Early Recognition of Sepsis

in Pregnancy
Malavika Prabhu, MD
Maternal Fetal Medicine, Massachusetts General Hospital
Assistant Professor, Harvard Medical School
Boston, MA

May 6, 2024
Disclosures

• Member of the Alliance for Innovation on Maternal Health (AIM)’s Sepsis in Obstetric Care Bundle

• Section Editor at UpToDate

• Consultant, BabyList Inc

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Learning Objectives

1. Epidemiology of maternal sepsis

2. Etiologies of maternal sepsis

3. Recognizing maternal sepsis

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Background
Puerperal sepsis & Ignaz Semmelweiss

• Vienna, 1840s: childbed fever incidence higher in physician patients

than midwife patients
• Cause: Pyemia
• Solution: Handwashing
• Mortality dropped from 18% to 2.5%

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Sepsis over the last 200 years

2023: Sepsis in
1914: Sepsis 1992: SEPSIS-1, Obstetric Care
defined SIRS defined Bundle

1928: Penicillin 2016: SEPSIS-3,

discovered SIRS abandoned

1914: “Sepsis is present if a focus has developed from which pathogenic bacteria, constantly or
periodically, invade the bloodstream in such a way that this causes subjective and objective symptoms.”
(Dr. Hugo Schottmuller)

2016: “Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to

infection.” (SEPSIS-3)

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Maternal sepsis – Pregnancy Mortality Surveillance System

www.cdc.gov 7
Maternal sepsis
National burden: 13-14% of maternal deaths attributable to sepsis
‒ 1 in 3,000-4,000 deliveries à 1 in 1,000 deliveries (2016-2020)
‒ 50% of peripartum sepsis hospitalizations are readmissions after delivery (14 days postpartum)
‒ Sepsis readmissions account for 45% of all maternal deaths due to sepsis
§ 8% of all PP readmissions due to sepsis
‒ Sepsis-related deaths: 1-2 in 100,000 deliveries
§ Delivery associated sepsis à 24% maternal death
§ PP readmission associated sepsis à 38% maternal death
‒ Undercounting likely

AJOG 2019; 220: 391.e1; AJOG MFM 2020; doi 100149; Anesth Analg 2013; 117: 944; 8
JAMA 2019; 322: 890; Obstet Gynecol 2017; 130: 366; Obstet Gynecol 2024;143; 345
Maternal sepsis
Risk factors for maternal sepsis
‒ Medicaid/Medicare insurance
‒ Retained products of conception
‒ Preterm premature rupture of membranes
‒ Cerclage
‒ Cesarean delivery
‒ Chronic medical conditions
‒ Exposure to systemic racism

Most cases of sepsis occur in the absence of risk factors

AJOG 2019; 220: 391.e1; AJOG MFM 2020; doi 100149; Anesth Analg 2013; 117: 944; 9
JAMA 2019; 322: 890; Obstet Gynecol 2017; 130: 366; Obstet Gynecol 2024;143; 345
Disparities in maternal sepsis

Sepsis incidence by race/ethnicity during delivery hospitalization

• White: 1.9 per 10,000 deliveries
• Black: 4.6 per 10,000 deliveries
• Hispanic: 2.2 per 10,000 deliveries
• Asian/Pacific Islander: 2.9 per 10,000 deliveries
• Native American: 3.4 per 10,000 deliveries
• No differences in mortality

Incidence and mortality by race/ethnicity during postpartum readmission for sepsis – data are limited

AJOG 2019: 220; 391.e1 10

Maternal sepsis
Sepsis associated morbidities
• Chronic kidney disease
• Chronic heart disease
• Amputation
• Infertility (hysterectomy)
• PICS/post sepsis syndrome
‒ Trauma, impaired cognition, PTSD, panic attacks, depression, anxiety
• Potential consequences of prematurity

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Causes of Maternal
Sepsis
Etiologies
• Uterus:
‒ Septic abortion
‒ Chorioamnionitis
‒ Endometritis

• Wound post-delivery:
‒ Necrotizing fasciitis
‒ Pelvic abscess

• Other sources:
‒ Pyelonephritis
‒ Influenza, COVID-19, Pneumonia
‒ Appendicitis / cholecystitis
‒ Mastitis
‒ Endocarditis, meningitis

Obstet Gynecol 2021; 138: 289 13

Bacterial causes

• Culture negative sepsis occurs in at least 15-

20% of cases
• Viral sepsis syndrome
• Influenza
• COVID-19
• Bacteremia associated with later
prematurity and/or pregnancy loss
(miscarriage, stillbirth)

Anes Analg 2013;117: 944 14

Diagnosing Sepsis
What Is Sepsis?

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Pregnancy or sepsis?

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Pregnancy versus pregnancy AND sepsis
Pregnancy Pregnancy + Sepsis
• ↓ SVR • Endothelial damage → ↓↓ SVR → acute collapse

• ↓ albumin • ↑ susceptibility to pulmonary edema

• Mild compensatory metabolic • ↓ buffer for acidosis of sepsis

acidosis

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Maternal sepsis

40-60% of sepsis-related deaths were preventable in statewide inquiries of

maternal mortality

Obstet Gynecol 2015; 126: 747; BJOG 2011;

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118: 1; Obstet Gynecol 2005; 106: 1228
Vital signs: SIRS criteria
Normal Heart Rate in Pregnancy Normal Respiratory Rate in Pregnancy

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Biomarkers: Lactate
Lactate
‒ Normal < 2mmol/L outside of pregnancy
‒ In pregnancy, OUTSIDE of labor, normal < 2
mmol/L
‒ In labor, normal overlaps with 2 mmol/L
‒ In the second stage of labor, lactate can
exceed 4 mmol/L
§ Values < 2 are reassuring
§ Serial follow–up indicated if patient is
clinically unwell
‒ Postpartum – poorly defined, but high risk
time

Am J Perinatol 2019; 36: 898; Clin Chim 21

Acta 2021; 513: 13; IJGO 2023;164: 484
Biomarkers: Procalcitonin

Procalcitonin
‒ Utility of procalcitonin to identify or manage sepsis unknown in pregnancy
‒ Originally a marker to guide antibiotic therapy for lower respiratory tract infections à expanded to
direct antibiotic therapy in sepsis
‒ Generally accepted cutoff 0.2-0.25 ng/mL
‒ Recent meta-analysis found
§ Procalcitonin levels normal in healthy pregnant women
§ Procalcitonin levels may be elevated during normal labor
‒ Many unanswered questions
§ Impact of comorbidities, preeclampsia, labor?
§ Helpful for diagnostics, or narrowing antibiotic therapy?
§ Relevant in non-bacterial infections?
§ Postpartum evaluation of sepsis?

Am J Perinatol 2019; 36: 898; Clin Chim 22

Acta 2021; 513: 13; IJGO 2023;164: 484
Diagnostic aids
Components Test characteristics Comments

RR > 22
Predicting sepsis Easy to use
SBP < 100
qSOFA Sensitivity: 50% Low sensitivity
Altered mental status
Specificity: 95% Need secondary testing
Positive screen: any 2 present
RR > 25
Easy to use
SBP < 90 Predicting sepsis
omqSOFA Not validated
Altered mental status No published data
Need secondary testing
Positive screen: any 2 present
Temperature, SBP, HR, RR, O2 sat,
Predicting ICU admission Predicts ICU admission for sepsis
Sepsis in Obstetrics Score WBC, % immature neutrophils,
Sensitivity: 64% (not sepsis)
(SOS) lactate
Specificity: 88% Requires lab data to calculate
Positive screen: score > 6
SBP < 90 / > 160
DBP > 100
HR < 50 / > 120
RR < 10 / > 30 Predicting sepsis Easy to use
Maternal Early Warning
O2 sat < 95% Sensitivity: 82% Not specific to sepsis
Criteria (MEWC)
Oliguria Specificity: 87% Alarm fatigue
Altered mental status; headache;
shortness of breath
Positive screen: any 1 present 23
Diagnostic aids
Components Test characteristics Comments

Temperature < 36 / > 38

HR > 100
UK Obstetric Surveillance Validation data in the next slides!
RR > 20 xxx
System (UKOSS) Obstetric SIRS
WBC > 17 / < 4
Positive screen: any 2
Step 1
Temperature < 36 / > 38
HR > 110
RR > 24
WBC > 15 / < 4 /> 10% bands
Positive screen: any 2
Predicting sepsis
California Maternal Quality Step 2 Unpublished data Validation data in the next slides!
Care Collaborative (CMQCC) Respiratory Sensitivity: 97%
Coagulation Specificity: 99%
Liver
CV
Renal
Mental status
Lactate
Positive screen: any 1
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Diagnostic aids: Labor/Delivery
Case-control study of sepsis screening tool performance across delivery hospitalizations in 59 hospitals
• SIRS
• CMQCC (step 1)
• UKOSS
• MEWT (some MEWT criteria not included)
• MEWC

Abnormalities to meet criteria for screening tool within 2h of each other (WBC within 24h)

1761 patients with delivery hospitalization-related sepsis

• 647 patients with sepsis, without chorioamnionitis/endometritis
• 1049 patients with sepsis AND with chorioamnionitis/endometritis

Common characteristics of patients with delivery-related sepsis:

• Cesarean delivery, heart disease, asthma, preeclampsia, stillbirth, preterm delivery

Obstet Gynecol 2024;143: 326; 25

Obstet Gynecol 2024;143: 336
Diagnostic Aids: Labor/Delivery
Sensitivity/specificity tradeoff,
and alarm fatigue

CMQCC and UKOSS have the

lowest false positive rates for
sepsis, in women with and
without chorio/endometritis

Pregnancy-adjusted evaluation of
vital signs critical

Positive Screening Tool ≠ Sepsis

Targeted clinical + lab evaluation
to follow

Obstet Gynecol 2024;143: 326; 26

Obstet Gynecol 2024;143: 336
Diagnostic Aids: Antepartum
525 patients with antepartum sepsis

Sepsis occurs at any gestational age

Heart disease, asthma are risk

factors

CMQCC and UKOSS optimize false

positive rate > 20 weeks

Pregnancy adjusted systems

perform poorly < 20 weeks

Obstet Gynecol 2024;143: 326; 27

Obstet Gynecol 2024;143: 336
Diagnostic Aids: Postpartum
728 patients with sepsis during PP
readmission

50% of readmissions within 14d

Diabetes, obesity, heart disease,

asthma risk factors

>3d postpartum, non-pregnancy

adjusted approach to sepsis
screening recommended

Obstet Gynecol 2024;143: 326; 28

Obstet Gynecol 2024;143: 336
Conclusions: When to modify for pregnancy

• Modify between 20 weeks gestation until 3 days postpartum

• Preferentially allow false positives outside of this window by using non-pregnancy modified
diagnostic aids

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Sepsis without a fever?

Fever is NOT a necessary criterion for sepsis to be considered

25% of maternal mortality attributable to sepsis – fever was absent from the initial presentation

Obstet Gynecol 2015;126: 747 30

Bundle Highlights:
Translating Knowledge
into Practice
Bundle Elements

• Readiness
‒ Establish inter- and intradepartmental protocols and policies
‒ Provide multidisciplinary education on obstetric sepsis, including non-L&D settings
‒ Utilize evidence-based criteria for sepsis assessment
‒ Create a culture that utilizes non-hierarchical communication

• Recognition & Prevention

• Response
• Reporting & Systems Learning
• Respectful, Equitable, & Supportive Care

https://saferbirth.org/psbs/sepsis-in-obstetric-care/ 32
Bundle Elements

• Readiness
• Recognition & Prevention
‒ Implement evidence-based measures to prevent infection
‒ Recognize and treat infection early
‒ Consider sepsis if deteriorating status, even in the absence of fever
‒ Assess and document if a patient is pregnant or has been pregnant in the last year
‒ Provide patient education, including sepsis signs and symptoms other than fever

• Response
• Reporting & Systems Learning
• Respectful, Equitable, & Supportive Care

https://saferbirth.org/psbs/sepsis-in-obstetric-care/ 33
Conclusions
Final thoughts

• Sepsis is challenging

• Sepsis incidence is increasing

• Sepsis is associated with high risks of mortality and severe maternal morbidity
• Early recognition is KEY to improving sepsis outcomes
• Diagnostic aids
‒ CMQCC 2-step approach, or UKOSS
‒ Lactate and procalcitonin aren’t ready to be independent screens

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Questions?
Maternal sepsis

KENDLE / Judette paper 37