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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Pediatrics: Cardiac Disease and Critical Care Medicine

      Chorioamnionitis Treatment & Management

      Updated: May 08, 2018
      • Author: Fayez M Bany-Mohammed, MD; Chief Editor: Ted Rosenkrantz, MD  more...
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      Treatment

      Approach Considerations

      Transfer, hospitalization, and discharge considerations

      Infected neonates born at hospitals with level 1 (normal) or level 2 (special care) nurseries may require transfer to a level 3 or 4 neonatal intensive care unit (NICU). Transfer depends on the circumstances of the neonatal infection, degree of prematurity, presence of anomalies, and other pathophysiologic states. Reasons for transfer of the neonate from a level 1 or 2 nursery to a higher-level facility are outlined in Consultations.

      Transfer requirements such as oxygen or assisted ventilation, mode of transportation (eg, ambulance, helicopter, fixed wing aircraft), and healthcare personnel to transport the patient are beyond the scope of this article.

      Both the mother with suspected chorioamnionitis and her newborn with suspected sepsis require frequent assessments over the first 48 hours following birth. Mothers with chorioamnionitis who appear well after a brief intravenous course of antibiotics may be discharged on oral antibiotic therapy, but comprehensive outpatient follow-up care is required. General and gynecologic health is usually normal after maternal chorioamnionitis.

      When the newborn exposed to chorioamnionitis is preterm (< 35 weeks' gestation) or symptomatic term, the decision to obtain laboratory evaluation (complete blood cell [CBC] count and blood culture) and treat with antibiotics is relatively straightforward. However, when late preterm or term neonates are asymptomatic and well appearing, the decision to obtain laboratory evaluation, start antibiotics, and separate infants from their mothers is difficult and has generated much debate in recent years. [4, 77, 202, 203, 204]

      One approach to limiting the unnecessary use of antimicrobials is to use the “sepsis calculator” developed by Puopolo et al [205] to estimate the probability of early-onset sepsis (EOS) using maternal risk factors in neonates born at 34 weeks of gestation or Later. Utilizing data from more than 600,000 infants at at least 34 weeks’ gestation at birth, the investigators developed a model for EOS risk prediction based on objective maternal factors, then combined that model with findings from examination of the infants. [206] The model uses three categorical variables: group B Streptococcus (GBS) status (positive, negative, uncertain), maternal intrapartum antimicrobial treatment (GBS-specific or broad spectrum), and intrapartum prophylaxis or treatment given 4 hours or longer before delivery (yes, no) in addition to the following continuous variables: highest maternal intrapartum temperature (centigrade or Fahrenheit), gestational age (weeks and days), and duration of rupture of membranes (hours). A predicted probability per 1,000 live births can be estimated using the calculator (http://newbornsepsiscalculator.org). Several retrospective studies demonstrated that the use of the sepsis calculator in a population of well-appearing neonates (≥34 weeks' gestation) exposed to the clinical maternal diagnosis of chorioamnionitis would have substantially reduced the proportion of neonates undergoing laboratory tests and receiving antimicrobial agents. [202, 207, 208, 209]

      Term neonates undergoing an evaluation to exclude sepsis who consistently appear well can probably go home with their mothers within 48 hours after birth. Septic-appearing neonates usually receive antibiotic therapy via the parenteral route until treatment is deemed complete and the infant is well. Depending on the nature of the infection and other risk factors associated with the hospitalization (eg, extreme prematurity, need for home oxygen), an outpatient follow-up visit may be scheduled from 1 day to 2 weeks after discharge. Home healthcare follow-up visits by a reliable and well-trained nursing service may also be indicated.

      Antimicrobial therapy

      Outpatient antibiotics used to treat a term neonate with rule-out sepsis have not been evaluated. Some managed care plans have discharged neonates with proven infection who appear well after antibiotic therapy. These newborns complete a course of intravenous antibiotics at home. The intravenous antibiotics are often administered via a percutaneous venous line placed before hospital discharge. A visiting nurse comes to the home to administer the antibiotics twice daily.

      Depending on the type of infection found in the neonate, the duration of intravenous therapy with antibiotics ranges from 7 days (eg, perhaps pneumonia with rapid improvement or “culture-negative sepsis” based on a mildly ill or well-appearing infant with abnormal inflammatory markers like high levels of C-reactive protein [CRP] and/or procalcitonin, white blood cells, or immature-to-total neutrophil ratio) to 4-6 weeks (eg, osteomyelitis). The actual duration of treatment for different types of neonatal infections has not been studied; it is often experience based rather than evidence based.

      Surgical intervention

      Surgical interventions are infrequently required in early-onset bacterial infections of the neonate. The conditions that may require intervention include epidural or brain abscess, subcutaneous abscesses, infections localized to the pleural space, certain intraabdominal infections (especially if intestinal perforation is present), and bone or joint infections.

      Next:

      Medical Care

      This section addresses two topics. The first topic includes maternal interventions to treat suspected chorioamnionitis and protect the fetus from infection. The second topic includes the diagnostic approach and the appropriate treatment of neonates born to mothers with suspected chorioamnionitis.

      The observation that epidural anesthesia during labor may create findings suggestive of maternal chorioamnionitis is discussed. A maternal fever that occurs when epidural anesthesia is administered during the intrapartum period has often been interpreted as chorioamnionitis. This may not be the case, and the neonate is often needlessly treated after birth.

      Using ampicillin as the chemoprophylactic agent to prevent group B streptococcal (GBS) disease in the neonate is associated with other issues and should be discouraged. Ampicillin-resistant E coli infections in the mother and her infant are reported as an increasing problem, possibly due to this prophylactic practice. [210, 211]  However, the use of penicillin rather than ampicillin to prevent GBS infections of the newborn is encouraged and should be the standard of care. [212] When the mother is allergic to penicillin, she is given clindamycin if her GBS isolate is documented to be susceptible to clindamycin. Approximately 30% of GBS isolates in the United States were clindamycin resistant in 2010, and the proportion varies by country. If, however, clindamycin susceptibility testing has not been performed, vancomycin should be administered instead. [170]

      Obstetric management influencing neonatal outcome

      When acute chorioamnionitis is evident, delivery must be expedited. Upon signs of serious fetal distress, delivery must be emergent. Withholding maternal antibiotics to obtain postnatal cultures from the neonate is no longer appropriate. This strategy was once an accepted practice based on the assumption that waiting to obtain cultures from the newborn helps to determine the cause of infection. The morbidity and mortality in the mother and newborn may actually increase because of a delay in administering antibiotics.

      The neonatal care provider (neonatologist, pediatrician, or family medicine physician) must decide whether the fetus was infected and whether antibiotics given before birth should be continued in the neonate. Those antibiotics may differ from those administered to the mother. The history, physical findings, and results of certain laboratory studies can assist the physician in deciding whether to continue antibiotics started during the intrapartum period. Because antibiotic chemoprophylaxis reduces the risk of GBS infection in neonates, the obstetrician must always consider beginning penicillin during the intrapartum period when a mother has defined risk factors for GBS disease. [212, 213] The neonatal care provider must judge whether the chemoprophylaxis was sufficient to prevent infection (especially in a healthy, full-term neonate) or whether the infant must continue antibiotic therapy after birth. The US Centers for Disease Control and Prevention (CDC) issued guidelines that outline the strategies for screening and treatment to prevent neonatal disease caused by GBS, the most recent guidelines were published in 2010, [170]  with an update in 2012. [171]

      A retrospective study evaluating daily gentamicin for the treatment of intrapartum chorioamnionitis in 500 women found that daily gentamicin dosing using ideal body weight compared with traditional 8-hour dosing regimens was associated with a 64% lower risk of postpartum endometritis and a 5% higher chance of successful outcome. [214] These results were adjusted for maternal factors such as race, parity, advanced maternal age (>34 years), body mass index, diabetes mellitus, gestational hypertension (>140/90 mmHg), and GBS status.

      Determining the appropriate procedures to prevent fetal infection in the setting of premature, prelabor, rupture of membranes is more complex. The mother who has preterm labor or premature rupture of membranes at less than 34 weeks' gestation and no clinical signs or symptoms of chorioamnionitis should receive corticosteroid therapy. [98]

      Attitudes toward antibiotic use have changed over time (see the discussion about the sepsis calculator under Treatment: Approach Considerations. If GBS colonization of the mother is not present, and signs and symptoms of chorioamnionitis are absent, pregnant women with preterm labor or premature rupture of membranes (PROM) at more than 36 weeks' gestation should be observed for infection. Thus, prophylactic antibiotics are not given in these circumstances. Mothers at term gestation with accepted risk factors for GBS infection in their fetus should receive chemoprophylaxis. Mothers at risk of preterm birth, and in whom GBS status is unknown, receive antibiotics during latency until the GBS screening is completed. A period of observation for maternal and/or fetal infection is also required after admission, although signs and symptoms may not be evident (ie, silent disease).

      A systematic review and meta-analysis of planned early birth versus expectant management for women with prelabor PROM (PPROM) prior to 37 weeks' gestation found no clinically important difference in the incidence of neonatal sepsis between women who birthed immediately and those managed expectantly. [215] Early planned birth was associated with an increase in the incidence of neonatal respiratory distress syndrome (RDS), need for ventilation, neonatal mortality, endometritis, admission to the neonatal intensive care unit, and the likelihood of birth by cesarean section; however, there was a decreased incidence of chorioamnionitis. Women randomized to early birth also had an increased risk of labor induction but a decreased length of hospital stay. [215] Babies of women randomized to early birth were more likely to be born at a lower gestational age. In women with PPROM before 37 weeks' gestation with no contraindications to continuing the pregnancy, a policy of expectant management with careful monitoring was associated with better outcomes for the mother and baby. [215, 216]

      Relatively recent randomized controlled studies [217] and a meta-analysis [218] have shown that antenatal corticosteroids benefits on fetal lung maturity extend beyond 32 weeks' gestation (up to 38 weeks); this led the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine to issue guidance statements about extending antenatal steroid use to selected late preterm singleton pregnancies. [219, 220] Studies have not clearly demonstrated that the use of corticosteroids increases the risk of bacterial infection in the fetus. [98]

      Magnesium sulfate (MgSO4) is typically given as an obstetric tocolytic; however, its administration also appears to act differentially to modulate infection-associated inflammation in fetal membranes. A 2018 study of human fetal membrane explants indicates that MgSO4 differentially modulates lipopolysaccharide-induced fetal membrane inflammation in a time-dependent manner, partially via modulation of caspase-1 activity. [221] The investigators suggest that MgSO4 may also have utility in prevention of fetal membrane inflammation caused by polymicrobial infection.

      Neonatal immunology and the risks created by maternal chorioamnionitis

      Newborns are vulnerable to infection because of an immature immune system. [222] Factors that render neonates susceptible to bacterial infections include reduced numbers and/or function of macrophages and dendritic cells in peripheral tissues (eg, lung); lower numbers of neutrophils in the bone marrow storage pool [188] ; decreased immunoglobulin G (IgG) and complement levels, especially in prematurely born infants; an inability to respond to bacterial carbohydrate antigens; an increased percentage of T cells bearing naïve cell surfaces and correspondingly underdeveloped functional behaviors related to foreign antigens; and anatomic and biochemical immaturity of skin and mucosal barriers (eg, lung and gut epithelia) as they relate to local host defenses.

      Emerging treatments, such as the use of intravenous immunoglobulins and hematopoietic growth factors, may correct deficiencies of the neonatal immune system. [223]  However, the use of immunotherapy still requires more investigation before these treatments become a standard of care. [224] Specifically, the routine use of intravenous immunoglobulins to treat neonatal sepsis is not established, [225] and the use of granulocyte colony stimulating factor (G-CSF) and granulocyte/macrophage colony stimulating factor (GM-CSF) may have a limited role in managing infected preterm infants with neutropenia. [226] The mainstays of current neonatal intensive care for bacterial sepsis in neonates are prompt recognition of bacterial infection, antimicrobial therapy, and supportive care. (In this review, supportive care is only briefly discussed below. See the Medscape Drugs and Disease article Neonatal Sepsis for a more in-depth care of these critically-ill neonates.)

      Treatment of the neonate

      Communication between obstetric and pediatric caregivers is essential to recognize neonatal infection. Recognition or suspicion of maternal chorioamnionitis is essential to reducing neonatal morbidity and mortality caused by early-onset bacterial infections in the neonate. Nurses and physicians who care for the mother must communicate their concerns about maternal infection to the nurses and physicians who care for the newborn after birth. Caregivers in the nursery must be critically aware of a neonate's signs and symptoms in relationship to the antepartum and intrapartum history.

      Signs and symptoms in the mother that suggest chorioamnionitis and increase the risk of fetal or neonatal infection are described under Physical Examination. Although numerous ways to approach the diagnosis and treatment of neonatal sepsis are recognized, a hands-on assessment is the main key to recognition. The experienced physician or nurse in the nursery may indicate to fellow caregivers that the newborn has a septic appearance.

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      Next:

      Consultations

      Depending on the hospital setting and the status of the neonate, a family physician may seek pediatric consultation. Depending on the severity or nature of infection in the neonate in a hospital setting, the pediatrician may seek consultation with a neonatologist, a pediatric infectious disease subspecialist, or both. If organ system failure is present or impending organ system failure (eg, respiratory, cardiovascular, renal) secondary to infection is a concern, the infant should be transferred to an appropriate level 3 or level 4 neonatal intensive care unit (NICU). Transportation to a level 3 or 4 NICU is clearly indicated for extremely premature infants requiring high-frequency oscillatory ventilation or near-term or term neonates (≥ 35 weeks' gestation) who are close to meeting criteria for extracorporeal membrane oxygenation (ECMO).

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      Diet and Activity

      Diet

      Seriously or critically-ill newborns with early-onset bacterial infections often require parenteral nutrition until their condition improves. The use of intravenous lipids during proven bacteremia is the subject of controversy. The fear is that lipid inclusions may interfere with phagocytosis of microbes by hepatic, splenic, or pulmonary macrophages. Infections involving the gastrointestinal tract may need a special approach to enteral nutrition when the feedings are reinstituted.

      Activity

      Activity and illness is generally related to adults because neonates are typically at rest and are not stressed when seriously or critically ill.

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      Prevention

      Maternal antibiotic chemoprophylaxis is related to urogenital colonization with group B Streptococcus (GBS). Mothers are screened for GBS-related colonization at 35-37 weeks' gestation. Preterm labor before 35 weeks' gestation indicates that knowledge of GBS-related colonization of the urogenital tract is not immediately available.

      The Centers for Disease Control and Prevention (CDC) continues to publish updated guidelines for prevention of perinatal GBS disease. [170, 171]  In 2011, the American Academy of Pediatrics (AAP) [227] and the American College of Obstetricians and Gynecologists (ACOG) [228]  released their recommendations regarding prevention of early-onset GBS disease in newborns on the basis of the 2010 CDC guidelines. The Society of Obstetricians and Gynaecologists of Canada (SOGC) published their recommendations for prevention of early-onset neonatal GBS disease in 2013. [229]

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