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PubMed2005

Programmed cell death (apoptosis) in placentas from normal pregnancy and pregnancy complicated by term (t) and preterm (p) premature rupture of membranes (PROM).

OBJECTIVE: The aim of this study was to determine the apoptotic index using three different apoptotic markers: terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL); M30 cytoDEATH antibody and fluorescein isothiocyanate (FTIC)-labeled annexin-V in the placenta and membranes from normal pregnancy and pregnancy complicated by premature rupture of membranes (PROM). STUDY DESIGN: Placentas from 16 pregnancies (22-40 weeks' gestation) and 13 pregnancies complicated by pPROM and tPROM were collected at delivery. Maternal and gestational age, mode of delivery, gravidity and parity, fetal birthweight, Apgar scores, presence of histologic chorioamnionitis, interval between membrane rupture and delivery were recorded among PPROM and tPROM cases. RESULTS: Only M30 cytoDEATH antibody (P=0.02) and TUNEL test (P=0.04) on fetal membranes gave statistically significantly higher levels in cases with premature rupture of membranes. The presence of histologic chorioamnionitis had no significant impact on apoptotic markers in PROM placentas. Preterm deliveries following the rupture of membranes had higher median AI values detected by M30M antibody, compared to those cases delivered without PROM (P=0.03). CONCLUSION: High apoptotic nuclei counts were found in fetal membranes of pPROM.

Annexin A5↗

PubMed2001

Missed abortion complicated by Candida infection in a woman with rested IUD.

Although Candida species are frequent saprophytes of the female genital tract, chorioamnionitis or intrauterine fetal infections are rarely caused by these fungi. The present report describes a 34-year-old woman G2, P2, presenting with vaginal bleeding in the 11.6 weeks of gestation. Clinical and sonographic examination revealed a missed abortion and rested IUD. Histopathologically, a fungal chorioamnionitis due to Candida spp. was found at the curetting material, confirmed by detection of C. albicans infection on mycological culture. Foreign intrauterine bodies, like IUD's and cerclage sutures predispose to fungal chorioamnitis or fetal infections. This conditions urge repetetive search for Candida spp. to establish early anti-fungal therapy which may be therapeutic for this hithero rare intrauterine infection.

Abortion, Missed↗

PubMed2005

Variations in the incidence of postpartum hemorrhage across hospitals in California.

OBJECTIVE: Because postpartum hemorrhage may result from factors related to obstetrical practice patterns, we examined the variability of postpartum hemorrhage and related risk factors (obstetrical trauma, chorioamnionitis, and protracted labor) across hospital types and hospitals in California. METHODS: Linked birth certificate and hospital discharge data from 507,410 births in California in 1997 were analyzed. Cases were identified using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes. Comparisons were made across hospital types and individual hospitals. Risk adjustments were made using 1) sample restriction to a subset of 324,671 low-risk women, and 2) Bayesian hierarchical logistic regression model to simultaneously quantify the effects of patient-level and hospital-level risk factors. RESULTS: Postpartum hemorrhage complicated 2.4% of live births. The incidence ranged from 1.6% for corporate hospitals to 4.9% for university hospitals in the full sample, and from 1.4% for corporate hospitals to 3.9% for university hospitals in the low-risk sample. Low-risk women who delivered at government, HMO and university hospitals had two- to threefold increased odds (odds ratios 1.98 to 2.71; 95% confidence sets ranged from 1.52 to 4.62) of having postpartum hemorrhage compared to women who delivered at corporate hospitals, irrespective of patient-level characteristics. They also had significantly higher rates of obstetrical trauma and chorioamnionitis. Greater variations were observed across individual hospitals. CONCLUSION: The incidence of postpartum hemorrhage and related risk factors varied substantially across hospital types and hospitals in California. Further studies using primary data sources are needed to determine whether these variations are related to the processes of care.

Bayes Theorem↗

PubMed1985

Preterm rupture of the membranes: combination therapy.

Preterm rupture of the membranes poses perhaps the greatest threat to perinatal survival. Unfortunately, the literature leaves us in a quandry as to the management of the problem. At the Medical University of South Carolina for the past 3 years, aspects of both active and passive management have been used. Vaginal pool phospholipid analysis, the use of corticosteroids whenever appropriate, and tocolysis (in an attempt to gain 48 hours) were used in 96 consecutive patients with premature rupture of the membranes between 26 and 36 weeks' gestation. Decisions about delivery were dictated by spontaneous onset of labor and/or evidence of chorioamnionitis. This regimen prolonged gestation an average of 4.6 days. Maternal and neonatal infectious morbidity was uncommon. Clinical chorioamnionitis was diagnosed in 5.2% of mothers, and only 8.5% of all neonates had evidence of serious infection. Respiratory distress syndrome was seen in 12.8% of neonates. There were only three perinatal deaths, and most babies (92.5%) were discharged without residual problems (average hospital stay, 18.1 days). A detailed analysis of the group by gestational age categories will be presented.

Adolescent↗

PubMed1990

Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial.

The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.

Administration, Oral↗

PubMed1991

The enhanced production of placental interleukin-1 during labor and intrauterine infection.

The purpose of this study was to determine the effect of labor and chorioamnionitis in interleukin-1 production by human placenta. We studied the activity of the placenta to produce interleukin-1 with an enzyme immunoassay by culturing tissue blocks. The placental tissue obtained after labor produced a larger amount of interleukin-1 than placental tissue obtained before labor. All the placental tissues produced more interleukin-1 beta than interleukin-1 alpha. The placentas with labor and chorioamnionitis produced about seventeenfold more interleukin-1 than placentas with labor only. We immunohistochemically identified interleukin-1--producing cells in the placenta and found that syncytiotrophoblasts produced both interleukin-1 alpha and interleukin-1 beta, while Hofbauer cells produced only interleukin-1 beta. In vitro analysis of the trophoblast activities to produce interleukin-1 revealed that microbial byproducts enhanced interleukin-1 production, possibly inducing accumulation of interleukin-1 receptor-positive cells at the sites of inflammation. In addition to stimulation of prostaglandin biosynthesis and labor, the placental interleukin-1 may act as an inflammatory mediator, leading to systemic and local changes at fetomaternal interface and activating fetomaternal immune systems against intrauterine infection.

Chorioamnionitis↗

PubMed1991

Amniotic fluid glucose and intraamniotic infection.

Thirty-nine patients with either premature labor and/or preterm premature ruptured membranes underwent transabdominal amniocentesis to enable the following amniotic fluid analyses to be performed: culture and sensitivity, Gram's stain, and glucose determination. All nine patients with intraamniotic infection had amniotic fluid glucose values less than 10 mg/dl. Three patients with amniotic fluid glucose levels less than 10 mg/dl but without chorioamnionitis were delivered of infants within 72 hours of admission. The mean amniotic fluid glucose level of patients with intraamniotic infection (5 +/- 2.4 mg/dl) was significantly lower than in those without intraamniotic infection (39.8 +/- 18.42 mg/dl). All patients with amniotic fluid glucose values less than 10 mg/dl had either bacteria and/or white blood cells on Gram's stain. Two patients without chorioamnionitis had white cells on Gram's stain and amniotic fluid glucose values greater than 10 mg/dl. It appears that amniotic fluid glucose is more sensitive and more specific than Gram's stain in the diagnosis of intraamniotic infection. All 12 patients with low amniotic fluid glucose values were delivered of infants within 72 hours as the result of either the presence of infection or the progression of labor.

Amniotic Fluid↗

PubMed1993

Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial.

OBJECTIVE: Our objective was to compare maternal and perinatal outcomes between two management schemes for women with preterm premature rupture of the membranes and documented fetal pulmonary maturity. STUDY DESIGN: Of 164 women with preterm premature rupture of the membranes at 32 weeks to 36 weeks 6 days' gestation, 93 eligible and consenting women were randomly selected for either induction of labor (n = 46) or expectant management (n = 47). Expectant management included hospitalization, assessment for fetal heart rate abnormalities, chorioamnionitis, and labor. Digital cervical examinations were prohibited until progressive labor occurred. Follow-up was also done for the 71 women who did not participate. RESULTS: The women in the induction of labor and expectant management groups had similar demographic characteristics and gestational ages (34.1 vs 34.3 weeks). Expectant management was associated with prolonged latencies to labor, delivery, and maternal hospitalization (p < 0.001), as well as increased hospitalization of infants at 2 to 5 days after delivery (p < 0.05). These patients had increased chorioamnionitis and fetal heart rate abnormalities before labor (p = 0.01, 0.03). Infants received more frequent (p < 0.001) and prolonged antimicrobial therapy after expectant management (p = 0.003) with no reduction in proven sepsis (6.8% vs 4.4%). These latter differences were influenced by the neonatologist's concern over potential neonatal infection. CONCLUSIONS: Among women with preterm premature rupture of the membranes at 32 to 36 weeks with mature surfactant profiles, immediate induction of labor reduces the duration of hospitalization and infection in both mothers and neonates.

Adult↗

PubMed1995

Short-term verus long-term prophylactic tocolysis in patients with preterm premature rupture of membranes.

A randomised prospective clinical trial was conducted over a 7-year period (1987-1993) in the Department of Obstetrics and Gynaecology, University of Patras. The purpose of this study was to compare two management protocols of Preterm Premature Rupture of Membranes (PPROM). Two-hundred forty-one women entered the study and were assigned randomly to one of two groups. Group A consisted of 105 subjects who were managed expectantly (tocolysis used for 48 h only, if necessary, to permit full course of steroid therapy), while Group B consisted of 136 subjects, in whom aggressive tocolysis was utilised. The differences in the latency period (time from rupture of membranes to the onset of labour) were not statistically significant between the two groups. On the contrary, statistically significant differences in the incidence of chorioamnionitis and postpartum endomyometritis were found between the two groups (higher in Group B). Twelve subjects in Group A (12/105, 11.4%) and 40 in Group B (40/136, 29.4%) had chorioamnionitis. The relative risk (RR) was 2.47 (95% C.I. 1.42-4.66, P < 0.001). Endomyometritis was diagnosed in 20 subjects in Group A (20/105, 19%) and in 45 in Group B (45/136, 33.3%). The RR was 1.74 (95% C.I. 1.10-2.75, P < 0.05). These data suggest that long term prophylactic tocolytic therapy in patients with PPROM, while without demonstrated benefit, may result in an increased risk of maternal infectious morbidity, and raise the cost of treatment.

Chorioamnionitis↗

PubMed1996

Elevations of amniotic fluid macrophage inflammatory protein-1 alpha concentrations in women during term and preterm labor.

OBJECTIVE: To determine whether elevated concentrations of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in amniotic fluid (AF) are related to term and preterm labor. METHODS: Amniotic fluid was obtained from women from five different clinical situations: 1) term cesarean delivery, no labor (n = 29); 2) normal term labor, no infection (n = 36); 3) preterm labor, delivery more than 1 week from sampling, no infection (n = 19); 4) preterm labor, delivery within 1 week from sampling, no infection (n = 18); and 5) preterm chorioamnionitis (n = 8). Amniotic fluid was collected aseptically at the time of amniocentesis, amniotomy, or hysterotomy. Concentrations of MIP-1 alpha were determined by enzyme-linked immunosorbent assay. Statistical analysis was by Wilcoxon rank-sum test, Kruskal-Wallis test, and unpaired t test. RESULTS: Women in normal term labor had significant elevations of AF MIP-1 alpha concentrations when compared with women at term undergoing repeat cesarean delivery (P < .001). In women with term gestation, AF MIP-1 alpha correlated well with cervical dilation (r2 = 0.479, P < .001). In women with preterm labor who later delivered within 1 week of presentation, AF MIP-1 alpha concentrations were higher than those from women who did not deliver within 1 week. Women who presented with clinically evident chorioamnionitis had the highest concentrations of AF MIP-1 alpha (P = .001). CONCLUSION: Women in labor have significantly elevated AF concentrations of MIP-1 alpha, particularly if labor is associated with intrauterine infection. We suggest that MIP-1 alpha is involved in the physiology of normal labor and in the pathogenesis of infection-associated preterm labor.

Amniotic Fluid↗

PubMed1992

The mechanisms of preterm labour; the interaction between amnion cells and leukocytes in the metabolism of arachidonic acid.

Chorioamnionitis is frequently associated with preterm labour. We have used a cell culture model system to examine the effects of leukocytes upon the metabolism of endogenous arachidonic acid from within amnion cells. We have demonstrated that activated leukocytes release substances which increase the overall release and metabolism of endogenous arachidonic acid within amnion cells causing an increase in prostaglandin E2 production as well as a smaller increase in non-cyclo-oxygenase metabolism. When amnion cells and leukocytes are cultured together, in addition to prostaglandin E2 production by amnion cells, arachidonic acid released by the amnion cells appears to be metabolised by leucocytes to prostaglandin F2 alpha, prostacyclin and thromboxane A2. Prostaglandins E2 and F2 alpha are the principal cyclo-oxygenase products of this interaction. We postulate that chorioamnionitis stimulates preterm labour not only by causing an increase in prostaglandin E2 synthesis by amnion cells but by metabolism of amnion derived arachidonic acid to the powerfully oxytocic prostaglandin F2 alpha by leukocytes.

Amnion↗

PubMedDate not supplied

Amniotic fluid epidermal growth factor levels in normal and abnormal pregnancies.

OBJECTIVE: To determine the concentrations of epidermal growth factor (EGF) in amniotic fluid (AF) from women during late pregnancy, with and without pathophysiologic complications. METHODS: All AFs were collected by amniocentesis from the following groups: gestational age at least 38 weeks (n = 15); gestational age 36-37 weeks (n = 10); gestational age 35 weeks (n = 5); labor 34 weeks or less, delivered within 7 days (n = 10); labor 34 weeks or less, undelivered (n = 10); chorioamnionitis (n = 7); gestational age-matched controls (n = 7); term, in labor (n = 8); term, not in labor (n = 8); intrauterine growth restriction (IUGR) 38 weeks or more (n = 8); macrosomia at 38 weeks or more (n = 10). Epidermal growth factor was assayed using a specific radioimmunoassay. RESULTS: Amniotic fluid EGF levels increase rapidly in late pregnancy but are not altered by chorioamnionitis or by term or preterm labor. Intrauterine growth restriction is associated with lower EGF levels in AF, but macrosomia is without effect. CONCLUSIONS: Epidermal growth factor levels in AF are increased near term and decreased in pregnancies complicated by IUGR; they may be an indicator of specific maturational events.

Amniotic Fluid↗

PubMed2004

Adverse outcomes after preterm labor are associated with tumor necrosis factor-alpha polymorphism -863, but not -308, in mother-infant pairs.

OBJECTIVE: Two single-base polymorphisms of the tumor necrosis factor-alpha gene (TNF-alpha) at positions -863 and -308 are associated with variation in production of TNF-alpha (TNF-alpha). TNF-alpha genotypes were tested for association with adverse outcomes in mother-infant pairs with preterm labor. STUDY DESIGN: We analyzed a cohort of 118 mother-infant pairs with preterm labor before 34 weeks' gestation. Polymerase chain reaction was used on extracted deoxyribonucleic acid for polymorphism assay. Outcomes included amniotic fluid TNF-alpha concentration, histologic chorioamnionitis, delivery gestational age, and composite neonatal morbidity. Statistical significance was determined by chi 2 and Kruskal-Wallis analysis of variance. RESULTS: Mothers homozygous for the -863 polymorphism (AA) had significantly earlier deliveries ( P = .02), more chorioamnionitis ( P = .03), and greater composite neonatal morbidity ( P = .03). Neither maternal nor fetal carriage of the -308 polymorphism was associated with adverse outcome. CONCLUSION: In women with preterm labor before 34 weeks' gestation, maternal homozygous carriage of the -863 polymorphism may be associated with preterm delivery and adverse neonatal outcome.

Adolescent↗

PubMed2006

Fetal thymic involution: a sonographic marker of the fetal inflammatory response syndrome.

OBJECTIVE: The purpose of this study was to evaluate whether there is a relationship between the sonographic fetal thymus size and the presence of an intrauterine infection in patients with preterm labor. STUDY DESIGN: Thirty-one women who had been admitted with preterm labor and intact membranes between 24 and 32 weeks of gestation were included. Fetal thymus perimeter was measured sonographically, and amniocentesis for the microbiologic assessment of the amniotic cavity was performed. Placentas and umbilical cords were examined for the presence of chorioamnionitis/funisitis. RESULTS: The prevalence of preterm delivery and intra-amniotic infection was 51.6% (16/31 women) and 32.3% (10/31 women), respectively. In all cases with intrauterine infection and in 23.8% of cases without intrauterine infection, the fetal thymus perimeter was below the 5th percentile for gestational age (10/10 women vs 5/21 women; P < .01). Isolated histologic chorioamnionitis and funisitis were found in 22.6% and 25.8% of fetuses, respectively. The fetal thymus was below the 5th percentile for gestational age in 100%, 71.4%, and 12.5% of patients with histologic signs of funisitis and isolated chorioamnionitis and without histologic signs of infection, respectively. CONCLUSION: Fetal thymus involution in preterm labor patients is strongly associated with funisitis, which is the histologic manifestation of the fetal inflammatory response syndrome.

Bacterial Infections↗

PubMed2005

Duration of labor and risk of cerebral white-matter damage in very preterm infants who are delivered with intrauterine infection.

OBJECTIVE: The purpose of this study was to assess whether the duration of labor has any effect on the occurrence of cerebral white-matter damage in very preterm infants who are delivered in the presence of intrauterine infection. STUDY DESIGN: From a cohort of infants who were born spontaneously at <32 weeks of gestation for whom placental information was available and who survived 7 days from birth, 126 infants had clinical, laboratory, or histologic evidence of intrauterine infection. Among them, variables were compared between those infants with white-matter damage (defined as intraventricular hemorrhage grade 3 plus, periventricular leukomalacia, or ventriculomegaly not associated with hydrocephaly [n = 13]) and those infants without it (n = 113). Comparisons were made with t test, chi-squared test, and survival analysis; a probability value of <.05 was considered significant. RESULTS: There were no differences between the 2 groups in gestational age at delivery and rates of labor or cesarean delivery. Duration of active labor (66 +/- 45 minutes vs 88 +/- 75 minutes; P =.49) and of clinical chorioamnionitis (310 +/- 186 minutes vs 529 +/- 544 minutes; P =.44) were similar in cases with and without neonatal white-matter damage. CONCLUSION: In 126 infants who were born at <32 weeks of gestation with intrauterine infection, we found no correlation between the duration of labor or clinical chorioamnionitis and neonatal white-matter damage.

Adult↗

PubMed2004

Severe umbilical cord inflammation-a predictor of periventricular leukomalacia in very low birth weight infants.

Chorioamnionitis has been associated with periventricular leukomalacia (PVL) in very low birth weight (VLBW) infants. We examined the association between the pathological severity of chorioamnionitis and PVL in VLBW infants. Thirty-four VLBW infants with PVL and 34 control infants matched for gestational age without a diagnosis of PVL or intraventricular hemorrhage were obtained from the Women and Infants' Hospital of Rhode Island's Neonatal Follow-up Clinic database. Placental samples, including the amnion/chorion, chorionic plate, and umbilical cord, were examined microscopically. Statistical analysis included Mantel-Haenszel chi-square, and Student's t-test. Severe inflammation in the umbilical cord was observed in 53% of infants with PVL and 32% without PVL (p<0.05). Severe umbilical cord inflammation is one of the risk factors associated with the development of PVL in VLBW infants.

Case-Control Studies↗

PubMed1987

Reduction of group B streptococcal maternal and neonatal infections in preterm pregnancies with premature rupture of membranes through a rapid identification test.

To establish the effect of rapid detection and chemoprophylaxis of group B streptococcal genital colonization in preterm gestations with premature rupture of membranes, 260 singleton pregnancies were cultured. Through the use of a rapid test based on coagulation methods, group B streptococcus was identified in 84 (32%) patients, of which 18 (7%) had heavily colonized infections. The treatment of 36 patients resulted in no cases of chorioamnionitis or neonatal sepsis compared with 11 (23%) cases of chorioamnionitis and 13 (27%) of neonatal sepsis among 48 untreated patients (p less than 0.01). Although the risk of infection was significantly higher in patients with heavily colonized infections, characterized by less than 5 hours' growth for detection, even light colonization, requiring 20 hours for detection, resulted in a 14% rate of maternal and 16% rate of neonatal infection, respectively.

Ampicillin↗

PubMed1994

Prophylactic amnioinfusion for meconium-stained amniotic fluid.

OBJECTIVE: Previous studies have demonstrated reduced perinatal morbidity in patients receiving amnioinfusion for meconium-stained amniotic fluid compared with control patients receiving no amnioinfusion. Because amnioinfusion for variable fetal heart rate decelerations has become accepted care, we sought to determine the benefit of prophylactic amnioinfusion for meconium compared with standard care, incorporating therapeutic amnioinfusion for variable decelerations. STUDY DESIGN: Ninety-three term patients with moderate to heavy meconium and no variable fetal heart rate decelerations were randomized to immediate prophylactic amnioinfusion (600 ml saline solution bolus followed by 3 ml/min) or to standard care (including therapeutic amnioinfusion for variable decelerations developing later). All babies had DeLee suctioning on delivery of the head. Laryngeal cords were visualized and tracheal suctioning performed when meconium was seen below the cords. Statistical comparisons were performed using Student t test, Fisher's exact test, or chi 2 analysis. RESULTS: There were no significant differences in the incidence of operative delivery, fetal distress, or meconium below the cords or in newborn Apgar scores and umbilical artery gas values between the amnioinfusion (n = 43) and control (n = 50) patients. There were four cases of meconium aspiration, three in the amnioinfusion group, one in the standard care group. The rate of endometritis-chorioamnionitis was higher (p = 0.3) in the amnioinfusion (16%) than in the control group (8%), although time from ruptured membranes to delivery (8.5 hours vs 7.3 hours) and duration of intrauterine monitoring (6.1 hours vs 5.3 hours) were not different. CONCLUSIONS: Although amnioinfusion does dilute amniotic meconium, prophylactic amnioinfusion for meconium in the absence of variable decelerations remains controversial. Prophylactic amnioinfusion in term pregnancies did not improve perinatal outcome and increased the risk for chorioamnionitis-endometritis. Together with recent reports, the current data suggest that the benefit of amnioinfusion for meconium-stained amniotic fluid is a result of the alleviation of variable fetal heart rate decelerations rather than meconium dilution.

Adult↗