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

Maternal Chorioamnionitis

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

Introduction

Background

Maternal fever during labor, and perhaps other signs and symptoms of chorioamnionitis, often results in a call to the family practitioner, pediatrician, or neonatologist related to concern for the neonate. This communication often causes an evaluation to rule out early onset neonatal sepsis.1  Because of this, 10-20 newborns are evaluated and treated with antibiotics for every infant with proven bacteremia. The reason for this clinical phenomenon is that newborns who develop an early onset sepsis (EOS), now defined as proven life-threatening infection at less than 72 hours of life, have a high mortality rate. A strong association is observed between very preterm infants dying when younger than 24 hours and chorioamnionitis.2

Frequent clinical evaluations of neonates for EOS began in the 1970s, when group B streptococcal (GBS) infections resulted in a neonatal mortality rate approaching 50%.3 Over the past 25 years, because of a heightened awareness of GBS-related infection in neonates, chemoprophylaxis with antibiotics has significantly reduced the risk of GBS disease and its associated morbidity and death.4 In the presence of maternal chorioamnionitis, the dilemma for the physician is determining whether the neonate is truly at risk for localized (eg, bacterial pneumonia, meningitis) or systemic (eg, bacteremia) infection.

Early onset bacterial infections in the newborn may occur when the mother has abnormal bacterial colonization of the urogenital tract, an ascending but silent amniotic fluid infection, or symptomatic chorioamnionitis. Thus, the physician cannot assume that maternal signs and symptoms may be used to identify all infected infants.

GBS infections are no longer the predominant cause of early onset neonatal sepsis; gram-negative organisms are now most predominant,5 particularly Escherichia coli.6  Some reports have not seen an increase in E coli -related EOS during the era of heightened intrapartum antibiotic use.7  

Additionally, methicillin-resistant Staphylococcus aureus (MRSA) , already a common cause of nosocomial infection in maternity and neonatal units, looms as a potential cause of EOS.8  So far, maternal colonization during pregnancy with MRSA and an increase in neonatal infection caused by this pathogen has not been reported.9

For the clinical setting of suspected chorioamnionitis, this article summarizes the history, physical examination, and laboratory findings in both mother and infant to provide appropriate decision-making tools for cost-effective management of the neonate. An entire issue of Clinics in Perinatology was devoted to infectious diseases during pregnancy.10  Several chapters in that monograph contain information on the pathophysiology of chorioamnionitis and its adverse consequences in the mother, fetus, and newborn. Since 2005, Romero (2007)11,12 has reviewed how inflammation and infection result in preterm birth, and Reilly and Faye-Petersen have contributed a monograph on chorioamnionitis and funisitis in NeoReviews.13

Pathophysiology

Abnormal bacterial colonization of the rectum and anus during pregnancy may create an abnormal vaginal and cervical microbial environment.14 More than 2 decades ago, rectovaginal colonization with GBS during pregnancy was found to be associated with this GBS infection of the fetus or newborn.3 Studies have demonstrated that other types of bacteria residing in the vagina, cervix, or both ascend through intact or ruptured fetal membranes and initiate amniotic fluid infection.15

Urinary tract infection during pregnancy can bathe the vagina with bacterial pathogens and is a recognized risk factor for neonatal sepsis. This observation is particularly true for untreated asymptomatic GBS-related bacteriuria.16  A high maternal body mass index increases the risk of EOS caused by GBS.17

Bacterial vaginosis has been recognized as an important cause of premature labor, although overt infection of the neonate with microbes causing bacterial vaginosis is uncommon. Screening for and treatment of bacterial vaginosis and other genital infections may prevent preterm birth,18 although recent Cochrane reviews conflict regarding the effectiveness of therapy.19

Many interesting associations related to infection and preterm birth have been made; however, the mechanisms of these relationships are not necessarily understood. Although controversy exists about its role, periodontitis has been linked to prematurity, low birth weight, and fetal growth restriction.20  Blood types A and O are also associated with an increased risk for chorioamnionitis.21  The same researchers found relationships between alcoholism, prolonged rupture of membranes, and maternal anemia as factors related to preterm birth.21  Obesity during pregnancy has been related to chorioamnionitis in several reports.22,23,17  

In the mid trimester of pregnancy, ultrasonographic evidence of a short cervix may be the only clinical finding in intraamniotic fluid infection.24  Cervical insufficiency, regardless of bacterial culture results in amniotic fluid, is associated with intraamniotic inflammation, preterm birth and other adverse outcomes of pregnancy.25  Related issues to cervical insufficiency are mechanical methods of cervical ripening that are also suspected of increasing maternal and neonatal infections.26  Each of these factors may be associated with altered host defenses that allow ascending infection from the urogenital tract to placental tissues and amniotic fluid.

Frequency

United States

Incidence of maternal chorioamnionitis in the US population cannot be stated with accuracy, but the occurrence declines as pregnancy advances toward term gestation.13  The risk of chorioamnionitis increases based on health conditions and behaviors, as outlined in Pathophysiology. Furthermore, factors such as gestational age, economic conditions, and ethnic differences influence the incidence. Histopathology of the placenta suggests inflammation may occur in the normal course of parturition at term gestation, thus complicating the definition of chorioamnionitis. An increase in histopathologic chorioamnionitis is noted in preterm birth compared with delivery of the healthy term infant. Signs of placental inflammation are present in 42% of extremely low birth weight infants.27  Most agree that infection is directly or indirectly associated with 40-60% of all preterm births.28

International

Developed countries (eg, Canada, western European countries, Australia) probably have an incidence equal to, or perhaps even less than, the rate of chorioamnionitis observed in the United States. In underdeveloped countries, premature rupture of membranes has a strong association with chorioamnionitis, and chorioamnionitis in this setting results in preterm birth with a high mortality rate.29  Classic studies by Naeye demonstrated that malnourished pregnant women in Africa had a higher risk of ascending urogenital infection with subsequent amniotic fluid infection.30

The pathophysiology increased the risk of fetal infection and perinatal death. Infection in these malnourished women was attributed to a decrease in host defense factors in amniotic fluid that regularly prevents disease in this liquor.31  In developed countries where women receive suboptimal care and have poor nutrition during pregnancy, a higher incidence of infection can be expected because of altered immune defenses.32

Mortality/Morbidity

Compared with neonatal deaths associated with maternal chorioamnionitis, mortality in mothers of these infants is rare. The same is not true for the neonate. In a study of infants born at 23-32 weeks' gestation with evidence of intrauterine infection and inflammation, the neonatal death rate was 9.9-11.1%.33  This study is well known because the analysis concluded that administration of corticosteroids did not worsen any neonatal outcome when intrauterine inflammation and infection were present. 

In a debatable publication from the same study, Andrews et al (2008)9 concluded that in utero inflammation was not associated with an increased risk of severe adverse neurodevelopmental outcomes at age 6 years. Rather, these preterm infants born at 23-32 weeks' gestation had unfavorable outcomes influenced more by gestational age at birth, neonatal complications, and the IQ of the caregiver in the home after discharge. As is discussed below, other evidence refutes conclusions about chorioamnionitis and neurodevelopmental outcomes made by Andrews et al.9

Another major insight is the long-term neurologic outcome of infants born to mothers with chorioamnionitis. Cerebral palsy (CP)34 and cognitive impairment without CP35 have a relationship to the presence of maternal chorioamnionitis. In particular, funisitis and the fetal inflammatory response syndrome are related to white matter brain injury or periventricular leukomalacia that is linked to activation of cytokine networks.36  Interleukin (IL)-1beta, IL-6, IL-8, IL-18, and tumor necrosis factor (TNF)-alpha are among the cytokines identified as agents related to this in utero and fetal pathophysiology.37,11  When extremely preterm infants have histopathologic evidence of inflammatory and/or infectious lesions and a severe vascular response in the placenta, the risk of CP is increased.38

In addition to activation of inflammation and adverse neurologic outcomes, the risk of long-term pulmonary disease may be heightened.39  Although controversy remains, in utero infections caused by Ureaplasma and Mycoplasma seem associated with chronic lung disease of prematurity.40  Congenital pneumonia caused by Ureaplasma and Mycoplasma occurs; however, during mechanical ventilation and oxygen therapy of preterm infants, these microorganisms may also initiate a prolonged cytokine release in the neonatal lung. Antibiotic treatment to reduce the incidence of chronic lung disease of prematurity when the neonatal lung is colonized or infected with Ureaplasma or Mycoplasma has been disappointing. Chorioamnionitis has been linked to EOS, necrotizing enterocolitis, and severe intraventricular hemorrhage in preterm infants41 and to spontaneous intestinal perforation.42  

Term infants born to mothers with chorioamnionitis have far less chance of dying; however, the long-term morbidity in term infants is still problematic. In a reasonably homogeneous population of near-term and term infants born in the Kaiser Permanente Care Program, Wu and colleagues (2003)43 concluded chorioamnionitis is an independent risk factor for CP. 

In preterm infants with EOS, elevated numbers of nucleated RBCs were related to increased concentrations of IL-6 in cord blood.44  Term infants with evidence of placental inflammation also have elevated circulating fetal nucleated RBCs, and this finding can be associated with CP.45

Race

In select populations, race may increase the risk of maternal chorioamnionitis and preterm delivery. Studying histologic chorioamnionitis and preterm birth, Holzman and others (2007)46 observed evidence of inflammatory pathology in 12% of placentas from white women and women of other race compared with 55% in black women. If one considers race in the context of adverse circumstances (ie, violence, human immunodeficiency virus [HIV]-infection) associated with inadequate care47,48 or malnutrition during pregnancy,49,50 then the incidence of placental inflammation is increased.

Sex

Gender plays an important role in neonatal infection.51 Along infants with a preterm birth at less than 34 weeks' gestation, prolonged rupture of the fetal membranes and male gender was a risk factor for EOS. More recent studies of EOS caused by ampicillin-resistant E coli did not find that male gender was a risk factor.6

Age

Advanced maternal age alone, defined as older than 35 years, has not been identified as a risk factor for chorioamnionitis. However, teenage pregnancy increases the risk of chorioamnionitis. Risks factors associated with teenage pregnancy and chorioamnionitis include smoking, alcohol use, anemia, unemployment, urinary tract infection, and bacterial vaginosis.52,53,54,55

Clinical

History

  • The time-honored clinical signs and symptoms of chorioamnionitis include the following:
    • Fever (an intrapartum temperature >100.4 º F or >37.8 º C)
    • Significant maternal tachycardia (>120 beats per minute [bpm])
    • Fetal tachycardia (>160-180 bpm)
    • Purulent or foul-smelling amniotic fluid or vaginal discharge
    • Uterine tenderness
    • Maternal leukocytosis (total blood leukocyte count >15,000-18,000 cells/μL)
  • Of these criteria, intrapartum maternal fever appears to be the most frequent.56  Other findings, such as fetal tachycardia, may be less important in the absence of maternal fever.
  • When at least 2 of the aforementioned criteria are present, the risk of neonatal sepsis is increased. Clinical signs and symptoms of chorioamnionitis, however, have low predictive value by themselves. Moreover, silent chorioamnionitis is prominent,57 and thus signs and symptoms in the infected newborn infant take on added significance.
  • An increasing total leukocyte count may be more important than a single determination. Abnormalities in either umbilical vein interleukin (IL)-6 levels or an increasing neonatal immature-to-total neutrophil ratio, along with clinical criteria for chorioamnionitis, improve the sensitivity and predictive accuracy of identifying the septic neonate.
  • Risk of neonatal infection increases as the duration of ruptured membranes lengthens.58 Chorioamnionitis may initiate uteroplacental bleeding or a placental abruption.59 Labor and delivery may be rapid in the presence of chorioamnionitis. Alternatively, infection may cause uterine atony, requiring labor to be augmented with oxytocin. Ultimately, a poor labor pattern may require an instrumented delivery or a cesarean delivery. Each of these antepartum and intrapartum factors must be considered when evaluating the newborn for the presence of bacterial infection.

Physical

The physical examination of the pregnant women with chorioamnionitis may reveal no signs or symptoms of infection.57 Conversely, a pregnant woman with chorioamnionitis may appear ill, even toxic.

  • Physical symptoms may include the following:
    • Fever
    • Tachycardia (>120 bpm)
    • Hypotension
    • Diaphoresis
    • Cool or clammy skin
    • Uterine tenderness
    • Foul-smelling or abnormal vaginal discharge
  • The fetus may also have tachycardia (>160-180 bpm). A biophysical profile (BPP) performed on the fetus using ultrasonography may reveal a lower than normal score, but ultrasonic biophysical profile assessment has not been predictive of clinical chorioamnionitis.60  Lack of fetal breathing has been associated with fetal infection.61,62 Recently, intrauterine ultrasonography has identified "sludge" at the amniotic fluid interface with the cervix that is also associated with hyperechogenic, free-floating material in the amniotic fluid.63  This finding was seen in asymptomatic women at risk for preterm delivery. Aseptic aspiration of the "sludge" showed the material had a low glucose content, many neutrophils, and gram-positive cocci. Furthermore, electronic fetal monitoring lacks precision to identify the fetal inflammatory response syndrome and subsequent neonatal sepsis.64  
  • Conditions falsely simulating chorioamnionitis include the following:
    • Clinical signs and symptoms of chorioamnionitis are not always associated with placental evidence of inflammation. This is particularly true if maternal fever is the sole criterion for the diagnosis.
      • Epidural anesthesia during the intrapartum period has been associated with fever in the mother and the neonate;65,66 however, the pathophysiology of the fever and its adverse effects on the mother, fetus, or infant remains controversial.67,68,69,70
      • Epidural anesthesia and maternal and/or neonatal fevers result in more evaluations for sepsis and antibiotic treatment in neonates, although the incidence of sepsis compared with that in a neonatal population whose mothers did not receive epidural anesthesia during labor is unknown. Epidural anesthesia during labor is associated with other types of neonatal morbidity that are also risk factors for sepsis.
      • Although the exact mechanisms for this phenomenon remain unclear, nulliparity, dysfunctional labor, prolonged labor, maternal exhaustion, dehydration, and/or prolonged rupture of membranes may result in maternal fever associated with epidural anesthesia.
    • In the setting of epidural anesthesia during labor, the following clinical course has been observed. The fetus usually has tachycardia when the mother is febrile during labor. At birth, the newborn may also have a fever (temperature >37.8 º C). If the neonate is not septic, the temperature elevation dissipates rapidly following birth, and the newborn subsequently exhibits normal behavior. Furthermore, these noninfected, febrile neonates have normal Apgar scores and appear remarkably well following birth. Such newborns can be observed for illness rather than undergoing a septic workup and antibiotic therapy. However, judgment must be based on many factors, including the intrapartum administration of broad-spectrum antibiotics to the mother.
  • Maternal chorioamnionitis increases the potential that the following clinical presentations may be evident in the neonate. Signs and symptoms of neonatal sepsis are often nonspecific and subtle. The neonate may demonstrate behavioral abnormalities such as lethargy, hypotonia, weak cry, and poor suck. Specific organ involvement may manifest as follows:
    • Tachypnea, respiratory distress (eg, expiratory grunt, retractions), cyanosis, pulmonary hemorrhage, and/or apnea (ie, pulmonary manifestations of pneumonia, sepsis, or both), must be immediately appreciated by caregivers. Nursery personnel must be aware that a neonate who is born without respiratory distress but who develops signs and symptoms of pulmonary disease in the first hours of life has a heightened risk for infectious pneumonia.
    • Tachycardia, hypotension, prolonged capillary refill time, cool and clammy skin, pale or mottled appearance, oliguria (ie, cardiovascular manifestations of sepsis), or a combination of these may be observed. Caregivers must also consider other explanations for these physical findings, such as developmental defects in the cardiovascular system or inborn errors of metabolism.
    • Abdominal distension, vomiting, diarrhea, bloody stools, or a combination of these may be observed. GI symptoms may be nonspecific in patients with early-onset bacterial disease.
    • Thermal regulatory abnormalities (ie, hypothermia or hyperthermia), behavioral abnormalities, apnea, seizures (ie, CNS manifestations), or a combination may be seen. A bulging fontanel or nuchal rigidity is not a reliable sign of meningitis in a neonate.
    • Pallor, petechiae or purpura, and overt bleeding (ie, hematopoietic involvement, liver involvement, or both) may be seen.
  • As one physiologic system may affect another, signs and symptoms may originate from more than one dysfunctional organ system. However, many neonatal conditions resemble neonatal sepsis; thus, physician caregivers must have an open mind regarding other clinical conditions that may involve signs and symptoms resembling neonatal sepsis. Those conditions include, but are not limited to, the following:
    • Cardiovascular malformations, especially left-sided obstructive lesions causing poor systemic cardiac output
    • Endocrine disorders that may also cause shocklike states, such as different types of congenital adrenal insufficiency or hypoglycemia associated with hyperinsulinemia
    • Serious CNS trauma or dysfunction from any cause
    • Anemia caused by unrecognized isoimmunization or blood loss from conditions such as fetomaternal transfusion syndrome

Causes

Maternal chorioamnionitis perhaps occurs when protective mechanisms of the urogenital tract and/or uterus fail during pregnancy or when increased numbers of microbial flora or highly pathogenic microorganisms are introduced into the genital environment.71,72,73,74,75,76

  • Ascending infection into the vagina, then the cervix, and finally into the uterine cavity, fetal membranes, and placenta is the consequence of many factors (ie, innate host defenses, healthy bacterial flora, bacterial burden, bacterial pathogenetic factors). Recently, a short cervix has been recognized as either a risk factor or a surrogate for microbial invasion of the amniotic fluid.77,24
  • Urogenital hygiene is obviously important in establishing healthy bacterial flora. Healthy bacteria (ie, lactobacilli)78 and natural peptide antibiotics in the vagina and cervix may have a role in preventing infections during pregnancy.79 Mucus, phagocytes, and natural antibiotic proteins (ie, lactoferrin, lysozyme, beta defensins) in the cervicovaginal secretions attempt to maintain a normal bacterial flora.72 Bacterial interference, mainly produced via lactobacilli living in an acid environment and producing bacteriocins, also helps to keep pathogenic bacteria from gaining a foothold in the cervicovaginal secretions.80,81 These mechanisms of host protection may be altered in a significant number of pregnant women who develop chorioamnionitis.
  • Oral hygiene may influence rectal and urogenital bacterial flora during pregnancy. Although the theory is controversial, intense interest has focused on a connection among periodontitis, abnormal rectal colonization, and preterm delivery.82,83
  • Rectal bacterial flora is believed to be important in establishing abnormal urogenital colonization during pregnancy.84,85,86 Alterations in vaginal and cervical host defense mechanisms during pregnancy cause vaginitis,87 bacterial vaginosis, urinary infections, and other urogenital infections. Currently, researchers are trying to understand how host defense mechanisms prevent urogenital infection during pregnancy.
  • Orogenital contact may also alter either colonic or urogenital microbial flora and ultimately cause ascending infection and chorioamnionitis.88,89 Similarly, coitus has been linked with chorioamnionitis.90,91
  • Clinical events associated with chorioamnionitis include the following:
    • History of premature birth (with increasing risk at earlier gestational age)
    • Presence of premature labor
    • Prematurely ruptured fetal membranes
    • Prolonged rupture of the fetal membranes
  • In a recent report of patients with clinical signs and symptoms of chorioamnionitis, 38% showed no histologic evidence of placental inflammation. Thus, other causes of signs and symptoms that may resemble maternal chorioamnionitis must be sought.
  • Epidural anesthesia during labor may be associated with maternal fever and fetal tachycardia (see Special Concerns). Other conditions, such as dehydration or maternal exhaustion during labor, may result in maternal fever and must be considered as causes of the febrile state.

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. 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. 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. 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. 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. 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. 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. 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.

RELATED EMEDICINE ARTICLES
RELATED MEDSCAPE ARTICLES
 
 
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.