30 days, the risk of death was higher with GBS LOD (1.90, [1.36-2.67]), compared to uninfected infants.</p>

<p><strong>CONCLUSIONS: </strong>In a cohort of extremely preterm infants, incidence of GBS disease did not change during the study period. Increased risk of death/NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction.</p>

10.1093/cid/ciac222

Clin Infect Dis

35323895

Racial/Ethnic Disparities Among Extremely Preterm Infants in the United States From 2002 to 2016.

2020

e206757

2020 Jun 01

2574-3805

<p><strong>Importance: </strong>Racial/ethnic disparities in quality of care among extremely preterm infants are associated with adverse outcomes.</p>

<p><strong>Objective: </strong>To assess whether racial/ethnic disparities in major outcomes and key care practices were changing over time among extremely preterm infants.</p>

<p><strong>Design, Setting, and Participants: </strong>This observational cohort study used prospectively collected data from 25 US academic medical centers. Participants included 20 092 infants of 22 to 27 weeks' gestation with a birth weight of 401 to 1500 g born at centers participating in the National Institute of Child Health and Human Development Neonatal Research Network from 2002 to 2016. Of these infants, 9316 born from 2006 to 2014 were eligible for follow-up at 18 to 26 months' postmenstrual age (excluding 5871 infants born before 2006, 2594 infants born after 2014, and 2311 ineligible infants including 64 with birth weight &gt;1000 g and 2247 infants with gestational age &gt;26 6/7 weeks), of whom 745 (8.0%) did not have known follow-up outcomes at 18 to 26 months.</p>

<p><strong>Main Outcomes and Measures: </strong>Rates of mortality, major morbidities, and care practice use over time were evaluated using models adjusted for baseline characteristics, center, and birth year. Data analyses were conducted from 2018 to 2019.</p>

<p><strong>Results: </strong>In total, 20 092 infants with a mean (SD) gestational age of 25.1 (1.5) weeks met the inclusion criteria and were available for the primary outcome: 8331 (41.5%) black infants, 3701 (18.4%) Hispanic infants, and 8060 (40.1%) white infants. Hospital mortality decreased over time in all groups. The rate of improvement in hospital mortality over time did not differ among black and Hispanic infants compared with white infants (black infants went from 35% to 24%, Hispanic infants went from 32% to 27%, and white infants went from 30% to 22%; P = .59 for race × year interaction). The rates of late-onset sepsis among black infants (went from 37% to 24%) and Hispanic infants (went from 45% to 23%) were initially higher than for white infants (went from 36% to 25%) but decreased more rapidly and converged during the most recent years (P = .02 for race × year interaction). Changes in rates of other major morbidities did not differ by race/ethnicity. Death before follow-up decreased over time (from 2006 to 2014: black infants, 14%; Hispanic infants, 39%, white infants, 15%), but moderate-severe neurodevelopmental impairment increased over time in all racial/ethnic groups (increase from 2006 to 2014: black infants, 70%; Hispanic infants, 123%; white infants, 130%). Rates of antenatal corticosteroid exposure (black infants went from 72% to 90%, Hispanic infants went from 73% to 83%, and white infants went from 86% to 90%; P = .01 for race × year interaction) and of cesarean delivery (black infants went from 45% to 59%, Hispanic infants went from 49% to 59%, and white infants went from 62% to 63%; P = .03 for race × year interaction) were initially lower among black and Hispanic infants compared with white infants, but these differences decreased over time.</p>

<p><strong>Conclusions and Relevance: </strong>Among extremely preterm infants, improvements in adjusted rates of mortality and most major morbidities did not differ by race/ethnicity, but rates of neurodevelopmental impairment increased in all groups. There were narrowing racial/ethnic disparities in important care practices, including the use of antenatal corticosteroids and cesarean delivery.</p>

10.1001/jamanetworkopen.2020.6757

JAMA Netw Open

32520359

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

2020

e200593

2020 May 04

2168-6211

<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>

10.1001/jamapediatrics.2020.0593

JAMA Pediatr

32364598

Identification of Extremely Premature Infants at Low Risk for Early-Onset Sepsis.

2017

2017 Oct 05

1098-4275

<p><strong>BACKGROUND: </strong>Premature infants are at high risk of early-onset sepsis (EOS) relative to term infants, and most are administered empirical antibiotics after birth. We aimed to determine if factors evident at birth could be used to identify premature infants at lower risk of EOS.</p>

<p><strong>METHODS: </strong>Study infants were born at 22 to 28 weeks' gestation in Neonatal Research Network centers from 2006 to 2014. EOS was defined by isolation of pathogenic species from blood or cerebrospinal fluid culture at ≤72 hours age. Infants were hypothesized as "low risk" for EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥5 days) was compared between low-risk infants and all others. Risks of mortality, EOS, and other morbidities were assessed by using regression models adjusted for center, race, antenatal steroid use, multiple birth, sex, gestation, and birth weight.</p>

<p><strong>RESULTS: </strong>Of 15 433 infants, 5759 (37%) met low-risk criteria. EOS incidence among infants surviving &gt;12 hours was 29 out of 5640 (0.5%) in the low-risk group versus 209 out of 8422 (2.5%) in the comparison group (adjusted relative risk = 0.24 [95% confidence interval, 0.16-0.36]). Low-risk infants also had significantly lower combined risk of EOS or death ≤12 hours. Prolonged antibiotics were administered to 34% of low-risk infants versus 47% of comparison infants without EOS.</p>

<p><strong>CONCLUSIONS: </strong>Delivery characteristics of extremely preterm infants can be used to identify those with significantly lower incidence of EOS. Recognition of differential risk may help guide decisions to limit early antibiotic use among approximately one-third of these infants.</p>

10.1542/peds.2017-0925

Pediatrics

28982710