Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis PDF

Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis Dustin D. Flannery, DO, MSCE,a,b,c,d Sagori Mukhopadhyay, MD, MMSc,a,b,d Knashawn H. Morales, ScD,c,e...

Delivery Characteristics and the Risk of Early-Onset Neonatal Sepsis Dustin D. Flannery, DO, MSCE,a,b,c,d Sagori Mukhopadhyay, MD, MMSc,a,b,d Knashawn H. Morales, ScD,c,e Miren B. Dhudasia, MBBS, MPH,a,b Molly Passarella, MS,b Jeffrey S. Gerber, MD, PhD,a,c,d,f Karen M. Puopolo, MD, PhDa,b,d Multiple strategies are used to identify newborn infants at high risk BACKGROUND AND OBJECTIVES: abstract of culture-confirmed early-onset sepsis (EOS). Delivery characteristics have been used to identify preterm infants at lowest risk of infection to guide initiation of empirical antibiotics. Our objectives were to identify term and preterm infants at lowest risk of EOS using delivery characteristics and to determine antibiotic use among them. METHODS: This was a retrospective cohort study of term and preterm infants born January 1, 2009 to December 31, 2014, with blood culture with or without cerebrospinal fluid culture obtained #72 hours after birth. Criteria for determining low EOS risk included: cesarean delivery, without labor or membrane rupture before delivery, and no antepartum concern for intraamniotic infection or nonreassuring fetal status. We determined the association between these characteristics, incidence of EOS, and antibiotic duration among infants without EOS. RESULTS:Among 53 575 births, 7549 infants (14.1%) were evaluated and 41 (0.5%) of those evaluated had EOS. Low-risk delivery characteristics were present for 1121 (14.8%) evaluated infants, and none had EOS. Whereas antibiotics were initiated in a lower proportion of these infants (80.4% vs 91.0%, P <.001), duration of antibiotics administered to infants born with and without low-risk characteristics was not different (adjusted difference 0.6 hours, 95% CI [ 3.8, 5.1]). CONCLUSIONS: Risk of EOS among infants with low-risk delivery characteristics is extremely low. Despite this, a substantial proportion of these infants are administered antibiotics. Delivery characteristics should inform empirical antibiotic management decisions among infants born at all gestational ages. a Center for Pediatric Clinical Effectiveness and Divisions of bNeonatology and fInfectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and cCenter for Clinical Epidemiology and Biostatistics, d Department of Pediatrics, and eDepartment of Biostatistics, Epidemiology & Informatics, University of WHAT’S KNOWN ON THIS SUBJECT: Low-risk delivery Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania characteristics, including cesarean delivery, no labor, no Dr Flannery conceptualized and designed the study, drafted the initial manuscript, and reviewed membrane rupture before delivery, and no concern for and revised the manuscript; Dr Mukhopadhyay contributed to the study design and analytic intraamniotic infection or nonreassuring fetal status, can plan, assisted with data acquisition and cleaning, and reviewed and revised the manuscript; Dr identify preterm newborns at lowest risk of infection to Dhudasia assisted with data acquisition and cleaning, and reviewed and revised the guide initiation of empirical antibiotics. manuscript; Ms Passarella contributed to the study design and analytic plan, and reviewed and revised the manuscript; Dr Morales contributed to the study design and analytic plan, and WHAT THIS STUDY ADDS: The risk of EOS among infants reviewed and revised the manuscript; Dr Gerber contributed to the study design and analytic of all gestational ages born in the setting of low-risk plan, and reviewed and revised the manuscript; Dr Puopolo conceptualized and designed the delivery characteristics is extremely low. Delivery study and reviewed and revised the manuscript; and all authors approved the final manuscript characteristics should inform empirical antibiotic as submitted and agree to be accountable for all aspects of the work. management decisions at birth among infants of all DOI: https://doi.org/10.1542/peds.2021-052900 gestational ages. Accepted for publication Oct 21, 2021 To cite: Flannery DD, Mukhopadhyay S, Morales KH, et al. Address correspondence to Dustin D. Flannery, DO, MSCE, Children’s Hospital of Philadelphia Delivery Characteristics and the Risk of Early-Onset Neonatal Newborn Care at Pennsylvania Hospital, 800 Spruce St, Philadelphia, PA 19107. E-mail: flanneryd@ Sepsis. Pediatrics. 2022;149(2):e2021052900 chop.edu PEDIATRICS Volume 149, number 2, February 2022:e2021052900 ARTICLE Downloaded from http://publications.aap.org/pediatrics/article-pdf/149/2/e2021052900/1255663/peds_2021052900.pdf by Univ Of South Alabama user  Newborn infants are at risk for of EOS.16 Additionally, studies of characteristics for all deliveries early-onset sepsis (EOS), defined as preterm infants investigating low- were extracted from hospital birth isolation of a pathogen from blood risk delivery criteria often exclude logs. Clinical diagnoses, laboratory or cerebrospinal fluid (CSF) culture moderately preterm and late data, and medication details were obtained at #72 hours after birth. preterm infants.15 Applying low-risk obtained from clinical data EOS causes significant morbidity delivery criteria to infants across all repositories. We conducted medical and mortality.1 Predicting which gestations may strengthen chart review to obtain data missing infants will develop EOS is prediction models in term infants, from data repositories. This study challenging for neonatal care improve risk categorization among was approved by the institutional providers and leads to relatively preterm infants, and lead to review board at the University of higher rates of antibiotic use improved antibiotic utilization in Pennsylvania with waiver of compared to the proportion both these populations. informed consent. infected.2 Multiple studies suggest that intrapartum, neonatal, and A robust estimate of EOS risk in Study Definitions especially prolonged neonatal relation to delivery characteristics Hypothesized low-risk delivery antibiotic exposures are associated among infants of all gestational ages characteristics were defined as in with adverse outcomes among at birth could significantly previous studies13,14 as the presence preterm infants and longer-term contribute to newborn clinical of all of the following: birth by morbidities among term infants, management by identifying cesarean delivery; rupture of underscoring the need for refined newborns unlikely to benefit from amniotic membranes at delivery; infection risk assessment among this empirical antibiotic therapy. absence of labor or attempts to population.3–10 Therefore, the objectives of this induce labor; absence of suspected study were to: (1) determine if or confirmed maternal intraamniotic The pathogenesis of EOS is most delivery characteristics used to infection; and absence of acute commonly that of ascending identify extremely preterm unexplained nonreassuring fetal colonization and infection of the newborns at lower risk for EOS status. We identified infants as low- fetus and newborn with maternal apply to infants born at all risk or not, using a stepwise gastrointestinal and genitourinary gestational ages; and (2) determine algorithmic approach based on bacteria.11,12 Therefore, delivery if such characteristics correlate with expected reliability and characteristics may help providers empirical antibiotic administration commonality of the variables of predict which infants are at lowest and duration. We hypothesized that interest, because not all variables risk of EOS and assist in infants born with specified low-risk were available for all infants (Fig 1). determining whether empirical delivery characteristics are at lowest We performed detailed chart review antibiotic therapy is indicated. For risk of infection, but this differential for all cases of EOS. instance, among extremely preterm risk does not translate to infants, the combination of cesarean proportionately lower antibiotic use. The primary outcome of interest delivery, rupture of membranes at was EOS, defined as at least 1 blood delivery, and absence of METHODS and/or CSF culture obtained #72 intraamniotic infection identifies hours after birth growing a infants with a 5- to 12-fold lower Data Source and Study Population pathogen. Cultures growing relative risk of EOS.13,14 This was a retrospective cohort coagulase-negative Staphylococci or Implementation of an algorithm to study. The study setting was 2 high- known commensal organisms were manage such infants without risk perinatal units at academic considered contaminants. The initiating antibiotics at birth was birth hospitals in Philadelphia, secondary outcomes of interest found to decrease antibiotic use in 1 Pennsylvania: Pennsylvania Hospital were initiation of empirical recent study without increasing and Hospital of the University of antibiotics (antibiotic therapy adverse events.15 For term infants, Pennsylvania. We included all beginning at #72 hours after birth) risk prediction models have been infants born between January 1, and duration of antibiotic developed to refine the approach to 2009 and December 31, 2014, with administration among infants EOS risk assessment and have at least 1 blood culture obtained at administered empirical antibiotics, substantially impacted antibiotic use #72 hours of age with or without for whom cultures were ultimately just after birth. However, these CSF culture. We excluded infants sterile. We analyzed duration of models do not incorporate labor or born outside of the study centers. antibiotics both as a continuous distinguish infants at the lowest risk Birth census and delivery variable (duration in hours) as well 2 FLANNERY et al Downloaded from http://publications.aap.org/pediatrics/article-pdf/149/2/e2021052900/1255663/peds_2021052900.pdf by Univ Of South Alabama user  FIGURE 1 Algorithmic approach for low-risk delivery characteristics determination. A, ROM $0.1 hours and #24 hours. B, If ROM 24 hours, or implausible (ie, negative number), then classified as not low-risk in the presence of any labor (duration between labor and delivery >0). C, SROM indicated among subjects with ROM negative, missing, or >24 hours. D, Labor and delivery admission reason indicating labor, preterm labor, or ROM. E, Attempt to VBAC or TOLAC. F, PTL and/or PROM indicated; G, cesarean delivery indicating labor, arrest of labor, arrest or failure of descent, secondary arrest of dilation, (Figure legend continues) PEDIATRICS Volume 149, number 2, February 2022 3 Downloaded from http://publications.aap.org/pediatrics/article-pdf/149/2/e2021052900/1255663/peds_2021052900.pdf by Univ Of South Alabama user  TABLE 1 Demographics and Clinical Characteristics of the Study Infants Characteristica All Infants N 5 7549 Low-Risk N 5 1121 Non-Low-Risk N 5 6428 P GA (completed weeks), median, IQR 37 (33–39) 34 (30–37) 38 (34–40)