Biomedical subjects

B H Yoon

Publications and source records attributed to B H Yoon.

At least 55 records · Page 3Linked to original sources

PubMed2000

Further observations on the fetal inflammatory response syndrome: a potential homeostatic role for the soluble receptors of tumor necrosis factor alpha.

OBJECTIVE: The fetal inflammatory response syndrome is a subclinical condition frequently present in preterm labor and preterm premature rupture of the membranes and is associated with increased perinatal morbidity and mortality. Tumor necrosis factor alpha is a mediator of septic shock and death, and it exerts its biologic effects by interacting with 2 receptors, TNF-R1 and TNF-R2. Soluble tumor necrosis factor receptors can buffer the biologic activity and protect against the deleterious effects of tumor necrosis factor alpha. The purpose of this study was to determine the behavior of soluble tumor necrosis factor receptors in fetuses with and without fetal inflammatory response syndrome. STUDY DESIGN: Fetal blood sampling was performed in patients with preterm labor (n = 95) and preterm premature rupture of the membranes (n = 39). Control samples were obtained from fetuses who were undergoing blood sampling for clinical indications and had normal outcomes (n = 21). Fetal inflammatory response syndrome was defined as a fetal plasma interleukin 6 concentration >11 pg/mL. Concentrations of interleukin 6 and TNF-R1 and TNF-R2 were determined by use of sensitive and specific immunoassays. Analysis of covariance was used for statistical analysis. RESULTS: (1) TNF-R1 and TNF-R2 were detectable in all samples, and their concentrations decreased with advancing gestational age (r = -0.8 and r = -0.7; P<.0001 and P<.001, respectively). (2) The mean fetal plasma concentrations of TNF-R1 and TNF-R2 were significantly higher in fetuses with fetal inflammatory response syndrome than in those without the syndrome after adjustment for gestational age and fetal membrane status (TNF-R1: no fetal inflammatory response syndrome, mean +/- SE, 3473.7+/-128.8 pg/mL; vs fetal inflammatory response syndrome, mean +/- SE, 4079.9+/-190.7 pg/mL; P<.005; TNF-R2: no fetal inflammatory response syndrome, mean +/- SE, 6033.2+/-235.4 pg/mL; vs. fetal inflammatory response syndrome, mean +/- SE, 7783.1+/-342.8 pg/mL; P<.0001). (3) Fetuses of patients who delivered within 72 hours of cordocentesis had significantly higher concentrations of TNF-R1 and TNF-R2 receptors than those with longer latency periods (P<.05 for each). CONCLUSION: The fetal inflammatory response syndrome is associated with increased availability of the soluble receptors of tumor necrosis factor alpha in fetal plasma. These factors may attenuate the deleterious effects of tumor necrosis factor alpha.

Adult↗

PubMed2000

Interleukin 6 determinations in cervical fluid have diagnostic and prognostic value in preterm premature rupture of membranes.

OBJECTIVE: Our aim was to determine whether interleukin-6 concentrations in cervical fluid samples are of value in the identification of microbial invasion of the amniotic cavity, prediction of the duration of the latency period, and assessment of the risk of neonatal complications in preterm premature rupture of membranes. STUDY DESIGN: A cohort study was performed in 86 patients with preterm premature rupture of membranes. Amniotic fluid and cervical fluid were collected. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Interleukin 6 was measured by a sensitive and specific immunoassay. The receiver operating characteristic curve, logistic regression, and survival techniques were used for analysis. RESULTS: (1) Patients with a positive amniotic fluid culture had a significantly higher median cervical fluid interleukin 6 concentration than those with negative results (median, 528 pg/mL; range, 174-825 pg/mL; vs median, 169 pg/mL; range, 8-986 pg/mL; P <.0001). (2) A cervical fluid interleukin 6 concentration of >350 pg/mL had a sensitivity of 92% and a specificity of 78% in the identification of a positive amniotic fluid culture. (3) Patients with a cervical fluid interleukin 6 concentration of >350 pg/mL had a significantly shorter median interval to delivery and higher rate of funisitis, preterm delivery within 2 days and 7 days, and the occurrence of significant neonatal morbidity than did those with a cervical fluid interleukin 6 concentration of <350 pg/mL (P <.05 for each). (4) The increased perinatal morbidity remained significant after adjustment for gestational age (P <.05). (5) There was a strong correlation between cervical fluid concentrations and amniotic fluid concentrations of interleukin 6 (P <.001). CONCLUSION: Cervical fluid interleukin 6 determinations are of value in the assessment of the likelihood of microbial invasion of the amniotic cavity, impending preterm delivery, and the occurrence of significant neonatal complications in the setting of preterm premature rupture of membranes.

Amniotic Fluid↗

PubMed2000

The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis.

OBJECTIVE: The purpose of this study was to determine whether funisitis (inflammation of the umbilical cord detected by histologic examination of the placenta) is associated with changes in the umbilical cord plasma concentration of interleukin 6, microbial invasion of the amniotic cavity, and neonatal sepsis. STUDY DESIGN: The relationship among the presence of funisitis, interleukin 6 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 3 days of birth, and the occurrence of congenital neonatal sepsis was examined in 315 consecutive singleton preterm births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. The interleukin 6 concentration was measured with a specific immunoassay. Amniocentesis was performed in 106 patients within 3 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. RESULTS: (1) Funisitis was present in 25% of patients (78/315). (2) Patients with funisitis had a significantly higher median cord plasma interleukin 6 and a lower gestational age at birth than did those without funisitis (cord interleukin 6: median, 52.4 pg/mL; range, 0.9-19,230 pg/mL; vs median, 4.6 pg/mL; range, 0-18,108 pg/mL; gestational age: median, 31.1 weeks' gestation; range, 21.0-35.0 weeks' gestation; vs median, 32.9 weeks' gestation; range, 21.4-35.0 weeks' gestation; P<.001 for each comparison). (3) A cord plasma interleukin 6 of > or =17.5 pg/mL had a sensitivity of 70% and a specificity of 78% in the identification of funisitis. (4) Microbial invasion of the amniotic cavity and clinical chorioamnionitis were more common among patients with funisitis than among those without funisitis (positive amniotic fluid culture: 53% [20/38]; vs. 12% [8/68]; clinical chorioamnionitis: 18% [14/78]; vs. 4% [9/237]; P<.001 for each comparison). (5) Neonates with funisitis had a significantly higher rate of congenital sepsis than did those without this lesion (12% [8/66] vs. 1% [3/216]; P<.001); this difference remained significant after adjustment for gestational age at birth (odds ratio, 7.2; 95% confidence interval, 1.8-29.0). CONCLUSION: (1) Umbilical cord plasma interleukin 6 concentrations were higher in neonates born with funisitis than in those without this lesion. (2) Funisitis is associated with amniotic fluid infection, congenital neonatal sepsis, and the fetal inflammatory response syndrome.

Adult↗

PubMed2000

Clinical implications of detection of Ureaplasma urealyticum in the amniotic cavity with the polymerase chain reaction.

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of the detection of Ureaplasma urealyticum by means of the polymerase chain reaction with specific primers in the amniotic fluid of patients with preterm premature rupture of membranes. STUDY DESIGN: Amniocentesis was performed in 154 patients with preterm premature rupture of membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Ureaplasma urealyticum was detected by means of the polymerase chain reaction with specific primers. Patients were divided into the following 3 groups according to the results of amniotic fluid culture and polymerase chain reaction for U. urealyticum: those with a negative amniotic fluid culture and a negative polymerase chain reaction (n = 99), those with a negative amniotic fluid culture but a positive polymerase chain reaction (n = 18), and those with a positive amniotic fluid culture regardless of the results of the polymerase chain reaction (n = 37). Contingency table and survival techniques were used for analysis. RESULTS: (1) U. urealyticum was detected by polymerase chain reaction in 28% (43/154) of patients and by culture in 16% (25/154). (2) Among the 43 patients with a positive polymerase chain reaction for U urealyticum, amniotic fluid culture was negative in 42% (18/43). (3) Patients with a negative amniotic fluid culture for U urealyticum but a positive polymerase chain reaction had a significantly shorter median interval from amniocentesis to delivery and a higher amniotic fluid interleukin 6 and white blood cell count than did those with a negative amniotic fluid culture and a negative polymerase chain reaction (interval to delivery; median, 53 hours; range, 0.3-335 hours; vs. median, 141 hours; range, 0.1-3552 hours; P<.05; amniotic fluid white blood cell count: median, 513 cells/mm(3); range, 1-2295 cells/mm(3); vs. median, 1 cell/mm(3); range, 0-7956 cells/mm(3); amniotic fluid interleukin 6: median, 16.6 ng/mL; range, 0.3-53.0 ng/mL; vs. median 0.4 ng/mL; range, 0-69.8 ng/mL; P<.0001 for all). (4) Patients with a positive polymerase chain reaction for U. urealyticum but a negative amniotic fluid culture had a higher rate of significant neonatal morbidity than did those with both a negative culture and a negative polymerase chain reaction (P<.05). (5) No significant differences in perinatal outcome were observed between patients with a negative culture but a positive polymerase chain reaction and those with a positive amniotic fluid culture. CONCLUSION: (1) Culture techniques for mycoplasmas missed 40% of cases of microbial invasion of the amniotic cavity with U. urealyticum. (2) Patients with a positive polymerase chain reaction but a negative amniotic fluid culture are at risk for adverse outcomes. (3) The use of molecular microbiologic techniques is likely to increase the detection of infection among patients with obstetric complications.

Adult↗

PubMed1999

Production and characterization of monoclonal antibodies to porcine brain pyridoxal kinase.

Six monoclonal antibodies that recognize porcine brain pyridoxal kinase have been selected and designated as PK67, PK86, PK91, PK144, PK252 and PK275. A total of six monoclonal antibodies recognizing different epitopes of the enzyme were obtained, of which four inhibited the enzyme activity. When total proteins of porcine brain homogenate separated by SDS-PAGE were subjected to monoclonal antibodies, a single reactive protein band of molecular weight 39 kDa which comigrated with purified porcine pyridoxal kinase was detected. Using the anti-pyridoxal kinase antibodies as probes, the cross reactivities of brain pyridoxal kinase from human and other mammalian tissues and from avian sources were also investigated. Among human and all animal tissues tested, immunoreactive bands on Western blots appeared to have the same molecular mass of 39 kDa. These results indicate that mammalian brains contain only one major type of immunologically similar pyridoxal kinase, although some properties of the enzymes reported previously differed from one another.

Animals↗

PubMed1999

The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition.

OBJECTIVE: The common terminal pathway of parturition describes the anatomic, biochemical, endocrine, and clinical events present in the fetus and mother in both term and preterm labor. Labor at term is thought to result from physiologic activation of this pathway, whereas preterm labor is the result of pathologic activating events. The purpose of this study was to determine whether physiologic and pathologic activation could be discerned by the analysis of a cytokine-receptor signaling system. Tumor necrosis factor alpha and its soluble receptors were used as probes because of their pivotal role in the regulation of several processes activated during parturition. Soluble receptors are thought to buffer the biologic and potentially deleterious effects of tumor necrosis factor alpha in pathologic conditions. STUDY DESIGN: The in vivo concentrations of tumor necrosis factor alpha and its soluble receptors were studied in patients in term labor and preterm labor. Amniotic fluid was retrieved from 175 women and tumor necrosis factor alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2 concentrations were measured by highly sensitive immunoassays. Patients were classified in the following groups: (1) term labor (n = 29), (2) term not in labor (n = 29), (3) preterm labor leading to term delivery (n = 34), (4) preterm labor without infection resulting in preterm delivery (n = 34), (5) preterm labor with intra-amniotic infection (n = 23), and (6) second trimester (n = 26). RESULTS: Tumor necrosis factor alpha and tumor necrosis factor receptor 1 concentrations decreased with advanced gestational age (r = -0.51 and r = -0.7; P <.01 for each). (1) Patients in spontaneous term labor had a higher median concentration of tumor necrosis factor alpha than those at term not in labor (median, 6.4 pg/mL; range, 2.4->500 pg/mL vs median, 4.1 pg/mL; range, 1.1-22.7 pg/mL; P <.01) but had lower concentrations of tumor necrosis factor receptor 1 (median, 3.2 ng/mL; range, 1.3-9.1 ng/mL vs median, 4.2 ng/mL; range, 1.6-8.3; P <.001) and tumor necrosis factor receptor 2 (median, 5.5 ng/mL; range, 0.73-12.8 ng/mL vs median, 6.8 ng/mL; range, 2.9-12.9 ng/mL; P <.01). (2) In contrast, patients with preterm labor leading to preterm delivery had higher concentrations of tumor necrosis factor alpha (median, 12.3 pg /mL; range, 1.5->500 pg/mL vs median, 4.8 pg/mL; range, 1-60.9 pg/mL; P <.01), tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.5-38 ng/mL vs median, 6.2 ng/mL; range, 1.4-28 ng/mL; P <.05), and tumor necrosis factor receptor 2 (median, 8.5 ng/mL; range, 3.5-45.4 ng/mL vs median, 6.1 ng/mL; range, 1.99-14.1 ng/mL; P <.01) than patients with preterm labor who delivered at term. (3) Microbial invasion of the amniotic cavity was associated with dramatic increases in the concentrations of tumor necrosis factor alpha (median, 93.5 pg/mL; range, 1.2->500 pg/mL) and its soluble receptors tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.1-36.7 ng/mL) and tumor necrosis factor receptor 2 (median, 11.8 ng/mL; range, 3.4-46. 3 ng/mL), concentrations that were significantly higher than in those with preterm labor who delivered at term and those who delivered preterm but were not infected. CONCLUSION: The tumor necrosis factor alpha and tumor necrosis factor alpha soluble receptor profiles are different in term and preterm parturition. Our observations provide support for the thesis that preterm parturition is a pathologic condition. Increased tumor necrosis factor alpha soluble receptor concentrations may attenuate the deleterious effects of the excess of tumor necrosis factor alpha found in pathologic labor.

Amniotic Fluid↗

PubMed1999

A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia.

OBJECTIVE: The purpose of this study was to test the hypothesis that a systemic fetal inflammatory response is a risk factor for the subsequent development of bronchopulmonary dysplasia in preterm neonates. STUDY DESIGN: The relationship between interleukin 6 concentrations in umbilical cord plasma at birth and the occurrence of bronchopulmonary dysplasia was examined in 203 preterm births (25-34 weeks). Ninety-six patients underwent transabdominal amniocentesis within 5 days of birth. The relationship between umbilical cord plasma interleukin 6 concentration and bronchopulmonary dysplasia was compared with the relationship between amniotic fluid interleukin 6 concentration and bronchopulmonary dysplasia. Interleukin 6 was measured by specific immunoassay. Logistic regression was used for statistical analysis. RESULTS: Bronchopulmonary dysplasia was diagnosed in 17% (34/203) of the infants. Neonates in whom bronchopulmonary dysplasia developed had a significantly higher median interleukin 6 concentration in umbilical cord plasma at birth than did those in whom bronchopulmonary dysplasia did not develop (median, 68.3 pg/mL and range, 0.3-6150.0 pg/mL vs median, 6.9 pg/mL and range 0-19,230.0 pg/mL; P <.001). This difference remained significant after adjustment for gestational age at birth (odds ratio, 4.2; 95% confidence interval, 1.6-11.2). Logistic regression analysis indicated that an elevated umbilical cord plasma interleukin 6 concentration was a better predictor of the development of bronchopulmonary dysplasia than was an elevated amniotic fluid interleukin 6 concentration (P <.005). CONCLUSION: An elevated interleukin 6 concentration in umbilical cord plasma at birth is an independent risk factor for the development of bronchopulmonary dysplasia. These data support the concept that the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth and is associated with the development of a fetal systemic inflammatory response, as determined by plasma concentrations of interleukin 6.

Adult↗

PubMed1999

Association of oligohydramnios in women with preterm premature rupture of membranes with an inflammatory response in fetal, amniotic, and maternal compartments.

OBJECTIVE: This study was undertaken to examine whether oligohydramnios in women with preterm premature rupture of membranes is associated with evidence of fetal, amniotic, and maternal inflammatory responses. STUDY DESIGN: Amniotic fluid index was measured before the performance of amniocentesis in patients with preterm premature rupture of membranes. Fifty-nine patients who were delivered of preterm neonates (gestational age </=35 weeks) within 3 days of amniocentesis were included in this study. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas. The intensity of the inflammatory response was evaluated by the following: presence of clinical and histologic chorioamnionitis; amniotic fluid concentrations of interleukin 6, interleukin 1beta, and tumor necrosis factor alpha; amniotic fluid white blood cell count; and interleukin 6 concentrations in umbilical cord plasma at birth. Proinflammatory cytokines were measured with specific and sensitive immunoassays. RESULTS: Thirty-two percent (19/59) of patients had an amniotic fluid index </=5 cm. Patients with an amniotic fluid index </=5 cm had significantly higher rates of positive amniotic fluid culture results and clinical and histologic chorioamnionitis; higher median amniotic fluid concentrations of interleukin 6, interleukin 1beta, and tumor necrosis factor alpha; and higher median cord plasma concentrations of interleukin 6 than did those with an amniotic fluid index >5 cm (positive amniotic fluid culture result, 79% [15/19] vs 30% [12/40]; clinical chorioamnionitis, 37% [7/19] vs 5% [2/40]; histologic chorioamnionitis, 100% [17/17] vs 69% [24/35]; median amniotic fluid interleukin 6 concentration, 13.5 ng/mL; range, 0.2-142.2 ng/mL vs 3.0 ng/mL and 0.001-115.2 ng/mL; median amniotic fluid interleukin 1beta concentration, 348.0 pg/mL; range, 0.7->80, 000 pg/mL vs 36.6 pg/mL and 0-2075 pg/mL; median amniotic fluid tumor necrosis factor alpha concentration, 132.0 pg/mL; range, 0-1600 pg/mL vs 11.2 pg/mL and 0-1305 pg/mL; median cord plasma interleukin 6 concentration, 49.7 pg/mL; range, 4.4-7400 pg/mL vs 9. 1 pg/mL and 0-5211 pg/mL; P <.05 for each). There was no significant difference between the 2 groups of patients in the mean umbilical artery pH at birth. CONCLUSION: Oligohydramnios in women with preterm premature rupture of membranes is associated with an inflammatory response in the fetal, amniotic, and maternal compartments.

Amniotic Fluid↗

PubMed1999

A role for the novel cytokine RANTES in pregnancy and parturition.

OBJECTIVE: RANTES (regulated on activation, normal T cell expressed and secreted), a potent and versatile chemokine, is capable of attracting monocytes, lymphocytes, basophils, and eosinophils. This cytokine has been implicated in the regulation of the inflammatory response and in the recruitment of macrophages to the implantation site in early pregnancy. RANTES messenger ribonucleic acid and protein have been detected in fetal tissue and first-trimester trophoblast in response to bacterial endotoxin. The purpose of this study was to determine whether intrauterine infection, parturition (preterm and term), and gestational age affect the amniotic fluid concentrations of RANTES in human pregnancy. STUDY DESIGN: A cross-sectional study was designed to examine the relationship between labor, microbial invasion of the amniotic cavity, gestational age, and RANTES expression in amniotic fluid. Amniotic fluid was obtained from 214 women in the following groups: (1) midtrimester (n = 22), (2) preterm labor with intact membranes in the presence (n = 20) or absence (n = 74) of microbial invasion of the amniotic cavity, (3) term, not in labor (n = 44) and term, in labor in the presence (n = 27) and absence (n = 27) of microbial invasion of the amniotic cavity. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. RANTES concentrations were determined by use of a sensitive and specific immunoassay. RESULTS: (1) Amniotic fluid RANTES concentrations decrease with advancing gestational age (r = 0. 43; P <.01). (2) Labor at term was associated with an increase in median concentrations of RANTES (labor-median, 8.4 pg/mL; range, <1.3-94.4 vs no labor-median, <1.3 pg/mL; range, <1.3-230.3; P <.01). (3) Women with preterm labor who delivered preterm (no microbial invasion of the amniotic cavity) had a higher median concentration of amniotic fluid RANTES than those who delivered at term (median, 12.7 pg/mL; range, <1.3-928 vs median, <1.3 pg/mL; range, <1.3-127. 5; P <.001). (4) Microbial invasion of the amniotic cavity was associated with a significant increase in median amniotic fluid RANTES in both preterm and term labor (preterm labor with microbial invasion of the amniotic cavity-median, 51.6 pg/mL; range, <1.3-2290 vs preterm labor without microbial invasion of the amniotic cavity-median, 12.7 pg/mL; range, <1.3-928 and vs preterm labor with delivery at term-median, <1.3 pg/mL; range, <1.3-127.5; P <.001 for each; term labor with microbial invasion of the amniotic cavity-median, 16.8 pg/mL; range, <1.3-171.4 vs term labor without microbial invasion of the amniotic cavity-median, 8.4 pg/mL; range, <1.3-94.4; P <.05 and vs no labor and no microbial invasion of the amniotic cavity-median, 1.4 pg/mL; range, <1.3-230.3; P <.001 and P <.05, respectively). CONCLUSION: These results support a role for RANTES in the mechanisms of human parturition and in the regulation of the host response to intrauterine infection.

Amnion↗

PubMed1998

An increase in fetal plasma cortisol but not dehydroepiandrosterone sulfate is followed by the onset of preterm labor in patients with preterm premature rupture of the membranes.

OBJECTIVE: The role of steroid hormones in the control of human parturition has been a subject of debate. Activation of the fetal hypothalamic-pituitary-adrenal axis leading to an increase in plasma cortisol is followed by the onset of parturition in sheep. In contrast, androgens, specifically, dehydroepiandrosterone sulfate, have been implicated in the control of parturition in nonhuman primates. The purpose of this study was to determine the relationship between human fetal plasma cortisol and dehydroepiandrosterone sulfate and the onset of preterm labor in patients with preterm premature rupture of the membranes. STUDY DESIGN: Fetal blood sampling was performed in 51 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Corticosteroids had not been administered before fetal blood sampling. Cortisol and dehydroepiandrosterone sulfate were measured with sensitive and specific immunoassays. Analysis was conducted with nonparametric statistics and survival analysis. RESULTS: (1) Patients who went into spontaneous labor and delivered within 7 days of cordocentesis had a significantly higher median level of fetal plasma cortisol but not of dehydroepiandrosterone sulfate than those delivered after 7 days (for fetal plasma cortisol: median 8.35 [4.7 to 12.4] micrograms/dL vs median 4.75 [3.0 to 10.4] micrograms/dL, P <.0001; for fetal plasma dehydroepiandrosterone sulfate: median 154.4 [8.6 to 333.8] micrograms/dL vs median 194.6 [96.7 to 402.5] micrograms/dL, P =.09). (2) The cordocentesis-to-delivery interval was significantly shorter in patients with a fetal plasma cortisol value of >/=7 micrograms/dL (derived by receiver-operating characteristic curve analysis) than in those with fetal cortisol <7 micrograms/dL (median 49 [4 to 1849] hours vs median 325 [11 to 2590] hours, P <.001). (3) Fetal plasma cortisol, but not maternal cortisol, was an independent predictor of the duration of pregnancy after we adjusted for gestational age and the results of amniotic fluid culture (hazards ratio 2.9, P <.05). (4) There was a significant correlation between fetal plasma cortisol and fetal plasma interleukin-6 (r = 0.3, P <.05). (5) A strong relationship was found between the fetal plasma cortisol/dehydroepiandrosterone sulfate ratio and the interval to delivery (P <.005). CONCLUSION: An elevation in fetal plasma cortisol but not dehydroepiandrosterone sulfate was followed by the onset of spontaneous preterm labor in patients with preterm premature rupture of the membranes.

Adult↗

PubMed1998

Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments.

OBJECTIVE: Ureaplasma urealyticum is the microorganism most frequently isolated from the amniotic fluid of women with preterm labor and preterm premature rupture of the membranes, yet the significance of amniotic fluid infection exclusively caused by this microorganism is unclear. This study was conducted to examine the presence and intensity of the inflammatory response in the fetal, amniotic, and maternal compartments in patients with preterm premature rupture of membranes and amniotic fluid infection with U urealyticum. STUDY DESIGN: One hundred twenty patients with preterm premature rupture of the membranes who delivered preterm neonates (gestational age </=36 weeks) within 5 days of amniocentesis were included. Amniotic fluid was cultured for aerobic and anaerobic bacterias and mycoplasmas. The intensity of the inflammatory response was evaluated by amniotic fluid concentrations of interleukin-6, tumor necrosis factor-alpha, interleukin-1beta, amniotic fluid white blood cell count, histologic chorioamnionitis, and interleukin-6 concentrations of umbilical cord plasma at birth. Cytokines were measured by sensitive and specific immunoassays. RESULTS: The prevalence of a positive amniotic fluid culture in which the only microbial isolate was U urealyticum was 21% (25/120) and that of positive cultures with other or mixed microorganisms was 9% (11/120). Intrauterine inflammatory response was significantly more intense in patients with positive amniotic fluid cultures limited to U urealyticum than in those with a negative culture (median and range of amniotic fluid interleukin-6, 13.4 [0.7-115.2] ng/mL vs 0.9 [0.001-137.2] ng/mL; median and range of amniotic fluid tumor necrosis factor-alpha, 85.5 [0.9-1600] pg/mL vs 2.4 [0-1142] pg/mL; median and range of amniotic fluid interleukin-1beta, 274.0 [0.3->80,000] pg/mL vs 3.4 [0-1449] pg/mL; median and range of amniotic fluid white blood cell count, 306 [0-19,764] cells/mm3 vs 3 [0-7956] cells/mm3; median and range of cord interleukin-6, 20.0 [2. 3-1199.6] pg/mL vs 6.7 [0-5550] pg/mL; histologic chorioamnionitis, 100% [22/22] vs 42% [30/72]; P <.01 for each) but was similar to values of patients with a positive amniotic fluid culture for other bacteria or mixed microorganisms. CONCLUSION: Patients with preterm premature rupture of membranes and microbial invasion of the amniotic cavity with U urealyticum are associated with a robust host inflammatory response in the fetal, amniotic, and maternal compartments.

Adult↗

PubMed1998

A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.

OBJECTIVE: There is no evidence for the participation of the human fetus in the mechanisms responsible for the onset of preterm labor. We propose that preterm labor in the setting of infection results from the actions of proinflammatory cytokines secreted as part of the fetal and/or maternal host response to microbial invasion. The objective of this study was to determine whether a systemic fetal inflammatory response, defined as an elevation of fetal plasma interleukin-6 concentrations, has a temporal relationship with the commencement of labor. STUDY DESIGN: After informed consent was obtained, amniocentesis and cordocentesis were performed in 41 patients with preterm premature rupture of membranes who were not in labor on admission. Amniotic fluid was cultured for both aerobic and anaerobic bacteria, as well as for mycoplasmas. Fetal plasma interleukin-6 was assayed by a sensitive and specific immunoassay. Statistical analyses included contingency tables and survival analysis with time-dependent Cox regression hazard modeling. RESULTS: Microbial invasion of the amniotic cavity was present in 58.5% (24/41) of patients. Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of spontaneous preterm delivery within 48 and 72 hours of the procedure than those with fetal plasma interleukin-6 levels < or = 11 pg/mL (88% vs 29% and 88% vs 35%, respectively; P < .05 for all comparisons). Moreover, patients with initiation of labor and delivery within 48 hours of the procedure had a higher proportion of fetuses with plasma interleukin-6 values > 11 pg/mL than patients delivered > 48 hours (58% [7/12] vs 8% [1/13], respectively; P < .05). Survival analysis indicated that fetuses with elevated fetal plasma interleukin-6 levels had a shorter cordocentesis-to-delivery interval than those without elevated fetal plasma interleukin-6 concentrations (median 0.8 days [range 0.1 to 5] vs median 6 days [range 0.2 to 33.6], respectively; P < .05). Time-dependent Cox regression hazard modeling indicated that fetal plasma interleukin-6 level was the only covariate significantly associated with the duration of pregnancy after we adjusted for gestational age, amniotic fluid interleukin-6 level, and the microbiologic state of the amniotic cavity (P < .01). CONCLUSION: A systemic fetal proinflammatory cytokine response is followed by the onset of spontaneous preterm parturition in patients with preterm premature rupture of membranes.

Acute-Phase Reaction↗

PubMed1998

The fetal inflammatory response syndrome.

OBJECTIVE: The objective of this study was to determine the frequency and clinical significance of a systemic inflammatory response as defined by an elevated plasma interleukin-6 concentration in fetuses with preterm labor or preterm premature rupture of membranes. STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with preterm labor and preterm premature rupture of membranes. Written informed consent and multi-institutional review board approvals were obtained. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6 concentrations were measured with a sensitive and specific immunoassay. Statistical analyses included contingency tables, receiver operating characteristic curve analysis, and multiple logistic regression. RESULTS: One hundred five patients with preterm labor and 52 patients with preterm premature rupture of membranes were included in this study. The overall prevalence of severe neonatal morbidity (defined as the presence of respiratory distress syndrome, suspected or proved neonatal sepsis, pneumonia, bronchopulmonary dysplasia. intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis) among survivors was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher concentrations of fetal plasma interleukin-6 than fetuses without development of severe neonatal morbidity (median 14.0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range 0.3 to 900, respectively; P < .005). Multivariate analysis was performed to explore the relationship between the presence of a systemic fetal inflammatory response and subsequent neonatal outcome. To preserve a meaningful temporal relationship between the results of fetal plasma interleukin-6 concentrations and the occurrence of severe neonatal morbidity, the analysis was restricted to 73 fetuses delivered within 7 days of cordocentesis who survived. The prevalence of severe neonatal morbidity in this subset of patients was 53.4% (39/73). A fetal plasma interleukin-6 cutoff value of 11 pg/mL was used to define the presence of a systemic inflammatory response. The prevalence of a fetal plasma interleukin-6 level > 11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin-6 concentrations > 11 pg/mL had a higher rate of severe neonatal morbidity than did those with fetal plasma interleukin-6 levels < or = 11 pg/mL (77.8% [28/36] vs 29.7% [11/37], respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fetal plasma interleukin-6 concentration was an independent predictor of the occurrence of severe neonatal morbidity (odds ratio 4.3, 95% confidence interval 1 to 18.5) when adjusted for gestational age at delivery, the cause of preterm delivery (preterm labor or preterm premature rupture of membranes), clinical chorioamnionitis, the cordocentesis-to-delivery interval, amniotic fluid culture, and amniotic fluid interleukin-6 results. CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma interleukin-6 value, is an independent risk factor for the occurrence of severe neonatal morbidity.

Acute-Phase Reaction↗

PubMed1998

Isolation of Ureaplasma urealyticum from the amniotic cavity and adverse outcome in preterm labor.

OBJECTIVE: To determine the relationship between the presence of Ureaplasma urealyticum in the amniotic cavity and adverse maternal and perinatal outcome in women with preterm labor. METHODS: Amniocentesis was performed in 181 patients with preterm labor and intact membranes. Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and mycoplasmas. Patients were divided into three groups according to the results of AF culture: those with negative AF cultures (n=160), those with positive AF cultures and in whom the only microbial isolate was U urealyticum (n=11), and those with positive cultures for non-ureaplasmas or mixed microorganisms (n=10). Survival techniques were used for analysis. RESULTS: The prevalence of positive AF cultures in which the only microbial isolate was Uurealyticum was 6.1% (11 of 181), and of positive cultures with non-ureaplasmas or mixed microorganisms was 5.5% (10 of 181). The amniocentesis-to-delivery interval was significantly shorter in patients with positive cultures limited to U urealyticum than in those with negative cultures (median 7 [range 0.1-149] hours versus median 264 [0.1-2659] hours, P < .001). Preterm delivery within 48 hours, 72 hours, and 7 days was more frequent in patients with U urealyticum in the AF than in those with sterile AF (48 hour: 91% versus 33%; 72 hour: 91% versus 36%; 7 days: 100% versus 45%, P < .001 for each). Patients with positive AF cultures limited to U urealyticum had a significantly higher rate of adverse perinatal outcome than those with negative culture. Adverse outcomes included low gestational age at birth, low birth weight, histologic chorioamnionitis, significant neonatal morbidity, and perinatal death. CONCLUSION: Microbial invasion of the amniotic cavity with U urealyticum is a risk factor for impending preterm delivery and adverse perinatal outcome.

Adult↗

PubMed1998

Elevated interleukin-8 concentrations in amniotic fluid of mothers whose neonates subsequently develop bronchopulmonary dysplasia.

OBJECTIVE: To determine if an intrauterine sub-clinical inflammatory process is a risk factor for the development of bronchopulmonary dysplasia. METHODS: A cohort study was conducted in patients who met the following criteria: (1) Singleton gestation; (2) preterm labor or preterm premature rupture of the membranes; (3) amniocentesis for microbiologic studies of the amniotic fluid and (4) delivery between 24 and 28 weeks of gestation. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen for 28 days or longer after birth, associated with compatible chest radiographic findings. Amniotic fluid interleukin-8, was measured using a specific immunoassay. Logistic regression analysis and bootstrap procedure were used for statistical purposes. RESULTS: Forty-seven patients met the inclusion criteria for this study. Among these patients, the prevalence of bronchopulmonary dysplasia was 23.4% (11/47). Amniotic fluid culture was positive in 21 out of 47 (44.7%) patients. Median (range) amniotic fluid interleukin-8 concentration was higher in patients whose neonates subsequently developed bronchopulmonary dysplasia than in those who did not (17 [9.8-583.7] ng ml(-1) versus 9.6 [0.91-744] ng ml(-1), P=0.057). An amniotic fluid IL-8 level greater than 11.5 ng ml(-1) was far more common in mothers whose fetuses went on to develop bronchopulmonary dysplasia than in those who did not (10/11 [90.9%] versus 17/36 [47%]; P=0.01). This relationship remained significant even after correcting for the effect of gestational age and birthweight (Odds ratio: 11.9; P<0.05). CONCLUSION: Sub-clinical intrauterine inflammation is a risk factor for the subsequent development of bronchopulmonary dysplasia. We propose that in utero aspiration of fluid with high concentration of pro-inflammatory mediators may contribute to the lung injury responsible for the development of bronchopulmonary dysplasia.

Amniotic Fluid↗

PubMed1998

Histotopographic distribution of placental inflammation: analysis of 22 cases.

Twenty-two placentas were investigated for the presence and patterns of inflammation by extensive examination, and divided into four groups: 1) term vaginal delivery [group I; n=6]; 2) term cesarean section delivery [group II; n=5]; 3) preterm vaginal delivery [group III; n=4], and 4) preterm cesarean section delivery [group IV; n=7]. In group I, all had deciduitis, and choriodeciduitis/ chorionitis was present in two cases (33.3%). In group II, four cases (80%) showed deciduitis and/or choriodeciduitis/chorionitis; three of these had intact membranes. In group III, three cases (75%) showed deciduitis, and two had chorionitis. In group IV, three cases (42.9%) showed no evidence of inflammation, three had deciduitis and one had deciduitis/chorioamnionitis. In all groups, membranitis was more severe, confined to the inner and mid segments in general, and deciduitis, choriodeciduitis/chorionitis and chorioamnionitis tended to overlap. The study newly demonstrates major characteristics of placental inflammation: higher prevalence and severity of inflammation in the inner segments of membrane and at the periphery of the placenta. Taking this histotopography into account, it is desirable to take sections from the placental margin, and the current concept of placental inflammation as a surrogate marker of intrauterine infection should be reevaluated.

Female↗

PubMed1997

High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia.

OBJECTIVE: Periventricular leukomalacia, a common neonatal brain white matter lesion, is a major risk factor for cerebral palsy. Subclinical chorioamnionitis is a risk factor for the development of periventricular leukomalacia, and inflammatory cytokines have been implicated as central mediators of brain injury in this disorder. To elucidate the relationship between the local expression of cytokines and periventricular leukomalacia, we studied neonatal brains to determine whether high expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was observed in these lesions. STUDY DESIGN: Immunohistochemical staining for cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) was performed in 10% formalin-fixed, paraffin-embedded brain sections of 17 cases with periventricular leukomalacia. Specimens were obtained from autopsies performed between 1987 and 1994. Brain sections from 17 cases of neonatal deaths without periventricular leukomalacia lesions matched for gestational age at birth, duration of postnatal survival, and presence or absence of infection-related morbidity were used as controls. RESULTS: The expression of tumor necrosis factor-alpha, interleukin-1 beta, or interleukin-6 was demonstrated in 88% (15/17) of cases with and in 18% (3/17) of cases without periventricular leukomalacia (p < 0.001). Cytokines were expressed mainly in hypertrophic astrocytes and microglial cells. The expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was identified in 82% (14/17), 29% (5/17), and 71% (12/17) of cases of periventricular leukomalacia, respectively. However, a significantly lower proportion of cases without periventricular leukomalacia expressed tumor necrosis factor-alpha (18%, 3/17) and interleukin-6 (6%, 1/17) than those with the disorder (p < 0.005 for each). CONCLUSIONS: Expression of tumor necrosis factor-alpha and interleukin-6 was observed more frequently in brain lesions with periventricular leukomalacia than in those without periventricular leukomalacia. These findings provide strong support for the hypothesis that proinflammatory cytokines play a role in the genesis of periventricular leukomalacia.

Brain Chemistry↗

PubMed1997

Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits.

OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit. STUDY DESIGN: Rabbits with timed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (70%). Animals were allocated in a ratio of 2:1 for inoculation with either Escherichia coli (0.2 ml containing 10(3) to 10(4) colony-forming units) or sterile saline solution. Both groups were treated with ampicillin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hours until they were killed 5 to 6 days after hysteroscopy. Histologic examination of the placentas and fetal brains was conducted. RESULTS: Forty-five animals underwent hysteroscopy; 31 were inoculated with E. coli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were fewer live fetuses in the E. coli-inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli-inoculated rabbits but none in the saline solution group (p < 0.05). All rabbits with brain white matter lesions had evidence of intrauterine infection. Evidence of white matter damage included increased karyorrhexis, rarefaction, and disorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies. CONCLUSION: Experimental ascending intrauterine infection can cause fetal brain white matter lesions.

Animals↗