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Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction.

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 <33 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.

Amniotic Fluid↗

Biovar diversity of Ureaplasma urealyticum in amniotic fluid: distribution, intrauterine inflammatory response and pregnancy outcomes.

OBJECTIVE: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with "parvo biovar" and those with "T960 biovar". STUDY DESIGN: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. RESULTS: 1) The "parvo biovar" was detected in 82% (63/77) and "T960 biovar" was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for "parvo biovar" and in 50% (7/14) of cases with positive for "T960 biovar"; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. CONCLUSIONS: 1) The "parvo biovar" is more frequently isolated from amniotic fluid of preterm gestations than the "T960 biovar"; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.

Amniocentesis↗

Perinatal mortality associated with intrauterine infection due to pseudomonads.

Pseudomonads are common causes of nosocomial infections but are rarely implicated in perinatal disease. In a retrospective autopsy study we found that 9% of all acute congenital bacterial infections were due to Pseudomonas species. Premature rupture of membranes occurred in half the cases and clinical maternal amnionitis in two-thirds. One case was apparently nosocomial in origin. No known risk factors were implicated in any other case. Seven infants were stillborn and two died within a few hours. Congenital pneumonia, funisitis, and chorioamnionitis were found at autopsy. Intrauterine infection due to the pseudomonads poses a serious problem that has not been previously recognized.

Female↗

Streptococcus viridans infections in midgestation.

During a 14-year period Streptococcus viridans was isolated at autopsy from 18 neonates or stillborn fetuses delivered in midgestation (18-28 weeks) at Women & Infants' Hospital in Providence, Rhode Island. Evidence of swallowed and/or aspirated, infected amniotic fluid by the fetus was found in 16 of 18 cases along with chorioamnionitis and funisitis. Of the 18 cases, maternal infection was documented in 6 cases; delivery was preceded by spontaneous rupture of membranes in 9 cases and vaginal bleeding in 7 cases. Poor maternal obstetric history was indicated by only 12 living children from 42 total pregnancies in the 12 multigravidas in the study. It is concluded that S. viridans may have a significant role in the pathogenesis of second trimester amniotic fluid infections with abortions and fetal and neonatal sepsis.

Chorioamnionitis↗

Giant cell and lymphocytic interstitial pneumonia associated with fetal pneumonia.

In a review of 96 consecutive perinatal autopsies (42 nonautolyzed stillborn and 54 liveborn infants 12 h or less of age) with histologic sections of placental tissues and an undistended lung, we were impressed by the frequent occurrence of lymphocytic infiltrates in the interstitium of the lung. To study this phenomenon further we analyzed the cases for 56 clinicopathologic variables. Lymphocytic interstitial infiltrates were present in 22 of the cases, 5 stillborn and 17 liveborn. The severity of the infiltrates was highly significantly correlated with the severity of chorioamnionitis, funisitis, and fetal pneumonia (P < .001). A positive association was found with livebirth and a negative association with hyaline membrane disease (both P < .05). No significant association was found with gestational age, body size, or other complications of pregnancy, labor, delivery, or the immediate perinatal period. Twenty-seven cases had fetal pneumonia without lymphocytic interstitial infiltrates. Two cases had interstitial lymphocytic infiltrates in the absence of fetal pneumonia, but both had chorioamnionitis. Two other cases had numerous giant cells, shown to be of macrophage origin by immunoperoxidase stains, in the airways in addition to severe fetal pneumonia and lymphocytic interstitial pneumonia. The observations show that lymphocytic interstitial infiltrates and giant cells may be a feature of fetal pneumonia.

Female↗

[Outcome of microbial invasion of amniotic cavity in the preterm premature rupture of membranes].

BACKGROUND: Microbial invasion of amniotic cavity occurs in 30 to 50% of patients with premature membrane rupture. AIM: To determine the outcomes associated with microbial invasion of the amniotic cavity (MIAC) in patients with preterm premature rupture of membrane (pPROM). PATIENTS AND METHODS: One hundred thirty four patients with preterm pPROM between 24 and 34 weeks of pregnancy, without clinical infection or labor, were studied. Cultures were obtained by transabdominal amniocentesis from the amniotic fluid and the lower genital tract. Four groups of MIAC were observed: MIAC1: due to S. agalactiae, F. nucleatum or H. influenzae as only etiologic agents, MIAC2: due to other bacteria, alone or mixed, MIAC3: due to U. urealyticum as only etiologic agent, MIAC0: No MIAC and no infection of the lower genital tract. Study patients received antibiotics and were managed expectantly until 35 weeks unless clinical chorioamnionitis developed or an amniotic fluid culture returned positive for S. agalactiae, F. nucleatum or H. influenzae. RESULTS: Ninety six patients were enrolled: MIAC1 (n=11), MIAC2 (n=30), MIAC3 (n=19) and MIAC0 (n=36). Clinical chorioamnionitis was more common in patients with MIAC1 than those with MIAC3 (p<0.01) and those without infection (p<0.001). The admission to delivery interval was shorter in patients with MIAC1 (2.8 days) than those with MIAC3 (10.1 days, p<0.05) and those without infection (18 days, p<0.001). Delivery within 48 h and within 7 days of admission were also more frequent in patients with MIAC1 than in patients with MIAC3 (p<0.05) or those without infection (p<0.001). Newborns to mothers with MIAC1 had a higher frequency of infection (36%), asphyxia (36%), admission to neonatal ICU (100%) and death (46%) than those of mothers with MIAC3 and those without infection. Birth weight was also significantly lower. Histological chorioamnionitis was more common in patients with MIAC1 than in patients with MIAC3 and those without infection. The rate of funisitis was higher in patients with MIAC1 than those without infection. CONCLUSIONS: In patients with preterm PROM, microbial invasion of the amniotic cavity by S. agalactiae, F. nucleatum or H. influenzae is associated with high frequency of adverse maternal and neonatal outcomes and neonatal death.

Adolescent↗

Elevated maternal glucose concentrations and placental infection in twin pregnancies.

OBJECTIVE: To evaluate the association between maternal screening glucose concentration and placental infection in nondiabetic twin pregnancies. STUDY DESIGN: One thousand sixty-one nondiabetic twin pregnancies at > or =28 weeks' gestation were divided into 3 groups based on the screening 50-g fasting glucose concentration at 24-28 weeks: lowest quartile (< 96 mg/dL), middle 2 quartiles (96-128 mg/dL) and upper quartile (> 128 mg/dL). Outcomes were modeled using general linear and multinomial logistic regression, controlling for confounding factors. RESULTS: The middle and highest glucose groups were associated with increased risks for clinical chorioamnionitis (adjusted OR [AOR] 3.18, 95% CI 1.34, 7.54; AOR 6.80, CI 1.89, 24.53, respectively). Birth at <32 weeks and histologic diagnosis of placental infection (chorioamnionitis, funisitis, necrosis, vasculitis or villitis) were significantly associated only with the highest glucose group (AOR 1.79, CI 1.02, 3.13; AOR 6.95, CI 1.10, 8.68, respectively). CONCLUSION: Elevated screening glucose in nondiabetic twin pregnancies may be a marker of placental inflammation and infection.

Adult↗

Placental abruption in the preterm gestation: an association with chorioamnionitis.

Thirty-seven women with acute severe preterm placental abruption were compared with a control group of 51 women requiring preterm delivery for a medical complication of pregnancy. Histologic chorioamnionitis and funisitis were present significantly more often in patients with abruption than in control patients (41 versus 4%; P less than .0001). No patient in either group had clinical evidence of chorioamnionitis. We conclude that a significant association exists between preterm placental abruption and histologic chorioamnionitis.

Abruptio Placentae↗

Isolation of genital mycoplasmas and Chlamydia trachomatis in stillborn and neonatal autopsy material.

Chlamydia trachomatis and the genital mycoplasmas are significantly prevalent in sexually active women. How these organisms may affect the outcome of pregnancy and the neonate was the principal thrust of this investigation. Placenta, liver, and lung tissue were cultured from Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, and aerobic as well as anaerobic bacteria in 432 stillborn and neonatal autopsies. Genital mycoplasmas were isolated from 36 cases (8.3%). Acute chorioamnionitis and funisitis were present significantly more often in cases with genital mycoplasma than in those without these organisms. Isolation of genital mycoplasmas was not associated with an increased incidence of intrauterine fetal death, villitis, hyaline membrane disease, congenital anomalies, or polymorphonuclear leukocytes in alveolar spaces. Chlamydia trachomatis was not found in any of the sites sampled.

Autopsy↗

Umbilical cord hematoma resulting in intrauterine fetal demise. A case report.

A 34-week male fetus experienced intrauterine death due to an umbilical cord hematoma. Rupture of the hematoma occurred at the time of delivery, but compression of the cord vessels and fetal blood loss into the hematoma, rather than the rupture itself, were the cause of death. Membranes had been ruptured for several days prior to the fetal demise, and both chorioamnionitis and funisitis were present. Inflammation of the umbilical cord, as well as a defect in the elastin and smooth muscle components of the vein, may have predisposed the cord to development of the hematoma.

Adult↗

Chorioamnionitis: a comparative histologic, bacteriologic, and clinical study.

Using morphologic and bacteriologic techniques, we examined placentas from 224 deliveries considered potentially complicated by infection. The severity of the chorioamnionitis was graded histologically according to the intensity of the inflammatory infiltrate. Chorioamnionitis or funisitis occurred in 111 placentas. Neonatal morbidity in this group was 48 (43%) as compared with 14 (12%) in those without chorioamnionitis. Pathogens were cultured from 49 of the 111 placentas with chorioamnionitis. Neonatal morbidity or mortality occurred in 28 (58%) of the group with positive cultures but occurred also in 20 (32%) of the 63 with chorioamnionitis from which no pathogens were cultured. Perinatal mortality was especially high (64%) among premature infants (less than 30 weeks) with infection. A comparison of culture techniques (surface swab versus swab of subchorionic fibrin after searing amnionic surface) showed similar rates of recovery but less contamination using the deep culture technique. Neonatal morbidity and mortality with severe chorioamnionitis (grades II and III; 62% and 82%) were significantly greater than with little or no chorioamnionitis (grades I and 0; 43% and 36%). Higher grades of histologically demonstrable chorioamnionitis are associated significantly with the highest rates of neonatal morbidity or mortality. In many instances, pathogens are not recovered by conventional aerobic and anaerobic bacteriologic study. A search for other infectious agents (viruses, mycoplasmas, chlamydiae) deserves attention.

Acute Disease↗

Congenital herpes infection: placental and umbilical cord findings.

BACKGROUND: Herpes simplex virus (HSV) fetal infections are rare, and the routes through which the virus reaches the fetus are insufficiently documented. CASE: We describe a case of congenital HSV ascending infection in an infant whose membranes were intact until cesarean delivery. The pathologic findings were remarkable for a mild lymphoplasmocytic funisitis and the presence of positive viral staining of cells in the subamniotic connective tissue, amniotic epithelium, and umbilical cord. Antigen-positive cells within the extraplacental membranes were mostly located in an area presumably adjacent to the cervix before birth. In the umbilical cord, positive viral staining was confined to cells in the subamniotic mesenchyma away from the perivascular mesenchyma of the central portion of the cord. CONCLUSION: Immunohistochemistry using herpes-specific antibodies, coupled with routine histologic examination, allows early diagnosis of congenital HSV infection and documentation of the ascending route of infection when the membranes are intact.

Adolescent↗

Obstetric performance, perinatal outcome and risk of infection to the newborn in spontaneous and artificial rupture of membranes during labour.

OBJECTIVE: To compare the obstetric performance, perinatal outcome and risk of neonatal infection in labour following spontaneous (SROM) and artificial (AROM) rupture of membranes. DESIGN: Prospective, non-randomised, comparative study during a one-month period in 1995. The study was approved by the ethics committee of the Faculty of Medicine, University of Colombo. SETTING: University Obstetrics Unit at De Soysa Hospital for Women, Colombo. PATIENTS: 324 women who were in early established labour after 37 weeks of gestation. 151 of these had SROM and 173 AROM. The AROM and SROM groups among primigravidae and multigravidae were considered separately. RESULTS: Oxytocin use in multigravidae was significantly higher in the AROM group than in the SROM group (p < 0.001). The emergency caesarean section (LSCS) rate in primigravidae was significantly higher in the AROM group than the SROM group (p < 0.001). A significantly larger number of primigravid AROM women had abnormal fetal heart rate changes on auscultation (p < 0.05) and cardiotopographic (CTG) patterns (p < 0.001) when compared with primigravid SROM women. Choreoamnionitis and funisitis were commoner in the AROM group although the difference was not statistically significant. CONCLUSIONS: AROM appears to be associated with a higher chance of fetal distress particularly in primigravidae. Both AROM and SROM are associated with a potential risk of infection at intrauterine sites.

Adult↗

Intra-amniotic infection: diagnosis, nomenclature, clinical significance, management, and microbiologic tools used for the diagnosis.

SUMMARYIntra-amniotic infection is the main cause of spontaneous preterm birth and adverse maternal-fetal outcomes; therefore, rapid, robust, and accurate diagnosis remains a clinical priority. Conventional microbiological techniques, especially culture-based methods, are limited by long turnaround times and the inability to detect fastidious or unculturable organisms. This review summarizes the diagnosis, nomenclature, clinical significance, management, and laboratory approaches for diagnosing intra-amniotic infection. Targeted nucleic acid amplification methods, including species-specific polymerase chain reaction and broad-range 16S rRNA gene sequencing, have improved the detection of bacterial DNA and enabled the identification of organisms that evade routine culture in intra-amniotic infection. More recently, whole-genome sequencing and metagenomic next-generation sequencing have provided culture-independent strategies for comprehensive pathogen profiling, allowing simultaneous detection of bacteria, viruses, and fungi, as well as characterization of antimicrobial resistance determinants and virulence-associated genes. However, challenges remain, particularly in low-biomass samples such as amniotic fluid, where contamination, host DNA background, and data interpretation can compromise specificity. This review critically evaluates the advantages and limitations of each molecular modality and discusses pre-analytical, analytical, and bioinformatic considerations essential for reliable implementation. Integration of molecular diagnostics into clinical workflows holds promise for improving etiological diagnosis and guiding targeted therapy in intra-amniotic infection, thereby improving maternal and fetal outcomes.

Humans↗