Andrew M. Ellefson, MD Neonatologist Christiana Care Health System

Andrew M. Ellefson, MD Neonatologist Christiana Care Health System
T.I.M.E. (Triple I to Manage Early-onset Sepsis): Changing our Management of Mothers and Their Newborns Andrew M. Ellefson, MD Neonatologist Christiana Care Health System

Agenda Background Comprehensive Pathway Overview
Simplified Pathway Overview L&D Process Review L&D Nurse Peds/DR Provider Well Baby Process Review Nurse and Newborn Physician

Background Why are we implementing a change to our care of mothers with fevers and their newborns?

Current State- CDC/COFN Guidelines
All infants born to mothers with a diagnosis of “chorioamnionitis” are admitted to the NICU; regardless of absence of symptoms. Blood culture on admission and CBC monitoring Minimum 48 hrs of ampicillin/gentamicin Diagnosis of chorioamnionitis sometimes loosely applied. Maternal fever > 37.8° C and: Significant maternal tachycardia (>120 beats/min) Fetal tachycardia (> beats/min) Purulent or foul-smelling amniotic fluid or vaginal discharge Uterine tenderness Maternal leukocytosis (total blood leukocyte count >15, ,000 cells/μL)

Issues with Current CDC/COFN Guidelines
Many of the references supporting IV abx for all infants of mothers with chorio include data before widespread GBS screening implementation1 GBS screening has reduced incidence of EOS GBS sepsis by 80% to rate of /1000 term newborns2 EOS due to E.coli estimated at 0.07/1000 newborns3 In these studies, I don’t want to overlook the impact of a maternal diagnosis of chorioamnionitis. The CDC guidelines highlight this risk as a 6 fold increase in the risk for early onset sepsis. However, when you look at the already low rate of early onset GBS and Ecoli disease, the increased risk from “chorio” gives you an estimate 0.42 to 2.2 per 1000 incidence; a number that is still fairly low. All of this without taking into account the clinical status of the newborn or the receipt of intrapartum antibiotics to the mother; both factors that further reduce the incidence or likelihood of early on set sepsis. Taylor JA, Opel DJ. Choriophobia: a 1-act play. Pediatrics Aug;130(2):342-6. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, MMWR Recomm Rep. 2010;59(RR-10):1–36. Stoll BJ et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics May;127(5):

Impact of “r/o sepsis chorio” admissions
Asymptomatic Infant admitted for 48 hrs to ICN: Mother/baby separation Reduction in bonding Increased parental stress/anxiety Reduction in maternal breast milk production and feeding Increased exposure to formula and IV fluids Unnecessary lab draws Risk for extended hospitalization due to “culture negative” prolonged antibiotic use due to non- specific CBC lab abnormalities Weaning off of IVFs Adverse Events - IV infiltrates Dollars $500/patient hospital day compared to admission to term nursery Based on CCHS 2015 “chorio admission” data, this would be ~ $86, ,000/year For adverse events, a study by researchers at Johns Hopkins in 1983 found that 20% of febrile neonates less than 60 days old who were admitted for rule out sepsis experienced a medical error, including gentamicin overdosing or IV fluid infiltration. So you can see, the treatment for “chorio” is not necessarily a benign path to pursue. As mentioned, the CDC and COFN guidelines don’t distinguish between well or ill appearing when the decision is made to rule out sepsis and start antibiotics.

Click Link Below for OB’s “Triple-I” reference
Bottom Line Evidence strongly supports modifying how we manage babies born to mothers with chorio by using a more EBM approach. Emphasis should be on the neonatal clinical exam and maternal risk factors as a whole, not isolated factors taken separately. *A detailed list of references, slides, and segments from Dr. Ellefson’s Peds Grand Rounds on this topic are included at end of this presentation. Click Link Below for OB’s “Triple-I” reference Higgins RD, Saade G, Polin RA, et al. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstet Gynecol 2016; 127:426.

Maternal Risk Factors – “Triple I”
Recommend - discontinue use of the term chorioamnionitis and use “intrauterine inflammation or infection or both” or “Triple I” “Triple I” is diagnosed when fever (>38 C) is present with one or more of the following: Fetal Tachycardia (> 160 bpm > 10 min.) Maternal WBC > 15,000 Purulent fluid from the cervical os Biochemical or microbiologic amniotic fluid results consistent with microbial invasion of the amniotic cavity

Pathway Overview

Pathway Overview (cont)

Simplified Pathway Overview

Powerchart Alerts/Notifications
A mother with fever ≥ 38˚ C delivers a baby.

Mom’s Chart Mom

Baby’s Chart Baby

Alert to Nurse / Vitals Documentation
Occurs on Open Chart for Newborns in LDR with an active Problem List tag for: PW-Newborn Sepsis Risk: Maternal Fever Fire alert to Nurse Provide URL access Open PowerForm from alert Document sepsis calculator score (SCS), provide visibility to the Attending Pediatrician Document of notification to the Delivery Room Pediatric provider (DRPP)

Nurse Opens Baby’s Chart- recording 30 Min of Life VSS

Baby’s Chart Alert to Nurse
1. Nurse clicks Sepsis Calculator Link (goes to URL)

Kaiser Permanente Sepsis Risk Score Calculator
This page will change 12/31/16. Click this link for new page if accessed before this date.

Using Sepsis Calculator
7. Click Calculate 1. Select 0.5/1000 (CDC Incidence) 2. Enter Gestational Age 3. Highest maternal temp. within 24 hrs of delivery 4. ROM Duration 5. GBS status 8. Record these Clinical Recommendations into Cerner Powerform “Neonatal Sepsis Risk Assessment” 6. GBS Specific IAP Abx: Penicillin Ampicillin Clindamycin Erythromycin Cefazolin Vancomycin Broad Spectrum Abx: Other cephalosporins Fluoroquinolones Any extended spectrum β-lactams Any GBS IAP plus an aminoglycoside *All of this data should be available from OBIS

8. Record these Clinical Recommendations into Cerner Powerform “Neonatal Sepsis Risk Assessment” *Vital signs on all Well Baby Floor Newborns on Floor are already Q4hrs

L&D Nurse Process Flow 2. Nurse clicks Neonatal Sepsis Calculator Powerform

L&D Nurse Process Flow …Space Holder for additional slides if needed

Neonatal Sepsis Calculator Power Form Completion
L&D Nurse Process Flow Neonatal Sepsis Calculator Power Form Completion

Peds/DR provider fills out the rest
L&D Nurse Process Flow Power Form Completion 2. Record Sepsis Calculator Clinical Recommendations. *Fill in all that apply from the calculator 1. Record newborn 30 min vitals 3. Notify Peds DR team/provider and document who was notified. 4. Complete form. 5. Sign form. Peds/DR provider fills out the rest

L&D Nurse/Peds DR Provider IMPORTANT Points
Peds/DR provider should be at all deliveries if there is a concern for fetal well being. Peds/DR does not need to be at all deliveries if the mother only had an isolated fever. But, these babies still need a Sepsis Calc score completed after delivery. Call Peds/DR provider to notify them of mothers with fevers (when able to do so) and then also after the Sepsis Calculator has been completed for the newborn (if Peds not present for delivery). Call Peds/DR provider if there is concern for newborn instability or vitals abnormality (e.g. tachypnea). Peds/DR provider should assess all babies with any sign of clinical instability (e.g. tachypnea).

L&D Nurse/Peds DR Provider IMPORTANT Points
If the baby appears to be stable and is demonstrating normal transitional physiology (ie: comfortable tachypnea), he/she may remain with the mother per routine in L&D. The baby can always be brought to the NICU for OBS if indicated. “Equivocal” exam babies, by definition in attached slide, require 2-4 hours of persistent symptoms. Therefore, a comfortably tachypnea baby at 1 HOL may simply be demonstrating transitional physiology and does not necessarily meet criteria for “equivocal exam”. If concerned, discuss with Peds/DR or Neonatology. When the mother is ready for transfer to Well Baby floor, only “Well Appearing” babies who do not require NICU admission (per their Sepsis Calc recs) are cleared for co-transfer to Well Baby floor. Any baby with ongoing transitional physiologic abnormalities, or any sign of distress must go to the NICU. If a baby goes to NICU for OBS and then has complete resolution of symptoms, clinical discretion can be used to allow this baby to return to Well Baby Floor with mother. The Peds/DR provider must notify the Well Baby physician or covering provider about the baby’s Sepsis Calc recommendation and clinical disposition. This will ensure proper physician-physician hand off. The L&D nurse must also report this information in their handoff to post-partum nursing. It is important to note that these babies will have Q4hr vitals on Well Baby floor for 48 hrs and that there must be a low threshold to transfer from floor to NICU at the earliest sign of new/developing distress.

Clinical Exam Description

Baby’s Chart

Peds/DR Alert and Process
Occurs as Peds/DR provider opens chart Does Newborn have active tag? Has the Sepsis Calculator Form been charted?

Peds/DR Provider clicks on Neonatal Sepsis Calculator Form Should already be filled in by L&D Nurse

5. Sign form Should already be filled in by L&D Nurse 1. Peds/DR provider fills out exam of baby. If DR nurse indicated the baby is well without any concerns, the DR provider can consider deferring exam. 2. DR Provider Assessment and Plan, reviews Sepsis Calculator Recommendations 3. Select what applies for blood culture per Sepsis Calculator recommendations. Contact newborn Pediatrician/FP well baby provider and review recommendations. 4. Complete form

Baby Transferred to Well Newborn Floor

Newborn Physician / Well Baby Nurse Alert
Occurs the first time any Nurse or Provider opens chart on PP As long as Newborn has active tag.

Well Baby Floor: Process Flow
Vitals signs on admission. Vital signs 1 hour after admission to floor, and then Q4hr until 48 hours of life. Nurse gets alert to review Neonatal Sepsis Calculator Form on baby Daily until 48 HOL Well Baby/Newborn Physician gets alert to review Neonatal Sepsis Calculator Form on baby Daily until 48 HOL

Well Baby Nurse Process Flow

Newborn Physician / Well Baby Nurse Alert
Reminds Well Baby Nurse and Physician Provider to review the Neonate Sepsis Calculator Form document.

Well Baby Floor Documentation on Chart

Key Issues to Remember The goal is to reduce unnecessary admissions to the NICU. Safety is key to making this successful. Any Well Baby/Floor newborn with any possible sign of distress needs to be discussed with NICU team and the covering well baby doctor. Don’t delay in transferring a baby who has abnormal vitals or signs of distress to the NICU.

Current Pathway Status
Jul 19th, first service line meeting Nov 15th Final TIMES pathway approved Education of Staff begins: thru Dec 2016 NLT January 4th, Sepsis calculator established as standard of care at Christiana and routine admission for asymptomatic “chorio” babies has stopped. Goal 20% reduction in admissions by June 2017.

Questions, Concerns, Thoughts?

Click Link Below for OB’s “Triple-I” reference
References Taylor JA, Opel DJ. Choriophobia: a 1-act play. Pediatrics Aug;130(2):342-6. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, MMWR Recomm Rep. 2010;59(RR-10):1–36. Stoll BJ, Hansen NI, Sánchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, Shankaran S, Kennedy K, Carlo WA, Watterberg KL, Bell EF, Walsh MC, Schibler K, Laptook AR, Shane AL, Schrag SJ, Das A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics May;127(5): Shakib B, Buchi K, Smith E, Young PC. Management of Newborns Born to Mothers with Chorioamnionitis: Is It Time for a Kinder, Gentler Approach. Acad. Pediatrics 2015;15: Puopolo KM, Draper D, Wi S, Newman TB, Zupancic J, Lieberman E, Smith M, Escobar GJ. Estimating the probability of neonatal early-onset infection on the basis of maternal risk factors. Pediatrics 2011;128:e Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/2000 grams at birth: A population-based study. Pediatrics. 2000;106 (2 pt 1): Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, Newman TB, Zupancic J, Lieberman E, Draper D. Stratification of risk of early-onset sepsis in newborns > 34 weeks' gestation. Pediatrics 2014;133:30-6. Higgins RD, Saade G, Polin RA, Grobman WA, Buhimschi IA, Watterberg K, Silver RM, Raju TN. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstet Gynecol 2016 Mar;127(3): Polin R, Watterberg K, Benitz W, Eichenwald E. The Conundrum of Early Onset Sepsis. Pediatrics 2014;133:1122. Management of the infant at increased risk for sepsis. Paediatrics & Child Health. 2007;12(10): Sagori M, Puopolo KM. Neonatal Early-Onset Sepsis: Epidemiology and Risk Assessment. NeoReviews Apr 2015, 16 (4) e221-e230; DOI: /neo.16-4-e221 Click Link Below for OB’s “Triple-I” reference Higgins RD, Saade G, Polin RA, et al. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstet Gynecol 2016; 127:426.

Holder Slide X

Slides that follow are reference slides from Dr
Slides that follow are reference slides from Dr. Ellefson’s Peds Grand Rounds

7. Click Calculate 1. Select 0.5/1000 (CDC Incidence) 2. Enter Gestational Age 3. Highest maternal temp. within 24 hrs of delivery 4. ROM Duration 5. GBS status 8. Record these Clinical Recommendations into Cerner Powerform “Neonatal Sepsis Risk Assessment” 6. GBS Specific IAP Abx: Penicillin Ampicillin Clindamycin Erythromycin Cefazolin Vancomycin Broad Spectrum Abx: Other cephalosporins Fluoroquinolones Any extended spectrum β-lactams Any GBS IAP plus an aminoglycoside

2 “Chorio” Patients What else do you want to know? Baby A
41 wks 1 days EGA Maternal Fever- 38.3˚C ROM- 15 GBS neg Mom received broad spectrum Abx > 4 hrs to delivery Baby B 41 wks 1 days EGA Maternal Fever- 39.4˚C ROM- 18 GBS neg Mom received no Abx prior to delivery What else do you want to know? Both well appearing on admission. Admit for r/o sepsis, Amp/gent, CBCs nl Both mom’s wanted to breast feed, but agreed to formula supplementation for one, the other received IVFs Both had 2 day stays to NICU, d/c on DOL #3

Historical Perspective

Chorioamnionitis AKA- Intra-amniotic infection 1-5% of all births
40-70% preterm births 1-13% term births Clinical or subclinical infection- up to 25% Hematogenous dissemination- rare ex: Listeria Ascending infection- most common GBS E.coli Prevotella sp Anaerobic streptococci Bacteroides Mycoplasma sp

Maternal Characteristic Risk Factors
Young age Low SES Nulliparity Extended duration of labor and ROM Multiple vaginal exams Pre-existing lower genital tract infections GBS colonization

Clinical Diagnosis Clinical findings Maternal fever
Maternal and fetal tachycardia Absence of localizing signs Lower uterine tenderness Purulent amniotic fluid “left shift in WBC” Maternal fever alone doesn’t constitute chorio. There is a broad differential diagnosis for fever which includes labor itself, epidural anesthesia, dehydration, and excessive ambient heat or an infection due to other causes not confined to the intrauterine environment.

Risks to Neonate Mortality- reported 2-16% case fatality rate
Birth asphyxia Septic shock Pneumonia Bacteremia Meningitis Long-term neurodevelopmental disability and CP As you can see from, chorioamnionitis has historically been associated with significant increased risks and consequences to the neonate.

Rate of Early- onset GBS Disease in the 1990s, United States
Group B Strep Association formed 1st ACOG & AAP statements CDC draft guidelines published Consensus guidelines RATE OF EARLY- AND LATE-ONSET GBS DISEASE IN THE 1990s, U.S. This slide plots the incidence of early-onset GBS disease in areas covered by the multi-state, population-based Active Bacterial Core surveillance system from 1989 to 2000. The white line represents early-onset GBS disease. The incidence of early-onset GBS disease in the United States since 1993 declined 70% (from 1.7 cases per 1,000 live births in 1993 to 0.45 cases per 1,000 live births in 1999) , coinciding with increased prevention activities. The graph shows that in 2000 the rates had plateaued at 0.5 cases per 1,000 live births. This graph was originally published by Schrag in New England Journal of Medicine, 2000, 342: Schrag, New Engl J Med : 15-20

Rate of Early- and Late-Onset GBS, 1990-2008
Early-onset GBS Early onset GBS- 2014 0.25/1000 live births Late-onset GBS RATE OF EARLY- AND LATE-ONSET GBS DISEASE , U.S. This graph plots the incidence of early-and late-onset GBS disease in the ABCs areas from 1989 to 2008. The yellow line represents late-onset disease in this graph. Even with the implementation of guidelines recommending GBS prophylaxis, late-onset GBS disease rates have remained stable since 1990 at approximately 0.3 cases per 1,000 live births. The white line represents early-onset disease. The incidence of early-onset GBS disease in the United States since 1993 has declined 84% (from 1.7 cases per 1,000 live births in 1993 to 0.28 cases per 1,000 live births in 2008) , coinciding with increased prevention activities. These data are from Active Bacterial Core surveillance, part of the CDC’s Emerging Infections Program with the graph being the one most recently available from their website. But they do have ongoing surveillance and the most recent 2014 data shows a 0.25/1000 live birth rate. Before national prevention policy Transition Universal screening Source: Active Bacterial Core surveillance / Emerging Infections Program Centers for Disease Control and Prevention Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Group B Streptococcus, 2014.

Newborn Management in the CDC 2010 Guidelines
This section will cover newborn management in the 2010 GBS guidelines.

CDC Revised Guidelines 2002-’10 Secondary Prevention of Early-Onset GBS Among Infants

CDC Guidelines Algorithm- 2010
No clear guidance regarding duration of antibiotics This slide shows an algorithm for the secondary prevention of early-onset GBS disease among newborns. An issue that some providers have had is that there is not clear guidance in this algorithm regarding duration of antibiotics.

Newborn Management in the COFN 2012 Recommendations

COFN- COnFusioN The COFN recommended continuation of broad-spectrum antibiotics in the neonate with a negative blood culture when the mother had received broad spectrum antibiotics and laboratory data were abnormal. The COFN also concluded, “Antibiotic therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low.” *after considerable discussion, the COFN modified its recommendations to not treat a well-appearing term infant with a negative blood culture (whose mother was treated for chorioamnionitis) longer than 48 to 72 hr even when the infant’s laboratory results are abnormal The Committee on Fetal and Newborn medicine convened in 2012 and provided recommendations for the management of these babies. Part of these recommendations did include the duration of antibiotics. However, there was confusion in their statement.

COFN Revised Comments Symptomatic neonates w/o risk factors who improve 0-6HOL may not require treatment, but must be monitored closely Chorio significantly increased risk for EOS; however the likelihood of sepsis in a well appearing infant at birth is low Risk for sepsis is reduced in infants born to mothers with chorio who receive IAP antibiotics Intrapartum Abx decrease SENS of Bl Cx Screening Lab tests have limited PPV and should never be used as rationale to continue treatment in an otherwise healthy term infant at HOL Physical exam is as good or better than most lab tests in rule-in/rule-out sepsis *Polin R, Watterberg K, Benitz W, Eichenwald E. The Conundrum of Early Onset Sepsis. Pediatrics 2014;133:1122.

All infants born to mothers with a diagnosis of “chorioamnionitis” are admitted to the NICU; regardless of absence of symptoms. Blood culture on admission and CBC monitoring Minimum 48 hrs of ampicillin/gentamicin Diagnosis of chorioamnionitis sometimes loosely applied. Maternal fever > 37.8° C and: Significant maternal tachycardia (>120 beats/min) Fetal tachycardia (> beats/min) Purulent or foul-smelling amniotic fluid or vaginal discharge Uterine tenderness Maternal leukocytosis (total blood leukocyte count >15, ,000 cells/μL)

Issues with Current CDC/COFN Guidelines
Many of the references supporting IV abx for all infants of mothers with choro include data before widespread GBS screening implementation1 GBS screening has reduced incidence of EOS GBS sepsis by 80% to rate of /1000 term newborns2 EOS due to E.coli estimated at 0.07/1000 newborns3 In these studies, I don’t want to overlook the impact of a maternal diagnosis of chorioamnionitis. The CDC guidelines highlight this risk as a 6 fold increase in the risk for early onset sepsis. However, when you look at the already low rate of early onset GBS and Ecoli disease, the increased risk from “chorio” gives you an estimate 0.42 to 2.2 per 1000 incidence; a number that is still fairly low. All of this without taking into account the clinical status of the newborn or the receipt of intrapartum antibiotics to the mother; both factors that further reduce the incidence or likelihood of early on set sepsis. Taylor JA, Opel DJ. Choriophobia: a 1-act play. Pediatrics Aug;130(2):342-6. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, MMWR Recomm Rep. 2010;59(RR-10):1–36. Stoll BJ et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics May;127(5):

Impact of “r/o sepsis chorio” admissions
Asymptomatic Infant admitted for 48 hrs to ICN: Mother/baby separation Reduction in bonding Increased parental stress/anxiety Reduction in maternal breast milk production and feeding Increased exposure to formula and IV fluids Unnecessary lab draws Risk for extended hospitalization due to “culture negative” prolonged antibiotic use due to non- specific CBC lab abnormalities Weaning off of IVFs Adverse Events - IV infiltrates Dollars $500/patient hospital day compared to admission to term nursery Based on CCHS 2015 “chorio admission” data, this would be ~ $86, ,000/year For adverse events, a study by researchers at Johns Hopkins in 1983 found that 20% of febrile neonates less than 60 days old who were admitted for rule out sepsis experienced a medical error, including gentamicin overdosing or IV fluid infiltration. So you can see, the treatment for “chorio” is not necessarily a benign path to pursue. As mentioned, the CDC and COFN guidelines don’t distinguish between well or ill appearing when the decision is made to rule out sepsis and start antibiotics.

Bottom Line Evidence strongly supports modifying how we manage babies born to mothers with chorio by using a more EBM approach. Emphasis should be on the neonatal clinical exam and maternal risk factors as a whole, not isolated factors taken separately. Advancement of neonatal care is coming to Christiana Care…

Presentation of Septic Neonate
Symptoms Develop Quickly Manroe et al ’77: 45/45 culture proven septic neonates had clinical signs of sepsis w/in 14 HOL Time to onset of symptoms is not delayed by maternal antibiotics: CDC surveillance (GBS) 208 no ABX 60 min prior to delivery; median illness 2 HOL (range HOL) 33 +ABX w/in 60 min of delivery; median illness 0 hrs (range 0-19 HOL) Since the development of symptoms is important in weighing the risks or benefits of empirically starting antibiotics, it is important to recognize the window of time during which an ill neonate will present. Given the marked concern for sepsis in a neonate, it’s important to mention that for the most part, studies support that these babies present fairly quickly after birth. Manroe BL, Rosenfeld CR, Weinberg AG, Browne R. The differential leukocyte count in the assessment and outcome of early-onset neonatal group B streptococcal disease. J Pediatr Oct;91(4):632-7.

Maternal +GBS (pre-IAP era) Maternal +GBS (IAP era)
Risk Factors in Asymptomatic Infants and Likelihood of Proven Sepsis- Escobar et al, Pediatrics, 2000 PROM > 18 hrs Maternal +GBS (pre-IAP era) Maternal +GBS (IAP era) Maternal +GBS, +PROM, fever, or preterm Chorioamnionitis +GBS and Chorio PROM +preterm PROM + Low APGAR 1% 0.5-1% % 4-7% 3-8 Escobar looked at the risk factors for sepsis in a large cohort of mothers and their babies in 2000 and determined the risk for sepsis in ill versus well appearing newborns. Some of the take away data that they reported are displayed here for asymptomatic infants. It should be stressed, without doubt, an ill appearing baby will not pass go and will proceed directly to a sepsis work up in any situation. 6-20% 4-6% 3-4% **Prematurity- risk of sepsis from any cause starts and continues to rise at any gestation < 36 wks

Predictive Values for EOS
One of the conclusions that their paper made was that Physical exam is as good or better than most laboratory tests in “ruling in or ruling out” sepsis. Escobar GJ, Li DK, Armstrong MA, et al. Neonatal sepsis workups in infants >/2000 grams at birth: A population-based study. Pediatrics. 2000;106 (2 pt 1):

Risk Factors for EOS Mukhopadhyay S, Puopolo KM. Neonatal Early-Onset Sepsis: Epidemiology and Risk Assessment NeoReviews 2015;16;e221

Stratification of Risk for EOS
Puopolo et al. 2011 Retrospective case-control 608,014 live births ≥ 34 wks, at 14 hospitals in KP system, CA from 350 cases of culture confirmed EOS < 72 HOL Matched control to 1063 subjects Goal of study was to stratify patients based on maternal risk factors. Case/controls divided into 2 groups for analysis: derivation dataset and validation data set

Stratification based on Maternal Factors- Puopolo et al- 2011
Predictive power: OR (95% CI) Duration of ROM (per hour) 3.41 ( ) Highest antepartum temperature 2.38 ( ) GBS Positive 1.78 ( ) GBS IAP given on time or any Abx <4 hrs 0.35 ( ) Broad Spectrum Abx > 4 hrs 0.31 ( ) Relative Contribution of Predictors Highest antepartum temperature (58.4%) Gestational age (16.7%) Length of time since ROM (12.6%) Intrapartum antibiotics (10%) GBS status (2.3%) The results of their study was the creation of a validated and objective data set that would allow for multivariate model for prediction of early onset sepsis among term and later-preterm infants.

Stratification of Risk for EOS
Escobar et al. 2014 Same subject group as Puopolo et al 2011 Retrospective case-control 608,014 live births ≥ 34 wks, at 14 hospitals in KP system, CA from Further developed risk stratification score based on newborn clinical examination and vital signs Escobar previously reported on the significance of infants with GBS disease and symptoms. That study in 2000 showed that 75% of infants with GBS disease are symptomatic at birth. Another study by Bromberger in 2000 showed that 95% of infants with Early onset sepsis present with clinical signs of illness within the 1st 24 hours of life. This and other data that support the significance of symptoms in the septic newborn were used by Escobar in when they reanalyzed the same data set of patients analyzed by Puopolo in Escobar further risk stratified these patients based on both maternal risk factor and newborn exams. *Escobar GJ, Puopolo KM, Wi S, Turk BJ, Kuzniewicz MW, Walsh EM, Newman TB, Zupancic J, Lieberman E, Draper D. Stratification of risk of early-onset sepsis in newborns > 34 weeks' gestation. Pediatrics 2014;133:30-6.

Escobar et al. 2014

Escobar et al. 2014 Infant Factors Likelihood Ratio for Sepsis
LR=14.5 (95% CI ) LR=3.75 (95% CI ) LR=0.36 (95% CI )

Escobar et al. 2014

Kaiser Permanente Sepsis Calculator
Maternal Risk Factors + Newborn Exam___ 1. Treat Empirically or 2. Observe and Evaluate or 3. Continued Observation/Routine Care

Variations in Practice
Shakib et al. 2015 Retrospective cohort study Newborns at University of Utah Hospital whose mothers were diagnosed with chorioamnionitis to mid-2013 Study Objectives: Determine variation in and measure outcomes from medical management of well appearing “chorio” babies. Compare current management of “chorio” babies with a hypothetical strategy based on risk stratification using Escobar et al. Sepsis Calculator. 743/20,262 (3.6%) neonates ≥34 wks born to mothers with diagnosis of chorio. Excluded 45/743 (6%) newborns because they were admitted to the NICU due to clinical illness; remaining 698 infants were initially “well appearing” and included for analysis. Study Group Characteristics: 26/698 (3.7%) /7 wks EGA Maternal temperature range 36.1° C- 40.5° C (40% were > 37.5° C) Rupture of Membranes hours (20% were ≥ 18 hrs) 65/698 (9.3%) GBS +; 203/698 (29%) GBS -; remainder 62% GBS unknown. Intrapartum antibiotics ≥ 4 hrs PTD– 38% of births Julie Shakib from Utah recognized that there was variation in many aspects of “chorio” management and that the CDC and COFN guidelines were infrequently being implemented. The body of data published the year before by Escobar in the Sepsis Calculator studies provided the opportunity to retrospectively study the outcomes for babies in their hospital. Their study objectives were: They identified 743 late preterm or term babies out of over live births who were born to mothers with the diagnosis of chorio. They excluded 45 babies because they wanted to only analyze those babies who were initially well appearing after birth. The study group characteristics were: Shakib B, Buchi K, Smith E, Young PC. Management of Newborns Born to Mothers with Chorioamnionitis: Is It Time for a Kinder, Gentler Approach. Acad. Pediatrics 2015;15:

Shakib et al. Variation from CDC/COFN Guidelines
Risk Stratification by “Sepsis Calculator” 90% 7% 3% When they looked at the medical management for those babies, only about 2/3 of newborns were managed according to CDC/COFN guidelines as seen in Table 1. On the right is another table from their study which shows the Sepsis Risk Score stratification for those babies. This initial risk categorization was based solely on maternal characteristics and did not yet stratify based on clinical exam. If stratification scheme according to Puopolo would have been utilized, the number of newborns who underwent testing and initial antibiotics administration would have decreased by almost 88%. Review bottom of slide. 408/430 (95%) of patients received only 48 hrs of antibiotics 22 patients received Abx ≥ 7 days duration for suspected/Culture NEG Sepsis 4 “well appearing” 2 “equivocal” based on exam 16 “Positive clinical illness” signs/symptoms 1/455 (0.22%) positive Blood Cultures- (+GBS) This patient Risk Score= 7.85/1000 based on clinical picture at admission 6 other POS blood cultures due to contaminant- (CONS or Micrococcus)

Shakib et al. Study Conclusions:
Finally, they analyzed the complete risk stratification including both maternal and newborn exam. Here you can see that 88% of the babies would have been identified “green” and would have been placed in the continued observation group in the top left corner box. About 7% of the babies would have fallen within the observe and evaluate group “yellow” group. And around 39 babies, or 5% of the group would have been identified as significantly increased risk “red” categorization and would have requirement empiric treatment. The conclusions of their study were: Study Conclusions: The EOS risk in well-appearing newborns of mothers with chorioamnionitis is low. Applying a strategy based on readily obtainable measures rather than the obstetrical diagnosis of chorioamnionitis would result in substantial reduction of newborns undergoing lab tests and being exposed to antibiotics.

2 “Chorio” Patients- Revisited
Baby A 41 wks 1 days EGA Maternal Fever- 38.3˚C ROM- 15 GBS neg Mom received broad spectrum Abx > 4 hrs to delivery Baby B 41 wks 1 days EGA Maternal Fever- 39.4˚C ROM- 18 GBS neg Mom received no Abx prior to delivery So, getting back to the 2 patients I discussed in the beginning of the presentation; lets score them using the sepsis risk calculator. SRS: maternal risk factors 0.47/1000 live births +Well appearing 0.19/1000 live births SRS: maternal risk factors 9.15/1000 live births +Well appearing 3.77/1000 live births

Christiana Care NICU Admissions
778 admissions for evaluation of EOS Jan 1st- Dec 31st, 2015: 125/778 (16%) for maternal chorioamnionitis 1 excluded from analysis for congenital anomalies Maternal Temp- mean= 38.5°C ( ) EGA- mean= 39 6/7 weeks (34 1/7-41 2/7) ROM- mean= 17 hrs (0-82) GBS Status POS- 23/124 (19%) NEG- 95/124 (77%) UNK- 6/124 (5%) Antibiotics Not given > 2 hrs prior to delivery 65/124 (52%) Length of Stay- mode= 3 days (2-9) Length of Abx- mode= 2 days (2-7) 5/124 (4%) patients received extended antibiotics for > 48hrs due to: Increased WOB/Fio2 requirement in 1st 24 HOL; +WBC shifted >20% Lethargic/low temps at 12HOL, Ecoli POS Mom Bl Cx; +WBC shifted >20% MAS/PPHN, transfer to AIDHC MAS/Fio2 requirement, +CXR changes, +WBC shifted >20% MAS only- 5 days abx Symptoms on admission: YES- 32/124 (25%), NO- 92/124 (75%) * 5/32 (16%) HIE; wks w/ low temp; 1- SGA with hypoglycemia; remainder all respiratory symptoms Blood Culture POS- 0/124 Sepsis Calculator Score: Green- 40/124 (32%) Yellow and well appearing- 51/124 (41%) Red- 33/124 (26%) Nutrition/IVFs: IV Fluids- 32/124 (25%), 3 were asymptomatic and exclusive MBM (ie: IVFs over Formula) Formula only- 4/124 (3%) MBM only- 9/124 (7%) MBM and Formula- 81/124 (65%) IV Infiltrates: 11 total events in 9/124 (7%) patients As part of the sepsis calculator working group we’ve put together here at Christiana, I retrospectively looked at all of our NICU admissions for chorio/Early onset sepsis from 2015. Review the slide

Christiana Care NICU Admissions
x40 “Green” 3 stayed in ICN > 2-3 days (Abx, Temps, IDM/gluc) 1 developed symptoms in 1st 24HOL (WOB/Fio2)+>20% shift 7 days Abx x51 “Yellow” and well appearing 1 with TTN for < 4 hrs which cleared All discharged home after 2-3 days x33 “Red” 3/33 (9%) ≥5 days Abx Length of Stay- mode 3 days (2-9) Placental Path C/w Chorio- No Chorio- 26/124 (21%) POS Chorio- 84/124 (68%) No results- 14/124 (11%) Review slide.

Graphic Display of Chorio Admissions
Review graph.

OB Change of Current Care
Jan 2015 Eunice Kennedy Shriver NICHD Expert Panel Addressed knowledge gaps Developed EBM guidelines for the diagnosis and management of pregnant women “Triple I”- Intrauterine inflammation or Infection or Both Now that I’ve reviewed the past to current trends in the data both nationally and locally on chorioamnionitis and neonates, its important to briefly review the direction that Christiana OB is going regarding the maternal diagnosis of chorio. In 2015, a NICHD expert panel convened to address the knowledge gaps in chorio and to develop guidelines. This is now being referred to with an acronym Triple I. *Higgins RD, Saade G, Polin RA, Grobman WA, Buhimschi IA, Watterberg K, Silver RM, Raju TN. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstet Gynecol 2016 Mar;127(3):

Triple I for Mom They categorize Triple I in 3 different groups, with the emphasis of acknowledging that not all fevers are associated with an intrauterine infection. Review the features. *Higgins et al. 2016

Triple I recs for Baby From NIHCD expert workshop by Higgins, a recommendation was made for the management of babies born to mothers with either isolated fever or Triple I. This figure from that publication highlights the strategy they recommend. Additionally, the expert panel recommended the use of the Sepsic Calculator in the decision to treat or not treat babies with maternal suspected Triple I. An additional highlight of the panel was that the well appearing neonate can have ongoing evaluation in the regular nursery or mother baby unit. The group commented that some newborns will initially be symptomatic immediately after birth and will become asymptomatic over the ensuing 4-6 hours. These transitional symptomatic babies were deemed to be otherwise healthy well appearing giving the rapid resolution of any equivocal exam findings for the brief period of time after birth. *Higgins et al. 2016

Canadian Paediatric Society- 2007
The well-appearing infant of a mother with possible chorioamnionitis requires only a limited diagnostic evaluation (screening CBC and close observation) for sepsis. (evidence level 2b, recommendation grade B) If a CBC reveals a total WBC count less than 5000, full diagnostic evaluation and empirical antibiotic therapy should be considered (evidence level 2b, recommendation grade B) Sited studies mentioned: “Abnormal CBC” PPV of 1.5% in well appearing term infants Highest PPV value is that of a low total WBC < If present, likelihood ratio is (post-test probability for sepsis of 10-20%) Some studies show only 22-44% of infants with sepsis will have a such a low total WBC. Finally, I wanted to review the work of a Canadian expert panel that convened in 2007 to publish a statement and guidelines for the management and evaluation of early onset sepsis in newborns. These are their recommendations. Of note, they did review the evidence of CBCs in screening for sepsis. They made recommendations regarding this review and emphasized caution with regard to the interpretation of CBCs and clinical management of neonates. Further more, their recommendations did not mention timing of the screening CBC and whether they feel it is best to obtain this lab study later in the first 24 hours of life.

Sepsis Calculator: Who’s using it?
Kaiser Permanente System, CA- 14 hospitals Pennsylvania Hospital University of Rochester Medical Center … more coming on line

Peds Change to Current Care
Proposal: Asymptomatic “maternal chorio” ≥35 wks-term infants. Undergo risk stratification screening using the KP Sepsis Calculator. Primary Pediatrician notified of risk stratification and plan of care “Green and Yellow/well appearing” infants admitted to late-term or term nursery based on gestational age. Consideration for observing infant in NICU for 4 hours if “equivocal” exam/signs Blood culture may be drawn prior to transfer from L&D if recommended by Calculator Frequent assessment/vital sign monitoring by nursery RN All symptomatic infants will be admitted to NICU From this data that I’ve presented thus far, we arrive at our current proposal to change the care of babies born to mothers with chorioamnionitis here at Christiana Care.

Working Draft Pathway: Patient Flow, Personnel, Location
#1- Mother has fever ≥ 38˚ C #2- L&D nursing notifies DR Peds Team if infection suspected #3- DR Peds Team is present for delivery if infection suspected #4- DR Peds Team assess infant if ? clinical stability #5- L&D RN and/or DR Peds Team will use the Sepsis Calculator to risk stratify the patient. #6- DR Peds Team will notify the patient’s pediatrician/CPH of the plan of care and risk stratification. “Green” babies will receive standard care and monitoring  remain with mother. Vitals Q4hr per 3rd-4th fl unit protocol “Yellow” Well appearing/Asymptomatic babies will receive Q4h Vital Signs assessment in post-partum and 3rd-4th fl/nursery. If babies are stable, but warrant blood culture obtainment, this will be performed by the DR Peds Team in L&D or Post-partum. If the patient develops equivocal or concerning symptoms in Post-partum/Nursery/3rd-4th fl, NICU will be notified for determination of admission. Symptomatic/Equivocal “Yellow” babies will be brought to the NICU for OBS. If after 4 hrs of OBS, the baby is deemed to be stable  transfer to post-partum/Nursery/3rd-4th fl for ongoing Q4hr vital signs assessment. If the baby is deemed unstable Admit to NICU. “Red” babies will be admitted to the NICU. This is outdated version and pathway development slide. Do not refer to this for future pathway.

Targeted Education L&D/Post-partum/3rd-4th floor Nursing
Familiarization with Pathway Vital signs monitoring NICU Transport and Charge Nursing L&D nursing, DR Peds Team (NNPs, Residents, Fellows, Neos) Application of the KP Sepsis Calculator for Risk Stratification Private Pediatricians and CPH Process Implementation OB Physicians/PAs/mid-wives

Key Members of Working Group
John Stefano, MD- neonatology Drew Ellefson, MD- neonatology Deborah Tuttle, MD- neonatology Janette Marston-Nelson, MD- CPH Karen Haritakis- ICN Nursing Susan Foster- ICN Nursing Elizabeth Igboechi- L&D/Post-partum Nursing Cheryl Swift- L&D Nursing Educator Mary Stirparo- 3B/Maternity Nursing Kathy Simpson- Education Counsel Andrea Miller, DO- Neo Fellow

Conclusion Evidence strongly supports modifying how we manage babies born to mothers with chorio by using a more EBM approach. Emphasis should be on the neonatal clinical exam and maternal risk factors as a whole, not isolated factors taken separately. Advancement of neonatal care is coming to Christiana Care…

CBC and Evaluation of EOS

Revised Neonatal Management Algorithm
Applies to all newborns born to mothers with “chorio” Regardless of whether mother received IAP Management based on clinical appearance, risk factors (maternal chorioamnionitis, prolonged rupture of membranes, preterm), and adequacy of IAP if indicated for mother Adequate IAP clarified ≥4 hours of IV penicillin, ampicillin, or cefazolin before delivery All other agents or durations are considered inadequate for purposes of neonatal management Aims to reduce unnecessary evaluations and antibiotics in newborns at relatively low risk for early-onset GBS disease The revised neonatal management algorithm applies to all newborns, regardless of whether mother received IAP Management is based on clinical appearance, risk factors (maternal chorioamnionitis, prolonged rupture of membranes, preterm), and adequacy of IAP if indicated for mother The definition of adequate IAP is clarified as ≥4 hours of IV penicillin, ampicillin, or cefazolin before delivery. All other agents or durations are considered inadequate for purposes of neonatal management. This is because there are no data from clinical trials, observational studies, or pharmacokinetics studies available that show that intrapartum prophylaxis with other agents is effective in preventing early-onset GBS disease. In contrast, data are available for penicillin, ampicillin, and cefazolin indicating their effectiveness in preventing early-onset GBS disease. The revised algorithms aims to reduce unnecessary evaluations and antibiotics in newborns at relatively low risk for early-onset GBS disease

COFN Impact on Clinical Care
Kiser et al 2014 Retrospective chart review 96% of infants admitted for EOS work-up we were appearing at birth 20.2% of infants received Abx ≥7 days solely on the basis of abnormal lab data

Failure Mode Effects Analysis
Process Step Potential Failure Mode #1- Mother is diagnosed with Chorioamnionitis #2- L&D nursing notifies DR Peds Team #3- DR Peds Team is present for delivery #4- DR Peds Team assess infant for clinical stability #5- DR Peds Team will use the Sepsis Calculator to risk stratify the patient. #6- DR Peds Team will notify the patient’s pediatrician or CPH of the plan of care and risk stratification. Mother is not correctly diagnosed with chorio. Peds is not notified about maternal chorio. Peds is not present for delivery. Peds miss-identifies patient as stable. Sepsis Calculator risk stratification underestimates true risk. Pediatrician does not accept plan of care. Patient with sepsis is stable at first, but becomes unstable in nursery. Patient does not receive appropriate frequency of VS checks. Patient develops symptoms after the first 24 hours of increased VS checks. Slide not intended as reference for education purposes. It only reflect historic development of pathway.

Andrew M. Ellefson, MD Neonatologist Christiana Care Health System

Similar presentations

Presentation on theme: "Andrew M. Ellefson, MD Neonatologist Christiana Care Health System"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Andrew M. Ellefson, MD Neonatologist Christiana Care Health System

Similar presentations

Presentation on theme: "Andrew M. Ellefson, MD Neonatologist Christiana Care Health System"— Presentation transcript:

Similar presentations

About project

Feedback