Skip to main content
PMC home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2016 Mar 1.
Published in final edited form as: Clin Perinatol. 2014 Nov 21;42(1):155–165. doi: 10.1016/j.clp.2014.10.011

Chorioamnionitis: Implications for the Neonate Jessica

Jessica E Ericson 1,2, Matthew M Laughon 3,*
PMCID: PMC4331454  NIHMSID: NIHMS638500  PMID: 25678002

Abstract

Chorioamnionitis (CA) is a perinatal condition characterized by inflammation of the fetal membranes. The incidence of CA increases with decreasing gestational age at birth. When CA is suspect based on clinical criteria, pathologic assessment of the placenta should be performed. While the mechanisms are not entirely clear, CA predisposes infants to premature birth, neonatal sepsis and intraventricular hemorrhage. The role of CA in respiratory distress syndrome, bronchopulmonary dysplasia, and neurodevelopmental impairment is mixed. Prevention and treatment of CA are not well defined. The use of antibiotics for preterm premature rupture of membranes reduces the incidence of CA and increases the length of time to delivery. Antibiotics are recommended for infants exposed to CA while laboratory studies are being performed.

Keywords: neonatal sepsis, fetal inflammatory response, Mycoplasma

Chorioamnionitis (CA) is a perinatal condition characterized by inflammation of the fetal membranes: the chorion and amnion. The incidence of CA increases with decreasing gestational age at birth. Ascending bacterial infection is thought to be the primary mode of acquisition; viruses and fungi are rarely implicated. While the mechanisms are not entirely clear, CA predisposes infants to premature birth, neonatal sepsis, and other adverse outcomes. In this manuscript, we will review the pathophysiology of CA (including definitions), risk factors for CA, management strategies for CA, and neonatal outcomes.

Definition

The definition of CA is inconsistent between clinicians and across epidemiologic studies, and this inconsistency has contributed to the conflicting associations between CA and fetal outcomes. The most rigorous definition of CA is inflammation of the chorionic and amniotic layers of the fetal membranes confirmed by pathologic review of the placenta1 (Table 1). The pathologic diagnosis requires the presence of a neutrophilic infiltrate to be present in the placental tissues. Early studies used a threshold of 10 neutrophils per high power field in at least 10 fields as a definition for histologic CA.2 More recently, the Extremely Low Gestational Age Newborn (ELGAN) Study group graded the severity of inflammation of each membrane and considers CA to be present when >20 neutrophils are present per 20× field of the chorion or the presence of numerous large or confluent foci of neutrophils or necrosis of the amnion.1

Table 1. Definitions of chorioamnionitis.

Histologic CA Pathologic diagnosis, inflammatory cells are present in the fetal membranes19,59
Clinical CA Typically maternal fever + at least 2 of: uterine tenderness, fetal or maternal tachycardia, maternal leukocytosis, foul smelling amniotic fluid15,52
Maternal inflammatory response Inflammatory changes limited to the subchorion, chorion and amnion5
Fetal inflammatory response Umbilical vasculitis, funisitis, elevated inflammatory markers in the cord blood5,60
Open in a new tab

Recently, attempts have been made to distinguish between involvement of only the maternal portion of the placenta and inflammation that involves both the maternal and fetal portions as there appear to be differences in neonatal outcomes for infants with more proximal inflammatory changes.3-6 Inflammation that involves the fetal portion is often referred to as fetal inflammatory response (FIR).6 CA can be further complicated by involvement of the umbilical cord, a condition called funisitis.7 Investigators from the ELGAN study group consider funisitis to be present when there is fetal vasculitis with neutrophils noted in the perivascular Wharton's jelly.1 Funisitis is evidence of a vigorous fetal response, and thus is considered a “severe” form of CA. However, even the pathologic diagnosis can vary, depending on how long the placenta was at room temperature before refrigeration, where the placental tissue was sampled, and the skill of the pathologist.

Some investigators define CA as the isolation of bacterial or fungal organisms from the placenta or amniotic fluid, regardless of the presence of inflammation. Histologic CA and the isolation of organisms are highly associated but can occur separately.2 Organisms can be isolated by culture or polymerase chain reaction (PCR) (Table 2). Placental cultures may be negative even in the presence of overt histological inflammation.8 One study found that only 4.6% of placental cultures revealed an organism when culture was performed for indications of preterm delivery, prolonged rupture of membranes, suspected infection or fetal death.9 This is likely due to difficulty culturing fastidious or intracellular organisms such as Mycoplasma and Ureaplasma species' or low colony counts. PCR has been used successfully to increase sensitivity but also fails to detect all pathogens.10,11 When 150 placentas were cultured and tested via PCR, 141 had no organisms, 10 had organisms detected by both PCR and culture; PCR alone was positive in 9 cases and culture alone was positive in 6 cases.12 Fastidious organisms were more likely to be identified by PCR. PCR failed to detect coagulase-negative Staphylococcus species, Bacillus species, Peptostreptococcus species and Gardnerella vaginalis.12 Anaerobic and mixed infections are common which can complicate detection by culture and PCR.13

Table 2.

Organisms commonly identified in chorioamnionitis.

Organism Prevalence Reference
Ureaplasma urealyticum 15-62% 18,28,61-63
Mycoplasma hominis 7-35% 18,61-63
Group B Streptococcus 8-11% 62,64
Escherichia coli 7-12% 62,64
Gardnerella vaginalis 8-25% 28,64
Bacteroides sp 8-30% 64
Fusobacterium sp 10-67% 28,64
Prevotella sp 17% 64
Peptostreptococcus sp 16% 64
Open in a new tab

Due to laboratory limitations, the diagnosis of CA is often made clinically. Fever, uterine tenderness, maternal or fetal tachycardia, maternal leukocytosis, and foul smelling uterine discharge are commonly considered to represent CA.14 These findings are nonspecific, however, and have variable relation to histologic CA. Using histologic CA as the reference standard, the sensitivity of maternal fever was only 42%.15 Maternal tachycardia and fetal tachycardia were 47% and 36% sensitive respectively.15 The sensitivity of clinical signs increased to 60% when maternal tachycardia, uterine tenderness, maternal leukocytosis or malodorous amniotic fluid was present in addition to maternal fever.16 A study that evaluated placental tissue from 2774 pregnancies found that maternal fever was absent in 92% of histologic CA cases.17 Conversely, of women with peripartum fever, 59% had findings of CA.17 The variability and limited sensitivity of findings used to diagnose CA clinically makes comparison of studies and outcomes more difficult.

Inflammatory changes themselves may have a stronger association with adverse outcomes, including preterm birth, than the presence of microorganisms alone.18 Intra-amniotic interleukin-6 (IL-6) predicts both preterm birth and neonatal morbidity. Investigators found that mothers presenting in preterm labor with amniotic fluid IL-6 levels > 11.3 ng/ml delivered after a median of 1 day; those without elevated IL-6 levels delivered after a median of 25 days.10 Another cohort of 261 very low birth weight (VLBW, <1500 g birth weight) infants found a C-reactive protein elevated > 10 mg/L was significantly more common in the 99 infants exposed to CA (25% vs 11%, p=0.005).19 For 799 infants born <27 weeks gestation, infants exposed to CA were more likely to have an elevated C-reactive protein, OR= 5.3 (95% confidence interval; 3.0, 9.6), as well as elevation of other cytokines.3 Inflammatory markers may add objective information to the clinical criteria used in diagnosis when pathological information is unavailable.

Pathophysiology

The introduction of organisms into the fetal membranes and the placenta is thought to occur via four anatomic pathways. The first, and most common, mechanism is ascending infection through the maternal genital tract. Vaginal and enteric floras are often implicated with this route of infection.20 Second, iatrogenic inoculation can occur following invasive procedures such as amniocentesis.21 Third, hematogenous spread can occur with migration of organisms from the maternal bloodstream across the placenta.22 Listeria monocytogenes in particular has been described to cause infiltration of the placenta following maternal infection.23 Fourth, and least common, peritoneal infections can enter the intrauterine space via the fallopian tubes. Mothers with chronic kidney or liver disease are most at risk for infection by this mechanism.24

Ascending infection can ultimately result in disease of the fetal membranes. Preterm and prolonged rupture of membranes has been associated with increased risk of CA.4 This may be because removal of the anatomic barrier provided by intact membranes allows for easier migration of organisms from the maternal genital tract into the fetal tissues. Conversely, the membranes may rupture due to the apparent tendency of infection to weaken the membranes, predisposing them to rupture.25 Separating which of these is the primary cause of CA is often challenging.

Neonatal Outcomes

Preterm Birth

Preterm birth is the most consistently demonstrated consequence of CA.26 An early prospective observational study of 2774 mother-infant pairs found that as many as 25% of preterm births are attributable to CA.17 This was later confirmed in a case-control study demonstrating that premature infants have significantly increased odds of both bacterial isolation and histologic findings of CA. 2 A recent prospective study of 871 pregnancies found that of those with histologic CA, premature delivery occurred nearly twice as often as those without CA.27 When Ureaplasma urealyticum was detected following preterm premature rupture of membranes of 154 pregnancies, the median gestational age at delivery was 4 weeks less than when it was not detected.11 Of 50 women who presented in preterm labor with intact membranes, elevated intra-amniotic levels of the proinflammatory cytokines IL-6, interleukin-1, prostaglandin E2 and tumor necrosis factor alpha were associated with progression to preterm birth.28

Neonatal Sepsis

Infants born following CA are at increased risk for neonatal infection. Organisms infecting the chorionic membranes are in close proximity to the fetus and can cause fetal infection as a natural consequence of this proximity. The organisms that most often cause early onset neonatal sepsis are those that are also frequent causes of CA: Escherichia coli and group B Streptococcus.29 Exposure to CA appears to confer a risk of early onset sepsis of 1-3%17, 10 times higher than the overall risk of early onset sepsis.

Premature infants are particularly susceptible to sepsis following CA. A case control study found that VLBW infants exposed to CA had significantly increased odds of early onset sepsis, OR= 4.7 (1.4, 15.9), p=0.015.30 For infants <32 weeks gestational age, 145 infants exposed to histologic CA developed clinical criteria consistent with sepsis syndrome significantly more often than 136 infants without CA, 39% vs 24% (p=0.007).31

Term infants are also at risk for neonatal infection following CA. Of 5144 term infants exposed to CA, 1.3% developed culture proven neonatal sepsis, OR=2.9 (2.1, 4.1)32. An analysis of 3094 births found that a clinical diagnosis of CA was independently associated with increased odds of early onset neonatal sepsis even with adjustment for initial severity of illness and baseline characteristics, OR=5.54 (2.87, 10.69), p<0.001.33

Funisitis seems to confer a higher risk of sepsis. When 315 preterm births were considered, 12% of infants with funisitis had a positive blood culture within 72 hours of delivery compared to 1% of infants without funisitis, OR=7.2 (1.8, 29.0).34 A prospective observational study of 231 infants found that early onset sepsis occurred in 18% of infants with funisitis compared to 4% of infants without funisitis, p=0.002.7

Brain Disease

CA is associated with an increased incidence of early neurologic insults, including severe intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which are established causes of neurodevelopmental impairment in premature infants. A multicenter study of Canadian Neonatal Network hospitals found that CA increased the odds of severe IVH even after adjusting for severity of illness, OR=1.62 (1.17, 2.24).33 The presence of mononuclear inflammatory cells in the fetal membranes has been found to be associated with increased severe IVH even after controlling for gestational age, OR=8.9 (2.1, 37.9).35 A study of 1367 VLBW infants found that exposure to clinical CA increased the odds of both IVH, OR=2.8 (1.6, 4.8), and PVL, OR=3.4 (1.6, 7.3).36 Recently, inflammatory changes that were classified as FIR were found to increase the odds of grades II-IV IVH, OR=4.1 (1.3, 13.2).5 However, for the 53 pregnancies where inflammation was isolated to only the maternal placental tissues there was no increase in IVH compared to the 112 with no placental inflammatory changes, OR=0.9 (0.2, 3.7).5

Even when a perinatal diagnosis of IVH or PVL is not documented, CA appears to be associated with an increased risk of cerebral palsy. A case control study of 424 infants with birth weights > 2500 g found that both clinical CA and histological evidence of placental infection were associated with significantly increased odds of spastic cerebral palsy.37 Similarly, 18 month developmental testing of 33 infants exposed to clinical CA was significantly worse in cognitive, language and motor domains than 146 control infants even though the incidence of PVL and grade III-IV IVH were similar between the 2 groups.38 The relationship between CA and neurodevelopmental impairment may partially be due to the intermediate of neonatal sepsis, which has a well described role in neurodevelopmental impairment.39-41 However, exposure to inflammatory cytokines likely exerts direct damaging effects on the developing brain.42-45

The relationship between CA and poor neurodevelopmental outcome has not been demonstrated in all studies. For 39 infants born <32 weeks gestation who were exposed to CA compared to 33 control infants, there was no difference between groups in mental and psychomotor developmental indices.31 Similarly, a case control study found no difference in performance on the Bayley Scales of Infant Development between the 71 infants exposed and the 259 infants not exposed to CA at 7 months corrected age.30

Lung Disease

The relationship of CA and neonatal pulmonary morbidity is conflicting. Various studies have evaluated the risk of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) following exposure to CA.

Respiratory distress syndrome

CA has been associated with a lower incidence of RDS in some studies. A lower incidence of RDS in infants exposed to CA may occur because exposure to prenatal inflammation appears to accelerate lung development and stimulate surfactant production. This rationale is supported by a study that found that RDS was significantly less common in infants exposed to CA than their unexposed counterparts, relative risk (RR)=0.56 (0.34-0.90).46 A more recent multivariable analysis of 301 premature infants similarly found that CA decreased the odds of severe RDS.47 Infiltration of the fetal membranes by polymorphonuclear cells was associated with a lower incidence of RDS in infants <32 weeks gestational age, OR=0.4 (0.3-0.7).35 Another study of 216 infants considered inflammation of the maternal aspect of the placenta alone versus inflammation on the maternal and fetal aspects as 2 distinct pathologies.5 They found that FIR conferred a protective effect with a reduced odds of RDS compared with placentas with no inflammation or with inflammatory changes only of the maternal placental tissues, OR=0.08 (0.01-0.62).5

However, several studies have found an increase in RDS associated with CA. One study of 95 infants with mean gestational age of 34 weeks found 0 cases of RDS among infants without histologic CA; 23% of infants exposed to CA developed RDS.48 RDS was also observed more frequently in infants exposed to clinical CA than those who were not in a study of 1367 VLBW infants, OR=2.9 (1.5, 5.5).36 A multicenter analysis of 3094 infants did find that RDS was more common after CA on univariable analysis but when gestational age and birth weight were included in a multivariable model, the relationship was no longer significant.33 A study of 1340 infants <27 weeks gestation also found no association between histologic CA or the detection of organisms and respiratory status during the first 2 weeks of life.49

Bronchopulmonary dysplasia

The relationship between BPD and CA is also conflicting. The rationale for an increased risk of BPD following CA is that intrauterine exposure to inflammation may cause subsequent lung development to be abnormal leading to BPD.50 In 1996, the first publication supporting an increased incidence of BPD following CA found a RR=2.18 (1.07, 4.43) for BPD in infants with birth weights <2000 g exposed to CA.46 A meta-analysis including studies from 1994-2009 found that histological, but not clinical, CA was associated with an increased odds of BPD, OR=2.19 (1.76, 2.72).51

Data that are not supportive of an association between CA and BPD include a histological evaluation of 446 placentas that failed to find a difference in BPD incidence for those with and without inflammatory cell infiltration.35 Evaluation of 529 infants born < 29 weeks gestation found that histological CA with FIR was associated with a decreased incidence of BPD, RR=0.88 (0.81, 0.95).4

Management of CA

Prenatal Antibiotics

Randomized, controlled trials support the use of antibiotics in women who present with preterm premature rupture of membranes. Six hundred and fourteen women with rupture of membranes between 24 and 32 weeks gestation were randomized to treatment with amoxicillin (or ampicillin IV) or placebo.52 More women treated with antibiotics were still pregnant at 2 (p=0.03), 7 (p=0.001), 14 (p=0.001) and 21 (p=0.008) days than those given placebo.52 Infants born to mothers treated with antibiotics had less RDS, RR=0.83 (0.69, 0.99), necrotizing enterocolitis, RR=0.40 (0.17, 0.95), and BPD, RR=0.64 (0.45, 0.92) than those given placebo.52 A recent Cochrane review found that use of antibiotics following preterm premature rupture of membranes decreased the risk of delivery within 7 days of rupture, RR=0.79 (0.71, 0.89), decreased the incidence of neonatal infection, RR=0.67 (0.52, 0.85), and reduced the incidence of CA, RR=0.66 (0.46, 0.96).53

For rupture of membranes occurring after 36 weeks gestation, a recent randomized trial found no reduction in the incidence of early onset sepsis, the need for mechanical ventilation or fetal death for 820 infants exposed to prenatal antibiotics compared to 820 infants exposed to placebo, RR=1.42 (0.85, 2.37).54

Postnatal Antibiotics

Due to the elevated risk of early onset neonatal sepsis in infants exposed to CA, the Committee on the Fetus and Newborn (COFN) of the AAP has recommended that infants exposed to CA have laboratory studies performed and be started on empirical broad-spectrum antibiotics.55,56 If studies are normal, cultures are negative and the infant is doing well, antibiotics should be stopped at 48 hours.55 Similarly, the CDC has recommended that infants exposed to CA be started on empirical antibiotics and undergo laboratory evaluation including blood cultures.57 Neither the AAP nor the CDC make a recommendation regarding duration of therapy. If the infant is clinically well and cultures are negative but the complete blood count or C-reactive protein is suggestive of infection, the role of additional or prolonged antibiotic treatment is unclear.

Antenatal Steroids

The benefits of antenatal steroid administration for preterm delivery are well described. For infants exposed to CA, antenatal steroids also improve outcomes. Exposure to antenatal steroids significantly decreased the incidence of both severe IVH and mortality for 53 infants with histologic CA.47 A Japanese Neonatal Research Network study of 7896 infants <34 weeks gestational age with histologic CA similarly found that RDS (OR=0.72, p<0.001), IVH (OR=0.68, p<0.001) and mortality (OR=0.50, p<0.001) occurred significantly less often in infants whose mothers received antenatal corticosteroid therapy.58

Conclusion

CA is a common problem, especially among preterm deliveries. Diagnosis is most accurately made from pathological specimens. For preterm premature rupture of membranes, antibiotics should be used to reduce the risk of preterm birth and its subsequent complications. Antibiotic administration to infants born following CA is recommended. Future studies should explore improved diagnostic and treatment modalities.

Key Points.

  • Chorioamnionitis is a pathologic diagnosis that is suggested by clinical findings.

  • Neonatal sepsis occurs in 1-3% of infants exposed to chorioamnionitis.

  • Infants exposed to chorioamnionitis require additional monitoring and testing.

  • Exposure to chorioamnionitis may lead to a variety of adverse neonatal outcomes but a causal relationship has been difficult to consistently demonstrate.

Best Practices Box.

What is the current practice?

  • Various strategies used to define chorioamnionitis

  • Most infants exposed to chorioamnionitis are evaluated for signs & symptoms of infection

Major Recommendations

  • Screen infants exposed to CA with complete blood count & blood culture

  • Evaluate the placentas of infants born prematurely or following prolonged rupture of membranes for evidence of CA

  • Mothers with preterm premature rupture of membranes should receive antibiotic therapy

Summary Statement

CA predisposes infants to premature birth, neonatal sepsis and IVH; the role of CA in RDS, BPD, and neurodevelopmental impairment is unclear. Antibiotics for preterm premature rupture of membranes reduces the incidence of CA. Antibiotics are recommended for infants exposed to CA while laboratory studies are being performed.

Acknowledgments

Dr. Laughon receives support from the U.S. government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, PI: Benjamin under the Best Pharmaceuticals for Children Act) and from NICHD (K23HD068497). Dr. Ericson receives support from the National Institute of Child Health and Human Development of the National Institutes of Health under award number 5T32HD060558.

References

  • 1.Hecht JL, Allred EN, Kliman HJ, et al. Histological characteristics of singleton placentas delivered before the 28th week of gestation. Pathology. 2008 Jun;40(4):372–376. doi: 10.1080/00313020802035865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. The New England journal of medicine. 1988 Oct 13;319(15):972–978. doi: 10.1056/NEJM198810133191503. [DOI] [PubMed] [Google Scholar]
  • 3.Hecht JL, Fichorova RN, Tang VF, et al. Relationship Between Neonatal Blood Protein Concentrations and Placenta Histologic Characteristics in Extremely Low GA Newborns. Pediatric research. 2011 Jan;69(1):68–73. doi: 10.1203/PDR.0b013e3181fed334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Plakkal N, Soraisham AS, Trevenen C, Freiheit EA, Sauve R. Histological chorioamnionitis and bronchopulmonary dysplasia: a retrospective cohort study. Journal of perinatology : official journal of the California Perinatal Association. 2013 Jun;33(6):441–445. doi: 10.1038/jp.2012.154. [DOI] [PubMed] [Google Scholar]
  • 5.Liu Z, Tang Z, Li J, Yang Y. Effects of placental inflammation on neonatal outcome in preterm infants. Pediatr Neonatol. 2014 Feb;55(1):35–40. doi: 10.1016/j.pedneo.2013.05.007. [DOI] [PubMed] [Google Scholar]
  • 6.Redline RW. Inflammatory response in acute chorioamnionitis. Semin Fetal Neonatal Med. 2012 Feb;17(1):20–25. doi: 10.1016/j.siny.2011.08.003. [DOI] [PubMed] [Google Scholar]
  • 7.Tsiartas P, Kacerovsky M, Musilova I, et al. The association between histological chorioamnionitis, funisitis and neonatal outcome in women with preterm prelabor rupture of membranes. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2013 Sep;26(13):1332–1336. doi: 10.3109/14767058.2013.784741. [DOI] [PubMed] [Google Scholar]
  • 8.Queiros da Mota V, Prodhom G, Yan P, Hohlfheld P, Greub G, Rouleau C. Correlation between placental bacterial culture results and histological chorioamnionitis: a prospective study on 376 placentas. J Clin Pathol. 2013 Mar;66(3):243–248. doi: 10.1136/jclinpath-2012-201124. [DOI] [PubMed] [Google Scholar]
  • 9.Bhola K, Al-Kindi H, Fadia M, Kent AL, Collignon P, Dahlstrom JE. Placental cultures in the era of peripartum antibiotic use. Aust N Z J Obstet Gynaecol. 2008 Apr;48(2):179–184. doi: 10.1111/j.1479-828X.2008.00833.x. [DOI] [PubMed] [Google Scholar]
  • 10.Combs CA, Gravett M, Garite TJ, et al. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. American journal of obstetrics and gynecology. 2014 Feb;210(2):125 e121–125 e115. doi: 10.1016/j.ajog.2013.11.032. [DOI] [PubMed] [Google Scholar]
  • 11.Yoon BH, Romero R, Kim M, et al. Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction. American journal of obstetrics and gynecology. 2000 Nov;183(5):1130–1137. doi: 10.1067/mob.2000.109036. [DOI] [PubMed] [Google Scholar]
  • 12.DiGiulio DB, Romero R, Amogan HP, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008;3(8):e3056. doi: 10.1371/journal.pone.0003056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Pankuch GA, Appelbaum PC, Lorenz RP, Botti JJ, Schachter J, Naeye RL. Placental microbiology and histology and the pathogenesis of chorioamnionitis. Obstet Gynecol. 1984 Dec;64(6):802–806. [PubMed] [Google Scholar]
  • 14.Greenberg MB, Anderson BL, Schulkin J, Norton ME, Aziz N. A first look at chorioamnionitis management practice variation among US obstetricians. Infectious diseases in obstetrics and gynecology. 2012;2012:628362. doi: 10.1155/2012/628362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Curtin WM, Katzman PJ, Florescue H, Metlay LA. Accuracy of signs of clinical chorioamnionitis in the term parturient. Journal of perinatology : official journal of the California Perinatal Association. 2013 Jun;33(6):422–428. doi: 10.1038/jp.2012.135. [DOI] [PubMed] [Google Scholar]
  • 16.Tokumasu H, Hinotsu S, Kita F, Kawakami K. Predictive value of clinical chorioamnionitis in extremely premature infants. Pediatr Int. 2013 Feb;55(1):35–38. doi: 10.1111/ped.12036. [DOI] [PubMed] [Google Scholar]
  • 17.Guzick DS, Winn K. The association of chorioamnionitis with preterm delivery. Obstet Gynecol. 1985 Jan;65(1):11–16. [PubMed] [Google Scholar]
  • 18.Marconi C, de Andrade Ramos BR, Peracoli JC, Donders GG, da Silva MG. Amniotic fluid interleukin-1 beta and interleukin-6, but not interleukin-8 correlate with microbial invasion of the amniotic cavity in preterm labor. Am J Reprod Immunol. 2011 Jun;65(6):549–556. doi: 10.1111/j.1600-0897.2010.00940.x. [DOI] [PubMed] [Google Scholar]
  • 19.Lee SY, Leung CW. Histological chorioamnionitis - implication for bacterial colonization, laboratory markers of infection, and early onset sepsis in very-low-birth-weight neonates. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2012 Apr;25(4):364–368. doi: 10.3109/14767058.2011.579208. [DOI] [PubMed] [Google Scholar]
  • 20.Sherman DJ, Tovbin J, Lazarovich T, et al. Chorioamnionitis caused by gram-negative bacteria as an etiologic factor in preterm birth. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 1997 Jun;16(6):417–423. doi: 10.1007/BF02471905. [DOI] [PubMed] [Google Scholar]
  • 21.Rode ME, Morgan MA, Ruchelli E, Forouzan I. Candida chorioamnionitis after serial therapeutic amniocenteses: a possible association. Journal of perinatology : official journal of the California Perinatal Association. 2000 Jul-Aug;20(5):335–337. doi: 10.1038/sj.jp.7200381. [DOI] [PubMed] [Google Scholar]
  • 22.Craig S, Permezel M, Doyle L, Mildenhall L, Garland S. Perinatal infection with Listeria monocytogenes. Aust N Z J Obstet Gynaecol. 1996 Aug;36(3):286–290. doi: 10.1111/j.1479-828x.1996.tb02712.x. [DOI] [PubMed] [Google Scholar]
  • 23.Becroft DM, Farmer K, Seddon RJ, et al. Epidemic listeriosis in the newborn. British medical journal. 1971 Sep 25;3(5777):747–751. doi: 10.1136/bmj.3.5777.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Tison A, Lozowy C, Benjamin A, Usher R, Prichard S. Successful pregnancy complicated by peritonitis in a 35- year old CAPD patient. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 1996;16(Suppl 1):S489–491. [PubMed] [Google Scholar]
  • 25.Lannon SM, Vanderhoeven JP, Eschenbach DA, Gravett MG, Waldorf KM. Synergy and Interactions Among Biological Pathways Leading to Preterm Premature Rupture of Membranes. Reproductive sciences. 2014 May 19; doi: 10.1177/1933719114534535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Erdemir G, Kultursay N, Calkavur S, et al. Histological chorioamnionitis: effects on premature delivery and neonatal prognosis. Pediatr Neonatol. 2013 Aug;54(4):267–274. doi: 10.1016/j.pedneo.2013.03.012. [DOI] [PubMed] [Google Scholar]
  • 27.Bastek JA, Weber AL, McShea MA, Ryan ME, Elovitz MA. Prenatal inflammation is associated with adverse neonatal outcomes. American journal of obstetrics and gynecology. 2014 May;210(5):450 e451–410. doi: 10.1016/j.ajog.2013.12.024. [DOI] [PubMed] [Google Scholar]
  • 28.Hillier SL, Witkin SS, Krohn MA, Watts DH, Kiviat NB, Eschenbach DA. The relationship of amniotic fluid cytokines and preterm delivery, amniotic fluid infection, histologic chorioamnionitis, and chorioamnion infection. Obstet Gynecol. 1993 Jun;81(6):941–948. [PubMed] [Google Scholar]
  • 29.Hornik CP, Fort P, Clark RH, et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early human development. 2012 May;88(Suppl 2):S69–74. doi: 10.1016/S0378-3782(12)70019-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Dexter SC, Malee MP, Pinar H, Hogan JW, Carpenter MW, Vohr BR. Influence of chorioamnionitis on developmental outcome in very low birth weight infants. Obstet Gynecol. 1999 Aug;94(2):267–273. doi: 10.1016/s0029-7844(99)00319-1. [DOI] [PubMed] [Google Scholar]
  • 31.Arayici S, Kadioglu Simsek G, Oncel MY, et al. The effect of histological chorioamnionitis on the short-term outcome of preterm infants </=32 weeks: a single-center study. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2014 Jul;27(11):1129–1133. doi: 10.3109/14767058.2013.850668. [DOI] [PubMed] [Google Scholar]
  • 32.Alexander JM, McIntire DM, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol. 1999 Aug;94(2):274–278. doi: 10.1016/s0029-7844(99)00256-2. [DOI] [PubMed] [Google Scholar]
  • 33.Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. American journal of obstetrics and gynecology. 2009 Apr;200(4):372 e371–376. doi: 10.1016/j.ajog.2008.11.034. [DOI] [PubMed] [Google Scholar]
  • 34.Yoon BH, Romero R, Park JS, et al. The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. American journal of obstetrics and gynecology. 2000 Nov;183(5):1124–1129. doi: 10.1067/mob.2000.109035. [DOI] [PubMed] [Google Scholar]
  • 35.Andrews WW, Goldenberg RL, Faye-Petersen O, Cliver S, Goepfert AR, Hauth JC. The Alabama Preterm Birth study: polymorphonuclear and mononuclear cell placental infiltrations, other markers of inflammation, and outcomes in 23- to 32-week preterm newborn infants. American journal of obstetrics and gynecology. 2006 Sep;195(3):803–808. doi: 10.1016/j.ajog.2006.06.083. [DOI] [PubMed] [Google Scholar]
  • 36.Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ. Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol. 1998 May;91(5 Pt 1):725–729. doi: 10.1016/s0029-7844(98)00056-8. [DOI] [PubMed] [Google Scholar]
  • 37.Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA : the journal of the American Medical Association. 1997 Jul 16;278(3):207–211. [PubMed] [Google Scholar]
  • 38.Nasef N, Shabaan AE, Schurr P, et al. Effect of clinical and histological chorioamnionitis on the outcome of preterm infants. American journal of perinatology. 2013 Jan;30(1):59–68. doi: 10.1055/s-0032-1321501. [DOI] [PubMed] [Google Scholar]
  • 39.Alshaikh B, Yusuf K, Sauve R. Neurodevelopmental outcomes of very low birth weight infants with neonatal sepsis: systematic review and meta-analysis. Journal of perinatology : official journal of the California Perinatal Association. 2013 Jul;33(7):558–564. doi: 10.1038/jp.2012.167. [DOI] [PubMed] [Google Scholar]
  • 40.Adams-Chapman I, Bann CM, Das A, et al. Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. The Journal of pediatrics. 2013 Oct;163(4):961–967 e963. doi: 10.1016/j.jpeds.2013.04.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA : the journal of the American Medical Association. 2004 Nov 17;292(19):2357–2365. doi: 10.1001/jama.292.19.2357. [DOI] [PubMed] [Google Scholar]
  • 42.Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia. American journal of obstetrics and gynecology. 1996 May;174(5):1433–1440. doi: 10.1016/s0002-9378(96)70585-9. [DOI] [PubMed] [Google Scholar]
  • 43.Yoon BH, Jun JK, Romero R, et al. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha), neonatal brain white matter lesions, and cerebral palsy. American journal of obstetrics and gynecology. 1997 Jul;177(1):19–26. doi: 10.1016/s0002-9378(97)70432-0. [DOI] [PubMed] [Google Scholar]
  • 44.Leviton A, Fichorova RN, O'Shea TM, et al. Two-hit model of brain damage in the very preterm newborn: small for gestational age and postnatal systemic inflammation. Pediatric research. 2013 Mar;73(3):362–370. doi: 10.1038/pr.2012.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.O'Shea TM, Shah B, Allred EN, et al. Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants. Brain, behavior, and immunity. 2013 Mar;29:104–112. doi: 10.1016/j.bbi.2012.12.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996 Feb;97(2):210–215. [PubMed] [Google Scholar]
  • 47.Been JV, Rours IG, Kornelisse RF, et al. Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. American journal of obstetrics and gynecology. 2009 Dec;201(6):587 e581–588. doi: 10.1016/j.ajog.2009.06.025. [DOI] [PubMed] [Google Scholar]
  • 48.Jones MH, Corso AL, Tepper RS, et al. Chorioamnionitis and subsequent lung function in preterm infants. PLoS One. 2013;8(12):e81193. doi: 10.1371/journal.pone.0081193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Laughon M, Allred EN, Bose C, et al. Patterns of respiratory disease during the first 2 postnatal weeks in extremely premature infants. Pediatrics. 2009 Apr;123(4):1124–1131. doi: 10.1542/peds.2008-0862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Kramer BW, Kallapur S, Newnham J, Jobe AH. Prenatal inflammation and lung development. Semin Fetal Neonatal Med. 2009 Feb;14(1):2–7. doi: 10.1016/j.siny.2008.08.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Hartling L, Liang Y, Lacaze-Masmonteil T. Chorioamnionitis as a risk factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Archives of disease in childhood Fetal and neonatal edition. 2012 Jan;97(1):F8–F17. doi: 10.1136/adc.2010.210187. [DOI] [PubMed] [Google Scholar]
  • 52.Mercer BM, Miodovnik M, Thurnau GR, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA : the journal of the American Medical Association. 1997 Sep 24;278(12):989–995. [PubMed] [Google Scholar]
  • 53.Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013;12:CD001058. doi: 10.1002/14651858.CD001058.pub3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Nabhan AF, Elhelaly A, Elkadi M. Antibiotic prophylaxis in prelabor spontaneous rupture of fetal membranes at or beyond 36 weeks of pregnancy. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2014 Jan;124(1):59–62. doi: 10.1016/j.ijgo.2013.07.018. [DOI] [PubMed] [Google Scholar]
  • 55.Polin RA Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012 May;129(5):1006–1015. doi: 10.1542/peds.2012-0541. [DOI] [PubMed] [Google Scholar]
  • 56.Committee on Infectious D, Committee on F, Newborn. Baker CJ, Byington CL, Polin RA. Policy statement-Recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011 Sep;128(3):611–616. doi: 10.1542/peds.2011-1466. [DOI] [PubMed] [Google Scholar]
  • 57.Verani JR, McGee L, Schrag SJ Division of Bacterial Diseases NCfI, Respiratory Diseases CfDC, Prevention. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recommendations and reports : Morbidity and mortality weekly report Recommendations and reports / Centers for Disease Control. 2010 Nov 19;59(RR-10):1–36. [PubMed] [Google Scholar]
  • 58.Miyazaki K, Furuhashi M, Ishikawa K, Tamakoshi K, Ikeda T Neonatal Research Network J. The effects of antenatal corticosteroids therapy on very preterm infants after chorioamnionitis. Archives of gynecology and obstetrics. 2014 Jun;289(6):1185–1190. doi: 10.1007/s00404-013-3106-3. [DOI] [PubMed] [Google Scholar]
  • 59.Torricelli M, Voltolini C, Toti P, et al. Histologic chorioamnionitis: different histologic features at different gestational ages. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2014 Jun;27(9):910–913. doi: 10.3109/14767058.2013.846313. [DOI] [PubMed] [Google Scholar]
  • 60.Gotsch F, Romero R, Kusanovic JP, et al. The fetal inflammatory response syndrome. Clinical obstetrics and gynecology. 2007 Sep;50(3):652–683. doi: 10.1097/GRF.0b013e31811ebef6. [DOI] [PubMed] [Google Scholar]
  • 61.Kwak DW, Hwang HS, Kwon JY, Park YW, Kim YH. Co-infection with vaginal Ureaplasma urealyticum and Mycoplasma hominis increases adverse pregnancy outcomes in patients with preterm labor or preterm premature rupture of membranes. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2014 Mar;27(4):333–337. doi: 10.3109/14767058.2013.818124. [DOI] [PubMed] [Google Scholar]
  • 62.Mendz GL, Kaakoush NO, Quinlivan JA. Bacterial aetiological agents of intra-amniotic infections and preterm birth in pregnant women. Frontiers in cellular and infection microbiology. 2013;3:58. doi: 10.3389/fcimb.2013.00058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.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. American journal of obstetrics and gynecology. 2008 Jan;198(1):43 e41–45. doi: 10.1016/j.ajog.2007.07.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Onderdonk AB, Delaney ML, DuBois AM, Allred EN, Leviton A Extremely Low Gestational Age Newborns Study I. Detection of bacteria in placental tissues obtained from extremely low gestational age neonates. American journal of obstetrics and gynecology. 2008 Jan;198(1):110 e111–117. doi: 10.1016/j.ajog.2007.05.044. [DOI] [PubMed] [Google Scholar]

RESOURCES