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PubMed1996

The epidemiology of placental features: associations with gestational age and neonatal outcome.

OBJECTIVE: To investigate the epidemiologic and pathogenetic significance of placental features and neonatal outcome in a high-risk population. METHODS: One pathologist examined 1252 placentas from clinically selected at-risk singleton pregnancies. Placental pathology features were analyzed relative to gestational age and status of the newborn, including fetal growth restriction (FGR), low 1-minute Apgar score, infection, liver disorder, anomalies, and death in the immediate postnatal period. RESULTS: The most frequent placental pathologic features were ischemic change, meconium staining, and chorioamnionitis. Only 8% of placentas were considered normal. The number of features per placenta increased with gestational age. Among preterm infants, chorioamnionitis occurred most frequently with low 1-minute Apgar score (40%), clinically apparent infection (43%), liver disorder (43%), and anomalies (42%), compared with healthy newborns (15%). Chorioamnionitis at term was most frequent among infants with low 1-minute Apgar score (26%), infection (30%), and liver disorder (23%), compared with healthy newborns (16%). Meconium and ischemic changes were most frequent in placentas from healthy newborns, compared with affected newborns, regardless of gestational age. Multivariable analyses revealed an independent association between chorioamnionitis and low 1-minute Apgar score (P < .05), and both chorioamnionitis and villitis were associated with newborn infection (P < .05). CONCLUSION: The frequency of many major pathologic placental features, especially ischemic changes and meconium, in the absence of immediately detectable abnormality is relatively high. Thus, continued follow-up is needed to determine their long-term clinical significance. In addition, associations of ischemic changes and infarction with FGR in term infants suggest that need for comprehensive investigations of the effects of histopathologically apparent low placental blood flow.

Apgar Score↗

PubMed1999

Relationship of amniotic fluid markers of intra-amniotic infection with histopathology in cases of preterm labor with intact membranes.

OBJECTIVE: To evaluate the correlation of amniotic fluid (AF) markers (AFMs) of intra-amniotic infection with histopathologic findings in cases of preterm labor with intact membranes, between 22 and 36 weeks' gestation. STUDY DESIGN: We reviewed the charts of patients admitted in preterm labor with intact membranes between January 1993 and December 1996. Those having amniocentesis were identified, and AFMs were compared with histopathology in patients who delivered within 48 hours of the amniocentesis. The AFMs evaluated were glucose, polymorphonuclear leukocytes, Gram stain, and culture. All placentae were reviewed by a single pathologist blinded to the AF findings. Histologic evidence of acute inflammation was defined by findings of both subchorial intervillositis and marginating choriodeciduitis. The sensitivities, specificities, and positive and negative predictive values of the various AFMs were calculated. RESULTS: Of 556 women with intact membranes presenting in preterm labor, 181 (32.6%) had amniocentesis and 88 delivered within 48 hours of the amniocentesis. Histopathologic chorioamnionitis was seen in 53 patients (60.2%). The findings (with their sensitivity, specificity, and positive and negative predictive values) were: polymorphonuclear leukocytes at > 10/high-power field (22.6%, 97.2%, 92.3%, and 46.1%), positive Gram stain (26.4%, 94.6%, 87.5%, and 47.3%), culture (28.3%, 92.1%, 83.3%, and 47.9%), and glucose of < 15 mg/dl (28.3%, 94.6%, 88.2%, and 47.9%), respectively. Using a receiver-operator characteristic curve for different level of AF glucose, a glucose level of < 20 mg/dl was the most sensitive AF predictor of histologic chorioamnionitis. CONCLUSION: Histopathologic evidence of chorioamnionitis was present in 60.2% of cases of preterm births due to preterm labor in women who at our institution were offered and accepted amniocentesis and subsequently delivered within 48 hours. AFMs may be useful predictors of histologic chorioamnionitis. The most efficient AFM for chorioamnionitis in this group of patients was glucose at < 20 mg/dl.

Adult↗

PubMed2005

The association between early tracheal colonization and bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the relationship between early tracheal colonization and bronchopulmonary dysplasia (BPD). STUDY DESIGN: This is a retrospective cohort study which included 308 inborn neonates admitted to the newborn intensive care unit at the University of Miami Jackson Memorial Medical Center between January 1997 and December 2000 with birthweight 500 to 1000 g, who required mechanical ventilation on the first day of life. Chorioamnionitis was diagnosed by maternal symptoms and histopathopathology. Tracheal cultures were obtained immediately after tracheal intubation. BPD was diagnosed in neonates who had supplemental oxygen requirement for more than 28 days. Pearson's chi(2) and Logistic Regression Analysis were used to evaluate the relationship between chorioamnionitis, positive initial tracheal cultures and BPD, after adjusting for confounding variables. RESULTS: In patients with chorioamnionitis, the incidence of early positive tracheal cultures was 41% compared to 16% in those without chorioamnionitis, (p < 0.00001). In patients with birthweight 700 to 1000 g, a positive early tracheal culture increased the risk of BPD (OR = 2.42, CI 1.05 to 5.62, p < 0.05). CONCLUSION: Preterm infants exposed to chorioamnionitis have an increased incidence of early tracheal colonization. This early tracheal colonization may predispose them to develop BPD.

Bronchopulmonary Dysplasia↗

PubMed1993

[Importance of plasma PMN granulocyte elastase concentration determination in pregnant patients with premature rupture of fetal membranes].

The aetiology of preterm rupture of membranes is not yet completely understood. Local infections of the vagina and cervix have attracted special attention during the last years. Ascending infection with subsequent chorioamnionitis is a common complication of preterm rupture of membranes. Recognition of the beginning of a chorioamnionitis is usually based on clinical symptoms and laboratory findings like white blood cell count and C-reactive protein. The purpose of this study was to find out the diagnostic value of elastase, a protease of polymorphonuclear granulocytes, which is known to be involved in inflammatory processes. Fifteen out of thirty-three patients with preterm rupture of membranes developed a chorioamnionitis. Elastase plasma concentration levels > or = 32 ng/ml one day before delivery showed a significant correlation (p = 0.02) to the development of a chorioamnionitis. At this time neither white blood cell count, nor rectal body temperature showed significant correlations. Low elastase levels do not exclude an infection, whereas high levels indicate an infectious process. We conclude that elastase is a relevant marker of chorioamnionitis.

Adult↗

PubMed2002

The Northwestern Twin Chorionicity Study: I. Discordant inflammatory findings that are related to chorionicity in presenting versus nonpresenting twins.

OBJECTIVE: The purpose of this study was to evaluate the association between chorionicity and discordant chorioamnionitis and funisitis in twin gestations. STUDY DESIGN: This was a retrospective analysis of 1156 twin placentas with a standardized diagnosis of chorionicity, chorioamnionitis, and funisitis for comparison between presenting and nonpresenting twins with dichorionic-separate, dichorionic-fused, and monochorionic placentas. RESULTS: Frequencies of chorioamnionitis in the nonpresenting twin were significantly lower in dichorionic placentas (odds ratio, 0.4; 95% CI, 0.3, 0.6, in dichorionic-separate placentas; odds ratio, 0.5; 95% CI, 0.3, 0.8, in dichorionic-fused placentas) compared with monochorionic placentas. The frequency of advanced inflammation (ie, chorioamnionitis with funisitis) was significantly lower in the nonpresenting twin than in the presenting twin, but only in dichorionic-separate placentas (odds ratio, 0.2; 95% CI, 0.1, 0.4). CONCLUSION: Dichorionic placentas confer significant protection against the spread of chorioamnionitis from the presenting to the nonpresenting gestational sac. In the more advanced process that involves the umbilical cord, only the subset of separate dichorionic placentas confers this protective effect against the spread of inflammation.

Adult↗

PubMed2002

Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome.

OBJECTIVE: To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6). METHODS: The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM. RESULTS: The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm labor and intact membranes and 55.6% (15/27) in patients with preterm PROM. The median values of fetal plasma IL-6 in patients with funisitis, chorioamnionitis without funisitis, and non-inflamed membranes were 51.4, 18.4 and 5.2 pg/ml, respectively. After log transformation of the fetal plasma IL-6 concentration, the means differed significantly from each other (ANOVA, p < 0.02). There was no difference in log fetal plasma IL-6 concentration between patients with funisitis and those with chorioamnionitis without funisitis. The difference in mean concentration of log fetal plasma IL-6 between patients with funisitis or chorionic vasculitis and those without inflammation was highly significant (post-hoc test, p = 0.01 and p < 0.01, respectively). Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of histological signs of inflammation in the extra-placental membranes and umbilical cord than those with fetal plasma IL-6 < 11 pg/ml (funisitis: 55.6% (15/27) vs. 27.8% (5/18), p < 0.05; chorionic vasculitis: 55.6% (15/27) vs. 12.5% (2/16), p < 0.01; chorioamnionitis only: 25.9% (7/27) vs. 16.7% (3/18), p < 0.05; no inflammation: 18.5% (5/27) vs. 55.6% (10/18), p < 0.05, respectively). Fetuses with funisitis had significantly higher rates of clinical and histological chorioamnionitis, and neonatal infectious morbidity (proven + suspected sepsis) than fetuses without funisitis (40% (8/20) vs. 8% (2/25), 90% (18/20) vs. 36% (9/25), and 40% (8/20) vs. 4% (1/25), respectively; p < 0.01 for each). Fetuses with chorionic vasculitis had significantly higher rates of clinical and histological chorioamnionitis as well as neonatal infectious morbidity (proven + suspected sepsis) than fetuses without chorionic vasculitis (100% (17/17) vs. 42.3% (11/26), p < 0.01; 82.4% (14/17) vs. 50.0% (13/26), p = 0.05; and 41.2% (7/17) vs. 7.7% (2/26), p = 0.01). CONCLUSION: Fetal plasma IL-6 concentration is significantly associated with the presence of inflammatory lesions in the extraplacental membranes and umbilical cord. Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of funisitis and/or chorionic vasculitis than fetuses with fetal plasma IL-6 < 11 pg/ml. These findings suggest that funisitis/chorionic vasculitis is the histological manifestation of the fetal inflammatory response syndrome.

Adult↗

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↗

PubMed2002

Placental and other perinatal risk factors for chronic lung disease in very low birth weight infants.

To clarify the relationship between chorioamnionitis and chronic lung disease (CLD) in very low birth weight (VLBW) infants, we performed a retrospective cohort study of all inborn patients between 1995-1997 with gestational age (GA) less than 32 wk, birth weight less than 1.5 kg, survival to 36 wk adjusted GA, and placentas submitted to pathology (n = 371). Racial distribution as defined by the mother was 40% white/60% nonwhite. Prevalence of CLD, defined as O(2) dependence at 36 wk adjusted GA, was 30%. In a preliminary analysis GA and birth weight for GA (standard deviations from the mean, Z-score), considered together, were inversely related to CLD. After adjustment for GA and Z-score, other risk factors for CLD were white race, acute respiratory distress, pulmonary air leak, patent ductus arteriosus, and septicemia. Two placental lesions were inversely related to CLD: histologic chorioamnionitis and acute atherosis (a placental indicator of preeclampsia). Following multivariate analysis, independent risk factors for CLD were GA (OR, 0.6; 95% CI = 0.5, 0.7), birthweight for GA (OR, 0.4; 95% CI = 0.3, 0.6), white race (OR, 1.9; 95% CI = 1.0, 3.3), patent ductus arteriosus (OR, 2.0; 95% CI = 1.0, 3.5), and pulmonary air leak (OR, 3.0; 95% CI = 1.3, 7.1). Acute atherosis was inversely related to CLD (OR, 0.2; 95% CI = 0.1, 0.8). Chorioamnionitis was stratified by subtype and again no association with CLD was seen in the population as a whole. Finally, chorioamnionitis of all subtypes tended to be increased in white infants and decreased in black infants with CLD. This dichotomy was not explained by differences in death rates, acute respiratory distress, intubation on d 2 of life, or total duration of assisted ventilation. We conclude that while chorioamnionitis was not a risk factor for CLD in our total population, racial differences in its relationship to CLD are worthy of further study.

Adult↗

PubMed1998

Study of interleukin-6 and tumor necrosis factor-alpha levels in maternal serum and amniotic fluid of patients with premature rupture of membranes.

To study the change and clinical significance of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in the maternal serum and amniotic fluid of pregnant women with chorioamnionitis and with premature rupture of membranes. Twenty-six normal-term pregnant women formed the control group, and forty-six pregnant women with premature rupture of membranes were enrolled for the study. Maternal serum and amniotic fluid IL-6 and TNF-alpha levels were measured using a sensitive radioimmunoassay and enzyme-linked immunosorbent assay (ELISA); chorioamnionitis was diagnosed by fetal membrane pathology. The maternal serum IL-6 levels and amniotic fluid IL-6 and TNF-alpha levels were higher than those of the control (P < 0.01). There was a significant relationship between maternal serum IL-6 and maternal serum and amniotic fluid IL-6 and TNF-alpha with the time of the premature rupture of membranes, i.e. the longer the time, the higher the maternal serum and amniotic fluid IL-6 and TNF-alpha. There were 12 patients with chorioamnionitis in premature rupture of membranes and their maternal serum and amniotic fluid IL-6 and TNF-alpha levels were higher than that of non-chorioamnionitis patients (P < 0.01-0.05). IL-6 and TNF-alpha levels in maternal and amniotic fluids are a valuable index in identification of the chorioamnionitis in patients with premature rupture of membranes.

Adult↗

PubMed1998

[Study of interleukin-6 and tumor necrosis factor-alpha levels in maternal serum and amniotic fluid in patients with preterm premature rupture of membrane].

OBJECTIVE: To study the change and clinical significance of maternal serum and amniotic fluid interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in patients with chorioamnionitis and premature rupture of membrane (PROM). METHODS: Twenty normal term-pregnant women as control, and fourty-six women with PROM were enrolled for study. Maternal serum and amniotic fluid IL-6, TNF-alpha levels were measured by radioimmunoassay and enzyme-labeled immunosorbent assay (ELISA). Chorioamnionitis was diagnosed histologically. RESULTS: The maternal serum IL-6 levels and amniotic fluid IL-6, TNF-alpha levels were higher in PROM group than that of control (P < 0.01). There was significant positive correlation between maternal IL-6, amniotic fluid IL-6, TNF-alpha levels and the duration from rupture of membrane, (the longer was time, the higher were the maternal IL-6 and the amniotic fluid IL-6. TNF-alpha). There were 12 cases with chorioamnionitis in patients with PROM and their maternal and amnotic fluid IL-6, TNF-alpha levels were higher than that of non-chorioamnionitis (P < 0.01-0.05). CONCLUSION: IL-6 and TNF-alpha levels in maternal serum and amniotic fluid are valuable clinical indices for identification of chorioamnionitis in patients with PROM.

Adult↗

PubMed1998

[Detecting cytokines in patients with preterm premature rupture of membrane].

OBJECTIVE: To study the relationship of maternal blood and amniotic fluid cytokine levels in patients with preterm premature rupture of membrane and chorioamnionitis. METHODS: IL8 and TNF alpha levels of maternal blood and amniotic fluid were determined by 125I radioimmunoassay (RIA) and an enzyme-labeled immunosorbent assay (ELISA). Chorioamnionitis was diagnosed by fetal membrane histology. RESULTS: The maternal serum IL8 levels and amniotic fluid IL8, TNF alpha levels were higher than those of controls (P < 0.05). There was significant relationship between maternal serum and amniotic fluid IL8, TNF alpha with the time of the premature rupture of membanes. The longer the time the higher the maternal serum IL8 and amniotic fluid IL8, TNF alpha; There were 13 patients with chorioamnionitis, and their maternal serum and amniotic fluid IL8, TNF alpha were higher than those of patients with non-chorioamnionitis (P < 0.01-0.05). CONCLUSION: IL8, TNF alpha levels of maternal serum and amniotic fluid are valuable clinical indexes in identification of chorioamnionitis in patients with preterm premature rupture of membranes.

Adult↗

PubMedDate not supplied

Maternal fever during labor--what does it mean?

BACKGROUND: Several studies have shown maternal fever to be associated with chorioamnionitis and neonatal sepsis if at least two of the following five criteria are also present: maternal tachycardia, purulent or foul-smelling amniotic fluid, fetal tachycardia, uterine tenderness, or maternal leukocytosis. Less is known about the risk of neonatal sepsis when the presence of maternal fever in labor is the only criterion. METHODS: A retrospective medical record review searching for women who had a fever greater than 100.4 degrees F while in the active phase of labor during a 1-year period at the University of Michigan was undertaken to investigate the relation between isolated maternal fever in labor and neonatal sepsis. Eighty-two cases of maternal fever were found. RESULTS: Forty-six women met the clinical criteria for chorioamnionitis, and 6 of the 7 neonates with sepsis diagnosed were born to these mothers. There were no significant differences found in admission or intrapartum factors between women who did and did not meet clinical criteria for chorioamnionitis, and there was no association between these factors and neonatal sepsis. Epidural anesthesia was administered to 91 percent of these women and might be associated with maternal fever during labor. Using maternal clinical criteria for chorioamnionitis and a neonatal band cell-total neutrophil ratio of 0.2 or greater instead of the current system to determine the need for newborn antibiotic administration would improve the positive predictive value (12.5 percent versus 9.3 percent) and specificity (34.6 percent versus 16 percent) without compromising sensitivity (100 percent). All septic and probably septic newborns would be treated, and neonatal antibiotic administration would be reduced by 17 percent. CONCLUSIONS: The addition of the maternal clinical criteria for chorioamnionitis to the criteria already used for diagnosing and treating neonatal sepsis could prove useful in decisions regarding the selective administration of intrapartum antibiotics and prediction of risk of neonatal sepsis.

Adolescent↗

PubMedDate not supplied

Application of telethermography in the evaluation of preterm premature rupture of the fetal membranes.

The development of chorioamnionitis is a serious complication associated with preterm premature rupture of the fetal membranes (PPROM). There is no reliable early indicator of this infection. The objective of this study was to determine the sensitivity of telethermography (TTG) in the detection of subclinical chorioamnionitis in women with PPROM. Fourteen pregnant women with PPROM between 23 and 34 weeks' gestation were the subjects of the study. Serial frontal-abdominal TTG scans were obtained up to the time of delivery using the MARK-1026 telethermography imager. Following delivery, placental cultures and pathology results were obtained and infant sepsis evaluation was performed. Images were analyzed for temperature differences between umbilical, inguinal, four-quadrant average, and abdominal-wall hot spots. Data were compared with norms obtained from 12 pregnant women with intact membranes who served as gestational age-matched controls. Of five patients with pathology-proven chorioamnionitis and TTG scans within three days of delivery, four demonstrated significant increases in temperature differences between umbilical and abdominal-wall hot spots versus inguinal and four-quadrant averages (z-scores > or = 2.0). All three patients with negative pathology and cultures as well as scans within three days of delivery showed no increase in temperature differences of the above variables. No patient had any overt clinical sign of chorioamnionitis. This limited but consistent evidence demonstrates that telethermography is a sensitive, noninvasive diagnostic method for detecting subclinical chorioamnionitis in pregnant women with preterm rupture of the fetal membranes.

Chorioamnionitis↗

PubMed1997

Premature rupture of membranes at term: a meta-analysis of three management schemes.

OBJECTIVE: To compare rates of cesarean birth, endometritis, chorioamnionitis, and serious neonatal infections among pregnancies complicated by premature rupture of membranes (PROM) at term and managed by immediate oxytocin induction, by conservative management (or delayed oxytocin induction), or by vaginal (or endocervical) prostaglandin E2, gel, suppositories, or tablets. DATA SOURCES: The English-language literature in MLD, LINE and other databases was searched through April 1996 using the terms "fetal membranes," "premature rupture," and "term." METHODS OF STUDY SELECTION: We included randomized trials comparing two or more management schemes for PROM at term. TABULATION, INTEGRATION, AND RESULTS: Twenty-three studies with a total of 7493 subjects met the inclusion criteria and were included for analysis. Data regarding chorioamnionitis, endometritis, neonatal infections, and cesarean delivery were extracted. Meta-analyses were performed for the three interventions for these outcomes of interest using the Der-Simonian and Laird and Mantel-Haenszel techniques to estimate the pooled odds ratios (ORs). No statistically significant differences in cesarean deliveries or neonatal infections were noted among management schemes. Vaginal prostaglandins resulted in more chorioamnionitis than immediate oxytocin (OR 1.55, 95% confidence interval [CI] 1.09, 2.21), but less chorioamnionitis than conservative management (OR 0.68, 95% CI 0.51, 0.91). Immediate oxytocin induction resulted in fewer cases of chorioamnionitis (OR 0.67, 95% CI 0.52, 0.85) and endometritis (OR 0.71, 95% CI 0.51, 0.99) than conservative management, although these results achieved significance only with the Mantel-Haenszel technique. CONCLUSION: Conservative management may result in more maternal infections than immediate induction with oxytocin or prostaglandins.

Clinical Protocols↗

PubMed2005

Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition. STUDY DESIGN: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intra-amniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis. RESULTS: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). CONCLUSIONS: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis.

Amniocentesis↗

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↗

PubMed1998

Elevated Amniotic Fluid Interleukin-6 as a Predictor of Neonatal Periventricular Leukomalacia and Intraventricular Hemorrhage.

> Objective: To investigate the relationship between amniotic fluid interleukin-6 levels and the development of periventricular leukomalacia and intraventricular hemorrhage in the preterm neonate and to compare the value of amniotic fluid interleukin-6 with amniotic fluid culture and histologic chorioamnionitis in the prediction of periventricular leukomalacia and intraventricular hemorrhage. Methods: 119 women, between 20 and 34 weeks gestation, in preterm labor with intact membranes, underwent transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum and Mycoplasma hominis. Amniotic fluid interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The placentas were examined for histopathologic evidence of inflammation. Where the birth weight was <2,000 g, transfontanelle cranial sonography was performed on the 3rd and 7th days of life for diagnosis of periventricular leukomalacia and intraventricular hemorrhage. Student's t test, the Mann-Whitney U test, likelihood ratio chi2, logistic regression, and receiver-operator characteristic curve were used for analysis. Results: 33 women were excluded from the analysis because they delivered at other institutions. The neonates of 33 women did not have sonography because they weighed >2,000 g at birth. Two neonates died before sonography was performed; four neonates who weighed <2,000 g at birth did not have sonography. In the definitive study group of 47 women, those with neonates who developed periventricular leukomalacia and intraventricular hemorrhage (n = 14) had higher median amniotic fluid interleukin-6 levels (42,795 pg/ml versus 8,020 pg/ml; P = 0.009), more positive amniotic fluid cultures (64% vesus 21%; P < 0.003), and a shorter median amniocentesis-to-delivery interval (16 h versus 24 h; P = 0.045) than women (n = 33) who delivered neonates without periventricular leukomalacia or intraventricular hemorrhage. The groups did not differ in gestational age at admission (P = 0.15), birth weight (P = 0.09), or histologic chorioamnionitis (P = 0.37). An amniotic fluid interleukin-6 level >/=20,000 pg/ml had a sensitivity of 71% and a specificity of 70% compared with a sensitivity of 69% and specificity of 79% for amniotic fluid culture, and a sensitivity of 71% and specificity of 42% for histologic chorioamnionitis in the prediction of periventricular leukomalacia and intraventricular hemorrhage. Women with amniotic fluid interleukin-6 levels >/=20,000 pg/ml (n = 20) had more neonates with periventricular leukomalacia or intraventricular hemorrhage than women with amniotic fluid interleukin-6 levels <20,000 pg/ml (n = 27) (50% versus 15%; P = 0.009). They also were of lower birth weight (P = 0.02), had more neonatal morbidity (P = 0.01), had more positive amniotic fluid cultures (P = 0.01), and more histologic chorioamnionitis (P = 0.02). Logistic regression analysis demonstrated that amniotic fluid interleukin-6 was an independent risk factor for the development of periventricular leukomalacia and intraventricular hemorrhage (odds ratio, 5.81; 95% confidence interval, 1.02-33.16; P = 0.05) after controlling for gestational age, birth weight, histologic chorioamnionitis, and amniotic fluid culture (odds ratio, 7.94; 95% confidence interval 1.22-51.77; P = 0.03). Conclusions: In women in preterm labor with intact membranes amniotic fluid interleukin-6 is useful in predicting neonatal periventricular leukomalacia and intraventricular hemorrhage.

Journal Article↗

PubMed2005

The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. METHODS: This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. RESULTS: The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length < or = 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' had a higher frequency of positive AF cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' had a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. CONCLUSION: The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery.

Adult↗