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≥ Chorioamnionitis and Management ofAmanda Asymptomatic I. Jan, MD,​a,b​ Rangasamy Ramanathan, MD,​a,b​ RowenaInfants G. Cayabyab, MD a 35 Weeks

BACKGROUND AND OBJECTIVE: Without Empiric≥ Antibiotics’ abstract

Management of asymptomatic infants 35 weeks gestation born to mothers with chorioamnionitis remains controversial, with many clinicians considering the need for changes to the current guidelines. The study objective was to evaluate the outcomes of asymptomatic chorioamnionitis-exposed neonates without the use of METHODS: immediate empirical antibiotics. ≥ ’ A retrospective data review was conducted from May 2008 to December 2014, including asymptomatic infants 35 weeks gestation with a maternal diagnosis of clinical RESULTS: chorioamnionitis. A total of 240 asymptomatic infants with chorioamnionitis exposure were identified. The majority of asymptomatic chorioamnionitis-exposed infants, 162 (67.5%), remained well in the mother-infant unit with a median stay of 2 days. There were 78 (32.5%) infants admitted to the NICU and exposed to antibiotics due to abnormal laboratory data or development of clinical symptoms. Of those infants admitted to the NICU, 19 (24%) received antibiotics for <72 hours, 47 (60%) were treated for culture-negative CONCLUSIONS: clinical , and 12 (15%) for culture-positive sepsis, with a median NICU stay≥ of 7 days.’ Nonroutine use of empirical antibiotics in asymptomatic newborns 35 weeks gestation with maternal chorioamninonitis prevented NICU admission in two-thirds of these infants. This prevented unnecessary antibiotic exposure, increased hospitalization costs, and disruption of mother-infant bonding and breastfeeding. Laboratory evaluation and clinical observation without immediate antibiotic administration may be incorporated into a management approach in asymptomatic chorioamnionitis-exposed neonates. Additional studies are needed to establish the safety of this approach. aDivision of Neonatal Medicine, Department of Pediatrics, LAC+USC Medical Center, Keck School of Medicine, Wha w t’s Kno n on This Subject: Current guidelines b University of Southern California, Los Angeles, California; and Division of Neonatology, Children’s Hospital Los recommend empirical antibiotic treatment of all Angeles, Los Angeles, California infants exposed to maternal chorioamnionitis Dr Jan conceptualized and designed the study, collected and analyzed the data, and drafted regardless of clinical symptoms. Many clinicians the initial manuscript; Dr Ramanathan provided data interpretation and critically reviewed are now advocating for change in this management the manuscript; Dr Cayabyab carried out the initial analyses and reviewed and revised the approach in asymptomatic well-appearing infants. manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. What This Study Adds: This study presents a management strategy that eliminates immediate DOI: https://​doi.​org/​10.​1542/​peds.​2016-​2744 empirical antibiotic therapy for asymptomatic Accepted for publication Mar 16, 2017 chorioamnionitis-exposed infants ≥35 weeks’ Address correspondence to Amanda I. Jan, MD, Department of Neonatology, Huntington Hospital, gestation. Intensive care admission, disruption in 100 W. California Blvd, PO Box 7013, Pasadena, CA 91105. E-mail: [email protected] mother-infant bonding, antibiotic exposure, and PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). increased hospitalization costs were avoided in a majority of infants. Copyright © 2017 by the American Academy of Pediatrics

To cite: Jan AI, Ramanathan R, Cayabyab RG. Chorioamnionitis and Management of Asymptomatic Infants ≥35 Weeks Without Empiric Antibiotics. Pediatrics. 2017;140(1):e20162744

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 1, July 2017:e20162744 Article Clinical chorioamnionitis is a Controversy exists regarding the diagnosis. Obstetrical diagnosis was complication of defined management of asymptomatic based on the presence of maternal as and of newborns as a result of fever plus additional criteria, . Chorioamnionitis inconsistencies in chorioamnionitis including maternal , is reported in1 3% to 10% of term diagnosis and its impact on neonates maternal or fetal , and has historically in an era of low EOS risk. The lack uterine tenderness, or purulent of consensus has led to variability . Infants included were caused concern for2 neonatal early- onset sepsis (EOS). Chorioamnionitis in the use of empirical antibiotics initially asymptomatic at birth and is a clinical challenge that lacks a in newborns at risk for EOS both14 admitted to the mother-infant unit. consistent approach to diagnosis and nationally and internationally. Infants were excluded if they were can be highly variable in practice. Recent studies reveal only a minority immediately admitted to the NICU or of institutions continue to strictly Datahad missing Collection medical records. Isolated maternal fever, caused 3,4​ by infectious and noninfectious ‍ follow recommended AAP/CDC sources, may be the only diagnostic guidelines to15 administer prophylactic trigger. Clinical suspicion is antibiotics. Research and Data were extracted from paper often formed with only 1 sign or discussion point toward the need to charts, the maternal database symptom that may not indicate a abandon previous guidelines to treat (QuadraMed Affinity, version GM12 true intrauterine infection. Efforts all well-appearing chorioamnionitis- Dev-3, Reston, VA), and the neonatal are being made to improve the exposed infants and instead16,17​ evaluate database (Neonatal Information alternative approaches. ‍ System, Medical Data Systems, diagnostic accuracy and management4 of maternal chorioamnionitis. At LAC+USC Medical Center, it has version 3 and 5, Rosemont, PA). been the guideline to complete Data collected included maternal Once chorioamnionitis is diagnosed, ≥ a laboratory evaluation in age, race, mode of delivery, duration however, it significantly impacts ’ the subsequent management of the asymptomatic newborn infants 35 of ruptureStreptococcus of membranes, highest newborn. weeks gestation born to mothers maternal temperature, maternal with clinical chorioamnionitis group B (GBS) status, and use of intrapartum antibiotics. Rates of neonatal EOS have without administration18 of empirical Neonatal demographics extracted dramatically declined since the antibiotics. The objective of were gestational age, birth weight, introduction of maternal intrapartum this study was to evaluate clinical 5,6​ and Apgar scores. Laboratory data antibiotic prophylaxis (IAP). ‍ outcomes of asymptomatic collected included complete Chorioamnionitis is a previously chorioamnionitis-exposed late 7 count (CBC) with manual differential identified risk factor for EOS,​ preterm and term infants by using count, high-sensitivity C-reactive but rates remain low even in our alternative guideline. 1,2,​ 8​ Methods protein (hsCRP; mg/L), blood chorioamnionitis-exposed infants. ‍ culture, and cerebrospinal fluid (CSF) Despite low risks, current Study Design analysis. Placental pathology reports recommendations from the American and neonatal clinical outcomes were Academy of Pediatrics (AAP) and Managementrecorded. of Asymptomatic the Centers for Disease Control and 9,10​ This retrospective cohort study Neonates ≥35 Weeks’ Gestational Prevention (CDC) ‍ advocate a included infants and mothers who Age limited laboratory evaluation and delivered at LAC+USC between May ≥ ’ immediate empirical antibiotic 1, 2008 and December 31, 2014. therapy in all chorioamnionitis- The Institutional Review Board All infants 35 weeks gestation ≥ ’ exposed infants. Diagnosis of at LAC+USC approved the study. born with chorioamnionitis exposure maternal clinical chorioamnionitis at Newborns 35 weeks gestational with any signs or symptoms of sepsis some institutions involves neonatal age born with a maternal diagnosis were immediately transferred to admission to intensive care to of chorioamnionitis were identified the NICU for antibiotic therapy. administer intravenous antibiotics. from paper medical records. Infant Asymptomatic infants were observed This management interferes with and mother were included if the with usual care in the mother-infant mother-infant bonding and successful chart had a documented diagnosis unit, including routine examinations breastfeeding, prolongs the length of chorioamnionitis made at the and vital signs every 4 hours, with a of stay, and increases overall health discretion of the obstetrician before4 NICU clinician immediately alerted care costs. These infants are exposed– or up to 4 hours after delivery and for changes in clinical status. Serial to broad-spectrum antibiotics 11that13 the mother received intravenous laboratory data were obtained. have potential adverse effects. ‍ antibiotic treatment accordingly after Empirical antibiotics were not Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 Jan et al administered. Initial blood culture, result was presented as an odds CBC, and hsCRP were obtained ratio with 95% confidence interval. between birth and 6 hours of Data were analyzed by using Stata life. Repeat CBC and hsCRP were Statistical Software: ReleaseP 14 (Stata collected at 12 to 24 hours and at Corp, College Station, TX). Statistical 24 to 48 hours of life. The hsCRP significance was set at < .05. was measured by using immune Results turbidimetric assay with a threshold of 10 mg/L (Roche Diagnostics, Maternal and Neonatal Indianapolis, IN). Based on updated Demographics institution guidelines, asymptomatic ≥ infants with normal laboratory− ’ – A total of 5637 infants were born 35 studies (a white blood cell [WBC]1 count of 5000 30000 mm , band weeks gestation during the study counts of <10%, and hsCRP of <10 period with 364 infants exposed to mg/L) are observed for signs and maternal chorioamnionitis (6.5%). ≥ symptoms of sepsis for 48 hours. There were 122 chorioamnionitis- exposed infants requiring direct Asymptomatic− infants with −1 of 5 FIGURE 1 NICU admission who were excluded laboratory criteria1 (a WBC count1 of Outline of the study population. >30000 mm or <5000 mm , band from the study (Fig 1) with 110 (90%) infants admitted with a counts of >24%, hsCRP of >10 mg/L, ≥ and/or positive blood cultures) diagnosis of rule out sepsis. Twelve infants were directly admitted for treatment 4 hours before delivery. were transferred to the NICU, and18 antibiotic therapy was initiated. reasons unrelated to sepsis. Clinical All mothers with chorioamnionitis The immature to total symptoms were documented in 55 had documented treatment with (45%) of the 122 infants directly antibiotics accordingly; however, neutrophil ratio was not used ≥ because our laboratory reports only admitted. Respiratory distress only half of the mothers, 121 (50%), band count range, and an accurate was the prominent symptom in 52 received antibiotics 4 hours before ratio cannot be calculated. Lumbar (95%) of these symptomatic infants. delivery. There were no significant puncture was performed for clinical Antibiotic exposure was documented differences in maternal age, race, sepsis, a positive blood culture, or in 106 (87%) of the 122 directly mode of delivery, hours of membrane persistent laboratory abnormalities. admitted infants. rupture, GBS status, or exposure to A decision was made at the discretion There were 242 asymptomatic intrapartum antibiotics between ≥ ’ of the attending neonatologist to chorioamnionitis-exposed infants infants requiring NICU admission treat with antibiotics beyond 48 35 weeks gestation admitted to and those that did not (Table 1). The highest recorded maternal hours if clinical symptoms persisted the mother-infant unit who qualified ° or if laboratory data remained for this study. Only 240 infants were temperatures ranged from 98.5 abnormal. to 103.2 F. Twenty-five mothers Data Analysis included in the analysis because 2 had no available laboratory (10%) received a diagnosis of information. Due to abnormal clinical chorioamnionitis without documentation of a fever, with the laboratory data, a positive blood ° Nominal variables were presented as culture, or the onset of clinical signs highest recorded temperatures percentages and continuous data as of sepsis, 78 (32.5%) infants were <100.4 F. The mean maximum means and SDs or median and 25th subsequently admitted to the NICU, temperature was significantly higher in mothers of neonates requiring to 75th percentiles, depending on and 162 (67.5%) infants remained ° distribution normality. Categorical well with a routine newborn course NICU admission compared with χ ° P variables were compared2 between in the mother-infant unit (Fig 1). those not admitted (101.2 F vs groups with the test. Differences Infants did notsignificantly differ in 100.9 F; = .04). With the exception ’ t in continuous variables were birth weight, gestational age, sex, or of fever, additional criteria for – U compared by 2-tailed Student s Apgar scores between NICU-admitted the diagnosis of chorioamnionitis tests or Mann Whitney test where and nonadmitted infants. Maternal were only documented positive in appropriate. Logistic regression GBS status was positive in 34 (14%) a minority of mothers, including was used to assess the association mothers. GBS-positive mothers were maternal leukocytosis (38%), between histologic chorioamnionitis started on IAP as soon as possible, maternal tachycardia (37%), or fetal (HCA) and NICU admission. The and 29 of 34 (85%) received tachycardia (33%). Only 4 mothers Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 1, July 2017 3 TABLE 1 Maternal and Neonatal Demographics NICU Admissions, N = 78 Nonadmissions, N = 162 P had documentation of uterine a tenderness, and only 1 with foul Birth weight, g 3425 (±399) 3414 (±410) .84 Gestational age, wka 39.6 (±1.3) 39.3 (±1.3) .15 smelling fluid. Girl 41 (53%) 87 (54%) .86 b There were 223 infants with available Apgar 1 min 8 (8–9) 9 (9–9) .46 Apgar 5 minb 9 (9 9) 9 (9 9) .65 placental pathology reports. HCA was – – Maternal agea 24.6 (±6) 25.1 (±6) .49 demonstrated in 52% (115/223) of Hispanic race 69 (88%) 136 (84%) .69 chorioamnionitis-exposed infants. Cesarean delivery 16 (21%) 51 (31%) .076 The diagnosis of HCA was significantly Rupture of membrane, hb 10 (6–18) 10 (6–16) .66 higher in infants requiring NICU GBS-positive 8 (10%) 26 (16%) .25 Tmax ( F) 101.2 ( 0.8) 100.9 ( 0.8) .04 admission (64% vs 46%; odds ° ± ± – P HCA 46/72 (64%) 69/151 (46%) .011 ratio, 2.1; 95% confidence interval, Maternal antibiotics before deliveryc 38 (49%) 83 (52%) .68 1.18 3.75; = .011) (Table 1). Positive Tmax, maximum maternal temperature. blood cultures did not differ betweenP a Mean (±SD). infants with HCA and those without (3 b Median (25th–75th percentile). c More than 4 h before delivery. ofIndication 108 [3%] for vs N9I ofCU 105 Admission [9%], = .08).

TABLE 2 Neonatal Laboratory Data Newborn infants were admitted to NICU Admissions, N = 78 Nonadmissions, N = 162 P the NICU with abnormal laboratory WBC counta values or signs and symptoms of Birth–12 h 20.7 (±7.9) 19.4 (±5.5) .19 ± sepsis at a mean postnatal age of 12–24 h 23.6 (±7.4) 20.7 (±5.2) .036 24–48 h 18.4 (±5.6) 16.5 (±4.3) .013 22 12 hours. A significant difference hsCRP (mg/L)b was seen between infants requiring Birth–12 h 0.3 (0.2–1.8) 0.2(0.2–0.4) <.001 NICU admission and those that did 12–24 h 12.05 (2.3–30.1) 2.2 (0.8–4.9) <.001 not in the median values of hsCRP 24–48 h 13.5 (3.2–25.6) 2 (0.8–4.6) <.001 obtained at all time points and the a Mean (±SD). b mean WBC count by 12 to 24 hours Median (25th–75th percentile). and 24 to 48 hours of life (Table 2). There was no significant difference in Enterococcus laboratory data between infants with bacteremia and those without (data included 7 withEnterococcus (58%) for suspected sepsis. The majority of not shown). and 5 with (42%). these infants, 59 (76%), were treated Six of the 7 species with antibiotics for >72 hours, with From the infants admitted to the were faecalis and 1 was faecium. a median of 7 days of treatment NICU, 59 of 78 (76%) remained Only 3 mothers of these 12 culture- (Table 3). Admitted infants required clinically asymptomatic and were positive infants received antibiotic a median hospital stayP of 7 days admitted due to abnormal laboratory treatment >4 hours before delivery, compared with a median of 2 days for results. The other 19 infants (24%) and thus the majority of infants nonadmitted infants ( < .001). None developed clinical symptoms of unlikely benefited significantly from of the NICU-admitted infants were sepsis, respiratory distress being the antibiotic exposure. Of the admitted able to exclusively breastfeed. Only most frequent presenting symptom, infants, 32 of 78 (41%) had a lumbar 85% of admitted infants received occurring in 9 infants (12%) (Table 3). puncture performed. CSF analysis any breast milkP compared with 94% Fourteen of the admitted infants had was normal in 30 infants. Two infants of infants remaining in the mother- positiveStaphylococcus blood cultures, of which were treated with antibiotics for 14 infant unit ( = .032). There were no 2 were considered contaminants days for presumed related deaths or morbidities identified in ( and mixed flora). Only to uninterpretable CSF analysis after any infant during the study period. 2 of 12 infants with a true-positive traumaticAntibiotic lumbarTherapy punctures and Length (Table of 3). No infant was readmitted to our blood culture presented signs and Stay institution for sepsis after discharge. symptoms of clinical sepsis, with the Discussion remaining 10 infants asymptomatic at the time of admission. These 10 infants were admitted after their Of the 240 asymptomatic blood cultures were reported positive chorioamnionitis-exposed infants, The aim of this study was to between 7 and 25 hours of life. The 78 (32.5%) were admitted to the present outcomes at a single 12 true-positive blood cultures NICU and treated with antibiotics institution for asymptomatic Downloaded from www.aappublications.org/news by guest on September 26, 2021 4 Jan et al TABLE 3 Neonatal Outcomes for NICU Admissions NICU Admissions (N = 78), n (%) risk factors were not significantly Asymptomatic 59 (76) different. Elevated hsCRP 21 (27) Elevated WBC/bandemia 10 (13) Laboratory evaluation, including Elevated hsCRP/elevated WBC/bandemia 16 (21) blood culture, CBC, and hsCRP for Positive blood culture 12 (15) Presenting clinical symptom 19 (24) chorioamnionitis-exposed infants Respiratory distress 9 (12) is part of our EOS monitoring Poor feeding 7 (9) strategy. Observation without a 1 (1) blood culture would have missed Hypoglycemia 1 (1) infants with a positive test that Temperature instability 1 (1) Blood culture remained asymptomatic. Ten out of Negative 64 (82) 12 bacteremic infants in our study Positive 12 (15) were asymptomatic. This finding E coli 5 was confirmed in a study reporting Enterococcus 7 asymptomatic cases of culture- Treated for sepsis 59 (76) Culture-positive sepsis 12 (15) confirmed EOS in chorioamnionitis-21 Days of antibioticsa 7 (5–7) exposed neonates. The utility of Lumbar puncture 32 (41) serial CBC and CRP in identifying a Median (25th–75th percentile). infants who are at risk for EOS has

been questioned9,22,​ 23​ and is not solely sufficient. ‍ ‍ Laboratory data were ≥ ’ not significantly different in infants chorioamnionitis-exposed infants this significant reduction in EOS, with and without bacteremia in our 35 weeks gestation with an presumptive antibiotic treatment study. These tests are acknowledged approach eliminating immediate of all infants is unwarranted. to have24, 25​poor positive predictive empirical antibiotic administration. Using current9,10​ CDC and AAP value ‍ and abnormal values Using our strategy, we avoided guidelines,​ ‍ maternal diagnosis of can be observed in asymptomatic antibiotic exposure in a majority chorioamnionitis commits infants and potentially uninfected (67.5%) of asymptomatic to laboratory evaluation, antibiotic neonates. Some of our infants were chorioamnionitis-exposed newborns. treatment, and hospitalization in asymptomatic, admitted to the NICU, No infant morbidities were identified higher acuity units. The optimal and treated for sepsis exclusively due to a potential delay in antibiotic management strategy to safely based on abnormal laboratory values. administration. There is a need to replace previous recommendations Laboratory data can be an adjunct revisit currently recommended continues to be intensely debated. diagnostic tool, but it is vital that guidelines and consider abandoning A majority of clinicians already clinicians refrain from diagnosis the approach of treating well- disagree with antibiotic treatment 4 and treatment based entirely24 on appearing infants because4,16,​ of17​ of asymptomatic infants and are nonspecific laboratory data. chorioamnionitis alone. ‍ ‍ no longer adhering15 to previous Additional studies are essential to guidelines. develop improved diagnostic testing A maternal clinical diagnosis of that will timely and accurately chorioamnionitis is often based An initiative has been undertaken for indicate EOS risk in asymptomatic on nonspecific signs, does not alternative management strategies chorioamnionitis-exposed infants. consistently convey the degree or to prevent EOS in chorioamnionitis- severity of illness, and may not exposed infants relying on maternal In an era where antibiotic resistance indicate true intrauterine infection. risk factors combined with 19,an20​ is on the rise, health care providers In our study, several mothers were infant clinical examination. ‍ In are increasingly conscious11,26,​ of27​ diagnosed with chorioamnionitis this model, maternal temperature antibiotic stewardship. ‍ ‍ When1,2,​ 5,​ 6,​ 8​ based solely on a single fever and, is used as a quantitative risk factor the overall risks of EOS are low,​ ‍ ‍ ‍ in a few cases, even in the absence adjusting for current variability in the exposure of large numbers of well- of an elevated temperature. With diagnosis of chorioamnionitis. Infants appearing infants to even short increased IAP use for maternal in our study requiring admission for courses of antibiotics is no longer chorioamnionitis, recent data suspected sepsis showed significantly justified. Alterations in the infant show the rate of culture-positive higher maternal maximum gut microbiome have been shown11 EOS has decreased from 80 to 200 temperatures compared with infants after antibiotic administration per 1000 to 4 per 1000 newborns1 remaining in the mother-infant with potential for lasting health exposed to chorioamnionitis. Given unit. However, all other maternal consequences on allergies, Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 1, July 2017 5 early wheezing12,13​ or asthma, and In our institution, the placenta maternal chorioamninonitis avoided . ‍ Once antibiotics are is routinely sent for pathology NICU admission in two-thirds of started in infants, they are often examination. Risk of NICU admission infants. This prevented unnecessary continued for prolonged courses was twofold higher for infants with antibiotic exposure, increased even if the infant remains clinically28 HCA compared with infants without, hospitalization costs, and disruption well with a negative blood culture. but culture-positive infection was in mother-infant bonding and The rate of antibiotic usage was 18% not different between those infants– breastfeeding. Laboratory evaluation at our institution for late preterm and with or without HCA. More 31often,33 and close clinical observation without term infants during this study period. HCA is associated with EOS ‍ ‍ in immediate antibiotic administration In California NICUs, there is a 40-fold preterm infants. In term infants, may be incorporated into an variation in antibiotic use, which HCA has shown to be a result of alternative management strategy does not correlate29 to the burden a noninfectious34 inflammatory of asymptomatic chorioamnionitis- of infection. Although the overall process. In general, the diagnosis exposed neonates. Additional studies majority of our asymptomatic infants of HCA does not aid in the are needed to establish the safety of were not exposed to antibiotics, management31,32​ of EOS in term this approach. those started on antibiotics were infants. ‍ Pathology results at our Acknowledgments often treated for a prolonged course. institution are not timely enough The threshold for initiating or to be a factor in immediate clinical continuing antibiotics in neonates decision-making. We thank Sue Keiper, PNP, Rose for suspected infection needs to be Our study has limitations. It was Neptune, PA, and Brenda Ybarra, RN, carefully considered29 and additionally performed retrospectively with who were invaluable in obtaining evaluated. a small population at a single the infant and maternal data. We Administration of antibiotics to institution of a predominantly would also like to thank Dr Manuel chorioamnionitis-exposed newborns high-risk Hispanic population. It Durand for his critical review of the often requires NICU admission. Using is possible for discrepancies in the manuscript and Dr Lorayne Barton our guidelines, we did not admit a identification of patient diagnosis for her assistance in navigating the majority of asymptomatic infants, and symptoms through paper neonatal database system. and instead the newborns were charts, although chorioamnionitis monitored in the mother-infant unit. was confirmed in both the infant Abbreviations Avoiding separation between mother and mother before study inclusion. and newborn promoted bonding Although all discharged newborns and prevented the detrimental have scheduled follow-up at an AAP: American Academy of consequences EOS evaluations have outpatient clinic, they are not 30 Pediatrics on successful breastfeeding. The consistently followed at our CBC: complete blood count cost of a stay in the mother-infant hospital clinic. We did not have CDC: Centers for Disease Control unit for 2 days compared with a any infant return to our institution and Prevention NICU stay, which averaged a week, is for readmission due to sepsis after CSF: cerebrospinal fluid substantial. The charge for our NICU discharge, but we have no knowledge EOS: early-onset sepsis is $12612 per day in contrast to of potential readmissions to other GBS: group B $5300 per day in the mother-infant institutions. HCA: histologic chorioamnionitis unit. The cost savings for the 162 Conclusions hsCRP: high-sensitivity infants who were cared for 2 days C-reactive protein in the mother-infant unit compared IAP: intrapartum antibiotic with an EOS evaluation and antibiotic Nonroutine use of empirical ≥ ’ prophylaxis therapy in the NICU totals $2369088 antibiotics in asymptomatic WBC: white blood cell or $359861 per year. newborns 35 weeks gestation with

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. COMPANION PAPER: A companion to this article can be found online at www.pediatrics.​ ​org/​cgi/​doi/​10.​1542/​peds.​2017-​1155.

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 140, number 1, July 2017 7 chorioamnionitis in term newborn. . Early Hum Dev. J Matern Fetal Neonatal Med. Front Pediatr. 2014;2:27 1994;40(1):51–58 2013;26(8):828–832 32. de Araujo MC, Schultz R, Vaz 33. Hoang D, Charlagorla P, Salafia C, et 34. Rober ts DJ, Celi AC, Riley LE, et al. FAC, Massad E, Feferbaum R, al. Histologic chorioamnionitis as a Acute histologic chorioamnionitis at Ramos JL. A case-control study of consideration in the management term: nearly always noninfectious. histological chorioamnionitis and of newborns of febrile mothers. PLoS One. 2012;7(3):e31819

Downloaded from www.aappublications.org/news by guest on September 26, 2021 8 Jan et al Chorioamnionitis and Management of Asymptomatic Infants ≥35 Weeks Without Empiric Antibiotics Amanda I. Jan, Rangasamy Ramanathan and Rowena G. Cayabyab Pediatrics 2017;140; DOI: 10.1542/peds.2016-2744 originally published online June 8, 2017;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/140/1/e20162744 References This article cites 32 articles, 12 of which you can access for free at: http://pediatrics.aappublications.org/content/140/1/e20162744#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Fetus/Newborn Infant http://www.aappublications.org/cgi/collection/fetus:newborn_infant_ sub Neonatology http://www.aappublications.org/cgi/collection/neonatology_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 26, 2021 Chorioamnionitis and Management of Asymptomatic Infants ≥35 Weeks Without Empiric Antibiotics Amanda I. Jan, Rangasamy Ramanathan and Rowena G. Cayabyab Pediatrics 2017;140; DOI: 10.1542/peds.2016-2744 originally published online June 8, 2017;

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2017 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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