Intraamniotic Infection/Inflammation

or

ChorioamnionitisSarah Belensky, MD

High Risk OB Fellow at Swedish First Hill Medical Center

My passions

Rural and international communities

Outdoors and exercising

Healthy living and wholeness

Objectives

Define and characterize IAI

Discuss options in treatment

Discuss care for newborns of mothers with IAI

Your patient

23 year old G1 originally from Mexico at 40 weeks and 5 days with PROM ->

Pitocin ->

Complete + 45 minutes of pushing ->

Fever of 102.2 + FHR of 170bpm ->

Unasyn and Tylenol ->

Two more hours of pushing -> SVD of well-appearing male infant.

ROM to delivery = 30hrs

Name Controversy

Triple I

IAI = Intraamniotic Infection/Inflammation

Chorioamnionitis

Maternal fever

Per ACOG’s March 2016 workshop summary - Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis

Isolated maternal fever

>39°C = 102.2°F once

>38°C = 100.4°F twice

Maternal fever

Consider alternative causes:

epidural

dehydration

hyperthyroidism

elevated ambient temperature

use of prostaglandins for induction

Suspected IAI

Fever without a source +

Wbc >15,000 (w/o steroids)

Fetal tachycardia >160bpm

Purulent fluid from os

Confirmed IAI

Suspected triple I +

Amniotic fluid Gram stain + for bacteria or high wbc (>30cells/mm^3)

Pathology confirmation in placenta, fetal membranes or cord

Mechanism

Migration of bacteria in vagina and cervix

through ruptured membranes

Diagnosis

Gold standard = amniotic fluid culture (takes 24-48hrs)

Markers of infection

IL-6 specificity 83%

MMP-8 60%

MMP-9 100%

MMP-9 + IL-6 100%

Organisms involved

Genital mycoplasmas

ureaplasma, mycoplasma hominis

GBS

E coli

Anaerobes

Prevalence

Clinical vs histologic (2014 Cochrane)

Clinical: 1-2% term 5-10% preterm

Histologic: 20% term 50% preterm

Maternal morbidity

C/S 2-3x

Infection

endomyometritis

pelvic abscess

wound infection

bacteremia 3-4x

(18% of maternal sepsis associated with IAI)

PPH 3-4x

Risk Factors

<18 years

non-Caucasian

primiparous

singleton

induction

prolonged or premature ROM

Risk Factors

1995 retrospective case-control study of 3109 patients published in ACOG

epidural

prolonged ROM (>24hrs)

long duration of labor (latent phase >8hrs)

Are cervical exams introducing vaginal flora into upper genital tract?

Cervical Exams?

7.2% developed intrapartum fever

Number of exams not associated

Even subanalyzing for rupture of membranes and labor type

Previous studies with high risk PROM pts

Increased duration of labor is likely underlying the association found in previous studies

Epidural Use

8% of patients with epidural developed IAI, 1% without

Epidural use was statistically associated with increased risk of IAI

Increased labor duration was highly associated with epidural use (OR 23)

Amnioinfusion for chorio?

Insufficient evidence based on August 2016 Cochrane Database Systematic Review

One small trial with 34 participants compared women already receiving antibiotics.

No decreased neonatal infection or postpartum

endometritis

Chorio an indication for C/S?

C/S does not routinely improve clinical outcomes in IAI

Antibiotic treatment

Goal = cover for anaerobes and beta-lactamase-producing aerobes

Ampicillin + gentamicin

Ampicillin + gentamicin + clindamycin

Ampicillin/sulfabactam

Cefotetan or cefoxitin (2nd gen)

Add clinda for C/S to cover anerobes

Duration of therapy

24hrs afebrile?

One postpartum dose?

No postpartum doses?

Continue on oral antibiotics?

Quench the fire?

Maternal fever + cord acidosis -> increased risk of encephalopathy

Tylenol

Preterm neonates

IAI associated with 50% of preterm deliveries

Accounts for 70% of perinatal deaths, 50% neurologic morbidity

Higher neonatal mortality - 1.4/1000 of infants with chorio vs 0.8/1000

Inflammation-induced white matter injury

Neonatal infection

Early onset sepsis = a leading cause of death

EOS incidence = ~1 in 1000 (0.061% vs 0.077% vs 0.098%)

A 2010 RCS showed EOS risk in IAI of 4 in 1000

IAI = 8.7 fold higher risk

IAI is associated with 40% of EOS

E coli and GBS

Neonatal mortality

2008 analysis of 2.28 million births at 37-42 weeks in US from birth and death certificate files revealed…

IAI prevalence was 0.97%.

In other studies rates up to 5%

Neonatal mortality rate for exposed infants was 0.14%

(vs 0.081% w/o chorio)

Mechanism

Mechanisms: altered BBB, endothelial damage, etc.

Infection exposure in utero stimulates fetal inflammatory response

Bronchopulmonary dysplasia

Periventricular leukomalasia

IVH

CDC+AAP+NIH Guidelines

From: “Prevention of perinatal group B streptococcal disease: revised guidelines from CDC 2010” in the Morbidity and Mortality Weekly Report (MMWR)

Empiric broad spectrum antibiotics +

Labs

blood cx

cbc with differential

+/- crp

Impact of maternal antibiotics

Start upon diagnosis!

2011 study including 400,000 infants: Intrapartum abx to women with chorioreduced risk of EOS by 82%.

In 1980s, EOS rate in IAI was 80-200/1000

Now 1-5/1000

Widespread GBS screening

Maternal and infant characteristics based on clinical chorioamnionitis statusCharacteristics No CAM

29,869CAM[a]1,243

p Value

Gestational age in wks, mean (SD)

38.9 (1.35) 39.3 (1.27) < 0.001

Highest temperature, °F, median (range)

98.8 (95.5, 105.0) 101.2 (96.8, 105.1) < 0.001

Maternal vaginal GBS

GBS test not done 3,468 (11.6) 52 (4.2) < 0.001

GBS test done 26,401 (88.4) 1,191 (95.8) < 0.001

Test positive 4,879 (16.3) 167 (13.4) 0.007

Intrapartum antibiotics

Overall 13,768 (46.1) 1,229 (98.9) < 0.001

GBS-positive mothers 4,306 (88.3) 165 (98.8) < 0.001

Neonatal infection and antibiotic treatment

Culture positive 14 (0.05) 5 (0.4) < 0.001

Mother received intrapartum antibiotics

6 (42.9) 5 (100)

Culture negative, antibiotics ≥ 5 days

211 (0.7) 42 (3.4) < 0.001

Mother received intrapartum antibiotics

133 (63.0) 42 (100)

Culture negative, antibiotics < 5 days

1,043 (3.5) 318 (25.6) < 0.001

Mother received intrapartum antibiotics

723 (69.3) 316 (99.4)

Serial Physical Exams

World Journal of Pediatrics: Multicenter retrospective cohort study over 4 months evaluated 2092 asymptomatic neonates >35 wks with 216 initially managed with SPEs

32 of the neonates were intrapartum fever/chorio-exposed

21.8% had signs of illness

62.5% had sepsis w/u

21.9% were given empirical antibiotics

Serial Physical Exams in IAI

All had a normal outcome and none had culture-proven sepsis

Standard intervals – 3/6/12/18/36/48 hrs

Standard forms: clinical appearance

However, 22% of term infants with EOS born to chorio mothers are asymptomatic at 72hrs of life

None of these infants died

According to an RCS of 400,000 infants with 81 cases of EOS in term infants, 22% had no clinical symptoms at 72 hours

Neonatal clinical signs of illness

Temp out side range 36.5-37.5 (rectal)

Pallor

Cyanosis

Lethargy

Irritability

Respiratory distress

Apnea

Concerning rash

Hypoglycemia

Physical exam + risk calculator

2015 Academy of Pediatrics: 698 well-appearing newborns >34 weeks born to chorio mothers.

One had culture positive EOS.

65% received lab tests+abx therapy

But EOS calculator and clinical appearance would lower lab tests+abxtherapy to 12% without missing any cases.

Newborn Sepsis Calculator

http://newbornsepsiscalculator.org/

Prevalence of culture-positive sepsis was 0.058%

Concerns

Labs

15% with abnormal I/T

22% with abnormal crp

0.7% with positive blood culture

21.6% underwent lumbar puncture

= Large numbers of chorio-exposed infants were treated with prolonged abx therapy due to abnormal labs alone.

Concerns

Most studies included in CDC guidelines were before widespread GBS screening

Neonatal risks with antibiotics:

exposure to MDR bacteria

attachment and breastfeeding issues

altered gut flora

Concerns

How many newborns would need labs and antibiotics to detect an infant with EOS?

NNT = 60-1400

To prevent death -> NNT = 1785

Treating all infants for 48hrs with abx in NICU = $$$

Back to your patient… 23 year old G1 from

Mexico at 40 weeks 5 days with PROM ->

Pitocin ->

Complete + 45 minutes of pushing ->

Fever of 102.2 + FHR of 170bpm ->

Unasyn and Tylenol ->

Two more hours of pushing -> SVD

ROM to delivery = 30hrs

What should we do with baby?

The bottom line for babies

Early onset sepsis rate is 0.5 to 1 in 1000

IAI increases this risk by 4-8 times

Neonatal morbidity is about 8 in 10,000

IAI doubles this risk

Labs, 48hr NICU stay and antibiotics are standard of care

Clinicians worldwide are questioning if a kinder, gentler approach is reasonable

Utilizing the sepsis calculator, serial physical exams and limited work up is one possible solution

Discussion with patient

Use neonatal sepsis calculator

Consider staff capabilities, ease of transfer

Discuss risks vs benefits of standard Abx+labs+NICU stay

Take home points for IAI care

Correctly establish diagnosis

Start antibiotics once diagnosis established

Provide optimum care for newborns of mothers diagnosed with IAI

References

Herbst A, Wølner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol 1995; 86 (5) 790-794

Alison G. Cahill, MD, MSCI, Cassandra R. Duffy, MD, MPH, Anthony O. Odibo, MD, MSCE, Kimberly A. Roehl, MPH, Qiuhong Zhao, MS, and George A. Macones, MD, MSCE. Number of Cervical Examinations and Risk of Intrapartum Maternal Fever. ACOG VOL. 119, NO. 6, JUNE 2012.

Fishman SG, Gelber SE. Chorioamnionitis. Seminars in Fetal and Neonatal Medicine. 2012; 17 (1) 46-50.

Safe Prevention of the Primary Cesarean Delivery. ACOG Obstetric Care Consensus March 2014

Adi Abramovici, Jeff Szychowski, Joseph Biggio, Yasser Sakawi, William Andrews, Alan TN Tita. Epidural Use and Clinical Chorioamnionitis among Women Who Delivered Vaginally. Amer J Perinatol 2014; 31(11): 1009-1014

Gibbs RS1, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol. 1991 May;164(5 Pt 1):1317-26.

Hofmeyr GJ1, Kiiza JA. Cochrane Database Syst Rev. Amnioinfusion for chorioamnionitis. 2016 Aug 24;(8):CD011622. doi: 10.1002/14651858.CD011622.pub2.

Chapman E1, Reveiz L, Illanes E, Bonfill Cosp X. Cochrane Database Syst Rev. Antibiotic regimens for management of intra-amniotic infection. 2014 Dec 19;(12):CD010976. doi: 10.1002/14651858.CD010976.pub2.

Impey LW, Greenwood CE, Black RS, Yeh PS, Sheil O, Doyle P. The relationship between intrapartum maternal fever and neonatal acidosis as risk factors for neonatal encephalopathy. Am J Obstet Gynecol. 2008;198(1):49.e1.

Soraisham, Amuchou; Singhal, Nalini; McMilan, Doug; Sauve, Reg; Lee, Shoo. A Multicenter Study on the Clinical Outcome of Chorioamnionitis in Preterm Infants. AJOG. Volume 200, Issue 4, pgs 372 e1-372.e6

Boardman. Association between preterm birth injury and exposure to chorioamnionitis during fetal life.

References

Berardi, Alberto; Buffagni; Rossi, Cecilia; Vaccina, Eleonora; Cattelini, Chiara; Gambini, Lucia; Baccillieri, Federica; Varioli, Francesca; Ferrari, Fabrizio. Serial physical examinations, a simple and reliable tool for managing neonates at risk for early-onset sepsis. World Journal of Clinical Pediatrics. November 8, 2016. 5(4): 358-364.

Brady, Michael; Polin, Richard. Prevention and management of infants with suspected or proven neonatal sepsis. Pediatrics. Pediatrics 2013; 132;166.

Devasuda Anblagan, Rozalia Pataky, Margaret J. Evans, Emma J. Telford, Ahmed Serag, Sarah SparrowChinthikaPiyasenaScott I. SempleAlastair Graham WilkinsonMark E. BastinJames P. Malloy MH. Chorioamnionitis: epidemiology of newborn management and outcome United States 2008. J Perinatol. 2014 Aug;34(8):611-5.

James A. Taylor, Douglas J. Opel. Pediatrics. Choriophobia: A 1-Act Play. August 2012, VOLUME 130 / ISSUE 2.

Higgins, Rosemary, Saade, George, Polin, Richard; Grobman, William; Buhimschi, Irina; Watterberg, Kristi; Silver, Robert; Raju, Tonse. Evaluation and Management of Women and Newborns with a Maternal Diagnosis of Chorioamnionitis. ACOG Vol 127, No 3, March 2016.

Stephanie D. Reilly, Ona M. Faye-Petersen. Chorioamnionitis and Funisitis. NeoReviews Sep 2008, 9 (9) e411-e417; DOI: 10.1542/neo.9-9-e411

Shakib J, Buchi K, Smith E, Young PC. Management of newborns born to mothers with chorioamnionitis: is it time for a kinder, gentler approach? Acad Pediatr. 2015 May-Jun;15(3):340-4. doi: 10.1016/j.acap.2014.11.007.

References

Kiser C, Nawab U, McKenna K, Aghai ZH. Role of guidelines on length of therapy in chorioamnionitis and neonatal sepsis. Pediatrics. 2014 Jun;133(6):992-8. doi: 10.1542/peds.2013-2927.

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):256–263

Van Dyke MK, Phares CR, Lynfield R, et al. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med. 2009;360(25):2626–2636

Stoll BJ, Hansen NI, Sánchez PJ, 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;127(5):817–826

Braun D, Bromberger P, Ho N, Getahun D. Low Rate of Perinatal Sepsis in Term Infants of Mothers with Chorioamnionitis. American Jounal of Perinatology 2016; 33(02): 143-150.

Wortham JM, Hansen NI, Schrag SJ, Hale E, Van Meurs K, Sánchez PJ, Cantey JB, Faix R, Poindexter B, Goldberg R, Bizzarro M, Frantz I, Das A, Benitz WE, Shane AL, Higgins R, Stoll BJ; Eunice Kennedy Shriver NICHD Neonatal Research Network. Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-2323. Epub 2015 Dec 30.

Image references

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http://www.nandanursingdiagnosislist.org/newborn-nursing-diagnosis/

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http://www.aocr.org/page/z67