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PubMed2005

C-reactive protein concentration in vaginal fluid as a marker for intra-amniotic inflammation/infection in preterm premature rupture of membranes.

OBJECTIVE: The purpose of this study was to determine whether C-reactive protein (CRP) concentrations in vaginal fluid can identify patients with intra-amniotic inflammation/infection (IAI) and predict adverse outcome in preterm premature rupture of membranes (PROM). METHODS: The study population consisted of 121 singleton pregnant women with preterm PROM (36 weeks of gestation) who had an amniocentesis and vaginal fluid collection. A Dacron polyester-tipped applicator was soaked with vaginal fluid for 10 seconds and diluted with 1 mL buffer solution. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Vaginal fluid CRP and amniotic fluid matrix metalloproteinase-8 (MMP-8) were determined by specific immunoassays. IAI was defined as an amniotic fluid MMP-8 concentration >23 ng/mL and/or a positive amniotic fluid culture. Nonparametric tests and survival techniques were used for statistical analysis. RESULTS: Patients with IAI had a significantly higher median vaginal fluid CRP concentration than those without IAI (median (range), 7.8 (0.1-1310.1) ng/mL vs. 1.0 (0.1-319.4) ng/mL, p < 0.005). The median amniotic fluid white blood cell (WBC) count was significantly higher in patients with a vaginal fluid CRP concentration of >10 ng/mL than in those with a lower concentration (median (range), 82.5 (0-8640) cells/mm3 vs. 2 (0->1000) cells/mm3, p < 0.001). Patients with vaginal fluid CRP concentration of >10 ng/mL had a significantly shorter sampling-to-delivery interval and higher rates of preterm delivery within five days, funisitis, and histologic chorioamnionitis than did those with a vaginal fluid CRP concentration below this cut-off. A vaginal fluid CRP cut-off of 10 ng/mL had a specificity of 89% and a sensitivity of 45% in the identification of IAI. CONCLUSION: An elevated CRP concentration in vaginal fluid collected by polyester-tipped applicator is a risk factor for intra-amniotic inflammation/infection and impending preterm delivery in preterm PROM.

Amniocentesis↗
PubMed2003

Maternal and fetal inflammatory responses in unexplained fetal death.

OBJECTIVE: The role of intra-amniotic infection in the etiology of fetal death has been proposed. This study was conducted to determine the prevalence of microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal and/or fetal inflammation in patients presenting with a fetal death. METHODS: A prospective study was conducted in patients with a fetal death. Amniocenteses were performed for clinical indications (karyotype), as well as to assess the microbiological and cytological state of the amniotic cavity. Fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. An amniotic fluid white blood cell count and glucose determinations were also performed. Histological examination of the placenta was conducted to identify a maternal inflammatory response (acute chorioamnionitis) or a fetal inflammatory response (funisitis). RESULTS: This study included 44 patients with intrauterine fetal death. The median gestational age at diagnosis was 30.1 weeks (range 16.3-40.4 weeks). One patient had documented MIAC (1/44). Acute histological chorioamnionitis was found in 20.9% (9/43), but a fetal inflammatory response was observed in only 2.3% (1/43) of cases. One patient had a positive amniotic fluid culture for Streptococcus agalactiae (group B streptococcus). CONCLUSION: Histological chorioamnionitis was present in 20.9% of cases, but MIAC could be demonstrated with conventional microbiological techniques in only one case. A fetal inflammatory response was nine times less frequent than a maternal inflammatory response (maternal 20.9% vs. fetal 2.3%, p = 0.008) in cases of fetal death.

Adult↗
PubMed2000

Placental abnormalities associated with human immunodeficiency virus type 1 infection and perinatal transmission in Bangkok, Thailand.

The effects of human immunodeficiency virus (HIV) type 1 on the placenta and the role of the placenta in mother-to-child HIV-1 transmission are not well understood. Placentas from 78 HIV-infected and 158 HIV-uninfected women were examined as part of a prospective perinatal HIV transmission study in Bangkok. HIV-infected women were more likely than HIV-uninfected women to have chorioamnionitis (odds ratio [OR], 2.1; P=.03), placental membrane inflammation (PMI; OR, 2. 7; P=.02), and deciduitis (OR, 2.3; P=.03) and less likely to have villitis (OR, 0.3; P=.02). However, among HIV-infected women, fewer women who transmitted infection to their child had chorioamnionitis (relative risk [RR], 0.2; P=.03), funisitis (RR, 0.4; P=.1), or PMI (RR undefined; P=.03). These findings suggest that, in this population, HIV-infected women are at increased risk for placental membrane inflammatory lesions, but that placental inflammatory lesions are not associated with increased perinatal HIV transmission.

Adolescent↗
PubMed1984

The effects of dietary supplementation during pregnancy on placental morphology, pathology, and histomorphometry.

We related the macroscopic and microscopic morphology and the histomorphometry of the placenta to prenatal nutritional supplementation. In the Prenatal Project, a controlled clinical trial, three dietary treatments (supplement, a high-protein beverage; complement, a balanced protein-calorie beverage, or routine vitamin and mineral tablets) were randomly allocated to poor Black pregnant women, and the outcome was assessed. Herein we report the effects on placental morphology and histomorphometry. There were significantly fewer preterm deliveries in the complement group, and this was reflected by an increase in the size of decidual cells, an index associated with placental aging. Several other characteristics of the placentas of the complement group may have been more directly associated with improved perinatal outcome: decreased intervillous fibrin, lower incidence of gross surface infarct, and smaller (and presumably less edematous) cells of the villous stroma, may have mediated increased placental perfusion. There was no evidence of any placental change associated with the increase in very preterm delivery and the highly significant depressed birth weight among preterm deliveries in the supplement group. The significantly lower incidence of meconium staining of Wharton's jelly among controls seems likely to have been a chance finding. While there were several other indices that reflected placental aging, the significantly increased chorioamnionitis, acute funisitis , and acute decidual inflammation among placentas of those who delivered prematurely [the former two associated with very early delivery (less than 35 wk gestation)] were likely to have been involved as causes of premature delivery.

Clinical Trials as Topic↗
PubMed1991

Pathology and human immunodeficiency virus expression in placentas of seropositive women.

The pathology of term placentas from seropositive human immunodeficiency virus (HIV)-infected and seronegative women was investigated by routine histologic, immunocytochemical, and in situ hybridization techniques. Placentas were evaluated for evidence of villitis, chorioamnionitis, and funisitis. Membranes, trophoblast, and decidua were also examined by immunohistochemistry using monoclonal HIV p24 antibody. Twenty placentas were evaluated by combined immunochemical and in situ hybridization techniques, using a 35S-labeled RNA probe complementary to the 3' long terminal repeat and envelope region of HIV-1. HIV-seropositive placentas did not show significant villitis; however, the incidence of chorioamnionitis increased (P less than .01). HIV antigens and nucleic acids were identified in the trophoblast of 10% of the placentas that also showed chorionitis. Term HIV-positive placentas may show histologic changes that may or may not be directly related to the virus. Analysis of tissues from earlier gestational placentas may prove more informative in clarifying the mechanism of maternal-fetal HIV transmission.

Chorion↗
PubMed1994

The correlation of prenatal brain damage with placental pathology.

Several epidemiological studies have emphasized that prenatal factors are the best predictors for cerebral palsy. Many placental pathologists have anecdotally recognized an association between placental pathology and poor pregnancy outcome, including neurologic injury. This study was undertaken to determine if correlations exist between specific types of placental pathology and prenatal brain injury. Ninety-eight stillbirths and livebirths with < 1 hour survival and complete placental and neuropathologic exams were reviewed. Most brain damage was in three categories: germinal matrix/intraventricular hemorrhage (GMH), white matter gliosis/necrosis (WMG/N), and neuronal necrosis. Statistical analysis of contingency tables showed significant associations of WMN with placental chronic vascular changes (PCV), umbilical cord problems, old infarction/abruptio, and meconium staining of the placenta. Associations were found between neuronal necrosis and PCV, surface vessel thrombosis, and old infarction/abruptio. GMH was associated with funisitis, but no other factors. Fetuses with WMN or neuronal necrosis were older than fetuses with GMH or no neuropathology. It is likely that these types of placental pathology can also be correlated with prenatal brain injury in liveborn infants, and examination of the placenta may indicate which infants are at greater risk for neurologic injury.

Brain↗
PubMed2000

Umbilical vein interleukin 6 and tumor necrosis factor alpha plasma concentrations in the very preterm infant.

OBJECTIVE: To examine the relationship between umbilical vein plasma concentrations of interleukin 6 (IL-6) and tumor necrosis factor (TNF)-alpha and early neonatal sepsis in the very preterm infant, and the histopathologic findings of chorioamnionitis in the placentas from these pregnancies. METHODS: A prospective study was conducted in 43 very preterm, singleton infants delivered at or before 32 weeks of gestation. IL-6 and TNF-alpha were measured by enzyme-linked immunoassay. Placentas from these pregnancies were histologically examined for the presence of chorioamnionitis. Infants were prospectively classified as confirmed sepsis group, clinical sepsis group or control group. IL-6 and TNF-alpha plasma concentrations were not normally distributed, so they were transformed to their natural log values for statistical analysis. RESULTS: The enrolled infants had a mean gestational age of 27.2 +/- 2.7 weeks and a mean birth weight of 956 +/- 325 g. Three (7%) infants had confirmed sepsis, 18 (42%) were in the clinical sepsis group and 22 (51%) were in the control group. IL-6 concentrations but not TNF-alpha were significantly higher (P < 0.05) in the confirmed (8.9 +/- 1.7) and clinical sepsis (5.5 +/- 2.4) groups in comparison with the control group (2.1 +/- 1.6). We examined 42 placentas. Twenty-three (55%) had no evidence of chorioamnionitis, 1 (2%) had mild grade, 8 (19%) had a moderate grade and 10 (24%) had a severe grade of chorioamnionitis. IL-6 was significantly elevated in the moderate (5.9 +/- 1.6 vs. 1.9 +/- 1.6) and severe grade (7.2 +/- 2.3 vs. 1.9 +/- 1.6) of chorioamnionitis, in the presence of acute deciduitis (6.0 +/- 2.7 vs. 2.1 +/-1.8), chorionic vasculitis (6.8 +/- 2.1 vs. 2.2 +/- 1.9) and funisitis (7.3 +/- 1.9 vs. 2.7 +/- 2.3) (P < 0.05) TNF-alpha plasma concentrations were not significantly different. CONCLUSION: An elevated umbilical vein IL-6 concentration is a good indicator of sepsis syndrome in the very preterm infant and also correlates with histologic chorioamnionitis in these pregnancies.

Blood Cell Count↗
PubMed1999

Placental membrane inflammation and risks of maternal-to-child transmission of HIV-1 in Uganda.

UNLABELLED: Prospective follow-up of 172 HIV-infected pregnant women and their infants was conducted at Mulago Hospital, Kampala, Uganda during 1990 to 1992. Information was collected on maternal immune status (CD4 counts or clinical AIDS), and concurrent infections with sexually transmitted diseases. Infants were observed on a follow-up basis to determine HIV infection, using polymerase chain reaction (PCR) under 15 months of age and enzyme immunoassay/Western blot for those older than 15 months. Placental membrane inflammation (chorioamnionitis and funisitis), and placental villous inflammation (villitis, intervillitis, and deciduitis) were diagnosed by histopathology. Mother-to-child HIV transmission rates were assessed, and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of transmission were estimated using women with no placental pathology or evidence of immune suppression as a reference group. RESULTS: The overall mother-to-child HIV transmission rate was 23.3%. Women with no placental membrane inflammation or immune suppression had a transmission rate of 11.3%; compared with 25.5% in women with placental inflammation and no immunosuppression (adjusted OR, 2.87; 95% CI, 1.04-7.90), and 37.0% in immunosuppressed women (OR, 3.07; 95% CI, 1.42-6.67). We estimate that 34% of HIV transmission could be prevented by treatment of placental membrane inflammation in nonimmunocompromised women. Transmission rates were 40.9% with genital ulcer disease (OR, 3.57; 95% CI, 1.28-9.66). Placental villous inflammation and artificial rupture of membranes did not increase transmission rates and cesarean section was associated with a nonsignificant reduction of risk (OR, 0.70; 95% CI 0.24-2.06). CONCLUSION: Placental membrane inflammation increases the rate of mother-to-child HIV transmission.

Blotting, Western↗
PubMed2006

Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes.

AIMS: Microbial invasion of the amniotic cavity (MIAC) elicits a fetal inflammatory response such as funisitis and chorionic vasculitis. However, little is known about the changes of fetal skin during MIAC. Toll-like receptors recognize microbial products and initiate an immune response. The aims of this study were to examine histopathological features of fetal skin exposed to MIAC and to assess the changes in Toll-like receptor (TLR)-2 and TLR-4 expression. METHODS AND RESULTS: Skin samples were obtained from fetal autopsies (n = 12). The cases were classified according to the presence (n = 8) or absence (n = 4) of acute chorioamnionitis and analysed by immunohistochemistry using a panel of antibodies. Leucocytic infiltrates into the superficial dermis were observed in cases with chorioamnionitis; the majority of inflammatory cells were neutrophils, lymphocytes and histiocytes. TLR-2 immunoreactivity in the skin was stronger in fetuses with chorioamnionitis than in those without this condition. However, immunoreactivity of TLR-4 in the fetal skin was constitutively expressed, regardless of the presence or absence of chorioamnionitis. CONCLUSIONS: This study demonstrates for the first time that fetal dermatitis can be detected and is part of the fetal inflammatory response syndrome (FIRS). We propose that this 'FIRS-associated fetal dermatitis' is a fetal counterpart of chorioamnionitis.

Abnormalities, Multiple↗
PubMed1984

Intrauterine infections with group B beta-haemolytic streptococci.

The case records of 15 infants with intrauterine infections due to group B beta-haemolytic streptococci were traced from the records of two geographically separate centres over a 4-year period (1979-1982). Six infants were stillborn and the other nine died within the first 6 h. All the infants weighed less than 1000 g and were less than 28 weeks gestation. Placental examination in 14 of the 15 infants showed the presence of chorioamnionitis and funisitis. The infants also showed evidence of pneumonitis. Four infants had evidence of otitis media, two had evidence of an early meningitis. A history of antepartum bleeding was present in six infants and abundant retroplacental clot was noted in four of them. The membranes had been ruptured for greater than 24 h in only three infants. In six of the infants the membranes were intact at the time of delivery. A history of intact membranes at the time of delivery does not exclude a diagnosis of an intrauterine infection with this organism, and this series of infants highlights the importance of routine bacteriologic studies of all perinatal deaths.

Extraembryonic Membranes↗
PubMed2000

Why is the placenta being ignored?

The relationship between the frequency of published recommended indications for placental pathological examination and the frequency of requests for such examination in a population-based study of term newborn encephalopathy was examined. Only 11.2% of placentas among 276 case infants and 0.7% of placentas among 564 term control infants were examined. Using the criteria set out in a consensus statement by the American College of Pathologists, all 276 cases fulfilled multiple maternal, fetal and placental indications for placental examination. Furthermore 43.3% of control infants fulfilled at least one criterion. Of the 25 case placentas that underwent pathological review, 16 were reported as having no diagnostic abnormality Six cases (24%) showed clinically important findings: four had evidence of infection, one had multiple chorangiomata and one had thrombosis and rupture of the umbilical vein. Of the three remaining placentas, one showed funisitis, one showed minor lymphohistiocytic villitis and one was from monochorionic twins. To our knowledge there are no agreed Australian guidelines for when a placenta should be submitted for pathological examination. We suggest that until guidelines based on properly designed studies are developed it may be appropriate to store all placentas for at least 72 hours. If the infant develops neurological symptoms or requires unexpected admission to a neonatal intensive care unit then placental examination may reveal important aetiological diagnostic and prognostic information.

Australia↗
PubMed1990

Congenital candidiasis limited to the nail plates.

Numerous case reports have been published of patients with cutaneous congenital candidiasis and neonatal candidiasis; however, this is the first reported case of congenital candidiasis confined to the nail plates. A subplacental candidal abscess, funisitis, and demonstration of hyphal invasion of fetal nail plates supported the diagnosis.

Candida albicans↗
PubMed1989

Umbilical cord sclerosis as an indicator of congenital syphilis.

In two cases of congenital syphilis examination of the umbilical cord showed a distinctive picture of perivascular sclerosis and inflammation. Large numbers of spirochaetes were shown in the sclerotic zone in both cases. No organisms were demonstrable in the placental disc and there were no morphological changes suggestive of syphilis. It is concluded that the finding of sclerosing funisitis, together with the clinical circumstances, should raise the possibility of congenital syphilis.

Adolescent↗
PubMed2006

Antibiotic treatment of intra-amniotic infection with Ureaplasma urealyticum. A case report and literature review.

BACKGROUND: Ureaplasma urealyticum is the most common pathogen cultured from the amniotic cavity of women with preterm labor and intact membranes. However, experience with antibiotic eradication of the pathogen in this setting is limited. CASE: We report a case of U. urealyticum isolation from the amniotic cavity of a woman with preterm labor at 27 weeks gestation. The patient was treated with erythromycin base for 1 week, followed by fluoroquinolones and clindamycin for 10 days. A healthy neonate was delivered after spontaneous labor began at 33 weeks. The cultures obtained from the placenta and membranes were sterile, but the histopathology of the placenta revealed acute chorioamnionitis with acute funisitis. CONCLUSION: We suggest that intra-amniotic colonization with Mycoplasma spp. remote from term may be managed expectantly, and that therapy with fluoroquinolones and/or clindamycin may be an appropriate choice.

Acute Disease↗
PubMed1991

Perinatal hematological profile of newborn infants with candida antenatal infections.

We serially studied hematological profiles of 8 newborns with proven antenatal candida chorioamnionitis and funisitis. Candida albicans was cultured from various sources in the infants; blood and CSF cultures were all negative. Seven of the 8 were premature; 5 were sick. We statistically compared hematological data of the 'well' and 'sick' babies. The latter showed neutrophilia (mean 52,381 vs. 11,326/microliters, p less than 0.01) accompanied by significant elevation of nonsegmented granulocytes (NSG) and a NSG/neutrophil ratio greater than 0.3. Significant monocytosis (mean 7,836 vs. 2,869/microliters, p less than 0.01) and eosinophilia (mean 4,723 vs. 782/microliters, p less than 0.05) were also noted. Remarkable toxic granulations, vacuolization, and Döhle bodies were found in the neutrophils of the 'sick' newborns. Hematological profiles correlated with the infants' clinical condition.

Blood Cell Count↗
PubMed1985

Significance of placental findings in early-onset group B streptococcal neonatal sepsis.

Assessment of placental pathology and its relationship to historical data, initial laboratory parameters, and outcome was undertaken in 22 cases of early-onset group B streptococcal sepsis of the neonate. Fourteen (64%) of the placentas demonstrated chorioamnionitis, six (27%) funisitis, and in nine (41%) gram stain demonstrated organisms within the membranes. Focal villous edema was observed in five (23%) cases and diffuse villous edema in four (18%). No placenta demonstrated chorangiosis. Placental inflammation was significantly (p less than 0.05) associated with prematurity, prolonged rupture of membranes, and onset of symptoms at less than 3 hours of age. No placental change was significantly associated with outcome or with neutropenia, which was the only parameter assessed that appeared to have prognostic value.

Chorioamnionitis↗
PubMed2003

Descriptive epidemiology of late-term abortions associated with the mare reproductive loss syndrome in central Kentucky.

Epidemiological and pathological findings of 433 late-term abortions associated with the mare reproductive loss syndrome (MRLS) in central Kentucky were identified by reviewing the records of the University of Kentucky Livestock Diseases Diagnostic Center. The distribution of dates of abortion was clustered during a brief period of time, presumably from a simultaneous environmental exposure. The most common pathological findings were microscopic pulmonary lesions consisting of squamous epithelial cells present in alveoli with or without concurrent infiltration of inflammatory cells (neutrophils, macrophages, or monocytes) in the interstitium or within alveoli. Isolation of a non-beta-hemolytic Streptococcus (52% of fetuses) or an Actinobacillus sp. (19% of fetuses) was common. Placentitis or funisitis was identified in 44% of fetuses. No single pathological finding, however, was pathognomonic for MRLS-associated late-term abortion. This report describes the pathological findings characterizing the MRLS-associated abortion. A cause of MRLS could not be determined from necropsy findings.

Aborted Fetus↗
PubMed2004

Cerebral palsy and placental infection: a case-cohort study.

BACKGROUND: The association between cerebral palsy in very preterm infants and clinical, histopathologic and microbiological indicators of chorioamnionitis, including the identification of specific micro-organisms in the placenta, was evaluated in a case-cohort study. METHODS: Children with a diagnosis of cerebral palsy at five years of age were identified from amongst participants in a long-term follow-up program of preterm infants. The comparison group was a subcohort of infants randomly selected from all infants enrolled in the program. The placentas were examined histopathologically for chorioamnionitis and funisitis, and the chorioamnionic interface was aseptically swabbed and comprehensively cultured for aerobic and anaerobic bacteria, yeast and genital mycoplasmas. Associations between obstetric and demographic variables, indicators of chorioamnionitis and cerebral palsy status were examined by univariate analysis. RESULTS: Eighty-two infants with cerebral palsy were compared with the subcohort of 207 infants. Threatened preterm labor was nearly twice as common among the cases as in the subcohort (p < 0.01). Recorded clinical choroamnionitis was similar in the two groups and there was no difference in histopathologic evidence of infection between the two groups. E. coli was cultured from the placenta in 6/30 (20%) of cases as compared with 4/85 (5%) of subcohort (p = 0.01). Group B Streptococcus was more frequent among the cases, but the difference was not statistically significant. CONCLUSIONS: The association between E. coli in the chorioamnion and cerebral palsy in preterm infants identified in this study requires confirmation in larger multicenter studies which include microbiological study of placentas.

Journal Article↗