Chorioamnionitis (Clinical)

Definition and Epidemiology

Definition

Also known as intraamniotic infection (IAI), chorioamnionitis Chorioamnionitis Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Chorioamnionitis is an infection, and resulting inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, of any combination of the fetal membranes ( chorion Chorion The outermost extraembryonic membrane surrounding the developing embryo. In reptiles and birds, it adheres to the shell and allows exchange of gases between the egg and its environment. In mammals, the chorion evolves into the fetal contribution of the placenta. Placenta, Umbilical Cord, and Amniotic Cavity and amnion Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the amniotic fluid. Amnion cells are secretory epithelial cells and contribute to the amniotic fluid. Placenta, Umbilical Cord, and Amniotic Cavity), amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity, placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity, umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity (funisitis), and/or the fetus.

Epidemiology^[1,4–7]

Chorioamnionitis Chorioamnionitis Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Chorioamnionitis is the most common cause of peripartum infection, with the following incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency rates:

• Overall incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 3.9%
• All term deliveries: 1%–5%
  • Term pre-labor rupture of membranes ( PROM PROM Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, refers to the rupture of the amniotic sac before the onset of labor. Prelabor rupture of membranes may occur in term or preterm pregnancies. Prelabor Rupture of Membranes), any length: 7%
  • Term PROM PROM Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, refers to the rupture of the amniotic sac before the onset of labor. Prelabor rupture of membranes may occur in term or preterm pregnancies. Prelabor Rupture of Membranes > 24 hours: 40%
• Preterm deliveries: 40%–70%
• Extreme preterm deliveries (< 24 weeks gestation): up to 94%

Etiology

Intraamniotic infection and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation may be caused by the following mechanisms:^[1,3,4,6,7]

• Ascending migration of cervicovaginal flora (primary mechanism)
• Hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases spread to intervillous space, associated with maternal bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
• Direct infection after invasive procedures (e.g., amniocentesis Amniocentesis Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. Polyhydramnios)
• Descending infection from the peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy via fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Uterus, Cervix, and Fallopian Tubes: Anatomy (very rare)

Risk factors:^[1,3,4,6,7]

• Prolonged rupture of membranes (ROM) > 18 hours
  • Most significant risk factor
  • In both term and preterm pregnancies
• Prolonged labor
• Preterm labor Preterm labor Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth
• Preterm PROM PROM Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, refers to the rupture of the amniotic sac before the onset of labor. Prelabor rupture of membranes may occur in term or preterm pregnancies. Prelabor Rupture of Membranes (PPROM)
• Multiple digital examinations (especially after ROM)
• Use of internal uterine and fetal monitors
• Genital-tract pathogens present during labor:
  • Group B streptococcus Group B Streptococcus Meningitis in Children colonization Colonization Bacteriology
  • STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)
• Primiparous Primiparous A woman’s 1st delivery Normal and Abnormal Labor pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Meconium-stained fluid
• Tobacco use
• Alcohol use

Pathophysiology

By far, the most common cause of chorioamnionitis Chorioamnionitis Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Chorioamnionitis is the ascending migration of cervicovaginal flora.^[1,3,4,6,7]

• Cervicovaginal flora introduced into the amniotic cavity Amniotic cavity Embryoblast and Trophoblast Development → infection → maternal and fetal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation 
• Can lead to:
  • Labor
  • ROM
  • Uterine atony, which may lead to:
    • Arrest of labor → operative delivery
    • Postpartum atony → postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage
  • Maternal and/or fetal sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
• Maternal immune response: neutrophilic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of membranes ( chorion Chorion The outermost extraembryonic membrane surrounding the developing embryo. In reptiles and birds, it adheres to the shell and allows exchange of gases between the egg and its environment. In mammals, the chorion evolves into the fetal contribution of the placenta. Placenta, Umbilical Cord, and Amniotic Cavity/ amnion Amnion The innermost membranous sac that surrounds and protects the developing embryo which is bathed in the amniotic fluid. Amnion cells are secretory epithelial cells and contribute to the amniotic fluid. Placenta, Umbilical Cord, and Amniotic Cavity)
• Fetal immune response: neutrophilic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity
• Microbiology:
  • Polymicrobial
  • Includes both aerobes and anaerobes Anaerobes Lincosamides (especially in preterm gestation)
  • Most common organisms:
    • Genital mycoplasmas: Ureaplasma and Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma
    • Gardnerella vaginalis Gardnerella vaginalis Polymicrobial, nonspecific vaginitis associated with positive cultures of gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli. Vulvovaginitis
    • Bacteroides Bacteroides Bacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine. Bacteroides species
    • Enteric gram-negative rods (e.g., Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli)
    • Group B Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
    • Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis monocytogenes ( hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases spread)
• Host defense mechanisms Defense mechanisms Defense mechanisms are normal subconscious means of resolving inner conflicts between an individual’s subjective moral sense and their thoughts, feelings, or actions. Defense mechanisms serve to protect the self from unpleasant feelings (anxiety, shame, and/or guilt) and are divided into pathologic, immature, mature, neurotic, and other types. Defense Mechanisms:
  • Cervical mucus plug
  • Intact fetal membranes:
    • Barrier function
    • Antimicrobial activity
    • Modulate immune response
  • Vaginal peroxide-producing lactobacilli → impair virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus of pathogens

Clinical Presentation

The vast majority of presenting women will either be in labor, have ruptured membranes, or both.^[1,3–7]

Primary manifestations:

• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Uterine fundal tenderness
• Purulent or foul-smelling fluid from the cervical os
• Maternal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children (> 100 bpm)
• Fetal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children (> 160 bpm) 
• Reduced fetal heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology variability

Diagnosis

The following information is based on a joint workshop between the US National Institute of Child Health and Human Development (NICHD), the American College of Obstetricians and Gynecologists (ACOG), the US Society for Maternal-Fetal Medicine (SMFM), and the American Academy of Pediatrics (AAP). Other organizations may have slightly different specific diagnostic criteria or use different categorization Categorization Types of Variables.^[5]

There are 3 categories of IAI:

• Isolated maternal fever Isolated maternal fever Fever (oral temperature) of > 39 °C (102.2 °F) once, 38.0–38.9 °C (100.4–102.2 °F) on 2 occasions, 30 minutes apart with other potential causes of fever ruled out Chorioamnionitis
• Suspected IAI
• Confirmed IAI

Isolated maternal fever Isolated maternal fever Fever (oral temperature) of > 39 °C (102.2 °F) once, 38.0–38.9 °C (100.4–102.2 °F) on 2 occasions, 30 minutes apart with other potential causes of fever ruled out Chorioamnionitis^[3,5]

• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever (oral temperature):
  • > 39 °C (102.2 °F) once
  • 38.0–38.9 °C (100.4–102.02 °F) on 2 occasions, 30 minutes apart
• Rule out other potential causes of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever:
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
  • Other testing based on associated signs and symptoms:
    • Blood cultures
    • Sputum testing
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza/ COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). testing
• If no other source is found, expert opinion recommends considering patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 39 °C (102.2 °F) as suspected IAI.

Suspected intraamniotic infection Suspected intraamniotic infection A condition encompassing fever and 1 of the following including fetal tachycardia > 160 bpm for ≥ 10 minutes, maternal leukocytosis with WBC > 15,000/mm3, and purulent cervical drainage on exam. Chorioamnionitis

Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and at least 1 of the following:

• Fetal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children: > 160 beats per minute for ≥ 10 minutes
• Maternal leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus (in the absence of corticosteroids Corticosteroids Chorioretinitis): WBC > 15,000/mm³
• Purulent cervical drainage on exam

Confirmed intraamniotic infection Confirmed Intraamniotic Infection Chorioamnionitis^[3,5,7]

Must meet criteria for “suspected IAI” and have at least 1 of the following:

• Positive amniotic-fluid test (obtained by amniocentesis Amniocentesis Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. Polyhydramnios):
  • Positive culture:
    • Gold standard
    • Takes days to obtain results → ↓ clinical utility
  • Positive Gram stain Gram stain Klebsiella 
  • ↓ Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance (≤ 14 mg/dL)^[7]
  • ↑ WBC (in the absence of a bloody tap, > 30 cells/mm³)^[7]
• Histopathology (after delivery) showing inflammatory infiltrates in membranes

Management

The goal of management is to minimize the risks of maternal and fetal complications. 

• Antibiotics:^[3,5,7]
  • Indicated in all 3 categories of IAI :
    • ACOG states that “antibiotics should be considered” in isolated maternal fever Isolated maternal fever Fever (oral temperature) of > 39 °C (102.2 °F) once, 38.0–38.9 °C (100.4–102.2 °F) on 2 occasions, 30 minutes apart with other potential causes of fever ruled out Chorioamnionitis owing to the significant potential benefits with low risk.
  • Given starting at diagnosis and continued through delivery
  • Standard regimen: ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins PLUS gentamicin Gentamicin Aminoglycosides
  • Dosing recommended by ACOG:
    • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins 2 g IV every 6 hours PLUS 
    • Gentamicin Gentamicin Aminoglycosides:
      • 5 mg/kg IV once daily OR 
      • 2 mg/kg IV load followed by 1.5 mg/kg every 8 hours
  • Alternative ACOG regimens for penicillin Penicillin Rheumatic Fever allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency use gentamicin Gentamicin Aminoglycosides PLUS:
    • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides 900 mg IV every 8 hours OR
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 1 g IV every 12 hours
  • If patient undergoes cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery:
    • Add anaerobic coverage; options include:
      • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides 900 mg IV once
      • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess 500 mg IV once
      • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides (single preoperative dose)
    • Give a single postpartum dose of the chosen regimen (e.g., 1 additional dose of ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins and gentamicin Gentamicin Aminoglycosides).
• Antipyretics:^[3,5,7]
  • To prevent risk to the fetus associated with ↑ maternal temperature
  • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
• Progress towards delivery:^[3]
  • Think of “delivery” like draining an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease:
    • Removes infection from the mother
    • Removes baby from the infection
  • Augment labor if it is dysfunctional (common):
    • Oxytocin
    • IAI does not necessitate immediate delivery, but continued progress should be made.
  • In preterm patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • IAI is an indication to initiate induction of labor (IOL).
    • Management is complex: based on gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care and clinical scenario
• Continuous fetal monitoring Fetal monitoring The primary goals of antepartum testing and monitoring are to assess fetal well-being, identify treatable situations that may cause complications, and evaluate for chromosomal abnormalities. These tests are divided into screening tests (which include cell-free DNA testing, serum analyte testing, and nuchal translucency measurements), and diagnostic tests, which provide a definitive diagnosis of aneuploidy and include chorionic villus sampling (CVS) and amniocentesis. Antepartum Testing and Monitoring^[7]
• Route of delivery:^[3] 
  • Based on routine obstetric indications
  • Vaginal delivery preferred (↓ morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status/ mortality Mortality All deaths reported in a given population. Measures of Health Status compared to cesarean)
• Postpartum care:^[3,5,7]
  • Usually routine care
  • Monitor for wound infection
  • IAI typically resolves quickly after delivery.
  • Indications that antibiotics should be continued postpartum:
    • Cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery (single dose only)
    • Persistent fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
    • Signs of sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock

Communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence with the neonatal team^[5]

Good communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence is critical to ensuring appropriate care of the newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn. These infants need to be monitored and/or worked up for sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock and potential complications. Critical items for the obstetric team to communicate with the neonatal team include:

• Gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
• Maternal and/or fetal tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Group B streptococcal status
• Duration of labor
• Duration of ROM
• Highest maternal temperature
• Results of any amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity tests
• Medications given to the mother:
  • Prostaglandins Prostaglandins A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. Eicosanoids
  • Antimicrobials
  • Antipyretics
  • Anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts use

Complications

Maternal complications^[3,5,7]

• Dysfunctional labor (infected uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy does not contract well)
• Operative delivery
• Postpartum hemorrhage Postpartum hemorrhage Postpartum hemorrhage is one of the most common and deadly obstetric complications. Since 2017, postpartum hemorrhage has been defined as blood loss greater than 1,000 mL for both cesarean and vaginal deliveries, or excessive blood loss with signs of hemodynamic instability. Postpartum Hemorrhage (infected uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy does not clamp down well)
• Maternal sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
• Postpartum endometritis Postpartum Endometritis Inflammation of the endometrium, usually caused by intrauterine infections. Endometritis is the most common cause of postpartum fever. Postpartum Endometritis
• Adult respiratory distress syndrome

Neonatal complications^[3,7]

The earlier the gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care at delivery, the higher the risk for neonatal complications.

• Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
• Intraventricular hemorrhage Intraventricular hemorrhage Bleeding within the cerebral ventricles. It is associated with intraventricular trauma, aneurysm, vascular malformations, hypertension and in very low birth weight infants. Intracerebral Hemorrhage (IVH)
• Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
• Bronchopulmonary dysplasia
• Cerebral palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies
• Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
• Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis birth (with many of its own associated complications):
  • Respiratory distress syndrome
  • Neurological abnormalities
  • Retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome of prematurity Prematurity Neonatal Respiratory Distress Syndrome (ROP)
  • Necrotizing enterocolitis Enterocolitis Inflammation of the mucosa of both the small intestine and the large intestine. Etiology includes ischemia, infections, allergic, and immune responses. Yersinia spp./Yersiniosis ( NEC NEC Necrotizing enterocolitis (NEC) is an intestinal inflammatory process that can lead to mucosal injury and necrosis. The condition is multifactorial, with underlying risk factors that include prematurity and formula feeding. The clinical presentation varies in severity from feeding intolerance, acute findings on abdominal exam, and systemic symptoms. Necrotizing Enterocolitis)
• Death

Differential Diagnosis

• Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection ( UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs))/ pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess: a common condition in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care with an increased risk of pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess. Symptoms of pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary Tract Infections (UTIs), suprapubic or flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma, costovertebral angle tenderness, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Diagnosis is made based on bacteriuria Bacteriuria The presence of bacteria in the urine which is normally bacteria-free. These bacteria are from the urinary tract and are not contaminants of the surrounding tissues. Bacteriuria can be symptomatic or asymptomatic. Significant bacteriuria is an indicator of urinary tract infection. Urinary Tract Infections (UTIs) in Children in the setting of the aforementioned symptoms. Treatment is with antibiotics.
• Upper respiratory tract infection (URI): a common condition, especially in winter Winter Pityriasis Rosea. Symptoms include nasal congestion, rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus, sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis, cough, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be tested for influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza and COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). . A chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests is usually required to confirm the diagnosis of pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, although the X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests can often be delayed until after delivery, except in more severe cases.
• Acute appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis: presents with severe abdominal pain Abdominal Pain Acute Abdomen, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. The diagnosis may be confirmed with an ultrasound or CT scan (CT scan exposes the fetus to significant radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma and should be used extremely judiciously). Appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis rarely presents intrapartum, whereas IAI is rare outside of labor or when membranes are still intact. Management is surgical.
• Epidural-associated fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: Evidence points to a frequent and significant association between a rise in maternal temperature and neuraxial anesthesia Neuraxial anesthesia Neuraxial anesthesia is commonly used for lower abdominal and lower extremity surgeries or for pain relief. Anesthesiology: History and Basic Concepts that typically occurs quickly. There are no reliable tests to identify neuraxial anesthesia Neuraxial anesthesia Neuraxial anesthesia is commonly used for lower abdominal and lower extremity surgeries or for pain relief. Anesthesiology: History and Basic Concepts as the cause of a fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever; therefore, close observation and/or presumptive treatment for IAI may be appropriate.
• Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage: occurs when the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity begins to separate prematurely, compromising fetal blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure and oxygenation. Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage typically presents with uterine cramping or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and vaginal bleeding. Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is usually not present. Lack of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, the presence of bleeding, and characteristic findings on fetal monitoring Fetal monitoring The primary goals of antepartum testing and monitoring are to assess fetal well-being, identify treatable situations that may cause complications, and evaluate for chromosomal abnormalities. These tests are divided into screening tests (which include cell-free DNA testing, serum analyte testing, and nuchal translucency measurements), and diagnostic tests, which provide a definitive diagnosis of aneuploidy and include chorionic villus sampling (CVS) and amniocentesis. Antepartum Testing and Monitoring make the diagnosis and help distinguish abruption from IAI. Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage is an obstetrical emergency that requires prompt management, including urgent delivery in most cases.