Although antenatal infection is thought to play an important role in the pathogenesis of preterm labor and neonatal diseases, the exact mechanisms are largely unknown. We sought to clarify the relationship between antenatal infection and intrauterine and neonatal inflammation. Samples were obtained from 41 preterm infants of Ͻ33 wk gestation delivered to 36 mothers and analyzed for the presence of 16s ribosomal RNA (16s rRNA) genes using PCR and for the proinflammatory cytokines IL-6 and IL-8. In 16 (44%) mother-baby pairings, at least one sample was found to be positive for the presence of 16s rRNA genes. All but one of the positive samples were from mothers presenting with preterm prelabor rupture of membranes (pPROM) or in spontaneous idiopathic preterm labor. A strong association was found between the presence of 16s rRNA genes and chorioamnionitis and with funisitis. A marked increase in IL-6 and IL-8 was noted in all tissues positive for 16s rRNA genes, including placenta, fetal membranes, cord blood serum, and, where samples were available, in bronchoalveolar lavage fluid (BAL) and in amniotic fluid. Interestingly, gastric fluid was always positive for 16s rRNA genes if any other intrauterine or BAL sample was positive, suggesting that this sample may provide an alternative to amniotic fluid to identify antenatal infection. In conclusion, we have found that microbial genes are particularly prevalent in pPROM and spontaneous preterm labor groups and that their presence is strongly associated with a marked intrauterine inflammatory response. (Pediatr Res 57: 570-577, 2005) Abbreviations BAL, bronchoalveolar lavage CLD, chronic lung disease pPROM, preterm prelabor rupture of membranes rRNA, ribosomal RNA Preterm birth is the most common cause of neonatal death (1) and is associated with increased neonatal morbidity and childhood disability (2,3). Evidence from studies over the past two decades suggests that subclinical infection and inflammation of the amnion/chorion/decidua is implicated in the pathogenesis of pPROM and "spontaneous" preterm labor (4,5). More recently, intrauterine infection/inflammation has been associated with neonatal morbidity, including white matter cerebral lesions (6 -8) and CLD (9 -11). It has been estimated that as many as 40% of spontaneous preterm births may be attributed to antenatal infection (12). Furthermore, because many infections are subclinical and the women have often been treated with antibiotics, culture results may underestimate the "true" infection rates.Many studies have used amniotic fluid to identify antenatal intrauterine infection. The organisms commonly identified are vaginal commensals, suggesting ascending infection as a route of entry to the uterine cavity (13). Few studies have investigated other components of the uterine cavity to accurately identify the presence of infection and the nature of the relationship between such infection and inflammation. A clear association has been demonstrated between chorioamnionitis and intrauterine infection (14 -16). Oft...

Previously, we have reported marked pulmonary inflammation in infants who develop chronic lung disease of prematurity. We revisited these infants who did not have clinical or laboratory evidence of infection and searched for Ureaplasma urealyticum, group B streptococci, and other microbes by reverse transcription-PCR performed on RNA extracted from 93 bronchoalveolar lavage samples. From infants ventilated for respiratory distress syndrome, 6 (gestation, 28 wk; birthweight, 880 g) were positive for U. urealyticum and 11 (25 wk, 800 g) were negative. Five (83%) positive and four (36%) negative infants developed chronic lung disease. Each infant was colonized with either biovar 1 or biovar 2 but not both. U. urealyticum was very weakly detectable in two infants on d 1 but was detected in five of six infants at d 10. Furthermore, pulmonary neutrophils, alveolar macrophages, soluble intercellular adhesion molecule-1, and IL-1␤ on d 10 and IL-6 and IL-8 at d 1 were significantly increased in the positive group. A variety of organisms were identified in six samples between 14 and 21 d of age, but all samples were negative for group B streptococci. Our data suggest that U. urealyticum colonization is associated with the development of pulmonary inflammation in infants who subsequently develop chronic lung disease. CLD remains a common respiratory disorder of preterm infants. Despite significant advances with therapeutic modalities, including the introduction of surfactant, various modes of mechanical ventilation and regular use of antenatal corticosteroids, morbidity and mortality remain high. Many risk factors have been identified and these include mechanical ventilation, oxygen therapy, patent ductus arteriosus, and nosocomial infection. An area that has recently received much attention is antenatal infection (1, 2). Even before the infant is delivered, an inflammatory response has been noted and this inflammation appears to be associated with the development of respiratory disease in the newborn infant (3, 4). One candidate for initiating this inflammation is the mycoplasma Ureaplasma urealyticum (5, 6). This organism has been isolated from the lungs of infants who have developed CLD, but whether U. urealyticum causes acute lung injury in preterm infants or whether the association is with the degree of prematurity remains controversial (7). One approach to confirming or refuting this association is to study the link between the pulmonary inflammatory response, which has now been regularly reported in infants who develop CLD (8 -11), and the presence of U. urealyticum in the lungs of infants who develop CLD.Our previous data have demonstrated that proinflammatory cytokines IL-1 and IL-6, the potent neutrophil chemoattractant IL-8, and soluble adhesion molecule ICAM-1, as well as inflammatory cells, namely neutrophils, are increased in the lungs of infants who subsequently develop CLD (8, 9). These findings have been confirmed by many others (10, 11), and it is now generally accepted that pulmonary inflammation is a r...

In spite of improved neonatal care, chronic lung disease of prematurity (CLD) remains a major cause of morbidity and mortality in extremely preterm infants. Our current understanding is that antenatal infection can trigger intra-uterine inflammation which then promotes preterm labour. Recent studies suggest that antenatal infection and inflammation can also increase the preterm infant's susceptibility to develop CLD. It may be that exposure of the fetal lung to high concentrations of pro-inflammatory cytokines is the cause of this increased susceptibility. One candidate for initiating intra-uterine inflammation is ascending infection by the vaginal commensal Ureaplasma urealyticum (Uu). Antibiotics administered to mothers prior to delivery appear to improve the neonatal outcome in cases of preterm prolonged rupture of membranes, but not in cases of preterm labour with intact membranes. Uu can be transmitted vertically to the airways of the preterm infant, but the role of Uu in causing CLD remains uncertain. Small trials of antibiotics given to preterm infants after delivery have not shown any consistent benefit in reducing CLD. Although CLD remains a significant problem for the extremely preterm infant, it is likely that molecular biology techniques, such as the polymerase chain reaction, will enhance the detection of antenatal infection and further our understanding of the pathogenesis of CLD.

In this study, cord blood cortisol was increased in the colonised group compared with non-colonised infants. It is unclear if infants born following prelabour premature rupture of the membranes mount an adequate anti-inflammatory response.

Empyema caused by Kingella denitrificans and Peptostreptococcus spp. was diagnosed in a patient with bronchogenic carcinoma. This appears to be the third report providing evidence of a pathogenic role for K. denitrificans, and the first concerning infection in the pleural space and in a patient with underlying immunosuppressive disease. K. denitrificans should be added to the list of fastidious gram-negative bacteria associated with opportunistic infections in the compromised host.