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Tumor necrosis factor-alpha allele lymphotoxin-alpha+250 is associated with the presence and severity of placental inflammation among preterm births.

Histologic inflammation of placenta has been associated with increased risk for bronchopulmonary dysplasia and periventricular leukomalacia among preterm infants. Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the regulation of inflammation. Some alleles of TNF (LT-alpha+250, TNF-alpha-308, and TNF-alpha-238) have been associated with susceptibility and/or severity of many diseases characterized by inflammation and/or involving the immune system. To determine whether alleles of TNF-alpha affect the risk and/or the severity of chorioamnionitis, we examined the placentas of 101 preterm births (birth weight <or=1250 g) for the presence of inflammation. Maternal and fetal chorioamnionitis (MCA and FCA, respectively) were graded for severity and staged for location of inflammatory infiltrate. Analysis for TNF-alpha alleles was done using PCR-restriction fragment length polymorphism technique on DNA extracted from infants' whole blood. MCA and FCA were seen in 45 and 38 placentas, respectively (p = 0.64). Genotypes of TNF-alpha-308 did not affect the development or the severity of placental inflammation. However, the AA genotype of LT-alpha+250 occurred more often when MCA and FCA were present compared with placentas without inflammation (p = 0.016 and p = 0.007, respectively). The GA genotype of TNF-alpha-238 was more common in placentas with severe MCA than with mild MCA (p = 0.015). The number of A alleles of LT-alpha+250 (GG = 0, GA = 1, AA = 2) correlated directly and significantly with grades and stages of MCA and FCA (p < 0.05). The AA genotype of LT-alpha+250 is associated with the development of chorioamnionitis among preterm births. The A allele of LT-alpha+250 seems to worsen the degree of placental inflammation.

Adult↗

Il-1 beta, Il-6, Il-8 and G-CSF in the diagnosis of early-onset neonatal infections.

OBJECTIVE: To determine whether inflammatory cytokine concentrations (Il-1 beta, Il-6, Il-8 and G-CSF) in umbilical cord blood are useful predictors of an early-onset neonatal infection. MATERIAL AND METHODS: 240 women and their newborns were enrolled in our study and umbilical cord blood samples collected from neonates (n = 240) were subjected to ELISA for Il-1 beta, Il-6, Il-8 and G-CSF. Clinical outcome of the neonates was followed and documented. Placenta histology was also available in majority of the cases (n = 195). RESULTS: Early-onset neonatal infection was diagnosed in 5.4% of neonates (13/240) and placental examination showed histologic chorioamnionitis in 17.9% (35/195). Both Il-1 beta and Il-6 cord blood concentrations were elevated in association with histologic chorioamnionitis (Il-1 beta-2.7 vs. 2.1 pg/ml, p < 0.05 and Il-6 15.6 vs. 12.8 pg/ml, p < 0.005). Only Il-6 was elevated (16.0 vs. 13.2 pg/ml, p < 0.05) in neonates with early-onset bacterial infections. ROC analysis showed acceptable diagnostic performance of Il-6 in the identification of acute histologic chorioamnionitis and clinical neonatal infection. CONCLUSION: Il-6 in umbilical cord blood seems to be a promising predictor for early-onset neonatal infections.

Chorioamnionitis↗

Multiple courses of antenatal corticosteroid therapy in patients with preterm premature rupture of membranes.

OBJECTIVE: This study was performed to determine the benefits and risks of multiple courses of corticosteroids in patients with preterm premature rupture of membranes (PPROM). METHOD: We retrospectively evaluated the pregnancy and neonatal outcomes of women with singleton pregnancies, who were admitted at 24-32 weeks of gestation due to PPROM. Patients were categorized into 3 groups according to antenatal corticosteoid exposure: (1) a non-user group, (2) a single-course group, and (3) a multiple-course group. RESULT: A total of 170 patients were included in the study, with 50 in the non-use group, 76 in the single-course group, and 44 in the multiple-course group. Univariate analyses showed that clinical chorioamnionitis occurred with highest incidence in multiple-course group (chi2=6.20, p<0.05) and the incidence of neonatal respiratory distress syndrome (RDS) was lowest in the multiple-course group (chi2=10.0, p<0.01). Multiple logistic regression analyses showed that multiple courses of corticosteroids were independently associated with clinical chorioamnionitis (odds ratio=13.15, p<0.05) whereas no significant association was found between RDS and multiple-course corticosteroids after adjusting for confounding variables (odds ratio=0.28, p=0.06). CONCLUSION: Multiple courses of antenatal corticosteroid therapy were found to be associated with an increased risk of clinical chorioamnionitis and seemed not to reduce the incidence of RDS and other neonatal morbidities in patients with PPROM.

Adrenal Cortex Hormones↗

Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial.

BACKGROUND: Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks' postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. METHODS: Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks' postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation > or =90%). RESULTS: Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect. CONCLUSIONS: Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.

Adrenal Insufficiency↗

Neonatal brain damage following prolonged latency after preterm premature rupture of membranes.

This study evaluated the risk of brain damage in neonates delivered at < 34 weeks following a prolonged latency after preterm premature rupture of membranes (pPROM). The medical records of 77 singletons delivered at < 34 weeks with pPROM and 66 singletons delivered at < 34 weeks with preterm labor and intact membranes were reviewed. Latency was divided into four intervals: < or = 24, > 24-< or = 72, > 72- < or = 168 hr, and > 1 week. Outcomes in the longer three intervals were compared with those in neonates delivered at < or = 24 hr after pPROM. The documented outcomes were placental (histologic chorioamnionitis, vasculitis, funnisitis) and neonatal (intraventricular hemorrhage, ventriculomegaly, germinal matrix hemorrhage, periventricular leukomalacia). Odds ratios and 95% CI for the risk of histologic chorioamnionitis according to the respective latency intervals were 4.8 (1.0-22.9), 7.0 (1.1-43.1), 7.4 (2.1-42.3) in patients with pPROM. The risks of intracranial ultrasonic abnormalities, however, did not increased with prolonged latency. In the patients with preterm labor and intact membranes, the both risks did not increased with increasing latency. Therefore, this study was suggested that the risk of histologic chorioamnionitis increased with increasing latency, but there was no relationship between neonatal brain damage and latency interval after pPROM.

Adult↗

[Placental infection in Rwanda: comparison an HIV infected population and a control population].

We report an histological study from term placentas of 286 HIV positive women born in Rwanda. We observed chorioamnionitis without any pathogen in 15% of the cases, cocci Gram positive infection in 12 observations and malaria infection in 75% of placentas. We noted 71 cases of active malaria infection with Plasmodium falciparum trophozoites in the erythrocytes of the intervillous spaces, and 135 cases of chronic infection with malaria pigment without any parasite. An ultrastructural study performed in 8 cases of active malaria infection showed characteristic features of trophozoites and schizontes, and malaria pigment. No viral particle were seen. We did not observe any significative difference concerning the incidence of chorioamnionitis and of malaria infection in 275 HIV negative placentas. In the literature as well as in the present study, the main lesions observed in the placentas of AIDS patients were chorioamnionitis. Opportunistic infections and neoplasias of the placenta are exceptional. Detection of HIV proteins by immunochemistry or in situ hybridization is possible, but the HIV could not be identified in the trophoblast by electron microscopy. Mechanisms of the materno-fetal transmission for HIV are currently unknown.

Acquired Immunodeficiency Syndrome↗

[Usefulness of determination of granulocyte elastase plasma level, c-reactive protein and white blood cell count in prediction in intrauterine infection in pregnant women after PROM].

UNLABELLED: The main markers of intrauterine infection: C-reactive protein and white blood cell count are dependent on medical management as steroids or antibiotics therapy. Granulocyte elastase is independent variable from influence of tocolysis, steroids, antibiotics, chemiotherapeutics, hours since PROM. The aim of the study was to evaluate and compare the usefulness of determination granulocyte elastase, (EG) C-reactive protein (CRP) and white blood cell count (WBC) in prediction of chorioamninitis in pregnant women after premature rupture of fetal membranes. MATERIALS AND METHODS: 67 women with single pregnancy between 24-36 week of gestation after PPROM were included into the study group. All women were managed expectantly (tocolysis, antibiotics, steroids, intravaginal chemiotherapeutics, bed rest), maternal and fetal (KTG, USG) vital signs were monitored every day. EG, CRP and WBC blood test were performed every day. Histopathologic examinations of all placentas were performed for chorioamnionitis confirmation or exclusion. Normal range for EG--88 micrograms/l, CRP--15 micrograms/l, WBC--15 x 10(9). RESULTS: The usefulness of granulocyte elastase plasma serial determination as biochemical marker of chorioamnionitis in cases of PPROM was confirmed: sensitivity--100%, specificity--33%, PPV--64.9%, NPV--100% in comparison with CRP: sensitivity--27%, specificity--80%, PPV--62.5%, NPV--47% and white blood cell count: sensitivity--27%, specificity--66.7%, PPV--50%, NPV-42.5%. CONCLUSIONS: We confirmed statistical correlation (p < 0.001) between granulocyte elastase plasma level > 88 micrograms/l and histological signs of intrauterine infection in pregnant women after PPROM. Granulocyte elastase determination in plasma is most sensitive indicator of histologic confirmed chorioamnionitis.

Adult↗

Amniocentesis for gram stain and culture in preterm premature rupture of the membranes.

A retrospective study was conducted to assess the predictive value and clinical usefulness of amniotic fluid Gram stain and culture in the management of preterm premature rupture of the membranes (PROM). Amniocentesis was attempted in 79 patients and was successful in 53 patients for a success rate of 67%. The complication rate was 1.8%. Fifty-three patients from whom amniotic fluid was obtained after preterm PROM were studied. Patients were managed expectantly unless clinical chorioamnioitis developed, a positive Gram stain or culture was found, or a mature lung profile after 34 weeks' gestation was established. A low incidence of chorioamnionitis (5.5%), postpartum endometritis (11%), and neonatal sepsis (3.5%) was found with expectant management. A statistically significant association between Gram stain and antepartum infection, postpartum infection, and neonatal infection was noted. Gram stain had a 100% sensitivity and 82% specificity as predictor of chorioamnionitis. Amniotic fluid culture had a 100% sensitivity and 76% specificity as predictor of chorioamnionitis. As predictor of a positive culture result, Gram stain had a sensitivity of 60% and specificity of 92%. No patient with a negative Gram stain or culture developed infectious sequelae regardless of the timing of amniocentesis. All positive Gram stains and cultures were found within 48 hours of rupture of membranes. Amniocentesis for Gram stain and culture has clinical usefulness in preterm PROM and, despite false-positive tests, the authors' data support intervention on the basis of a positive Gram stain.

Amniotic Fluid↗

The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies.

The clinical relevance of histologic evidence of acute ascending intrauterine infection has been called into question by descriptions of "silent" chorioamnionitis. The described frequencies of silent chorioamnionitis in normal and abnormal pregnancies vary widely because of differences in the definition of a normal pregnancy, methods of placental examination, and pathologic criteria. Therefore, we examined placentas from 161 uncomplicated gestations for the presence and severity of acute inflammation in the amnion, chorion-decidua, chorionic plate, and umbilical cord using strict gross and microscopic protocols. Indicators of amniotic fluid infection, specifically umbilical cord inflammation, amnionitis, and inflammation within the chorionic plate were present in 0, 1.2, and 4% of the cases, respectively. Silent chorioamnionitis was rare. There was a statistical association between the presence of acute inflammation and the occurrence of labor at term. Methods of tissue sampling that included a more extensive examination of the site of membrane rupture resulted in an increased frequency of diagnosis of acute inflammation at the site of rupture in vaginal deliveries at term.

Acute Disease↗

Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease.

BACKGROUND: A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood. EXPERIMENTAL DESIGN: The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8. RESULTS: In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed. CONCLUSIONS: Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine production within the feto-maternal unit.

Amniotic Fluid↗

[Immunological analysis of the mechanism of maternal tolerance of a fetus and the cytokine-mediated regulation of feto-placental functions].

Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.

Chorioamnionitis↗

[The amnioinfusion therapy of saline solution for premature rupture of the membranes before 27 weeks' gestational age].

Saline solution amnioinfusion was performed for 12 cases of preterm PROM before 27 weeks gestational age complicated by oligohydramnios in order to suppress chorioamnionitis, prevent fetal pulmonary hypoplasia and delay delivery. The results were as follows. 1. The mean gestational ages at diagnosis of premature rupture of membranes and initiating saline solution amnioinfusion were 23.6 +/- 2.9 weeks and 24.9 +/- 1.5 weeks, respectively. The mean duration of saline solution amnioinfusion was 14.7 +/- 11.9 days. The mean gestational age at delivery was 27.2 +/- 1.7 weeks. The mean birth weight was 1,056 +/- 220g. 2. Saline solution amnioinfusion was effective in relieving oligohydramnios in all cases. No pulmonary hypoplasia was observed in the infants. 3. Clinically saline solution amnioinfusion was effective in suppressing chorioamnionitis in 9 cases out of 12. Histologically the picture of chorioamnionitis was revealed in 10 cases out of 12. no serious infection was observed in the infants. 4. Nine infants out of 12 survived. There were 2 IUFD and one neonatal death. The perinatal survival rate was 75%. 5. It is concluded from the above results that saline solution amnioinfusion is an effective treatment for preterm PROM before 27 weeks' gestational age.

Amnion↗

Pregnancy outcome and placental weights: their relationship to HIV-1 infection.

The relationship between placental characteristics, including weight and inflammation, and pregnancy outcome was examined as part of a case control study looking into the impact of maternal HIV-1 infection on pregnancy outcome. Cases defined as low birth weight (< 2500g) or stillbirth deliveries, were compared to controls defined as mothers who delivered a live born neonate weighing 2500g or more. The mean placental weight and the mean foetal/placental weight ratio were significantly lower in cases (n = 253) than in controls (n = 216) (p < .05). Placental inflammation (chorioamnionitis) was significantly associated with prematurity (p < .001) and with stillbirth (p < .05), maternal HIV-1 antibody being a risk factor for chorioamnionitis in the preterm group. These data support a correlation between placental weight and pregnancy outcome, and suggest that maternal HIV-1 infection is a risk factor for chorioamnionitis in HIV-1 seropositive preterm deliveries.

Case-Control Studies↗

Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors.

BACKGROUND: Bilateral cystic periventricular leukomalacia (PVL) is a major cause of neurodevelopmental delay in the premature infant. Thus, early identification of the preterm infant at highest risk for the subsequent development of this lesion is critical. OBJECTIVES: The three objectives of this case-control study were: (1) to determine the basic characteristics of cystic PVL, (2) to assess the relationship of perinatal clinical events and PVL, and (3) to ascertain the feasibility of identifying early those preterm infants at highest risk for the development of PVL. METHODS: The medical records and cranial ultrasound scans (HUSs) were reviewed for 632 infants weighing less than 1750 g who were admitted to the neonatal intensive care unit between January 1992 and December 1993. PVL developed in 14 infants of 1285 +/- 301 g birth weight (BW) and 29.4 +/- 1.5 weeks' gestational age (GA); severe intraventricular hemorrhage (n = 21) and intraparenchymal echodensity (n = 12) developed in 33 infants of 904 +/- 248 g BW and 26.6 +/- 1.8 weeks' GA; and 585 infants of 1315 +/- 324 g BW and 29.7 +/- 2.4 weeks' GA with normal HUS findings (n = 473) or grade I or II intraventricular hemorrhage (n = 112) served as a comparison group. RESULTS: Cystic PVL was observed in 14 (2.3%) of 632 infants weighing less than 1750 g, more specifically, in 3.2% of infants weighing less than 1500 g. Cysts were noted from the 7th to 14th days of life in 10 infants and from the 20th to 46th days of life in 4 infants. Ten (70%) of the infants had relatively benign clinical courses, and most cases were detected by routine HUS surveillance. Over hypotension in the immediate perinatal period was noted in 3 (21%) infants; late hypotension developed in 1 additional infant. Univariate analysis indicate that two clinical indicators, prolonged rupture of membranes (PROM) and chorioamnionitis, were significant predictors of PVL. For PROM, the odds ratio estimate and the 95% confidence limit are 6.59 and 1.96 to 22.10, with a sensitivity of 28.6% and positive predictive value of 11.5%. Similar values for chorioamnionitis are 6.77 (1.77 to 25.93), with a sensitivity of 21.4% and positive predictive value of 11.5%. CONCLUSIONS: (1) Most cases of symmetric cystic PVL occurred in infants with relatively benign clinical courses and were only detected by routine ultrasound screening. (2) Postnatal systemic hypotension seems to be an uncommon associated event. (3) Preterm infants born to mothers with PROM and/or chorioamnionitis seem to be at an increased risk for the development of PVL and should be carefully evaluated.

Analysis of Variance↗

Preterm premature rupture of membranes: comparison between twin and singleton gestations.

The purpose of this study was to evaluate the clinical characteristics and pregnancy outcomes of twin and singleton pregnancies complicated by preterm premature rupture of membranes (PROM) and to compare the groups to evaluate for differences in these areas. In this retrospective study, patients with a gestational age of < 36 weeks admitted between 1993 and 1996 with PROM were evaluated for their clinical characteristics and pregnancy outcomes. Twin and singleton pregnancies were compared and the results were evaluated for significant differences. Patients with lethal fetal anomalies, clinical chorioamnionitis at presentation, or fetal distress at presentation were excluded from analysis. Liberal use of tocolysis was provided to both groups of patients, as were serial doses of betamethasone and vitamin K. Twenty-eight sets of twins and 119 singleton pregnancies were included in the analysis. Differences were noted with respect to twin and singleton pregnancies for both latency period (4.26 days vs 8.6 days, P < 0.001) and birthweight (1,464 vs 1,698 g, P < 0.03). The birthweight for twins was an average of the pair. No differences were noted with respect to gestational age at time of rupture, maternal age, gravidity, parity, race, tocolytic use, steroid use, prophylactic antibiotics, or sexually transmitted diseases. The incidence of chorioamnionitis showed a trend for a higher occurrence in singleton pregnancies. The latency period for twin pregnancies complicated by preterm PROM is shorter than for singleton pregnancies. The incidence of chorioamnionitis may be higher in singleton pregnancies, but this may be related to their longer latency period. A knowledge of these differences may be of benefit when counseling these patients.

Adult↗

Eosinophilic/T-cell chorionic vasculitis.

Chorionic vasculitis is the hallmark of a fetal response in chorioamnionitis. There are five highly characteristic findings: (1) leukocyte migration is not concentric but rather radiates toward the infected amniotic fluid; (2) the infiltrate is primarily neutrophils; (3) multiple chorionic vessels, first veins and then arteries, are usually involved; (4) the infiltrate never extends into the vasculature of stem villi; and (5) it is rare in the absence of chorioamnionitis (or its precursors). Here we describe a new form of chorionic vasculitis characterized by an infiltrate composed primarily of eosinophils and CD3+ T lymphocytes that very focally involves a single chorionic vessel (artery or vein), that radiates away from the amniotic fluid (i.e., toward the intervillous spaces), and that may extend into the stem villous vasculature; this lesion occurs in the absence of any evidence of chorioamnionitis. During the past 7+ years, using accepted placental review criteria, we have examined 7104 placentas and identified 14 cases of eosinophilic/T-cell chorionic vasculitis (or related lesions). Although the frequency of diagnosis in the placentas examined was 0.197%, its true incidence cannot be estimated because of its very focal nature and the limited nature of placental disk sampling. Its etiology and significance are unknown, but it may represent a focal immune-mediated vasculitis.

Antigens, CD↗

An analysis of antenatal tests to detect infection in preterm premature rupture of the membranes.

The purpose of this study was to critically review published studies regarding sensitivity, specificity, and positive and negative predictive values of antenatal tests to diagnose chorioamnionitis or fetal-neonatal sepsis in preterm premature rupture of the membranes. A Medline Data-Base computer program search from 1980 to 1988 identified 39 studies, 23 of which were accepted after independent review with preset criteria. An ideal test to predict chorioamnionitis or neonatal sepsis was not found. The low success rate for amniocentesis and the need for repeat taps preclude the acceptance of tests on the basis of amniotic fluid. Single, small studies, the precision of which has never been tested, show good indices for repeatedly increased serum levels of C-reactive protein (greater than 20 mg/L), a high level of C-reactive protein greater than 40 mg/L, or a day-to-day coefficient of variation for C-reactive protein of greater than 30% in the prediction of histologic or clinical chorioamnionitis. Ultrasonographic observation of fetal activity, if published study results are confirmed, may be of value to predict amniotic fluid bacterial colonization.

Amniotic Fluid↗

A review of premature birth and subclinical infection.

Premature birth causes high rates of neonatal morbidity and mortality. There are multiple causes of preterm birth. This article reviews the evidence linking subclinical infection and premature birth. Although maternal genital tract colonization with specific organisms has been inconsistently associated with preterm birth and/or premature rupture of membranes, some infections have been consistently associated with preterm delivery. The association of histologic chorioamnionitis with prematurity is a consistent finding, but the mechanisms require further study. The relationship between histologic chorioamnionitis infection and the chorioamnionitis of prematurity requires additional research. A varying number of patients in "idiopathic" preterm labor have positive amniotic fluid cultures (0% to 30%), but it is not clear whether infection preceded labor or occurred as a result of labor. Evidence of subclinical infection as a cause of preterm labor is raised by finding elevated maternal serum C-reactive protein and abnormal amniotic fluid organic acid levels in some patients in preterm labor. Biochemical mechanisms for preterm labor in the setting of infection are suggested by both in vitro and in vivo studies of prostaglandins and their metabolites, endotoxin and cytokines. Some, but by no means all, antibiotic trials conducted to date have reported decreases in prematurity. These results support the hypothesis that premature birth results in part from infection caused by genital tract bacteria. In the next few years, research efforts must be prioritized to determine the role of infection and the appropriate prevention of this cause of prematurity.

Anti-Bacterial Agents↗