Maternal Fever & What it Means for Baby: A Changing Definition Andrew M. Ellefson, MD Neonatologist Christiana Care Health System Edited by Cem Soykan, MD Pediatric Hospitalist at CCHS

Background & Definitions Maternal Chorioamnionitis A sometimes vague term with flexible definitions that is applied fairly inconsistently to mother’s with varying degrees of fever during the peripartum period. “Triple I” = Intrauterine Inflammation and/or Infection “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 T.I.M.E. = Triple I to Manage Early-onset Sepsis: *** Our new protocol for these babies ***

Issues with Current CDC/COFN Guidelines Many of the references supporting IV abx for all infants of mothers with chorioamnionitis include data before widespread GBS screening implementation1 GBS screening has reduced incidence of Early Onset Sepsis (EOS) due to GBS by 80% to rate of 0.34-0.37/1000 term newborns2 Early Onset Sepsis 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. 2012 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, 2010. 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. 2011 May;127(5):817-26.

Impact of “R/O Sepsis - Chorio” Admissions Asymptomatic Infant admitted for 48 hrs to NICU: 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 prolonged antibiotic use due to “culture negative sepsis” 2nd to non-specific CBC lab abnormalities Weaning off of IVF’s 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 ~ $86,000-129,000/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 “chorioamnionitis” by using a more EBM approach. Emphasis should be on: Neonatal clinical exam Maternal risk factors NOT isolated factors taken separately. Recommend: Discontinue use of the term chorioamnionitis Start using the term “intrauterine inflammation or infection or both” (A.K.A. “Triple I”) *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.

The Newborn Sepsis Calculator Kaiser Permanente study looked at the genuine need for antibiotics in setting of maternal fever They found the following things were most crucial in determining risk Gestational Age Tmax of the fever Duration of ROM GBS status Antibiotic treatment

The Newborn Sepsis Calculator: Results / Output Kaiser Permanente then found a way to risk stratify the kids. Based on the clinical exams, there were 3 different potential courses of action to be pursued: No additional care (= q4h VS here @ CCHS) CBC, Blood culture & VS q4 hours x48 hours Admit to NICU for empiric Antibiotics www.newbornsepsiscalculator.org

Newborn Clinical Exam – Definitions Well Appearing No persistent physiologic abnormalities Equivocal Exam Any ONE Persistent Physiologic Abnormalities for ≥4 hours Tachycardia (≥160) Tachypnea (≥60) Temperature Instability - Fever (≥100.4°F [≥ 38°C]) Temperature Instability – Hypothermia (< 97.5°F [<36.3°C]) Respiratory Distress (grunting, flaring, retracting) without O2 needs OR Any TWO or MORE Physiologic Abnormality Lasting ≥2 hours See above list again Note physiologic abnormalities can be intermittent & still count

Newborn Clinical Exam – Definitions Clinical Illness Simply PUT = Everything worse than Equivocal Exam, but defined below: O2 Supplementation (outside of the delivery room) Need for supplemental O2 for ≥2 hours to maintain oxygen saturation >90% Respiratory Support (outside of the delivery room) Persistent need for Nasal CPAP Persistent need for High Flow Nasal Canula or Persistent need for mechanical ventilation Blood Pressure Support Hemodynamic instability requiring vasoactive drugs Neonatal encephalopathy/ Perinatal depression Apgar Score of <5 @ 5 minutes Seizure

Triple I to Manage Early-Onset Sepsis T.I.M.E. The New Process at CCHS Andrew M. Ellefson, MD Neonatologist Christiana Care Health System Edited by Cem Soykan, MD Pediatric Hospitalist at CCHS

L&D Nurse Responsibilities The Powerform: Neonatal Sepsis Calculator A mother with fever ≥38˚ C delivers a baby. L&D Nurse gets a notification in PowerChart when she opens the baby’s chart. L&D Nurse must complete the “Neonatal Sepsis Calculator” Powerform L&D Nurse must notify Pediatric DR provider

DR Provider Responsibilities The Alerts we will get Open Baby’s Chart Review Nursing portion & complete their portion of the “Neonatal Sepsis Calculator” Powerform Call/Notify PMD of baby’s status Does NOT have to examine the baby, but may be asked to if any other concerns Peds/DR Provider clicks on Neonatal Sepsis Calculator Form Should already be filled in by L&D Nurse

Scenario Questions & IMPORTANT Points Stable baby (even with normal transitional physiology - comfortable tachypnea) 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, require 2-4 hours of persistent symptoms. Therefore, a comfortably tachypneic baby at 1 HOL may simply be demonstrating transitional physiology When the mother is ready for transfer to Well Baby floor, only “Well Appearing” babies are cleared for co-transfer to Well Baby floor. At the time of maternal transfer, any baby with ongoing transitional physiologic abnormalities, or any sign of distress must go to the NICU (Equivocal & Clinical Illness Babies) 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 attending about the baby’s Sepsis Calculator recommendations & disposition. Ensure proper provider-physician hand off. The L&D nurse must also report this information in their handoff to post-partum nursing.

Newborn Physician & Postpartum Nurse Alerts Occurs the 1st time each & every Nurse or Provider opens the baby’s chart on the Well Baby unit Reminds Well Baby Nurse and Physician Providers to review the Neonate Sepsis Calculator Form document.

Where to Find the Sepsis Calculator Recommendations in Baby’s Chart

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

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