Clinical Management of Intra-Amniotic Infection and Chorioamnionitis: A Review of the Literature Jenifer O. Fahey, CNM, MSN, MPH

Authors and Disclosures

Posted: 06/23/2008; J Midwifery Womens Health. 2008;53(3):227-235. © 2008  Elsevier Science, Inc.

Abstract and Introduction

Abstract

Intra-amniotic infection (IAI), or chorioamnionitis, complicates up to 10% of all pregnancies and up to 2% of labors at term. There is a significant risk of complications for the mother and the neonate following IAI, including sepsis and pneumonia. In addition, there is a correlation between IAI and premature rupture of membranes, preterm premature rupture of membranes, preterm labor, and preterm birth. Research in the last decade has also revealed a complex and significant association between IAI and cerebral palsy and other central nervous system damage in both the preterm and term fetus. Timely diagnosis and treatment of IAI can significantly reduce the risk of both maternal and neonatal complications.

Introduction

Strictly defined, chorioamnionitis is a histopathologic finding of inflammation of the amnion and/or the chorion. This inflammation most commonly results from bacterial infection of the amniotic fluid, the fetal membranes, the placenta, and/or the uterus. In clinical practice, the terms "chorio" and "chorioamnionitis" are used to refer to the clinical symptoms suggestive of these bacterial infections whether or not there is actual histopathologic chorioamnionitis. For the purpose of this article, these infections will be referred to as intra-amniotic infection (IAI). Other terms that are commonly used in medical literature to refer to these infections include amnionitis and intrapartum infection.

National data on the incidence of chorioamnionitis are not readily available, so rates commonly quoted in textbooks and other literature are taken from research studies, many of which are more than a decade old and vary widely in characteristics of the population being studied. These studies indicate that IAI complicates between 0.5% and 10% of all pregnancies and approximately 0.5 to 2.0% of term pregnancies.[1,2] While maternal mortality caused by IAI is rare, neonatal mortality directly related to IAI is between 1% to 4% for term infants and more than 10% for preterm infants.[3] Furthermore, it is now believed that subclinical IAI is a cause of preterm premature rupture of membranes (PPROM) and/or preterm labor (PTL) and, as such, is an important contributor to the leading cause of infant morbidity and mortality --

complications from prematurity. Evidence has also emerged that supports a connection between IAI and cerebral palsy in children born either prematurely or at term.[4] This article reviews the basic pathophysiology, complications, diagnosis, and management of IAI.

Pathogenesis

The most common route of intrauterine infection is ascending bacteria from the lower genital tract. This occurs most commonly in the presence of rupture of membranes, but is also possible with intact membranes. IAI is usually polymicrobial and in a majority of cases is caused by a combination of anaerobic and aerobic organisms. The pathogens that are most frequently isolated in the amniotic fluid of patients with IAI are those that are found in the vaginal flora, including Gardnerella vaginalis, Ureaplasma urealyticum, Bacteroides bivius, group A, B, and D streptococci, Peptococcus, Peptostreptococcus, and Escherichia coli. [5] Other routes of infection include hematogenous (blood borne) or transplacental infection, retrograde infection from the pelvis, and transuterine infection caused by medical procedures, such as amniocentesis and chorionic villus sampling (CVS), but these are all comparatively rare.

Once they have colonized the uterine cavity, bacteria can not only infect the fetus but also can release endotoxins that, in sufficient quantities, are believed to initiate a maternal and fetal inflammatory response that may result in premature rupture of membranes (PROM), PTL, and neurologic damage in the fetus. Briefly, this inflammatory response is believed to progress as follows: bacterial endotoxins trigger a release of cytokines in maternal and fetal tissue that leads to a release of additional cytokines, leukocyte migration, and then prostaglandin release from the myometrium and fetal membranes.[6] This prostaglandin release, which can lead to rupture of the fetal membranes and/or to the initiation of uterine contractions, is believed to be the mechanism (or one of the mechanisms) by which IAI is a direct cause of preterm labor. Figure 1 provides a simplified overview of the links between IAI and PTL, PPROM, and maternal and neonatal complications, including cerebral palsy.

Risk Factors/Associated Conditions

Any factor that increases the risk of prolonged exposure of the fetal membranes and/or the uterine cavity to ascending microbes from the vagina will increase the risk of IAI. These factors include nulliparity (as it increases the average length of labor), premature labor, prolonged rupture of membranes, digital vaginal exams, intrauterine pressure catheters, fetal scalp electrodes, and urogenital infections (particularly vaginal or cervical infections, including sexually transmitted infections [STIs]).[3] There is evidence that meconium in the amniotic fluid also may increase the risk of maternal infection and/or chorioamnionitis, possibly by compromising maternal immune response or by altering the composition of amniotic fluid in a way that reduces its antimicrobial properties.[7] There are additional risk factors for infection, such as maternal chronic disease, maternal nutritional status, and emotional stress, all of which may increase a woman's susceptibility to infection by effects on the function of the immune system.[8,9] The exact relationship between these risk factors, host immunity, and IAI, however, is complex and still under investigation. When considering risk factors, it is important to remember that PTL and PPROM can not only lead to, but can also be caused by, intrauterine infection.

Maternal Complications

Approximately 5% to 10% of women with IAI will develop bacteremia.[10] Other maternal complications include labor abnormalities, increased need for oxytocin, and

increased risk of cesarean birth. IAI also increases the risk of postpartum hemorrhage and surgical complications such as wound infection, pelvic abscess, and postpartum endometritis.

Because of the availability of broad-spectrum antibiotics and effective in-hospital care, life-threatening maternal complications from IAI, such as septic shock and respiratory distress syndrome, are rare in the United States.

Fetal/Neonatal Complications

Risks to the fetus and neonate from IAI are significant and include sepsis, pneumonia, respiratory distress, and death. The rate of these complications increases dramatically with decreasing gestational age at delivery.

In addition to complications in the neonatal period, IAI has now been linked to long-term neurologic impairment in infants. In particular, IAI increases the risk for cystic periventricular leukomalacia (PVL) and cerebral palsy (CP) in both term and preterm neonates.[11] PVL -- damage or softening of white matter in the fetal brain -- can lead to motor dysfunction and/or cerebral palsy in affected neonates. In an early study on this relationship, IAI was associated with nearly a five-fold increase in the risk of CP.[12] A meta-analysis of approximately 30 studies that was conducted in 2000 also found an association between IAI and development of PVL (relative risk [RR], 3.0; 95% confidence interval [CI], 2.2-4.0) and cerebral palsy in the preterm (RR, 1.9; 95% CI, 1.4-2.5) and term (RR, 4.7; 95% CI, 1.3-16.2) neonate.[13] Of note is that in this study, it was not only clinical chorioamnionitis that was found to increase the risk of PVL and CP, but that histologic chorioamnionitis (i.e., silent or subclinical infection) was also found to increase this risk. Newer studies have supported these findings and found that chorioamnionitis is an independent risk factor for CP not only among preterm infants, but among term and near-term infants as well (odds ratio [OR], 4.1; 95% CI, 1.6-10.1).[4,14,15]

The mechanism by which IAI appears to lead to neurologic injury in the fetus/neonate is similar to the mechanism that is believed to cause PPROM and PTL in the patient with IAI and which was outlined in Figure 1. The fetus, like the mother, mounts an inflammatory response to IAI. As part of this inflammatory response, the fetus appears to have a particularly "exuberant" production of cytokines (interleukins-1 and -6; tumor necrosis factor-α). It is believed that these cytokines are involved in initiating necrosis of white matter in the fetal brain and to long-tern neurologic sequelae, including CP.[14] This "inflammatory response syndrome" was described by Gomez et al.,[6] who demonstrated that an increased level of fetal plasma interlekin-6 (>11 pg/mg) was an independent predictor of severe neonatal mortality (OR, 4.3; 95% CI, 1.0-18.5) and of PTL. It is not yet known why only certain fetuses exposed to IAI will have permanent neurologic sequelae, nor is the exact mechanism by which cytokines lead to white matter damage fully understood. It is possible that some cytokines released during the fetal inflammatory response trigger the production of other inflammatory factors that can directly damage cells. It is also possible that this cytokine-mediated inflammation of placental membranes can result in compromised placental circulation and lead to or exacerbate existing hypoxic brain injury in the fetus.[4] The work done by Yoon et al.[15] suggests that genetic predisposition may determine the intensity of the fetal inflammatory response, and that the development

of IAI-related CP may occur through the interaction of multiple factors, including genetics.[15] It is important to underscore that this fetal inflammatory response syndrome and subsequent damage to fetal brain tissue can occur in the antepartum period and before the development of clinical symptoms in the mother. IAI with a fetal inflammatory response is also associated with a higher incidence of non-neurologic morbidity and mortality than IAI with maternal inflammatory response only.[16]

Diagnosis

The diagnosis of IAI is most commonly made on the basis of clinical symptoms, in particular the presence of maternal fever of more than 38°C (100.4°F) when there are no other identifiable reasons for fever (e.g., urinary tract infection). Other symptoms include maternal tachycardia (≥100-120 bpm), fetal tachycardia (≥160 bpm), uterine tenderness, purulent or foul-smelling amniotic fluid, and maternal leukocytosis (>15,000-18,000 cells/mm3).

In making the diagnosis of chorioamnionitis, however, providers must keep in mind that research has shown that even in the presence of clinical symptoms suggestive of IAI, the placental pathology often does not support the diagnosis. One such study found that in 38% of cases of clinically diagnosed chorioamnionitis, there was no histologic evidence of infection.[17] This indicates that there are likely normal and/or noninflammatory causes for this constellation of signs and symptoms. Smulian et al.[18] found that women who were diagnosed with chorioamnionitis but had no histologic evidence of infection were significantly more likely to have had an epidural in labor than women who had histologic evidence of infection. Maternal fever related to epidural anesthesia has been described in the literature.[18] A meta-analysis found a 5.6-fold increase in the risk of maternal fever (>38°C) in women with epidurals (95% CI, 4.0-7.8; P < .001) when compared to the incidence of intrapartum fever in women who do not have epidurals.[19] Epidural-related maternal fever is not associated with neonatal sepsis. Close observation rather than an invasive work-up may, therefore, be considered for the febrile but healthy-appearing newborn of a mother who received epidural anesthesia -- especially if the mother had no additional risk factors and/or received broad-spectrum antibiotics during labor. In these neonates, the fever present at birth usually resolves quickly and there are no additional signs of infection.

Conversely, histologic chorioamnionitis can be present without clinical symptoms. In one study, subclinical infection was present two to three times more commonly than clinical infection.[20] As described earlier, subclinical intrauterine infection has been implicated in the development of PTL, PROM and PPROM, PVL, and CP. Antepartum diagnosis of subclinical chorioamnionitis would, therefore, help providers determine whether the benefits of prolonging pregnancy outweigh the risks in the woman with PTL or PPROM at less than 34 weeks estimated gestational age. Because management of these women is not within the scope of midwifery care, these diagnostic methods are not described in detail here, but include the following: analysis of amniotic fluid obtained through amniocentesis using Gram stain, glucose concentration measurement, white blood cell count, measurement of leukocyte esterase, measurement of cytokines, and culture. Testing for glucose concentration of amniotic fluid from pooling in the vaginal vault rather than through amniocentesis is

another method sometimes employed. Culture of the amniotic fluid obtained through amniocentesis remains the gold standard to diagnose subclinical infections.

Prevention

Different vaginal organisms appear to have different potentials for causing chorioamnionitis and maternal and neonatal morbidity.[5] Researchers have aimed, therefore, to identify the more virulent agents and determine whether antibiotic treatment can reduce the rates of IAI and related complications. Infection with Gram-negative bacteria, including those that cause bacterial vaginosis (BV), appears to be associated with a higher risk of PROM and PPROM, premature birth, and postpartum endometritis than infection with predominantly Gram-positive bacteria.[10,21]

Treatment of Bacterial Vaginosis

A 2006 Cochrane systematic review of the research on the treatment of BV in pregnancy indicates that although antibiotic therapy appears to eradicate infection, a policy of routine screening and treatment of all pregnant women does not translate into an improvement in outcomes -- primarily, there is no reduction in the incidence of preterm birth (PTB) among women treated for BV antenatally when compared to the incidence of PTB in women with BV who were not treated.[22]

Studies on the management of BV in women with a history of previous PTB have produced mixed results. The Cochrane analysis of grouped data from two studies revealed a significant decrease in the risk of PPROM (OR, 0.14; 95% CI, 0.05-0.38) and low birth weight (OR, 0.31; 95% CI, 0.13-0.75) among these women when treated for BV antentally.[22] However, neither the incidence of PTB nor neonatal sepsis was significantly reduced. Meta-analysis of five clinical trials (n = 2387) indicates that there may be a benefit to early treatment (≤20 weeks' gestation) of BV among asymptomatic women with a history of PTB. In this analysis, the use of antibiotics was associated with a decrease in PTB (<37 weeks) in this population (OR, 0.63; 95% CI, 0.48-0.84).[22]

The research reviewed above indicates that a policy of universal screening for and treatment of asymptomatic BV in pregnancy is not efficacious, but that there may be a benefit to early treatment of asymptomatic infection among women with a history or PTB. Furthermore, given (1) the strong association between BV and adverse perinatal outcomes, (2) the fact that most of the large clinical trials included in the Cochrane analysis have not included women with symptomatic BV infection, and (3) that treatment for BV has not been associated with adverse outcomes, treatment of symptomatic BV in pregnancy is probably warranted. The Centers for Disease Control and Prevention (CDC) currently recommend treatment of all women with symptomatic BV in pregnancy.[23] Table 1 describes the CDC's recommended treatment regimens for BV in pregnancy.

Treatment of Trichomoniasis

Trichomoniasis has also been associated with increased risk of PROM, PPROM, PTL, and PTB. However, antenatal treatment for trichomoniasis has not been demonstrated to reduce the rates of these adverse outcomes, and may actually be associated with an

increase in the risk of PTB.[24,25] In a randomized controlled trial in Uganda, treatment of trichomoniasis was associated with increased rates of low birth weight (RR, 2.49; 95% CI, 1.12-5.50), PTB (RR, 1.28; 95% CI, 0.81-2.02), and 2-year mortality (RR, 1.58; 95% CI, 0.99-2.52).[25] The current CDC sexually transmitted diseases treatment guidelines do not make recommendations on whether or not to treat trichomoniasis in pregnancy (particularly asymptomatic infection) and leave the decision of whether to treat to provider discretion.[23] The guidelines do recommend counseling women on the risks of both infection and treatment. The CDC's recommended treatment regimen for trichomoniasis in pregnancy is shown in Table 2 .

Group B Streptococcus

Group B streptococcus (GBS) is the leading cause of neonatal sepsis.[26] Infants born to women with chorioamnionitis are at significantly higher risk of GBS sepsis (OR, 6.4).[27] Treatment of chorioamnionitis with ampicillin and gentamicin reduces the likelihood of neonatal GBS infection by more than 80%.[28] A policy of intrapartum prophylactic antibiotic treatment for women who are found to be GBS carriers by culture following CDC guidelines as described in Table 3 has resulted in a 50% to 80% reduction in GBS-related neonatal disease.[29]

In addition to antibiotic treatment when appropriate, other IAI prevention strategies include: 1) avoiding digital vaginal examination if possible in patients with PPROM and PROM; 2) minimizing digital vaginal examinations in labor, especially in latent phase labor and/or in the presence of rupture of membranes; and 3) avoiding the use of intrauterine pressure catheters unless needed to diagnose arrest disorders. There are currently no strategies for the prevention of CP (including IAI-related CP) in term neonates.

Treatment and Management

Intrapartum antibiotic therapy is associated with improvement in both maternal and fetal outcomes; therefore, once the clinical diagnosis of chorioamnionitis has been made, parenteral antibiotic therapy should be initiated.[30,31] Antibiotic therapy should be broad-spectrum (effective against a wide range of both Gram-positive and Gram-negative organisms) and cover both aerobes and anaerobes. There is, however, a lack of evidence to clearly support one particular regimen of antibiotics over another.[32] A combination of a ß-lactam (e.g., penicillins, cephalosporins, carbapenems, or monobactams) and an aminoglycoside (e.g., gentamicin or tobramycin) is commonly recommended.[32] Ampicillin plus gentamicin is a familiar and efficacious regimen and has become the standard treatment for IAI in many birth sites. The addition of clindamycin or metronidazole for women with IAI undergoing cesarean birth is recommended in order to reduce the risk of postpartum endometritis.[33] In women receiving ampicillin or penicillin GBS prophylaxis, an additional agent such as gentamicin is indicated if the patient becomes febrile. Selected antibiotic regimens for treatment of IAI are described in Table 4 , although as was reviewed above, there is no evidence supporting the use of one regimen over another.[30-33]

While some sources advise delaying antibiotic treatment until postpartum in women who will deliver within 1 to 2 hours, there is no research evidence to support this approach.[34] Once initiated, antibiotic therapy should continue throughout labor and

for at least one dose after delivery. Some sites continue therapy for 24 hours post-vaginal delivery and, following a cesarean birth, most sites continue antibiotic therapy until a woman has been afebrile for 24 to 48 hours. However, in a study published in 2003, researchers found that, in women who had received intrapartum antibiotic treatment, one postpartum dose of each agent (plus a single dose of 900 mg clindamycin at umbilical cord clamping if delivered by cesarean birth) was as efficacious as antibiotic treatment that was continued until the woman had been afebrile and asymptomatic for 24 hours.[33]

Chorioamnionitis is an indication for delivery but it is not an indication for cesarean birth. If appropriate antibiotic therapy has been initiated and labor is progressing, shortening labor by performing a cesarean birth has not been shown to significantly improve either maternal or neonatal outcomes.[10] Cesarean birth in women with chorioamnionitis should be performed for standard obstetric indications. It is important to note, however, that chorioamnionitis is associated with an increased incidence of dysfunctional labor, and therefore also to an increased risk of cesarean birth.[35]

Intrapartum antipyretic administration (e.g., acetaminophen) is advisable for fetal indications, especially in the presence of maternal or fetal tachycardia. Administration of acetaminophen has been demonstrated to reduce maternal temperature to normal and is associated with an improvement in fetal acid-base balance (measured through bicarbonate concentration and base deficit) and return of abnormal fetal heart rate tracing to normal (reduction in fetal tachycardia, return of variability and resolution of late decelerations).[36] Fetal tachycardia that persists once maternal fever and/or maternal tachycardia is alleviated by antipyretic therapy may indicate fetal acidemia, especially when present in combination with decreased or loss of variability and/or late decelerations. In this scenario, intrauterine resuscitation methods should be instituted and delivery may need to be expedited. Preparations for neonatal resuscitation should be made. Because of the increased risk of fetal acidemia in the presence of chorioamnionitis, continuous fetal heart rate monitoring is recommended.

Whenever clinical or subclinical IAI is suspected, umbilical cord gases should be obtained and the placenta should, if possible, be sent to pathology.[37] IAI-related indications for histologic examination of the placenta include the following: suspicion of or confirmed infection, premature delivery (especially before 34 weeks), maternal fever, thick or particulate meconium, prolonged rupture of membranes (>24 hours), neonatal admission to the neonatal intensive care unit, stillbirth, death in the perinatal period, umbilical cord blood pH less than 7.0, Apgar score less than 6 at 5 minutes, neonatal ventilatory assistance more than 10 minutes, neonatal intubation, and neonatal seizures. A finding of funisitis (acute inflammation of the umbilical cord) upon histologic examination is suggestive of fetal inflammatory response syndrome and possibly of a poorer neonatal prognosis. In a retrospective analysis, Pacora et al.[38] found that newborns whose umbilical cords were noted to have funisitis had higher rates of clinical chorioamnionitis, histologic chorioamnionitis, and neonatal sepsis than in those who did not (40% vs. 8%, 100% vs. 40%, and 40% vs. 4%, respectively; P < .01).[38]

When reviewing the results of cord gas analysis, the provider should keep in mind that intrauterine infection (confirmed through placental pathology as histologic

chorioamnionitis or funisitis) alone without concomitant recurrent fetal heart rate decelerations and/or minimal/absent variability is not associated with a finding of metabolic acidosis on umbilical cord gas results.[39]

Depending on the status of the mother and the fetus and the availability of and response to antibiotic therapy, the management of the woman with chorioamnionitis may require consultation, collaboration, and/or transfer of care to the consulting physician. Collaborative management or transfer of care is indicated for women with signs and symptoms of chorioamnionitis before term; women at term who are unresponsive to antibiotic therapy; or women who have signs and symptoms of worsening status or of sepsis and/or impeding septic shock (tachypnea, confusion, lethargy, changes in mentation, falling blood pressure, oliguria, or pale and cold extremities). Communication with the neonatal provider(s) is also essential; neonatal transport may need to be arranged.

Management of Premature Rupture of Membranes at Term and Intrauterine Infection

The management of the approximately 8% of women at term with PROM can present a clinical dilemma to midwives and other health care providers who want to balance the risks of induction and augmentation with the risk of IAI. Research has shown that approximately 60% of women with PROM at term will enter spontaneous labor on their own within 24 hours of rupture. A large, multisite, randomized trial studied the outcomes of 5041 women with PROM at term. The participants were randomized to immediate induction of labor with either oxytocin or prostaglandin E2 versus expectant management with induction for complications only. There was a higher incidence of maternal infection in the group managed expectantly but similar rates of neonatal infection and cesarean birth among the groups.[40] It must be noted that while digital exams were avoided in the initial evaluation of all women (the women were evaluated using a sterile speculum and sterile vaginal swabs), once labor had commenced, women who underwent expectant management and those who underwent induction with prostaglandin gel had more digital exams, longer labors, and higher rates of maternal infection than those in the group of women who were induced with oxytocin at the time of diagnosis of rupture of membranes. The expectant management group had the longest time intervals between rupture of membranes and onset of labor, the longest labors, and the highest rates of clinical chorioamnionitis.[40] The researchers did not, however, control for number of digital exams or the length of labor when calculating the increased risk of maternal infection. In addition, many of the women in the expectant group received an initial digital exam when admitted to the study. It is possible, therefore, that reducing the number of intrapartum exams and/or eliminating an initial digital exam would have reduced the incidence of infection in the expectant management group.

The American College of Obstetricians and Gynecologists in their most recent (2007) Practice Bulletin on PROM makes the recommendation that for "women with PROM at term, labor should be induced at the time of presentation, generally with oxytocin infusion, to reduce the risk of chorioamnionitis."[41] This contrasts with their previous bulletin (1998) on this same topic, which recommended that "with term PROM, labor may be induced at the time of presentation or patients may be observed for up to 24-72 hours for the onset of spontaneous labor."[42] Interestingly, both these

recommendations reference the same 1996 randomized trial conducted by Hannah et al.[40] (described earlier) in which there was not a statistically significant difference in neonatal outcomes between the groups managed by induction versus those managed expectantly.[40]

It is likely that the emerging evidence on the role of infection in the development of central nervous system damage in the fetus coupled with increasing rates of both elective cesarean delivery and elective induction of labor explain the recent recommendation for induction upon presentation with PROM at term. There is currently no evidence that definitively supports induction of labor for all women with PROM at term who do not have other indications for induction (e.g., chorioamnionitis). The decision to induce labor in this population should be made taking into consideration first and foremost maternal and fetal status at the time of assessment. In the presence of a healthy mother and fetus and the absence of signs and symptoms of infection, providers should take into account the favorability of the cervix, maternal history, GBS status, ability of the provider to monitor the woman and the fetus for signs of infection, and maternal wishes when making a decision as to whether to induce labor upon presentation of PROM. Women who present with PROM at term should be counseled on the management options and the risks and benefits of these options. Women should also be counseled that there is a higher risk of infection if PROM is managed expectantly, but that with antibiotic therapy the risk of neonatal infection is not increased. Women who are managed expectantly should know that signs or symptoms of infection are an indication for delivery. Furthermore, women should also be made aware that neither induction of labor nor antibiotic treatment can completely eliminate the risk of fetal central nervous system damage or neonatal sepsis, pneumonia, or death caused by infection.

Summary

IAI, most often a polymicrobial infection that ascends into the uterus from the vagina, is a significant cause of maternal and neonatal morbidity, including prematurity and CP. GBS antibiotic prophylaxis has been demonstrated to reduce the rate of GBS-related chorioamnionitis and neonatal GBS infection. Treatment of BV and trichomoniasis in pregnancy may help reduce the rate of IAI and should be considered in symptomatic women, especially in women at high risk for PTB, but treatment of trichomoniasis may carry a risk in itself of triggering PTL. Prompt diagnosis and treatment of clinically-evident IAI is essential in order to optimize maternal and neonatal outcomes. All women should, therefore, receive antenatal education on the risks and signs and symptoms of IAI and on the importance of reporting signs and symptoms of infection as well as of PROM, especially if this occurs before term.

When IAI is diagnosed, antibiotic and antipyretic treatment should be initiated promptly, and if labor is not already underway, induction is indicated. Digital vaginal exams in women who present with PROM should be minimized or avoided, especially in latent phase labor. In the absence of other indications for cesarean birth, vaginal birth is preferred for women with IAI, because these women are already at increased risk of postpartum endometritis, a risk that is further increased following cesarean birth. Timely diagnosis, prompt antibiotic treatment, and appropriate management of labor in women with IAI as described above can significantly improve the outcome for both the mother and her newborn.

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