eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Maternal Chorioamnionitis: Differential Diagnoses & Workup

Author: Michael P Sherman, MD, Professor, Department of Pediatrics, Southern Illinois University School of Medicine; Coordinator, Pediatric Residency Education in Neonatal Intensive Care, St John's Children's Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis School of Medicine
Coauthor(s): Katsufumi Otsuki, MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
Contributor Information and Disclosures

Updated: Jan 20, 2009

Differential Diagnoses

Herpes Simplex Virus Infection
Urinary Tract Infection

Other Problems to Be Considered

Urinary tract infections (particularly cystitis)
Vaginitis and cervicitis
Sexually transmitted diseases that cause pelvic infection and inflammation
Viral infections (eg, urogenital disease caused by herpes simplex virus)
Pelvic inflammatory disease
Pelvic adenitis (eg, herpes simplex, enteroviral infections [coxsackievirus])

Workup

Laboratory Studies

  • During the intrapartum period, diagnosis of chorioamnionitis is usually based on the clinical criteria. This is particularly true for pregnancies at term.
  • Bacteriologic cultures of amniotic fluid and urogenital discharge may be diagnostic for causative pathogens. Investigators have suggested that obtaining cervical cultures is associated with an increased risk of initiating amniotic fluid infection in the presence or absence of ruptured membranes. Silent chorioamnionitis is recognized as an important cause of premature labor.57
  • The asymptomatic pregnant mother who presents with premature labor or premature rupture of the membranes may require certain studies to exclude silent chorioamnionitis. To diagnose silent or obvious amniotic fluid infection or chorioamnionitis, the physician often uses laboratory examinations of the amniotic fluid, maternal blood, maternal urine, or a combination to make a diagnosis of infection.
  • Examination of amniotic fluid and urogenital secretions involves the following:
    • Amniotic fluid, obtained with amniocentesis, may be screened for leukocyte count, Gram stain, pH, glucose concentration, endotoxin, lactoferrin, cytokine levels (eg, interleukin [IL]-6), or a combination of these measured factors.
    • Cytokines commonly quantified in either amniotic fluid or blood include IL-6, tumor necrosis factor-alpha, IL-1, and IL-8.92,37 No consensus exists regarding which cytokine offers the best sensitivity, specificity, and positive versus negative predictive accuracy, although IL-6 is most often cited in the literature. Elevated IL-6 levels in cord blood and amniotic fluid have been related to adverse long-term neurologic outcomes in the neonate.93,94  This testing has not become routine, and such diagnostic aids are not used in rural communities.
    • Polymerase chain reaction (PCR) has rapidly developed as a diagnostic aid. It is used to identify microbes such as human immunodeficiency virus, cytomegalovirus, herpes simplex, parvovirus, toxoplasmosis, and bacterial DNA in amniotic and other body fluids. PCR has been used for the diagnosis of amniotic fluid infection caused by bacterial pathogens,95 but only university or academic centers may have this technology available to caregivers.
    • Amniocentesis to obtain amniotic fluid carries the risk of rupturing the fetal membranes. For this reason, screening tests that use cervicovaginal secretions to indicate chorioamnionitis have been reported. Potential markers of cervical or chorion inflammation include cervicovaginal secretion concentrations of fetal fibronectin, insulinlike growth factor binding protein-1, and sialidase. Significant association is noted among levels of cervical IL-6, fetal fibronectin, and amnionitis. Conversely, a positive mid gestational fetal fibronectin assay was not associated with acute histologic placental inflammation at birth.96  Proteomic profiling of amniotic fluid detects intrauterine inflammation and/or infection and predicts subsequent neonatal sepsis.97 Caregivers should follow this research that is not yet widely available in hospitals.   
    • Antenatal screening examinations demonstrate that the presence of group B streptococcal (GBS) colonization increases the risk of chorioamnionitis, and intrapartum prophylaxis with antibiotics reduces the incidence of neonatal infection from GBS.98,99 Intrapartum screening for GBS using the rapid Streptococcus B test on vaginal secretions identifies more at-risk infants than any other test. The use of the rapid screen for GBS to select mothers who would receive intrapartum chemoprophylaxis may also reduce the cost by approximately $12,000 per prevented case of neonatal infection.100  More recent studies from Europe have also shown effectiveness of GBS screening and intrapartum chemoprophylaxis, but the investigators have also made suggestions how PCR can improve screening.101
  • Examinations of maternal blood
    • WBC counts or C-reactive protein (CRP) levels in maternal blood have been used to predict acute chorioamnionitis when maternal fever is present. Different studies have supported or refuted the use of CRP to diagnose chorioamnionitis.102,103 The CRP level may be a better predictor of the risk of chorioamnionitis than peripheral WBC counts, especially if the mother has received corticosteroids, which may falsely increase the total WBC count.
    • Other investigators have suggested that the alpha1-proteinase inhibitor complex in maternal blood is a better predictor of amniotic fluid infection than either CRP or WBC count.
      • Analyzing amniotic fluid for leukocytes appears to be a better predictor of amniotic fluid infection than levels of either CRP or total WBC count in maternal blood. In fact, the combination of leukocytosis and a low glucose concentration in the amniotic fluid is highly indicative of chorioamnionitis and may be the best predictor of this condition.
      • Analysis of maternal serum for either IL-6 or ferritin content may also be helpful, because elevations in these mediators are associated with maternal or neonatal infection. Serum IL-6 levels may be more predictive than CRP concentrations in maternal blood.
      • Alpha1-proteinase inhibitor complex, cytokines, and ferritin in maternal blood have not gained widespread use as markers of acute chorioamnionitis.
  • The criterion standard for making a diagnosis of early-onset bacteremia, pneumonia, or meningitis in the neonate is the growth of bacteria in an appropriate specimen (ie, blood, tracheal secretions, cerebrospinal fluid [CSF]). Urinary tract infection is an infrequent cause of early onset bacterial disease in the neonate; thus, suprapubic bladder taps are not usually required as part of the evaluation.104,105
    • In recent years, controversy has arisen regarding the inclusion of the lumbar puncture as part of the evaluation for sepsis. Some clinicians have argued that the neonate with meningitis has obvious manifestations, and the asymptomatic term neonate does not require a lumbar puncture as part of the evaluation for sepsis. Other caregivers argue that a lumbar puncture can only be performed safely when life-threatening pulmonary dysfunction resolves.
    • Other investigators have stressed that cases of meningitis may be missed with this approach.106 The medical literature contains good evidence that meningitis may exist in association with sterile blood cultures. As meningitis can be such a devastating infection and sterile blood culture in association with no lumbar puncture may result in inadequate therapy for meningitis, a lumbar puncture should continue to be performed as part of the evaluation for neonatal sepsis.
  • Studies that are also considered specific for infection include positive findings on Gram stains of CSF or tracheal secretions.107
    • The tracheal secretions must be obtained shortly after birth (<4-8 h). Both tracheal fluids and CSF should be sterile at birth. The presence of bacteria on microscopic analysis (ie, Gram stain) indicates that more than 10,000 colony-forming units of bacteria are present per milliliter of specimen (body fluid). However, the absence of bacteria in either CSF or tracheal secretions does not exclude infection. A final diagnosis should be made after culture results are available.
    • An absence of neutrophils in CSF or tracheal secretions is expected. The presence of neutrophils in tracheal aspirates obtained after birth indicates that the fetus has mounted an inflammatory response to infection in the environment.
    • Studies by the primary author and separate studies by pathologists indicate that neutrophils present in tracheal secretions shortly after birth originate from the fetus or neonate and do not represent aspirated maternal neutrophils found in infected amniotic fluid.
      • This conclusion is based on examining Y-body fluorescence of the neutrophils present in the tracheal secretions of infected male neonates.
      • In some studies, 50% of the neutrophils present in tracheal secretions of infants with suspected congenital pneumonia had Y-chromosome fluorescence, indicating a fetal origin. 
      • Conversely, 10% of neutrophils in gastric aspirates from the same infants had Y-chromosomal fluorescence. Thus, neutrophils in gastric aspirates are primarily maternal neutrophils, and they represent WBCs present in infected amniotic fluid that is swallowed by the fetus.
      • Alternatively, the flux of fetal airway fluid is outward from the lung. Maternal neutrophils can gain access to the fetal lung only when gasping occurs during fetal asphyxia.
      • The male neutrophils observed in the gastric aspirates of these infants with congenital pneumonia indicated that neutrophils were swallowed after they left the fetal lung via the outward flux of airway fluid.
  • Bacterial antigen detection in CSF is also a useful test to indicate bacterial infection. Bacterial antigen detection in the urine should not be a part of the neonate's evaluation for sepsis. Many factors can cause false-positive or false-negative test results in bacterial antigen detection in the urine. Surface cultures have no role in decision-making regarding the diagnosis and treatment of the neonate with early onset bacterial infection.
  • All other tests used to diagnose early-onset bacterial infection in the neonate should be considered screening tests. The most common laboratory studies used to screen for neonatal sepsis are WBC profiles and CRP determinations. These tests, at best, are presumptive indicators of infection.
    • WBC profiles (leukopenia [<5000/µL], leukocytosis [>30,000/µL], a markedly diminished absolute neutrophil count [<500-1500/µL], an immature-total neutrophil ratio [>0.3-0.4]) are a commonly used screening test for the septic neonate. Note that the immature-to-total neutrophil ratio of 0.3-0.4 is higher than the previous value of 0.2 reported in the classic studies of Manroe (1977 and 1979).108,109 Clinical pathologists have been less accepting of the immature-to-total neutrophil ratio as a diagnostic aid in neonatal sepsis.110  
    • Recent studies have reexamined the WBC counts and the leukocyte profiles that are seen in extremely preterm infants111 and at high altitude.40  Other diagnostic tests (eg, inflammatory factors, adhesion molecules, cytokines, neutrophil surface antigens, or even bacterial DNA) may be superior alternatives to this test. To date, these markers of neonatal inflammation/infection have not replaced leukocyte counts as diagnostic aids.
    • WBC profiles and kinetics are influenced by the genetic makeup of the patient, the gestational age, maternal noninfectious disorders such as pregnancy-induced hypertension (PIH), medications administered to the mother, fetal disease, and many other factors. Reference range WBC counts in the neonate do not exclude infection, and serial studies of WBC indices at approximately 6-hour intervals may be more useful in detecting sepsis.112 A continued assessment of WBC kinetics offers more information regarding decision making. For example, a physician should be particularly concerned when a falling total WBC count, a declining absolute neutrophil count, and a rising immature-to-total neutrophil ratio are observed. This finding may indicate depletion in the bone marrow–related storage pool of neutrophils.113  
    • Transfusion of neutrophils in this scenario is no longer used because preparation of granulocytes without degranulation of their antimicrobial peptides and downregulation of the respiratory burst is problematic. 
    • The predictive accuracy of WBC indices for the diagnosis of the early onset sepsis (EOS) is poor. Likewise, the accuracy of CRP determinations to predict neonatal infections shortly after birth is low. However, persistently negative findings on CRP may be useful in the decision to stop antibiotic therapy after 48 hours.114
    • Akin to maternal diagnostic studies for infection, alpha1-proteinase inhibitor complex, cytokines (eg, IL-1 and IL-6 in particular, IL-1 receptor antagonist), and detection of bacterial products in neonatal blood have not gained widespread use as markers of neonatal sepsis. However, they may prove to have better predictive accuracy than WBC tests or the CRP. Procalcitonin may have better sensitivity, specificity, and positive and negative predictive value than CRP in the diagnosis of early onset neonatal sepsis.115 None of these tests for EOS are in widespread use, especially in rural hospitals.
    • The study of surface markers of inflammation on leukocytes has provided variable diagnostic use in EOS.116,117  More research is needed in this field.
    • Molecular methods to identify pathogenic bacteria in neonatal blood have engendered enormous interest because rapid diagnosis is possible.118,119,120,121  Most hospital laboratories do not have the equipment, the wide range of molecular probes, or the trained personnel to accomplish this diagnostic task. Caregivers should pay close attention to field.

Imaging Studies

  • Ultrasonography may be used to ascertain fetal well-being. A biophysical profile (BPP) provides information about the status of the fetus. A low BPP score, and especially the loss of fetal breathing movements, has been associated with fetal bacterial infection after premature rupture of membranes.62,61 Other investigations have not confirmed the importance of a low BPP score, and specifically the absence of fetal breathing, as a reliable test for amnionitis prior to 32 weeks' gestation.122,123
  • Before the fetus is viable, vaginal ultrasonography can be used to identify women with a shortened cervical canal that has been associated with a higher risk of preterm delivery.124,24,63 Researchers suggest a shortened cervical canal or cervical insufficiency are linked to ascending urogenital infection that initiates premature labor, premature rupture of the membranes, or both.

Other Tests

  • The common tests used to diagnose maternal chorioamnionitis are discussed above.
  • Tests still in investigational stages and that have not yet come to the bedside are discussed if the testing can reasonably improve clinical outcomes.

Procedures

  • Needle aspiration and analysis of amniotic fluid is the only invasive procedure used to confirm diagnosis of acute chorioamnionitis. This procedure can be risky with intact fetal membranes, because the fetal membranes can rupture during or after the procedure.
  • Bleeding or placental abruption can also be a consequence of the procedure. The procedure should be performed using ultrasonographic guidance to avoid fetal injury. For these reasons, aspiration of amniotic fluid to diagnose maternal chorioamnionitis has had limited application in obstetric practice.

Histologic Findings

  • Gross and microscopic examinations of the placenta, fetal membranes, and umbilical cord for evidence of inflammation and infection are crucial to make a definitive diagnosis of chorioamnionitis.13 Histologic chorioamnionitis is a reliable indicator of infection whether or not it is clinically apparent.125  Nevertheless, anatomic studies should be correlated with an aseptic culture obtained from the fetal surface of the placenta when caregivers are considering EOS.
  • The microbiologic cultures should include an attempt to isolate aerobic and anaerobic bacteria. Special microbiologic techniques may be required for certain microorganisms such as Listeria monocytogenes. Only in these ways can the pathologist help the bedside clinician delineate the cause of maternal chorioamnionitis and neonatal sepsis. Clinicians are encouraged to ask pathologists for help in their search for infections causing disease in the pregnant woman, fetus, and newborn. Obstetricians must also obtain the placenta, fetal membranes, and umbilical cord samples for analytical studies when suspicious clinical circumstances are noted.

Staging

  • Redline and colleagues (2003) proposed a scoring system for placental examination that promotes consistency when pathologists judge the severity of chorioamnionitis.126
  • Several physiologic scores have been proposed for neonates who have life-threatening illness, but a recent report could not conclude that one of those scores accurately predicted neonatal morbidity and mortality during neonatal infection.127

More on Maternal Chorioamnionitis

Overview: Maternal Chorioamnionitis
Differential Diagnoses & Workup: Maternal Chorioamnionitis
Treatment & Medication: Maternal Chorioamnionitis
Follow-up: Maternal Chorioamnionitis
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Escobar GJ. The neonatal "sepsis work-up": personal reflections on the development of an evidence-based approach toward newborn infections in a managed care organization. Pediatrics. Jan 1999;103(1 Suppl E):360-73. [Medline].

  2. Callaghan WM, MacDorman MF, Rasmussen SA, Qin C, Lackritz EM. The contribution of preterm birth to infant mortality rates in the United States. Pediatrics. Oct 2006;118(4):1566-73. [Medline].

  3. Larsen JW, Sever JL. Group B Streptococcus and pregnancy: a review. Am J Obstet Gynecol. Apr 2008;198(4):440-8; discussion 448-50. [Medline].

  4. Baltimore RS. Consequences of prophylaxis for group B streptococcal infections of the neonate. Semin Perinatol. Feb 2007;31(1):33-8. [Medline].

  5. Stoll BJ, Hansen NI, Higgins RD. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J. Jul 2005;24(7):635-9. [Medline].

  6. Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG. Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics. Apr 2008;121(4):689-96. [Medline].

  7. Schrag SJ, Hadler JL, Arnold KE, Martell-Cleary P, Reingold A, Schuchat A. Risk factors for invasive, early-onset Escherichia coli infections in the era of widespread intrapartum antibiotic use. Pediatrics. Aug 2006;118(2):570-6. [Medline].

  8. Bratu S, Eramo A, Kopec R. Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units. Emerg Infect Dis. Jun 2005;11(6):808-13. [Medline].

  9. Andrews WW, Schelonka R, Waites K, Stamm A, Cliver SP, Moser S. Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol. Jan 2008;111(1):113-8. [Medline].

  10. Hollier LM, Wendel GD Jr [Editors]. Infectious Diseases in Pregnancy. Clin Perinatol. 2005;32 (3):523-814.

  11. Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med. Jan 2007;25(1):21-39. [Medline].

  12. Romero R, Gotsch F, Pineles B, Kusanovic JP. Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev. Dec 2007;65(12 Pt 2):S194-202. [Medline].

  13. Reilly SD, Faye-Petersen OM. Chorioamnionitis and Funisitis: Their Implications for the Neonate. NeoReviews [serial online]. September 2008;9:e411-e417. Available from: American Academy of Pediatrics. Accessed September 21, 2008. Available at http://neoreviews.aappublications.org/cgi/content/full/neoreviews;9/9/e411.

  14. Hitti J, Hillier SL, Agnew KJ, Krohn MA, Reisner DP, Eschenbach DA. Vaginal indicators of amniotic fluid infection in preterm labor. Obstet Gynecol. Feb 2001;97(2):211-9. [Medline].

  15. Al-Adnani M, Sebire NJ. The role of perinatal pathological examination in subclinical infection in obstetrics. Best Pract Res Clin Obstet Gynaecol. Jun 2007;21(3):505-21. [Medline].

  16. Anderson BL, Simhan HN, Simons KM, Wiesenfeld HC. Untreated asymptomatic group B streptococcal bacteriuria early in pregnancy and chorioamnionitis at delivery. Am J Obstet Gynecol. Jun 2007;196(6):524.e1-5. [Medline].

  17. Hakansson S, Kallen K. High maternal body mass index increases the risk of neonatal early onset group B streptococcal disease. Acta Paediatr. Oct 2008;97(10):1386-9. [Medline].

  18. [Best Evidence] Swadpanich U, Lumbiganon P, Prasertcharoensook W, Laopaiboon M. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database Syst Rev. Apr 16 2008;CD006178. [Medline].

  19. [Best Evidence] McDonald HM, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. Jan 24 2007;CD000262. [Medline].

  20. Siqueira FM, Cota LO, Costa JE, Haddad JP, Lana AM, Costa FO. Intrauterine growth restriction, low birth weight, and preterm birth: adverse pregnancy outcomes and their association with maternal periodontitis. J Periodontol. Dec 2007;78(12):2266-76. [Medline].

  21. Aly H, Alhabashi G, Hammad TA, Owusu-Ansah S, Bathgate S, Mohamed M. ABO phenotype and other risk factors associated with chorioamnionitis. J Pediatr. Jul 2008;153(1):16-8. [Medline].

  22. Kabiru W, Raynor BD. Obstetric outcomes associated with increase in BMI category during pregnancy. Am J Obstet Gynecol. Sep 2004;191(3):928-32. [Medline].

  23. Raatikainen K, Heiskanen N, Heinonen S. Transition from overweight to obesity worsens pregnancy outcome in a BMI-dependent manner. Obesity (Silver Spring). Jan 2006;14(1):165-71. [Medline].

  24. Hassan S, Romero R, Hendler I, et al. A sonographic short cervix as the only clinical manifestation of intra-amniotic infection. J Perinat Med. 2006;34(1):13-9. [Medline].

  25. Lee SE, Romero R, Park CW, Jun JK, Yoon BH. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency. Am J Obstet Gynecol. Jun 2008;198(6):633.e1-8. [Medline].

  26. [Best Evidence] Heinemann J, Gillen G, Sanchez-Ramos L, Kaunitz AM. Do mechanical methods of cervical ripening increase infectious morbidity? A systematic review. Am J Obstet Gynecol. Aug 2008;199(2):177-87; discussion 187-8. [Medline].

  27. Verma RP, Kaplan C, Southerton K, Niwas R, Verma R, Fang H. Placental histopathology in the extremely low birth weight infants. Fetal Pediatr Pathol. Aug 2008;27(2):53-61. [Medline].

  28. Newton ER. Preterm labor, preterm premature rupture of membranes, and chorioamnionitis. Clin Perinatol. Sep 2005;32(3):571-600. [Medline].

  29. Obi SN, Ozumba BC. Pre-term premature rupture of fetal membranes: the dilemma of management in a developing nation. J Obstet Gynaecol. Jan 2007;27(1):37-40. [Medline].

  30. Naeye RL, Tafari N, Judge D, Gilmour D, Marboe C. Amniotic fluid infections in an African city. J Pediatr. Jun 1977;90(6):965-70. [Medline].

  31. Appelbaum PC, Ross SM, Dhupelia I, Naeye RL. The effect of diet supplementation and addition of zinc in vitro on the growth-supporting property of amniotic fluid in African women. Am J Obstet Gynecol. Sep 1 1979;135(1):82-4. [Medline].

  32. Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. May 15 2008;46(10):1582-8. [Medline].

  33. Goldenberg RL, Andrews WW, Faye-Petersen OM, Cliver SP, Goepfert AR, Hauth JC. The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to 32-week newborns with various markers of intrauterine infection. Am J Obstet Gynecol. Oct 2006;195(4):1020-4. [Medline].

  34. Neufeld MD, Frigon C, Graham AS, Mueller BA. Maternal infection and risk of cerebral palsy in term and preterm infants. J Perinatol. Feb 2005;25(2):108-13. [Medline].

  35. Versland LB, Sommerfelt K, Elgen I. Maternal signs of chorioamnionitis: persistent cognitive impairment in low-birthweight children. Acta Paediatr. Feb 2006;95(2):231-5. [Medline].

  36. Bashiri A, Burstein E, Mazor M. Cerebral palsy and fetal inflammatory response syndrome: a review. J Perinat Med. 2006;34(1):5-12. [Medline].

  37. Hagberg H, Mallard C, Jacobsson B. Role of cytokines in preterm labour and brain injury. BJOG. Mar 2005;112 Suppl 1:16-8. [Medline].

  38. Redline R, Minich N, Taylor H, Hack M. Placental lesions as predictors of cerebral palsy and abnormal neurocognitive function at school age in extremely low birth weight infants (<1 Kg). Pediatr Dev Pathol. Mar 22 2007;1. [Medline].

  39. Viscardi RM, Muhumuza CK, Rodriguez A, et al. Inflammatory markers in intrauterine and fetal blood and cerebrospinal fluid compartments are associated with adverse pulmonary and neurologic outcomes in preterm infants. Pediatr Res. Jun 2004;55(6):1009-17. [Medline].

  40. Schelonka RL, Waites KB. Ureaplasma infection and neonatal lung disease. Semin Perinatol. Feb 2007;31(1):2-9. [Medline].

  41. Adams-Chapman I, Stoll BJ. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis. Jun 2006;19(3):290-7. [Medline].

  42. Ragouilliaux CJ, Keeney SE, Hawkins HK, Rowen JL. Maternal factors in extremely low birth weight infants who develop spontaneous intestinal perforation. Pediatrics. Dec 2007;120(6):e1458-64. [Medline].

  43. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA. Nov 26 2003;290(20):2677-84. [Medline].

  44. Dulay AT, Buhimschi IA, Zhao G, et al. Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis. Am J Obstet Gynecol. Apr 2008;198(4):426.e1-9. [Medline].

  45. Redline RW. Elevated circulating fetal nucleated red blood cells and placental pathology in term infants who develop cerebral palsy. Hum Pathol. Sep 2008;39(9):1378-84. [Medline].

  46. Holzman C, Lin X, Senagore P, Chung H. Histologic chorioamnionitis and preterm delivery. Am J Epidemiol. Oct 1 2007;166(7):786-94. [Medline].

  47. Berenson AB, Wiemann CM, Wilkinson GS. Perinatal morbidity associated with violence experienced by pregnant women. Am J Obstet Gynecol. Jun 1994;170(6):1760-6; discussion 1766-9. [Medline].

  48. Turner BJ, McKee LJ, Silverman NS. Prenatal care and birth outcomes of a cohort of HIV-infected women. J Acquir Immune Defic Syndr Hum Retrovirol. Jul 1996;12(3):259-67. [Medline].

  49. Scholl TO. High third-trimester ferritin concentration: associations with very preterm delivery, infection, and maternal nutritional status. Obstet Gynecol. Aug 1998;92(2):161-6. [Medline].

  50. Romero R, Chaiworapongsa T, Espinoza J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr. May 2003;133(5 Suppl 2):1668S-1673S. [Medline].

  51. St Geme JW, Murray DL, Carter J. Perinatal bacterial infection after prolonged rupture of amniotic membranes: an analysis of risk and management. J Pediatr. Apr 1984;104(4):608-13. [Medline].

  52. Rickert VI, Wiemann CM, Hankins GD, McKee JM, Berenson AB. Prevalence and risk factors of chorioamnionitis among adolescents. Obstet Gynecol. Aug 1998;92(2):254-7. [Medline].

  53. Jolly MC, Sebire N, Harris J, Robinson S, Regan L. Obstetric risks of pregnancy in women less than 18 years old. Obstet Gynecol. Dec 2000;96(6):962-6. [Medline].

  54. O'Brien RF. Bacterial vaginosis: many questions--any answers?. Curr Opin Pediatr. Aug 2005;17(4):473-9. [Medline].

  55. Raatikainen K, Heiskanen N, Verkasalo PK, Heinonen S. Good outcome of teenage pregnancies in high-quality maternity care. Eur J Public Health. Apr 2006;16(2):157-61. [Medline].

  56. Snyder M, Crawford P, Jamieson B, Neher JO. Clinical inquiries. What treatment approach to intrapartum maternal fever has the best fetal outcomes?. J Fam Pract. May 2007;56(5):401-2. [Medline].

  57. Driscoll SG. Chorioamnionitis: perinatal morbidity and mortality. Pediatr Infect Dis. Nov-Dec 1986;5(6 Suppl):S273-5. [Medline].

  58. [Best Evidence] Tran SH, Cheng YW, Kaimal AJ, Caughey AB. Length of rupture of membranes in the setting of premature rupture of membranes at term and infectious maternal morbidity. Am J Obstet Gynecol. Jun 2008;198(6):700.e1-5. [Medline].

  59. Nath CA, Ananth CV, Smulian JC, Shen-Schwarz S, Kaminsky L. Histologic evidence of inflammation and risk of placental abruption. Am J Obstet Gynecol. Sep 2007;197(3):319.e1-6. [Medline].

  60. Miller JM Jr, Kho MS, Brown HL, Gabert HA. Clinical chorioamnionitis is not predicted by an ultrasonic biophysical profile in patients with premature rupture of membranes. Obstet Gynecol. Dec 1990;76(6):1051-4. [Medline].

  61. Vintzileos AM, Campbell WA, Nochimson DJ. Fetal breathing as a predictor of infection in premature rupture of the membranes. Obstet Gynecol. Jun 1986;67(6):813-7. [Medline].

  62. Vintzileos AM, Campbell WA, Nochimson DJ. The fetal biophysical profile in patients with premature rupture of the membranes--an early predictor of fetal infection. Am J Obstet Gynecol. Jul 1 1985;152(5):510-6. [Medline].

  63. Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. Oct 2007;30(5):706-14. [Medline].

  64. Aina-Mumuney AJ, Althaus JE, Henderson JL, Blakemore MC, Johnson EA, Graham EM. Intrapartum electronic fetal monitoring and the identification of systemic fetal inflammation. J Reprod Med. Sep 2007;52(9):762-8. [Medline].

  65. Lieberman E, Lang JM, Frigoletto F Jr. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. Mar 1997;99(3):415-9. [Medline].

  66. Lieberman E, Lang J, Richardson DK. Intrapartum maternal fever and neonatal outcome. Pediatrics. Jan 2000;105(1 Pt 1):8-13. [Medline].

  67. Vallejo MC, Kaul B, Adler LJ. Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour. Can J Anaesth. Dec 2001;48(11):1122-6. [Medline].

  68. Leighton BL, Halpern SH. Epidural analgesia: effects on labor progress and maternal and neonatal outcome. Semin Perinatol. Apr 2002;26(2):122-35. [Medline].

  69. Goetzl L, Evans T, Rivers J. Elevated maternal and fetal serum interleukin-6 levels are associated with epidural fever. Am J Obstet Gynecol. Oct 2002;187(4):834-8. [Medline].

  70. Alexander JM. Epidural analgesia for labor pain and its relationship to fever. Clin Perinatol. Sep 2005;32(3):777-87. [Medline].

  71. Otsuki K, Yoda A, Saito H. Amniotic fluid lactoferrin in intrauterine infection. Placenta. Mar-Apr 1999;20(2-3):175-9. [Medline].

  72. Hein M, Valore EV, Helmig RB. Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. Jul 2002;187(1):137-44. [Medline].

  73. King AE, Critchley HO, Kelly RW. Innate immune defences in the human endometrium. Reprod Biol Endocrinol. Nov 28 2003;1:116. [Medline].

  74. Akinbi HT, Narendran V, Pass AK. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. Dec 2004;191(6):2090-6. [Medline].

  75. Soto E, Espinoza J, Nien JK, et al. Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med. Jan 2007;20(1):15-22. [Medline].

  76. King AE, Kelly RW, Sallenave JM, Bocking AD, Challis JR. Innate immune defences in the human uterus during pregnancy. Placenta. Nov-Dec 2007;28(11-12):1099-106. [Medline].

  77. Gomez R, Romero R, Nien JK. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol. Mar 2005;192(3):678-89. [Medline].

  78. Wilks M, Wiggins R, Whiley A. Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. Feb 2004;42(2):713-7. [Medline].

  79. Balu RB, Savitz DA, Ananth CV. Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. Obstet Gynecol. May 2003;101(5 Pt 1):862-8. [Medline].

  80. Simoes JA, Aroutcheva A, Heimler I. Bacteriocin susceptibility of Gardnerella vaginalis and its relationship to biotype, genotype, and metronidazole susceptibility. Am J Obstet Gynecol. Nov 2001;185(5):1186-90. [Medline].

  81. Reid G, Burton J. Use of Lactobacillus to prevent infection by pathogenic bacteria. Microbes Infect. Mar 2002;4(3):319-24. [Medline].

  82. McGaw T. Periodontal disease and preterm delivery of low-birth-weight infants. J Can Dent Assoc. Mar 2002;68(3):165-9. [Medline].

  83. Urban E, Radnai M, Novak T. Distribution of anaerobic bacteria among pregnant periodontitis patients who experience preterm delivery. Anaerobe. Feb 2006;12(1):52-7. [Medline].

  84. Matorras R, Garcia Perea A, Omenaca F, Usandizaga JA, Nieto A, Herruzo R. Group B streptococcus and premature rupture of membranes and preterm delivery. Gynecol Obstet Invest. 1989;27(1):14-8. [Medline].

  85. Sanchez PJ, Regan JA. Vertical transmission of Ureaplasma urealyticum from mothers to preterm infants. Pediatr Infect Dis J. Jun 1990;9(6):398-401. [Medline].

  86. Spiegel CA. Bacterial vaginosis. Clin Microbiol Rev. Oct 1991;4(4):485-502. [Medline].

  87. Donder GG, Vereecken A, Bosmans E. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG. Jan 2002;109(1):34-43. [Medline].

  88. Dixon NG, Ebright D, Defrancesco MA. Orogenital contact: a cause of chorioamnionitis?. Obstet Gynecol. Oct 1994;84(4 Pt 2):654-5. [Medline].

  89. Hansen LM, Dorsey TA, Batzer FA. Capnocytophaga chorioamnionitis after oral sex. Obstet Gynecol. Oct 1996;88(4 Pt 2):731. [Medline].

  90. Naeye RL, Ross S. Coitus and chorioamnionitis: a prospective study. Early Hum Dev. Jan 1982;6(1):91-7. [Medline].

  91. [Best Evidence] Yost NP, Owen J, Berghella V. Effect of coitus on recurrent preterm birth. Obstet Gynecol. Apr 2006;107(4):793-7. [Medline].

  92. Figueroa R, Garry D, Elimian A. Evaluation of amniotic fluid cytokines in preterm labor and intact membranes. J Matern Fetal Neonatal Med. Oct 2005;18(4):241-7. [Medline].

  93. Volante E, Moretti S, Pisani F. Early diagnosis of bacterial infection in the neonate. J Matern Fetal Neonatal Med. Nov 2004;16 Suppl 2:13-6. [Medline].

  94. Kayem G, Goffinet F, Batteux F. Detection of interleukin-6 in vaginal secretions of women with preterm premature rupture of membranes and its association with neonatal infection: a rapid immunochromatographic test. Am J Obstet Gynecol. Jan 2005;192(1):140-5. [Medline].

  95. Straka M, Dela Cruz W, Blackmon C. Rapid detection of group B streptococcus and Escherichia coli in amniotic fluid using real-time fluorescent PCR. Infect Dis Obstet Gynecol. Sep-Dec 2004;12(3-4):109-14. [Medline].

  96. Akers A, Jarzembowski JA, Johnson CT, Lieberman RW, Dalton VK. Examining the relationship between positive mid-gestational fetal fibronectin assays and histological evidence of acute placental inflammation. J Perinat Med. 2007;35(1):36-42. [Medline].

  97. Buhimschi CS, Bhandari V, Hamar BD, et al. Proteomic profiling of the amniotic fluid to detect inflammation, infection, and neonatal sepsis. PLoS Med. Jan 2007;4(1):e18. [Medline].

  98. Perinatal group B streptococcal disease after universal screening recommendations--United States, 2003-2005. MMWR Morb Mortal Wkly Rep. Jul 20 2007;56(28):701-5. [Medline].

  99. Elvedi-Gasparovic V, Peter B. Maternal group B streptococcus infection, neonatal outcome and the role of preventive strategies. Coll Antropol. Mar 2008;32(1):147-51. [Medline].

  100. Benitz WE, Gould JB, Druzin ML. Preventing early-onset group B streptococcal sepsis: strategy development using decision analysis. Pediatrics. Jun 1999;103(6):e76. [Medline].

  101. Akker-van Marle ME, Rijnders ME, Dommelen P, et al. Cost-effectiveness of different treatment strategies with intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease. BJOG. Jun 2005;112(6):820-6. [Medline].

  102. Shim SS, Romero R, Jun JK. C-reactive protein concentration in vaginal fluid as a marker for intra-amniotic inflammation/infection in preterm premature rupture of membranes. J Matern Fetal Neonatal Med. Dec 2005;18(6):417-22. [Medline].

  103. Wiwanitkit V. Maternal C-reactive protein for detection of chorioamnionitis: an appraisal. Infect Dis Obstet Gynecol. Sep 2005;13(3):179-81. [Medline].

  104. Visser VE, Hall RT. Urine culture in the evaluation of suspected neonatal sepsis. J Pediatr. Apr 1979;94(4):635-8. [Medline].

  105. Sherman MP, Chance KH, Goetzman BW. Gram's stains of tracheal secretions predict neonatal bacteremia. Am J Dis Child. Sep 1984;138(9):848-50. [Medline].

  106. Wiswell TE, Baumgart S, Gannon CM. No lumbar puncture in the evaluation for early neonatal sepsis: will meningitis be missed?. Pediatrics. Jun 1995;95(6):803-6. [Medline].

  107. Sherman MP, Goetzman BW, Ahlfors CE. Tracheal asiration and its clinical correlates in the diagnosis of congenital pneumonia. Pediatrics. Feb 1980;65(2):258-63. [Medline].

  108. Manroe BL, Rosenfeld CR, Weinberg AG. The differential leukocyte count in the assessment and outcome of early-onset neonatal group B streptococcal disease. J Pediatr. Oct 1977;91(4):632-7. [Medline].

  109. Manroe BL, Weinberg AG, Rosenfeld CR. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr. Jul 1979;95(1):89-98. [Medline].

  110. Cornbleet PJ. Clinical utility of the band count. Clin Lab Med. Mar 2002;22(1):101-36. [Medline].

  111. Christensen RD, Henry E, Wiedmeier SE, Stoddard RA, Lambert DK. Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system. J Perinatol. Nov 2006;26(11):682-7. [Medline].

  112. Christensen RD. Morphology and concentration of circulating neutrophils in neonates with bacterial sepsis. Pediatr Infect Dis J. May 1987;6(5):429-30. [Medline].

  113. Christensen RD, Rothstein G, Anstall HB, Bybee B. Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils. Pediatrics. Jul 1982;70(1):1-6. [Medline].

  114. Benitz WE, Han MY, Madan A. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics. Oct 1998;102(4):e41. [Medline].

  115. Joram N, Boscher C, Denizot S. Umbilical cord blood procalcitonin and C reactive protein concentrations as markers for early diagnosis of very early onset neonatal infection. Arch Dis Child Fetal Neonatal Ed. Jan 2006;91(1):F65-6. [Medline].

  116. Ng PC, Li G, Chui KM, et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatr Res. Nov 2004;56(5):796-803. [Medline].

  117. Ng PC, Li G, Chui KM, et al. Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection. Biol Neonate. 2006;89(2):75-81. [Medline].

  118. Mishra UK, Jacobs SE, Doyle LW, Garland SM. Newer approaches to the diagnosis of early onset neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. May 2006;91(3):F208-12. [Medline].

  119. Brozanski BS, Jones JG, Krohn MJ, Jordan JA. Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay. J Perinatol. Nov 2006;26(11):688-92. [Medline].

  120. Makhoul IR, Sprecher H, Smolkin T, Sawaid R, Ben-David S, Sujov P, et al. Approach to term neonates born after maternal intrapartum fever and unknown maternal group B Streptococcus status: value of serum C-reactive protein and 16S rRNA gene PCR amplification. Pediatr Infect Dis J. Nov 2007;26(11):1064-6. [Medline].

  121. Ohlin A, Backman A, Bjorkqvist M, Molling P, Jurstrand M, Schollin J. Real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal bacteraemia. Acta Paediatr. Oct 2008;97(10):1376-80. [Medline].

  122. Sherer DM, Spong CY, Salafia CM. Fetal breathing movements within 24 hours of delivery in prematurity are related to histologic and clinical evidence of amnionitis. Am J Perinatol. Jul 1997;14(6):337-40. [Medline].

  123. Ghidini A, Salafia CM, Kirn V. Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks. Obstet Gynecol. Aug 2000;96(2):201-6. [Medline].

  124. Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. Ultrasonographic assessment of the uterine cervix and interleukin-8 concentrations in cervical secretions predict intrauterine infection in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol. Aug 1998;12(2):86-92. [Medline].

  125. Heller DS, Rimpel LH, Skurnick JH. Does histologic chorioamnionitis correspond to clinical chorioamnionitis?. J Reprod Med. Jan 2008;53(1):25-8. [Medline].

  126. Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C. Amniotic infection syndrome: nosology and reproducibility of placental reaction patterns. Pediatr Dev Pathol. Sep-Oct 2003;6(5):435-48. [Medline].

  127. Lim L, Rozycki HJ. Postnatal SNAP-II scores in neonatal intensive care unit patients: relationship to sepsis, necrotizing enterocolitis, and death. J Matern Fetal Neonatal Med. Jun 2008;21(6):415-9. [Medline].

  128. Winn HN. Group B streptococcus infection in pregnancy. Clin Perinatol. Sep 2007;34(3):387-92. [Medline].

  129. Schrag SJ, Zell ER, Lynfield R. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. Jul 25 2002;347(4):233-9. [Medline].

  130. Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. Aug 16 2002;51:1-22. [Medline]. [Full Text].

  131. Apgar BS, Greenberg G, Yen G. Prevention of group B streptococcal disease in the newborn. Am Fam Physician. Mar 1 2005;71(5):903-10. [Medline].

  132. Amstey MS, Gibbs RS. Is penicillin G a better choice than ampicillin for prophylaxis of neonatal group B streptococcal infections?. Obstet Gynecol. Dec 1994;84(6):1058-9. [Medline].

  133. Alarcon A, Pena P, Salas S, et al. Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis. Pediatr Infect Dis J. Apr 2004;23(4):295-9. [Medline].

  134. Gibbs RS, Schrag S, Schuchat A. Perinatal infections due to group B streptococci. Obstet Gynecol. Nov 2004;104(5 Pt 1):1062-76. [Medline].

  135. Schelonka RL, Infante AJ. Neonatal immunology. Semin Perinatol. Feb 1998;22(1):2-14. [Medline].

  136. Suri M, Harrison L, Van de Ven C, Cairo MS. Immunotherapy in the prophylaxis and treatment of neonatal sepsis. Curr Opin Pediatr. Apr 2003;15(2):155-60. [Medline].

  137. Shaw CK, Thapalial A, Shaw P, Malla K. Intravenous immunoglobulins and haematopoietic growth factors in the prevention and treatment of neonatal sepsis: ground reality or glorified myths?. Int J Clin Pract. Mar 2007;61(3):482-7. [Medline].

  138. Boggess KA. Pathophysiology of preterm birth: emerging concepts of maternal infection. Clin Perinatol. Sep 2005;32(3):561-9. [Medline].

  139. [Best Evidence] Shennan A, Crawshaw S, Briley A. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG. Jan 2006;113(1):65-74. [Medline].

  140. Borchardt SM, DeBusscher JH, Tallman PA, et al. Frequency of antimicrobial resistance among invasive and colonizing Group B streptococcal isolates. BMC Infect Dis. Mar 20 2006;6:57. [Medline].

  141. Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. May 7 2008;299(17):2056-65. [Medline].

  142. Young TE, Mangum B. Antimicrobials. In: NEOFAX 2008. 21st Edition. Montvale, NJ: Thomson Reuters; 2008:1-79.

  143. Speer CP. Pulmonary inflammation and bronchopulmonary dysplasia. J Perinatol. May 2006;26 Suppl 1:S57-62; discussion S63-4. [Medline].

  144. Ryan RM, Ahmed Q, Lakshminrusimha S. Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia. Clin Rev Allergy Immunol. Apr 2008;34(2):174-90. [Medline].

  145. Weinstein L. A multifacited approach to improve patient safety, prevent medical errors and resolve the professional liability crisis. Am J Obstet Gynecol. Apr 2006;194(4):1160-5; discussion 1165-7. [Medline].

  146. Donn SM. Medical liability, risk management, and the quality of health care. Semin Fetal Neonatal Med. Feb 2005;10(1):3-9. [Medline].

  147. Shwayder JM. Liability in high-risk obstetrics. Obstet Gynecol Clin North Am. Sep 2007;34(3):617-25, xiv. [Medline].

  148. Bonadio WA. Medical-legal considerations related to symptom duration and patient outcome after bacterial meningitis. Am J Emerg Med. Jul 1997;15(4):420-3. [Medline].

  149. Shalak LF, Laptook AR, Jafri HS. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics. Oct 2002;110(4):673-80. [Medline].

  150. Grether JK, Nelson KB, Walsh E. Intrauterine exposure to infection and risk of cerebral palsy in very preterm infants. Arch Pediatr Adolesc Med. Jan 2003;157(1):26-32. [Medline].

  151. Graham EM, Holcroft CJ, Rai KK. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis. Am J Obstet Gynecol. Oct 2004;191(4):1305-10. [Medline].

  152. Seubert DE, Huang WM, Wasserman-Hoff R. Medical legal issues in the prevention of prematurity. Clin Perinatol. Jun 2007;34(2):309-18, vii. [Medline].

  153. Yancey MK, Zhang J, Schwarz J, Dietrich CS 3rd, Klebanoff M. Labor epidural analgesia and intrapartum maternal hyperthermia. Obstet Gynecol. Nov 2001;98(5 Pt 1):763-70. [Medline].

  154. Mantha VR, Vallejo MC, Ramesh V, Phelps AL, Ramanathan S. The incidence of maternal fever during labor is less with intermittent than with continuous epidural analgesia: a randomized controlled trial. Int J Obstet Anesth. Apr 2008;17(2):123-9. [Medline].

  155. Impey L, Greenwood C, MacQuillan K, Reynolds M, Sheil O. Fever in labour and neonatal encephalopathy: a prospective cohort study. BJOG. Jun 2001;108(6):594-7. [Medline].

  156. Goldenberg RL, Andrews WW, Goepfert AR, et al. The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants. Am J Obstet Gynecol. Jan 2008;198(1):43.e1-5. [Medline].

  157. Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstet Gynecol. Jun 2003;101(6):1183-9. [Medline].

  158. Matlow A, Th'ng C, Kovach D, Quinn P, Dunn M, Wang E. Susceptibilities of neonatal respiratory isolates of Ureaplasma urealyticum to antimicrobial agents. Antimicrob Agents Chemother. May 1998;42(5):1290-2. [Medline].

  159. ACOG Statement. ACOG practice bulletin. Premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Number 1, June 1998. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. Oct 1998;63(1):75-84. [Medline].

  160. Alanen A. Polymerase chain reaction in the detection of microbes in amniotic fluid. Ann Med. Jun 1998;30(3):288-95. [Medline].

  161. Andrews WW, Cliver SP, Biasini F, et al. Early preterm birth: association between in utero exposure to acute inflammation and severe neurodevelopmental disability at 6 years of age. Am J Obstet Gynecol. Apr 2008;198(4):466.e1-466.e11. [Medline].

  162. Badri MS, Zawaneh S, Cruz AC. Rectal colonization with group B streptococcus: relation to vaginal colonization of pregnant women. J Infect Dis. Feb 1977;135(2):308-12. [Medline].

  163. Benitz WE, Gould JB, Druzin ML. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics. Jun 1999;103(6):e77. [Medline].

  164. Berger C, Uehlinger J, Ghelfi D. Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicemia. Eur J Pediatr. Feb 1995;154(2):138-44. [Medline].

  165. Bint AJ, Hill D. Bacteriuria of pregnancy--an update on significance, diagnosis and management. J Antimicrob Chemother. May 1994;33 Suppl A:93-7. [Medline].

  166. Boggess KA, Trevett TN, Madianos PN. Use of DNA hybridization to detect vaginal pathogens associated with bacterial vaginosis among asymptomatic pregnant women. Am J Obstet Gynecol. Sep 2005;193(3 Pt 1):752-6. [Medline].

  167. Brocklehurst P. Infection and preterm delivery. BMJ. Feb 27 1999;318(7183):548-9. [Medline].

  168. Carey JC, Klebanoff MA, Hauth JC. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. Feb 24 2000;342(8):534-40. [Medline].

  169. Christensen RD, Rothstein G, Hill HR. Fatal early onset group B streptococcal sepsis with normal leukocyte counts. Pediatr Infect Dis. May-Jun 1985;4(3):242-5. [Medline].

  170. Churgay CA, Smith MA, Blok B. Maternal fever during labor--what does it mean?. J Am Board Fam Pract. Jan-Feb 1994;7(1):14-24. [Medline].

  171. Dashe JS, Rogers BB, McIntire DD. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol. Mar 1999;93(3):341-4. [Medline].

  172. Dobson SR, Isaacs D, Wilkinson AR. Reduced use of surface cultures for suspected neonatal sepsis and surveillance. Arch Dis Child. Jan 1992;67(1 Spec No):44-7. [Medline].

  173. Dudley DJ. Immunoendocrinology of preterm labor: the link between corticotropin-releasing hormone and inflammation. Am J Obstet Gynecol. Jan 1999;180(1 Pt 3):S251-6. [Medline].

  174. Espinoza J, Chaiworapongsa T, Romero R. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. Jan 2003;13(1):2-21. [Medline].

  175. Garcia-Prats JA, Cooper TR, Schneider VF. Rapid detection of microorganisms in blood cultures of newborn infants utilizing an automated blood culture system. Pediatrics. Mar 2000;105(3 Pt 1):523-7. [Medline].

  176. Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol. May 1982;59(5):539-45. [Medline].

  177. Gibbs RS, Davies JK, McDuffie RS Jr. Chronic intrauterine infection and inflammation in the preterm rabbit, despite antibiotic therapy. Am J Obstet Gynecol. Feb 2002;186(2):234-9. [Medline].

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

  179. Gilstrap LC 3d, Leveno KJ, Cox SM. Intrapartum treatment of acute chorioamnionitis: impact on neonatal sepsis. Am J Obstet Gynecol. Sep 1988;159(3):579-83. [Medline].

  180. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. May 18 2000;342(20):1500-7. [Medline].

  181. Goldenberg RL, Mercer BM, Miodovnik M. Plasma ferritin, premature rupture of membranes, and pregnancy outcome. Am J Obstet Gynecol. Dec 1998;179(6 Pt 1):1599-604. [Medline].

  182. [Best Evidence] Goldenberg RL, Mwatha A, Read JS. The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth. Am J Obstet Gynecol. Mar 2006;194(3):650-61. [Medline].

  183. Gomez R, Ghezzi F, Romero R. Premature labor and intra-amniotic infection. Clinical aspects and role of the cytokines in diagnosis and pathophysiology. Clin Perinatol. Jun 1995;22(2):281-342. [Medline].

  184. Gonzalez-Bosquet E, Cerqueira MJ, Dominguez C. Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes. J Matern Fetal Med. Jul-Aug 1999;8(4):155-8. [Medline].

  185. Hachey WE, Wiswell TE. Limitations in the usefulness of urine latex particle agglutination tests and hematologic measurements in diagnosing neonatal sepsis during the first week of life. J Perinatol. Sep 1992;12(3):240-5. [Medline].

  186. Hauth JC, Gilstrap LC 3d, Hankins GD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol. Jul 1985;66(1):59-62. [Medline].

  187. Heighton BL, Halpren SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systematic review. Am J Obstet Gynecol. 2002;186(5 Suppl Nature):S69-77.

  188. Hemming VG, McCloskey DW, Hill HR. Pneumonia in the neonate associated with group B streptococcal septicemia. Am J Dis Child. Nov 1976;130(11):1231-3. [Medline].

  189. Hillier SL, Martius J, Krohn M. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med. Oct 13 1988;319(15):972-8. [Medline].

  190. Hussey MJ, Levy ES, Pombar X. Evaluating rapid diagnostic tests of intra-amniotic infection: Gram stain, amniotic fluid glucose level, and amniotic fluid to serum glucose level ratio. Am J Obstet Gynecol. Sep 1998;179(3 Pt 1):650-6. [Medline].

  191. Ismail MA, Zinaman MJ, Lowensohn RI. The significance of C-reactive protein levels in women with premature rupture of membranes. Am J Obstet Gynecol. Feb 15 1985;151(4):541-4. [Medline].

  192. Johnson CE, Whitwell JK, Pethe K. Term newborns who are at risk for sepsis: are lumbar punctures necessary?. Pediatrics. Apr 1997;99(4):e10. [Medline].

  193. Joseph TA, Pyati SP, Jacobs N. Neonatal early-onset Escherichia coli disease. The effect of intrapartum ampicillin. Arch Pediatr Adolesc Med. Jan 1998;152(1):35-40. [Medline].

  194. Kaftan H, Kinney JS. Early onset neonatal bacterial infections. Semin Perinatol. Feb 1998;22(1):15-24. [Medline].

  195. Kurlat I, Stoll BJ, McGowan JE Jr. Time to positivity for detection of bacteremia in neonates. J Clin Microbiol. May 1989;27(5):1068-71. [Medline].

  196. Maeda K, Matsuzaki N, Fuke S. Value of the maternal interleukin 6 level for determination of histologic chorioamnionitis in preterm delivery. Gynecol Obstet Invest. 1997;43(4):225-31. [Medline].

  197. Mangurten HH, Angst DB, See C, Boyle D, Beckman S. Professional liability in a neonatal intensive care unit: a review of 20 years' experience. J Perinatol. Jun 2000;20(4):244-8. [Medline].

  198. Mercer BM, Lewis R. Preterm labor and preterm premature rupture of the membranes. Diagnosis and management. Infect Dis Clin North Am. Mar 1997;11(1):177-201. [Medline].

  199. Miura E, Procianoy RS, Bittar C. A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis. Pediatrics. Jan 2001;107(1):30-5. [Medline].

  200. Moore SE, Cole TJ, Collinson AC. Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa. Int J Epidemiol. Dec 1999;28(6):1088-95. [Medline].

  201. Murtha AP, Greig PC, Jimmerson CE. Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection. Am J Obstet Gynecol. Oct 1996;175(4 Pt 1):966-9. [Medline].

  202. Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev. 2004;CD001239. [Medline].

  203. Philip J, Alexander JM, Sharma SK. Epidural analgesia during labor and maternal fever. Anesthesiology. May 1999;90(5):1271-5. [Medline].

  204. Pourcyrous M, Bada HS, Korones SB. Significance of serial C-reactive protein responses in neonatal infection and other disorders. Pediatrics. Sep 1993;92(3):431-5. [Medline].

  205. Puopolo KM. Bacterial and fungal infections. In: Cloherty JP, Eichenwald EC, Stark AR, eds. Manual of Neonatal Care. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:287-313.

  206. Romem Y, Artal R. C-reactive protein as a predictor for chorioamnionitis in cases of premature rupture of the membranes. Am J Obstet Gynecol. Nov 1 1984;150(5 Pt 1):546-50. [Medline].

  207. Sanghvi KP, Tudehope DI. Neonatal bacterial sepsis in a neonatal intensive care unit: a 5 year analysis. J Paediatr Child Health. Aug 1996;32(4):333-8. [Medline].

  208. Schmutz N, Henry E, Jopling J, Christensen RD. Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J Perinatol. Apr 2008;28(4):275-81. [Medline].

  209. Schuchat A, Zywicki SS, Dinsmoor MJ. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics. Jan 2000;105(1 Pt 1):21-6. [Medline].

  210. Seaward PG, Hannah ME, Myhr TL. International multicenter term PROM study: evaluation of predictors of neonatal infection in infants born to patients with premature rupture of membranes at term. Premature Rupture of the Membranes. Am J Obstet Gynecol. Sep 1998;179(3 Pt 1):635-9. [Medline].

  211. Seo K, McGregor JA, French JI. Preterm birth is associated with increased risk of maternal and neonatal infection. Obstet Gynecol. Jan 1992;79(1):75-80. [Medline].

  212. Sherman MP. Macrophage function in bacterial and fungal infections of newborns. In: Lipscomb MF, Russell SW, eds. Lung macrophages and dendritic cells. Lung Biology in Health and Disease Series. Vol 102. New York, NY:. Marcel Dekker;1997:409-436.

  213. Smulian JC, Shen-Schwarz S, Vintzileos AM. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gynecol. Dec 1999;94(6):1000-5. [Medline].

  214. Smulian JC, Vintzileos AM, Lai YL. Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis. J Matern Fetal Med. May-Jun 1999;8(3):88-94. [Medline].

  215. Sreenan C, Osiovich H. Myeloid colony-stimulating factors: use in the newborn. Arch Pediatr Adolesc Med. Sep 1999;153(9):984-8. [Medline].

  216. Stoll BJ, Hansen N, Fanaroff AA. Changes in pathogens causing early-onset sepsis in very-low-birth- weight infants. N Engl J Med. Jul 25 2002;347(4):240-7. [Medline].

  217. Stoll BJ, Holman RC, Schuchat A. Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics. Aug 1998;102(2):e18. [Medline].

  218. Teichmann AT, Arendt P, Speer CP. Premature rupture of the membranes and amniotic infections--the significance of laboratory tests. Eur J Obstet Gynecol Reprod Biol. Mar 1990;34(3):217-22. [Medline].

  219. Terrone DA, Rinehart BK, Einstein MH. Neonatal sepsis and death caused by resistant Escherichia coli: possible consequences of extended maternal ampicillin administration. Am J Obstet Gynecol. Jun 1999;180(6 Pt 1):1345-8. [Medline].

  220. Towers CV, Carr MH, Padilla G. Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol. Oct 1998;179(4):879-83. [Medline].

  221. Vollman JH, Smith WL, Ballard ET. Early onset group B streptococcal disease: clinical, roentgenographic, and pathologic features. J Pediatr. Aug 1976;89(2):199-203. [Medline].

  222. Wolach B. Neonatal sepsis: pathogenesis and supportive therapy. Semin Perinatol. Feb 1997;21(1):28-38. [Medline].

  223. Yoon BH, Jun JK, Romero R. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. Am J Obstet Gynecol. Jul 1997;177(1):19-26. [Medline].

  224. Yoon BH, Romero R, Lim JH. The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor. Am J Obstet Gynecol. Oct 2003;189(4):919-24. [Medline].

  225. Yoon BH, Romero R, Shim JY. C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis. J Matern Fetal Neonatal Med. Aug 2003;14(2):85-90. [Medline].

  226. Yoon BH, Yang SH, Jun JK. Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count. Obstet Gynecol. Feb 1996;87(2):231-7. [Medline].

[ CLOSE WINDOW ]

Further Reading

Readers of this article are also encouraged to read chapters with a similar name in textbooks of Maternal and Fetal Medicine. Chapters on neonatal sepsis in textbooks of neonatal and perinatal medicine (ie, neonatology) enhance knowledge regarding recognition and management of early onset newborn infections. 

[ CLOSE WINDOW ]

Keywords

maternal chorioamnionitis, acute chorioamnionitis, early-onset neonatal sepsis, early onset neonatal sepsis, early onset sepsis, maternal and fetal effects of amniotic fluid infection, pregnancy and fetal infection with bacteria, preterm labor, premature rupture of membranes, epidural anesthesia, intrapartum fever, abnormal bacterial colonization of the urogenital tract, ascending amniotic fluid infection, asymptomatic chorioamnionitis, symptomatic chorioamnionitis, placental infection, funisitis, bacteremia, pneumonia, Escherichia coli, methicillin-resistant Staphylococcus aureus, urinary tract infection, UTI, bacterial vaginosis, alcoholism, prolonged rupture of membranes, maternal anemia, obesity, cerebral palsy, CP, periventricular leukomalacia, Ureaplasma, Mycoplasma, necrotizing enterocolitis, maternal leukocytosis, hypotension, vaginitis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Michael P Sherman, MD, Professor, Department of Pediatrics, Southern Illinois University School of Medicine; Coordinator, Pediatric Residency Education in Neonatal Intensive Care, St John's Children's Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis School of Medicine
Michael P Sherman, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, European Society for Paediatric Research, Perinatal Research Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Katsufumi Otsuki, MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
Disclosure: Nothing to disclose.

Medical Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center
Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.