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Management of Neonates Born at ≤34 6/7 Weeks' Gestation with Suspected Or Proven Early-Onset Bacterial Sepsis Karen M

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Management of Neonates Born at ≤34 6/7 Weeks' Gestation with Suspected Or Proven Early-Onset Bacterial Sepsis Karen M CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care ≤ ’ Management of Neonates Born at 34 Karen M. Puopolo, MD, PhD, FAAP, a, b William E. Benitz, MD, FAAP, c Theoklis E. Zaoutis, MD, MSCE, FAAP, a, d 6/7COMMITTEE ONWeeks FETUS AND NEWBORN, GestationCOMMITTEE ON INFECTIOUS DISEASES With Suspected or Proven Early-Onset Bacterial Sepsis Early-onset sepsis (EOS) remains a serious and often fatal illness among abstract infants born preterm, particularly among newborn infants of the lowest gestational age. Currently, most preterm infants with very low birth weight are treated empirically with antibiotics for risk of EOS, often for prolonged aDepartment of Pediatrics, Perelman School of Medicine, University periods, in the absence of a culture-confirmed infection. Retrospective of Pennsylvania, Philadelphia, Pennsylvania; bChildren’s Hospital of studies have revealed that antibiotic exposures after birth are associated Philadelphia, and dRoberts Center for Pediatric Research, Philadelphia, Pennsylvania; and cDivision of Neonatal and Developmental Medicine, with multiple subsequent poor outcomes among preterm infants, making the Department of Pediatrics, School of Medicine, Stanford University, Palo risk/benefit balance of these antibiotic treatments uncertain. Gestational Alto, California age is the strongest single predictor of EOS, and the majority of preterm This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have births occur in the setting of other factors associated with risk of EOS, filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process making it difficult to apply risk stratification strategies to preterm infants. approved by the Board of Directors. The American Academy of Laboratory tests alone have a poor predictive value in preterm EOS. Delivery Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. characteristics of extremely preterm infants present an opportunity to Clinical reports from the American Academy of Pediatrics benefit from identify those with a lower risk of EOS and may inform decisions to initiate expertise and resources of liaisons and internal (AAP) and external or extend antibiotic therapies. Our purpose for this clinical report is to reviewers. However, clinical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations provide a summary of the current epidemiology of preterm neonatal sepsis or government agencies that they represent. and provide guidance for the development of evidence-based approaches to The guidance in this report does not indicate an exclusive course of sepsis risk assessment among preterm newborn infants. treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. DOI: https:// doi. org/ 10. 1542/ peds. 2018- 2896 Antibiotics are administered shortly after birth to nearly all preterm Address correspondence to Karen M. Puopolo, MD, PhD, FAAP. E-mail: – [email protected] infants with very low birth weight (VLBW) (birth weight <1500 g) 1 4 PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). because of the risk of early-onset sepsis (EOS).‍ Physicians are often reluctant to discontinue antibiotics once initiated for many reasons, including the relatively high risk of EOS among preterm infants and the To cite: Puopolo KM, Benitz WE, Zaoutis TE, AAP COMMITTEE relatively high rate of mortality attributable to infection.‍ Particularly ON FETUS AND NEWBORN, AAP COMMITTEE ON INFECTIOUS DISEASES. Management of Neonates Born at ≤34 6/7 Weeks’ among infants with VLBW, neonatal clinicians must determine which Gestation With Suspected or Proven Early-Onset Bacterial infants are most likely to have EOS when nearly all have some degree Sepsis. Pediatrics. 2018;142(6):e20182896 of respiratory or systemic instability.‍ Poor predictive performance of common laboratory tests and concerns regarding the unreliability Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 142, number 6, December 2018:e20182896 FROM THE AMERICAN ACADEMY OF PEDIATRICS of blood cultures add to the whereas studies from the early 1990s when these occur at the lowest difficulty in discriminating at-risk revealed10, rates 11 of 19 to 32 per 1000 gestational ages; evidence suggests infants.‍ Because gestational age infants.‍ Improvements among that microbial-induced maternal is the strongest predictor of EOS VLBW incidence may be limited to inflammation –can initiate parturition and approximately two-thirds of those born at older gestational ages.‍ and elicit fetal inflammatory 5, 15 18 preterm births are associated with No significant change over time responses.‍ Organisms isolated preterm labor, premature rupture was observed in a study of 34636 from the intrauterine compartment ’ of membranes (PROM),5 or clinical infants born from 1993 to 2012 at of women with preterm labor, PROM, chorioamnionitis, risk stratification 22 to 28 weeks gestation, with the or both are primarilyUreaplasma vaginal in strategies cannot be applied to reported incidence ranging8 from 20.‍5 origin and include low-virulence preterm newborn infants in the same to 24.‍4 per 1000 infants.‍ Morbidity species, such as , as manner as for term neonates.‍ and mortality from EOS remain well as anaerobicEscherichia species coli and well- PATHOGENESIS AND CURRENT substantial: 95% of preterm infants recognizedStreptococcus neonatal pathogens,– EPIDEMIOLOGY OF PRETERM with EOS require neonatal intensive such as 16 and18 group NEONATAL EOS care for respiratory distress and/or B Listeria (GBS).‍ monocytogenes The blood pressure support, and 75% of isolation of maternal oral flora and, deaths from6, EOS 10 occur among infants more rarely, – , Preterm EOS is defined as a blood with VLBW.‍ The mortality rate suggests a transplacental16, 18 20 pathway or cerebrospinal fluid (CSF) culture among those with EOS is an order of for some IAIs.‍ Inflammation obtained within 72 hours after birth magnitude higher among preterm inciting parturition may not, compared with term infants, whether however, always be attributable to that is growing a pathogenic bacterial ≥ – measured by gestational age (1.‍6% IAI.‍ Inflammation resulting from species.‍ This microbiological – definition stands in contrast to at 37 weeks, 30% at 25 28 weeks, immune-mediated rejection of the and approximately 50% at 22 24 fetal or placental compartment (from the functional definitions of sepsis 7, 8, 10 ≥ used in pediatric and adult patients, weeks) or birth weight (3.‍5% maternal extrauterine infection), as for whom the definition is used to among those born at 15006 g vs 35% well as that incited by reproductive specify a series of time-sensitive for those born at <1500 g).‍ or nonreproductive microbiota, may interventions.‍ The current overall all contribute to the pathogenesis incidence of EOS in the United States The pathogenesis of preterm of preterm labor and PROM, is approximately 0.‍8 cases per 1000 EOS is complex.‍ EOS primarily complicating the interpretation of 6 “ 15, 20 live births.‍ A disproportionate begins in utero and was originally placental pathology.‍ ” number of cases occur among infants described as the amniotic 12,13 RISK FACTORS FOR PRETERM EOS born preterm in a manner that is infection syndrome.‍ Among inversely proportional to gestational term infants, EOS pathogenesis age at birth.‍ The incidence of EOS is most commonly develops during ≥ ’ approximately 0.‍5 cases per 1000 labor and involves ascending Multiple clinical risk factors have ≤ infants born at 37 weeks gestation, colonization and infection of the been used to assess the risk of EOS ’ compared with approximately 1 case uterine compartment with maternal among infants born at 34 6/7 ’ per 1000 infants born at 34 to 36 gastrointestinal and genitourinary weeks gestation.‍ Univariate analyses ’ weeks gestation, 6 cases per 1000 flora, with subsequent colonization of risk factors for EOS among infants born at <34 weeks gestation, and invasive infection of the fetus preterm infants have been used to ’ 20 cases per 1000 infants born at <29 and/or fetal aspiration of infected identify gestational age, birth weight, ’ weeks gestation,– and 32 cases per amniotic fluid.‍ This intrapartum PROM and prolonged rupture of 1000 infants6 10 born at 22 to 24 weeks sequence may be responsible for EOS membranes (ROM), preterm onset gestation.‍ The incidence of EOS that develops after PROM or during of labor, maternal age and race, has declined among term infants over preterm labor that is induced for maternal intrapartum fever, mode the past 25 years, a change attributed maternal indications.‍ However, the of delivery, and administration to the implementation of evidence- pathogenesis of preterm EOS likely of intrapartum antibiotics to be based intrapartum antimicrobial begins before the onset of labor in associated with risk of EOS; however, therapy.‍ The impact of such therapies many cases of preterm labor and/or the independent contribution of any on preterm infants is less clear.‍ PROM.‍ Intraamniotic infection (IAI) specific factor other than gestational
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