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PubMed2003

Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes.

OBJECTIVE: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI and calprotectin in amniotic fluid were determined by specific and sensitive immunoassays. Placentae of patients in both preterm labor with intact membranes and preterm PROM groups who delivered within 72 h of amniocentesis were examined. Non-parametric statistics, receiver-operating characteristic (ROC) curves and Cox regression models were used for analysis. A p value of < 0.05 was considered statistically significant. RESULTS: Intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin in both women with preterm labor and intact membranes, and women with preterm PROM. Preterm PROM was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Preterm parturition was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin, while parturition at term was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3. Among patients with preterm labor and intact membranes, elevation of amniotic fluid HNP 1-3, BPI and calprotectin concentrations was associated with intra-amniotic inflammation, histological chorioamnionitis and a shorter interval to delivery. CONCLUSION: MIAC, preterm parturition and preterm PROM are associated with increased amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Moreover, elevated amniotic fluid concentrations of BPI, immunoreactive HNP 1-3 and calprotectin are associated with intra-amniotic inflammation, histological chorioamnionitis and shorter amniocentesis-to-delivery interval in patients presenting with preterm labor with intact membranes.

Amnion↗

PubMed2004

Septic pelvic thrombophlebitis and preeclampsia are related disorders.

OBJECTIVE: To elicit factors associated with the postpartum development of septic pelvic thrombophlebitis in a single large referral tertiary patient population. METHODS: A nine-year single institution retrospective case review of all patients with enigmatic fever and septic pelvic thrombophlebitis was analyzed. RESULTS: A total of 55 patients with septic pelvic thrombophlebitis were provided care during the study interval. The average gestational age at delivery was 36.8 +/- 4.3 weeks. The most prevalent concurrent medical complication of pregnancy was preeclampsia (45%) while chorioamnionitis affected only 13%. The average length of ruptured membranes was 22.8 +/- 56.8 hours (median 10.5, 95% confidence interval [CI] 7.0-38.7 hours), with 22% of patients undergoing amnion rupture at the time of cesarean delivery. Prolonged (>24 hours) amnion rupture occurred in only 9% of patients. Most affected patients were delivered abdominally (91%) but a minority delivered vaginally (9%). Antibiotic therapy for presumed infection was initiated at 27.4 +/- 24.6 hours postpartum. Subsequently intravenous heparin therapy was initiated 128.9 +/- 54.2 hours thereafter enigmatic fever defervesed 37.2 +/- 36.8 hours later (median 34.0, 95% CI 27.2-47.3 hours). Patients received 6.3 +/- 1.8 days of heparin therapy. CONCLUSION: In this series, septic pelvic thrombophlebitis was frequently preceded by cesarean delivery and commonly associated with preeclampsia. Unexpectedly, a small number of patients suffered prolonged rupture of membranes or chorioamnionitis. We speculate that the cesarean delivery of a population of at-risk patients with preeclampsia may predispose them to develop septic pelvic thrombophlebitis.

Anti-Bacterial Agents↗

PubMed2000

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

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

Adolescent↗

PubMed1993

Bacterial vaginosis and anaerobes in obstetric-gynecologic infection.

Anaerobic infections of the upper genital tract are common. Antibiotic regimens designed to inhibit anaerobes markedly reduce morbidity. A vaginal infection associated with an increased concentration of anaerobic bacteria (bacterial vaginosis) has been recently linked to a wide variety of upper genital tract infections. Bacterial vaginosis has an important role in the development of clinical chorioamnionitis, postpartum endometritis, posthysterectomy vaginal-cuff cellulitis, postabortion pelvic inflammatory disease, and upper genital tract infections such as amniotic fluid infection and chorioamnion infection associated with premature delivery.

Abortion, Spontaneous↗

PubMed1993

Use of the polymerase chain reaction for detection of Mycoplasma fermentans and Mycoplasma genitalium in the urogenital tract and amniotic fluid.

In an attempt to further define the natural history of Mycoplasma genitalium and Mycoplasma fermentans infections in humans, we used cultures and the polymerase chain reaction (PCR) to determine whether these organisms were present in the urethra and cervix of sexually active adults and in the amniotic fluid of women whose membranes were intact and collected at the time of cesarean delivery (to preclude cervical contamination). M. genitalium was detected by PCR but not by culture in 11% of patients with urethritis or cervicitis. It was not detected by either PCR or culture in the 232 amniotic fluid samples analyzed. In contrast, M. fermentans was not detected by either method in patients with urethritis or cervicitis but was detected by PCR in 4 of 232 amniotic fluid samples tested. These results indicate that in these four cases M. fermentans was transferred transplacentally. Histological evidence of chorioamnionitis was present in two of the four patients, a finding suggesting that M. fermentans may be a cause of chorioamnionitis. These results must be confirmed by other investigators, and further studies should be undertaken to determine the potential clinical significance of M. fermentans infection.

Adolescent↗

PubMed1998

Listeriosis during pregnancy.

Listeriosis is an uncommon infection that has a unique predilection for pregnant women and may result in pregnancy loss. Contaminated food is the usual source of infection, and increased federal surveillance of foodstuffs is the most effective strategy for prevention of disease. Although dramatic epidemics have received the most publicity, more cases of perinatal listeriosis are isolated. If Listeria chorioamnionitis is diagnosed preterm, in contrast to other types of chorioamnionitis, in utero therapy with high-dose penicillin or trimethoprim-sulfamethoxazole is possible, and preterm delivery may be avoided. The clinical characteristics of neonatal listeriosis are similar to neonatal Group B Streptococcus sepsis, with early and late onset forms of disease. The epidemiology, diagnosis, and management of Listeria infection in pregnancy are reviewed.

Abortion, Habitual↗

PubMed2006

Hepatitis C and pregnancy.

UNLABELLED: Hepatitis C is the most common chronic bloodborne infection in the United States. The diagnosis of vertical transmission is reliably established by a positive serum hepatitis C virus (HCV) RNA on 2 occasions 3 to 4 months apart after the infant is at least 2 months old and/or by the detection of anti-HCV antibodies after the infant is 18 months old. Vertical transmission in HCV RNA-negative pregnant women is approximately 1% to 3% versus approximately 4% to 6% in HCV RNA-positive women. From the standpoint of vertical transmission, no critical HCV RNA titer has been established. Coinfection with HIV has been shown to increase the risk of vertical transmission of HCV, but highly active antiretroviral therapy may decrease the risk significantly. In HIV-negative women, route of delivery does not influence vertical transmission. In HCV/HIV-coinfected women, decisions regarding mode of delivery should be based on HIV status. There is no association between vertical transmission of HCV and gestational age at delivery or the presence of chorioamnionitis. The use of a scalp electrode has been associated with vertical transmission and this practice is discouraged. Data are conflicting regarding duration of ruptured membranes and the risk of vertical transmission of hepatitis C. When the duration of membrane rupture exceeds 6 hours, the risk may be increased. There is no evidence demonstrating an increased risk of HCV transmission in HIV-negative women who breast feed. In HCV/HIV-coinfected women, breast feeding is discouraged in women who have consistent access to safe infant formula. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that vertical transmission of hepatitis C (HCV) does occur, state that coinfection with HIV increases the transmission rate, and summarize that there is no association between gestational age or presence of chorioamnionitis and no evidence that a cesarean delivery prevents transmission.

Breast Feeding↗

PubMed1987

The role of mycoplasmas, ureaplasmas and chlamydiae in the genital tract of women presenting in spontaneous early preterm labour.

The genital carriage of Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis was assessed in 72 women admitted to hospital in spontaneous preterm labour and in 26 women requiring preterm delivery for other reasons who formed a control group. Women in preterm labour significantly more often carried ureaplasmas, had large numbers of M. hominis and subsequently developed chorioamnionitis than women in the control group. M. hominis, in particular, occurred more frequently and in large numbers in women who had chorioamnionitis associated with ruptured membranes. Genital carriage of the various micro-organisms appeared not to be associated with fetal growth retardation, although subsequent isolation of ureaplasmas from infants was common. It is suggested that mid-second-trimester vaginal specimens should be cultured on a research basis to establish whether these various micro-organisms identify women at risk of labouring preterm.

Birth Weight↗

PubMed2005

Risk factors for the different types of chronic lung diseases of prematurity according to the preceding respiratory distress syndrome.

BACKGROUND: Recently, atypical chronic lung disease (CLD) of prematurity that develops in the absence of preceding respiratory distress syndrome (RDS) have been observed frequently. The specific risk factors for atypical CLD that are presumed to be different from those for classical CLD that develops following RDS were assessed. METHODS: Prospective cohort analysis was done from 115 very low-birthweight infants who were born in Seoul National University Hospital, Seoul, Korea, and survived more than 36 weeks postmenstrual age or 28 days of life. All subjects were classified into either a preceding RDS group (n = 35) or a non-RDS group (n = 80). Logistic regression analysis was done for the multivariate assessment of specific risk factors for CLD in both groups. RESULTS: The analysis showed that short gestational age (GA; relative risk [RR], 3.1 per 1 week decrement; 95% confidence intervals [CI], 2.7-3.4), of the male gender (RR, 9.8; CI, 0.9-112), and poor response to surfactant (RR, 14; CI, 1.2-156) were significant risk factors for CLD in the preceding RDS group. In the non-RDS group, chorioamnionitis was one of the significant risk factors for CLD (RR, 4.8; CI, 1.1-21) along with short GA and high mean airway pressure (MAP) during the first 3 days of life. CONCLUSION: Chorioamnionitis was a risk factor for atypical CLD in addition to short GA and high MAP during the early postnatal period, and poor response to surfactant was a risk factor for classical CLD in addition to short GA and being male. Therefore, CLD is considered to have type-specific risk factors.

Chorioamnionitis↗

PubMed1986

Spontaneous early preterm labour associated with abnormal genital bacterial colonization.

The association between infection and preterm labour was studied in 72 women in spontaneous preterm labour between 26 and 34 weeks gestation and in 26 control subjects having an elective caesarean section at the same gestational age. The genital microbial flora of each group was studied comprehensively and included mycoplasmas, chlamydiae, ureaplasmas and anaerobes. Subsequent neonatal infection and chorioamnionitis was also studied. Abnormal bacterial colonization, the presence of ureaplasmas, heavy growth of mycoplasmas and chorioamnionitis were all found significantly more often in the study group. This supports the premise that a significant proportion of idiopathic preterm labour is associated with infection and this may permit better prediction and prevention of preterm birth. The continued use of tocolytics should depend upon the identification of the presence or absence of infection. Infection appeared to be the result rather than the cause of ruptured membranes. A recommendation with respect to the classification of abnormal or normal bacterial colonization between 26 and 34 weeks is suggested on the basis of strict criteria.

Bacteria↗

PubMed1994

Chorionic villous haemorrhage is associated with retroplacental haemorrhage.

OBJECTIVE: To examine the frequency of occurrence of chorionic villous haemorrhage in placentas with retroplacental haemorrhage, and to discuss the pathogenesis of these conditions. DESIGN: A retrospective study using histological sections of formalin-fixed, paraffin-embedded placental tissue stained with haematoxylin and eosin. SETTING: Department of Histopathology, Rotunda Hospital, Dublin. SUBJECTS: Sixty cases of retroplacental haemorrhage, 34 cases of chorioamnionitis, and 24 histologically normal placentas. MAIN OUTCOME MEASUREMENT: Presence or absence of chorionic villous haemorrhage. RESULTS: Chorionic villous haemorrhage was present in 31 of 60 cases of retroplacental haemorrhage (51%), one of 34 cases of chorioamnionitis (2.9%) and in no normal placentas. CONCLUSIONS: It is postulated that chorionic villous haemorrhage reflects a disturbance of fetal vascular dynamics and precedes retroplacental haemorrhage. Such a disturbance could trigger the events leading to abruption.

Chorioamnionitis↗

PubMed1998

Are neonatal brain lesions due to intrauterine infection related to mode of delivery?

Studies of antenatal and intrapartum factors involved in the development of cerebral palsy have identified intrauterine infection and chorioamnionitis as high risk situations for white matter damage, especially periventricular leukomalacia. To characterise adverse or protective perinatal factors further, we undertook a multiple regression analysis of selected perinatal events in a population of 110 inborn premature neonates with documented chorioamnionitis. In the total population of 110 infants delivered at between 25 and 32 weeks, 101 (92%) survived the first week of life and two were subsequently excluded. Of the 99 remaining infants, 20 (20%) developed periventricular leukomalacia including 16 (80%) cystic lesions. Forty-five (45%) babies were born by lower segment caesarean section, and for 37 of these, this was carried out before labour. Fetal presentation at delivery was breech in 14 (26%) of those born vaginally and 23 (52%) of those born by lower segment caesarean section (OR 3 [95% CI 1.3-7]). Among predetermined perinatal risk factors for periventricular leukomalacia, logistic regression analysis showed that delivery by caesarean section was associated with a dramatic decrease in the incidence of periventricular leukomalacia (OR 0.15 [95% CI 0.04-0.57]). These preliminary results warrant confirmation and preferably a prospective study before considering caesarean section as a protective perinatal factor of periventricular leukomalacia.

Adult↗

PubMed1997

Survival and neonatal and neurodevelopmental outcome of 24-29 week gestation infants according to primary cause of preterm delivery.

A total of 189 infants of 24-29 weeks' gestation were born in a regional perinatal centre during a 2-year period. They were divided into groups according to the primary cause of preterm delivery: antepartum haemorrhage (n = 37, 20%), preeclampsia (n = 27), 14%), preterm premature rupture of membranes (n = 64, 34%), preterm labour (n = 27, 14%), chorioamnionitis (n = 16, 8%), other complications (n = 18, 10%). The perinatal mortality rate (PMR) was 286/1,000 of whom 44% were stillbirths. The 'other complication' group had the highest PMR due to a large number of intrauterine deaths, with no differences in neonatal mortality between the groups. Preeclampsia was associated with an increased risk of necrotizing enterocolitis and chorioamnionitis was associated with an increased risk of periventricular haemorrhage. Follow-up to at least 2 years was performed in 122 (97%) of survivors. Cerebral palsy occurred in 7%, while 18% had neurodevelopmental disability. No relationship was found between primary cause of preterm delivery and outcome. This information should be of value in counselling parents when preterm delivery is imminent.

Child Development↗

PubMed2005

Experimental genital mycoplasmosis causes increased levels of mRNA for IL-6 and TNF-alpha in the placenta.

PROBLEM: Previous studies with animal models have shown that injection of lipopolysaccharide (LPS) results in fetal loss and increases production of proinflammatory cytokines at the maternal-fetal interface. Most intrauterine infections, however, are associated with Ureaplasma urealyticum, a microorganism that lacks a cell wall and therefore does not contain LPS. Previous work in our laboratory with an animal model for genital infection with a similar organism, Mycoplasma pulmonis, revealed that widespread infection in maternal and fetal tissues can be experimentally induced with minimal manipulation of the animal. For this project, we tested the hypothesis that administration of the organism by a hematogenous route at gestational day (gd) 14 would result in increased tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production by the placenta. STUDY DESIGN: Timed-pregnant, Sprague-Dawley rats were anesthetized on gd 14 and 10(7) CFU of M. pulmonis strain X1048 or an equivalent volume of sterile medium was injected into the heart. Rats were necropsied on gd 18 or 21, and ex vivo production of TNF-alpha and IL-6 was evaluated from six randomly selected placentas from each litter. The remaining placentas were harvested and either snap-frozen or placed in formalin. Frozen placentas were processed for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of TNF-alpha and IL-6 mRNA. Formalin-fixed placentas were sectioned and stained with hematoxylin and eosin for lesion analysis. RESULTS: Concentrations of TNF-alpha but not IL-6 were significantly higher in conditioned medium from placentas harvested from infected dams at gd 21. Levels of mRNA for IL-6 and TNF-alpha, however, were increased by M. pulmonis at gd 18 and 21. Analysis of gd 21 placentas by light microscopy revealed that significant histological chorioamnionitis was present in infected animals with accumulations of neutrophils in the capsular decidua. CONCLUSION: These data indicate that experimental infection with M. pulmonis causes histological chorioamnionitis, elevated mRNA levels of TNF-alpha and IL-6 in placental tissues, and the secretion of TNF-alpha by the placenta during late gestation.

Animals↗

PubMed2006

Evidence for interleukin-10-mediated inhibition of cyclo- oxygenase-2 expression and prostaglandin production in preterm human placenta.

PROBLEM: Interleukin-10 (IL-10) is thought to be a key cytokine for the maintenance of pregnancy. Here we examined the expression profiles of IL-10 and cyclo-oxygenase-2 (COX-2), and the effect of IL-10 on COX-2 expression and prostaglandin release in the human placenta from preterm labor deliveries associated with chorioamnionitis. METHOD OF STUDY: Placental tissues from preterm labor and term labor deliveries were processed for ex vivo placental explant culture system. IL-10 expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. COX-2 expression was evaluated by IHC, Western blotting and reverse transcriptase-polymerase chain reaction. Prostaglandin E2 (PGE2) release was measured by ELISA. RESULTS: IL-10 was significantly reduced in chorioamnionitis-associated preterm labor as well as in term labor placental tissues compared with second trimester normal pregnancy samples obtained from elective terminations. Similar results were obtained with freshly isolated cytotrophoblasts from these deliveries. As expected, COX-2 mRNA was detected at significant levels in tissues from term and preterm labor deliveries compared with no labor term deliveries. Importantly, IL-10 inhibited COX-2 expression in cultured placental explants from preterm labor deliveries, but not from term labor samples. Inhibition of COX-2 expression coincided with reduced PGE2 release. CONCLUSION: These results demonstrate the importance of IL-10 in countering inflammation associated with preterm labor, and suggest that term and preterm parturition may, in part, represent different conditions.

Adolescent↗

PubMed1998

Placental candidiasis: report of four cases, one with villitis.

Four cases of placental candidiasis, an uncommon complication of rupture of the membranes, are presented. In addition to chorioamnionitis, in one of these cases villitis was also observed. Villitis is a rare occurrence in Candida infection and this represents only the second case in the literature. The involvement of villi may be suggestive of blood-borne infection. However, since neither the mother nor the foetus presented any signs of systemic dissemination, the authors suggest a hypothesis of contamination of the villi from foci of chorioamnionitis.

Adult↗

PubMed1993

Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns.

Ureaplasma urealyticum, a common commensal of the urogenital tract of sexually mature humans, is gaining recognition as an important opportunistic pathogen during pregnancy. While its etiologic significance in many aspects of adverse pregnancy remains controversial, recent evidence indicates that U. urealyticum in the absence of other organisms is a cause of chorioamnionitis. Furthermore, ureaplasmal infection of the chorioamnion is significantly associated with premature spontaneous labor and delivery. In at least some cases, it appears to be causal. Present evidence indicates that U. urealyticum is a cause of septicemia, meningitis, and pneumonia in newborn infants, particularly those born prematurely. There is strong but not definitive evidence that ureaplasmal infection of the lower respiratory tract can lead to development of chronic lung disease in very low-birth-weight infants. Although risk factors for colonization of the lower genitourinary tract have been identified, little information is available concerning risk factors for intrauterine infection and host immune responses to invasive infection. Recent establishment of animal models of respiratory and central nervous system diseases should provide an opportunity to evaluate risk factors, pathogenic mechanisms, and operative immune mechanisms. However, the most critical need is additional information concerning indications for diagnosis and treatment as well as efficacy of treatment.

Bacteremia↗

PubMed2004

Infection with Ureaplasma urealyticum: is there a specific clinical and radiological course in the preterm infant?

BACKGROUND: Despite having mild early respiratory disease, many preterm babies develop chronic lung disease (CLD). Intrauterine infection with Ureaplasma urealyticum has been associated with preterm labour and CLD. OBJECTIVE: To test the hypothesis that infection with U urealyticum results in a specific clinical and radiological picture in the first 10 days of life. METHODS: Retrospective study of 60 ventilated babies < 30 weeks gestation, who had tracheal secretions tested for U urealyticum. Placental histology was reviewed by a paediatric pathologist for signs of chorioamnionitis. Chest radiographs were independently reviewed by two paediatric radiologists according to previously agreed criteria. All reviewers were blinded to the infection status of the babies. RESULTS: Twenty five babies were U urealyticum positive. These were more likely to experience chorioamnionitis (p = 0.004), premature rupture of membranes (p = 0.01), and spontaneous vaginal delivery (p = 0.09). U urealyticum positive babies had fewer signs of respiratory distress syndrome on early chest radiographs (p = 0.038), and they could be weaned from their ventilation settings (fraction of inspired oxygen (FIO(2)) and mean airway pressure) more quickly in the first few days. Subsequently U urealyticum positive babies deteriorated clinically and radiologically. More often they required ventilation to be restarted (p = 0.051), a higher proportion being ventilated on day 10 (p = 0.027) with higher FIO(2) (p = 0.001) and mean airway pressure (p = 0.002). Their chest radiographs showed more emphysematous changes as early as day 5 (p = 0.045), with a pronounced difference by day 10 (p = 0.009). CONCLUSIONS: Preterm ventilated babies with U urealyticum in their tracheal secretions have a different clinical and radiological course, with less acute lung disease but early onset of CLD, compared with those with negative cultures.

Birth Weight↗