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PubMed1996

Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: a comparison with amniotic fluid white blood cell count.

OBJECTIVE: To compare the diagnostic and prognostic performance of maternal blood C-reactive protein, white blood cell count (WBC), and temperature with that of amniotic fluid (AF) WBC in preterm labor. METHODS: One hundred two women with preterm labor and intact membranes were studied. Maternal blood was collected to measure C-reactive protein concentration and WBC, and maternal temperature was also measured. Amniotic fluid obtained by amniocentesis was cultured and WBC determined. Receiver operating characteristic curve, logistic regression, and survival techniques were used for analysis. RESULTS: Patients with acute histologic chorioamnionitis had significantly higher median C-reactive protein concentration, WBC, temperature, and AF WBC than patients without this lesion (P < .05). Receiver operating characteristic curve and survival analysis demonstrated that an elevated C-reactive protein, WBC, or AF WBC was strongly associated with the likelihood of histologic chorioamnionitis, shorter interval to delivery, clinical chorioamnionitis, and neonatal morbidity (P < .05 for each). Of all the tests, AF WBC was the best independent predictor of a positive AF culture (odds ratio [OR] 16.8), interval to delivery (hazard ratio 5.7), clinical chorioamnionitis (OR 15.2), neonatal sepsis (OR 16.8), and significant neonatal complications (OR 7.4), after other confounding variables were adjusted (P < .05 for each). CONCLUSION: An elevated C-reactive protein, WBC, or AF WBC identified patients with intrauterine infection and adverse perinatal outcomes. Amniotic fluid WBC was a better independent predictor of these outcomes than C-reactive protein, WBC, or temperature.

Acute Disease↗

PubMed1994

Premature rupture of the membranes between 20 and 25 weeks' gestation: role of amniotic fluid volume in perinatal outcome.

OBJECTIVE: Our purpose was to prospectively study the relationship between amniotic fluid volume and perinatal outcome in pregnancies complicated by premature rupture of the membranes before fetal viability. STUDY DESIGN: The study population consisted of 178 singleton pregnancies with premature rupture of membranes between 20 and 25 weeks' gestation who were managed expectantly. Serial amniotic fluid volume measurements were made and their relationship to the neonatal survival rate, incidence of chorioamnionitis, and other perinatal outcomes was determined. RESULTS: Seventy-four patients were delivered before 25 weeks of gestation and only five infants (6.7%) survived. In contrast, 104 patients were delivered between 26 and 34 weeks, and 93 infants (89.4%) survived (p < 0.001). There were 107 pregnancies with adequate amniotic fluid volume after premature rupture of membranes on admission. Of these 16 patients were delivered before 25 weeks of gestation, and the remaining 91 patients were able to carry their pregnancies beyond 25 weeks of gestation. This was significantly different from 71 patients who demonstrated inadequate amniotic fluid volume on admission to the hospital, of whom 58 were delivered before 25 weeks and only 13 continued the pregnancy beyond 25 weeks (p < 0.05). At gestations between 26 and 34 weeks chorioamnionitis occurred in 22 of 91 (24.1%) patients with adequate amniotic fluid volume versus nine of 13 patients (69.2%) with inadequate amniotic fluid volume (p < 0.001). The incidence of perinatal death for pregnancies between 26 and 34 weeks with adequate versus inadequate amniotic fluid volume was 2.1% and 69.2%, respectively (p > 0.001). Overall survival rate and incidence of chorioamnionitis were 55% and 26.4%, respectively. CONCLUSIONS: Delivery of pregnancies between 20 and 25 weeks of gestation with premature rupture of membranes carries very high risk of neonatal mortality. The results of this study suggest that women with adequate amniotic fluid volume have a better chance to continue their pregnancy beyond 25 weeks of gestation and have a higher neonatal survival rate than those with inadequate amniotic fluid volume. The incidence of perinatal death and chorioamnionitis in patients who carry a pregnancy beyond 25 weeks is correlated with inadequate amniotic fluid volume.

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↗

PubMed2002

Is meconium passage a risk factor for maternal infection in term pregnancies?

OBJECTIVE: To study the association between meconium and maternal infection. METHODS: This was a retrospective cohort study of 678 pregnant women. All term deliveries during a 31-month period with meconium passage were included. Each meconium delivery was matched with a consecutive delivery without meconium at the same gestational age. RESULTS: The overall infection rate was 16%, with 13% of the infections directly related to the pregnancy, labor, and delivery. The endometritis rate was 5%, with 7.1% and 3% in the meconium and no-meconium group, respectively. The chorioamnionitis rate was 8.3%, with 9.5% in the meconium and 7.1% in the no-meconium group. Factors found to be associated with overall obstetric infections had the following odds ratios (ORs) and 95% confidence intervals (CIs): meconium (OR 1.8, 95% CI 1.1, 2.8), internal monitoring (OR 3.4, 95% CI 1.9, 5.9), amnioinfusion (OR 2.0, 95% CI 1.3, 3.3), number of vaginal exams (OR 4.5, 95% CI 2.8, 7.1), length of labor (OR 2.8, 95% CI 1.8, 4.4), and cesarean (OR 3.1, 95% CI 1.9, 5.1). Logistic regression analyses revealed the following ORs and 95% CIs: 1) for endometritis-cesarean (OR 4.2, 95% CI 1.9, 8.9), internal monitoring (OR 2.5, 95% CI 1.1, 5.9), and meconium (OR 2.5, 95% CI 1.1, 5.5), and 2) for chorioamnionitis-length of labor greater than 10 hours (OR 2.7, 95% CI 1.4, 5.6), number of vaginal exams greater than seven (OR 3.4, 95% CI 1.7, 6.6), and use of internal monitors (OR 2.5, 95% CI 1.2, 5.3). CONCLUSION: Meconium passage increases the risk of postpartum endometritis but not chorioamnionitis. Length of labor, internal monitoring, and number of vaginal exams are risk factors for chorioamnionitis.

Adult↗

PubMed1998

Choriodecidual inflammation: a potentially preventable cause of perinatal HIV-1 transmission?

The obstetric risk factors for perinatal transmission of HIV-1 include preterm birth, prolonged rupture of the chorioamniotic membranes, and clinical and histological bacterial chorioamnionitis. A chronic chorioamnionitis precedes many cases of preterm labour and spontaneous rupture of membranes, whereas an acute chorioamnionitis is more common after rupture of the membranes at term. Amniotic fluid cytokines are raised in the presence of term and preterm intrauterine bacterial infections, and various cytokines seem able to attract HIV-1-infected leucocytes into the amniotic cavity and to increase replication of HIV-1. We postulate that the association of preterm birth and prolonged rupture of membranes with perinatal transmission of HIV-1 may result from an associated chronic or acute bacterial chorioamnionitis marked by the migration of HIV-1-infected maternal leucocytes into the amniotic cavity. Antibiotic treatment could prevent this sequence of events.

Cesarean Section↗

PubMed2005

Cervical incompetence and the role of emergency cerclage.

OBJECTIVE: To evaluate the role of emergency cerclage for women who present with a dilated external cervical os and bulging or "hour-glassing" membranes. We examined overall experiences at Kingston General Hospital (KGH) from 2000 to 2004 and conducted a literature review for the period January 1, 1995, to December 31, 2004. METHODS: A search for cerclages placed by operators in Kingston revealed 12 pregnancies in the period between 2000 and 2004. We reviewed the charts for these women and for their infants. We conducted a literature review, using the terms "cerclage," "cervical," "emergent or emergency cerclage," "rescue cerclage," and "incompetent cervix," using an OVID interface to access MEDLINE records. We excluded articles in which the diagnosis of cervical incompetence was made using ultrasound, because its predictive value has not been shown in randomized trials. The most recent review of this type was carried out in 1995; since then, an additional 24 articles have been published that met our inclusion and exclusion criteria. RESULTS: The average time between cerclage placement and delivery at KGH was 7 weeks, which allowed for 10 of 13 infants (one twin pregnancy) to be born at 28 weeks or later. Three infants were born weighing under 1 kg; the 10 remaining infants weighed over 1 kg. Histological data are available for 12 placentas of the 13 infants delivered; 7 infants had a histological diagnosis of chorioamnionitis; none of the blood cultures from any of the infants post-delivery revealed septicemia. The literature review identified 638 women. Where reported, the average prolongation of the pregnancy was 7 weeks plus 1 day. This allowed for 60% of infants (range 26% to 80%) to be born after 28 weeks, with an average neonatal survival of over 70% (range 47.2% to 96%). Preterm premature rupture of membranes complicated an average of 29% of pregnancies (range 1% to 58%), and chorioamnionitis was reported in 5% to 80% of pregnancies. CONCLUSIONS: The KGH data collected and the data available in the literature suggest that emergency cerclage, under ideal circumstances, can significantly prolong pregnancy and increase the chance of viable pregnancy outcome. However, in counselling women about the potential therapeutic benefit of emergency cerclage, the increased risk of chorioamnionitis and its associated risk of fetal inflammatory brain injury, as well as the risk of extending a pregnancy from pre-viability to severe prematurity, should be discussed. A longer-term follow-up than has been carried out here is required for better elucidation of the effect of chorioamnionitis on those infants in childhood and beyond.

Cerclage, Cervical↗

PubMedDate not supplied

Group B streptococcus: to culture or not to culture?

OBJECTIVE: To determine if universal Group B Streptococcus (GBS) culturing and antibiotic prophylaxis of obstetric patients decreased the incidence of neonatal early-onset GBS sepsis and mortality and maternal chorioamnionitis. STUDY DESIGN: A time series observational study was conducted to compare the cohort of all obstetric patients delivering at the University of Chicago neonatal center from January 1989 through December 1993, before a GBS surveillance policy existed, with the cohort delivering January 1994 through December 1996, after initiation of a GBS policy. Included in the policy were universal GBS cultures at 28 weeks' gestation, antibiotic prophylaxis at the time of labor for all those with positive cultures and for all with risk factors of preterm delivery, preterm premature rupture of membranes, prolonged rupture of membranes greater than 18 hours, and a previous child affected by GBS or maternal fever in labor. Predictor variables were GBS culturing and antibiotic usage; outcome variables were incidence of GBS sepsis and mortality in the neonates and maternal chorioamnionitis. chi-squared and Fisher exact analyses were used with p < 0.05 being significant. RESULTS: Before the GBS policy, there were 16,272 deliveries with a 2.24/1000 deliveries rate of early-onset GBS sepsis (n = 35); after initiating the GBS policy, 9130 deliveries occurred with an early-onset GBS sepsis rate of 2.29/1000 (n = 20). Early-onset GBS sepsis case fatality rates before and after initiation of the policy were 14.3% and 0%, respectively (p = 0.09). Antibiotic use almost doubled (relative risk = 1.84; confidence interval, 1.74 to 1.93, p < 0.001) over the two time periods, and the relative risk of chorioamnionitis decreased to 0.95 (confidence interval, 0.73 to 0.99, p = 0.04). CONCLUSION: Despite universal GBS culturing and very liberal use of antibiotics in labor, we were unable to effect a statistically significant change in the rate of early-onset GBS sepsis or mortality, and there was only a slightly decreased chorioamnionitis rate.

Anti-Bacterial Agents↗

PubMed2002

Ultrasonographic evaluation of cervical length in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVE: To evaluate the usefulness of transvaginal ultrasonography in the determination of the risk of preterm delivery and chorioamnionitis in pregnancies affected by preterm premature rupture of membranes preterm premature rupture of membranes. DESIGN: One hundred and one singleton pregnancies with preterm premature rupture of membranes were included in this prospective study over a 3-year period. Patients underwent cervical length measurement by transvaginal ultrasonography at admission and thereafter, in the absence of chorioamnionitis, were managed expectantly. RESULTS: The median time interval between admission and delivery (latency period) was 48 h. A cervical length of less than 20 mm was associated with a significant risk of early delivery (mean latency period was 59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation between cervical length and occurrence of chorioamnionitis or neonatal sepsis. CONCLUSIONS: These data suggest that the use of transvaginal ultrasonography for cervical length measurement during preterm premature rupture of membranes may predict an early delivery but cannot anticipate the risk of chorioamnionitis or neonatal sepsis.

Adult↗

PubMed2001

Reactive oxygen species and preterm premature rupture of membranes-a review.

Preterm premature rupture of membranes (PPROM) results initially from damage to collagen in the chorioamnion leading to a tear in the membrane. Tissue-damaging molecules called reactive oxygen species (ROS) are capable of damaging collagen in the chorioamnion that could lead to PPROM. This hypothesis is supported by epidemiological studies linking clinical conditions known to produce ROS or reduce antioxidant protection to PPROM, by in-vitro studies in which membrane segments exposed to ROS exhibited tissue alterations consistent with PPROM, and by clinical studies showing that chorioamnion and amniotic fluid samples obtained from PPROM patients exhibit excessive collagen degradation. The role of antioxidants to protect the chorioamnion from ROS damage has been demonstrated in one in-vitro study. A prospective, randomized blinded trial of antioxidant therapy during pregnancy is needed to evaluate this approach for the prevention of PPROM.

Adult↗

PubMed1990

Leukocyte esterase activity in amniotic fluid: normal values during pregnancy.

Chorioamnionitis during pregnancy is a common diagnostic dilemma for the obstetrician. Fast and accurate diagnosis poses the most significant problem. Since leukocytes are known to be released in response to infections, examination of amniotic fluid for their presence is an important part of the evaluation for chorioamnionitis. These neutrophils contain several esterases that are not present in serum, urine, or vaginal secretions. The esterases are not influenced by bacteria or by commonly used drugs. We have previously described the reliability of leukocyte esterase (LE) activity for the detection of chorioamnionitis in term pregnancies uncomplicated by other diseases. A prospective study was performed to assess the presence or absence of LE activity to establish normal values in amniotic fluid at various gestational ages prior to term before its use as a possible predictor for chorioamnionitis. Sterile amniotic fluid specimens were obtained from 13 patients undergoing second trimester genetic amniocentesis (with gestational ages varying from 15 to 19 weeks) and from 11 patients with a wide variety of medical problems, undergoing amniocentesis for Rh sensitization or lung maturation studies (with gestational ages ranging from 25 to 27 weeks). All patients with ruptured membranes or preterm labor were excluded. Each amniotic fluid sample was divided into two parts, one of which was transported to the laboratory for aerobic and anaerobic cultures and the other used for LE activity detection as measured by dipstick. The LE results were retrospectively compared with the results of the cultures. LE activity was always found to be negative when the culture results were negative. negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗

PubMed2000

Elevations of group II phospholipase A2 concentrations in serum and amniotic fluid in association with preterm labor.

OBJECTIVE: The purpose of this study was to determine whether the elevation of secretory group II phospholipase A(2) concentration in the serum and amniotic fluid in preterm labor is associated with intrauterine inflammation. STUDY DESIGN: Serum and amniotic fluid were collected from women with preterm delivery (<37 weeks' gestation; n = 38) and term delivery (n = 20). Phospholipase activity was measured with a highly sensitive system that was based on reverse-phase high-performance liquid chromatographic separation of 9-anthracenylmethyl derivatives of fatty acids released by phospholipase A(2). The concentrations of immunoreactive isozymes (group I or II) of secretory phospholipase A(2) were assayed with a radioimmunoassay kit with a monoclonal antibody against human pancreatic phospholipase A(2) and splenic IIA phospholipase A(2). Localization of immunoreactive group II phospholipase A(2) in the amniotic membrane was determined by immunostaining visualized with the Vectastain ABC (Vector Laboratories, Inc, Burlingame, Calif) method. RESULTS: Enzymatic activities of phospholipase A(2) in the serum and amniotic fluid specimens obtained from patients in preterm labor with chorioamnionitis were significantly higher than those in specimens from patients in term labor. Significant elevations of phospholipase A(2) activities were observed in patients with preterm labor without histologically evident chorioamnionitis. The activity of phospholipase A(2) was clearly correlated with the concentration of the immunoreactive group II phospholipase A(2). Group II phospholipase A(2) was localized in amniotic cells obtained from patients with a pathologically determined diagnosis of chorioamnionitis. The predictive value for chorioamnionitis of the group II phospholipase A(2) concentration was relatively higher than the predictive values of the concentrations of C-reactive protein and interleukins 6 and 8. CONCLUSION: Significant elevations of group II phospholipase A(2) concentrations were detected in the serum and amniotic fluid of women with preterm labor. Group II phospholipase A(2) concentration may be a useful indicator for preterm labor, and phospholipid metabolism is certainly activated both in preterm labor and in apparent inflammatory diseases.

Amniotic Fluid↗

PubMed2003

Decreased cervical proinflammatory cytokines permit subsequent upper genital tract infection during pregnancy.

OBJECTIVE: The purpose of this study was to test the hypothesis that suppressed immune function in the lower genital tract, as represented by decreased concentrations of cervical proinflammatory cytokines early in pregnancy, is a risk factor for clinical chorioamnionitis. STUDY DESIGN: Interleukin-1beta, interleukin-6, and interleukin-8 were measured by enzyme-linked immunosorbent assay in cervical fluid from a cohort of 403 women at 8 to 20 weeks of gestation. RESULTS: Of the 88 women with one low cytokine concentration, 8.0% of the women had clinical chorioamnionitis compared with 4.4% among the 228 women with no low cytokines (adjusted odds ratio, 2.0; 95% CI, 0.7-5.8). Clinical chorioamnionitis occurred in 15 of the 87 women (17.2%), with two or three depressed cytokine concentrations compared with women with no low cytokines (adjusted odds ratio, 5.1; 95% CI, 2.0-13.0). CONCLUSION: Genital tract immune hyporesponsiveness, as represented by low cervical concentrations of multiple cytokines, permits subsequent clinical chorioamnionitis.

Adolescent↗

PubMed2003

The relationship between placental histopathology findings and perinatal outcome in preterm infants.

OBJECTIVE: To determine the correlation between placental histopathology findings and perinatal outcome in preterm infants. METHODS: Placental histopathology in 774 neonates delivered at 24-32 weeks between 1992 and 2000 was classified as follows: 254 (33%) had histological chorioamnionitis, 263 (34%) had coagulation-related lesions, 228 (30%) had vasculopathy. Perinatal outcome was compared between cases positive and negative for each histopathological classification. RESULTS: Histological chorioamnionitis occurred in 46% of cases with premature rupture of membranes and 45% with preterm labor. Positivity versus negativity for histological chorioamnionitis was associated with earlier presentation (191 vs. 205 days, p = 0.0001) and delivery (199 days vs. 209 days, p = 0.0001), increased risk of intraventricular hemorrhage (71% vs. 23%, p = 0.001, odds ratio (OR) 2.2), bronchopulmonary dysplasia (26% vs. 15%, p = 0.0001, OR 2), retinopathy (36% vs. 24%, p = 0.001, OR 1.8), neonatal sepsis (28% vs. 13%, p = 0.0001, OR 2.5) and neonatal death (12% vs. 7%, p = 0.012, OR 2). Vasculopathy versus no vasculopathy was associated with decreased birth weight (1245 g vs. 1341 g, p = 0.011), decreased Apgar score at 5 min (20% vs. 13%, p = 0.011, OR 1.7) and necrotizing enterocolitis (6% vs. 2%, p = 0.001, OR 4). Cases positive for coagulation-related lesions correlated only with necrotizing enterocolitis (5% vs. 2%, p = 0.02, OR 2.6). CONCLUSIONS: The presence of histological chorioamnionitis significantly increases the risk of earlier delivery and neonatal mortality. Vascular and coagulation placental findings increase the risk of necrotizing enterocolitis.

Apgar Score↗

PubMed1994

Histology and Ureaplasma urealyticum culture in 63 cases of first trimester abortion.

The association between chorioamnionitis caused by Ureaplasma urealyticum and preterm delivery has been well documented. In contrast, a pathogenic role for Ureaplasma has been postulated in early spontaneous abortions, but definitive evidence for this association has been lacking. In 42 early spontaneous abortions and 21 elective abortions (both first trimester), the chorion was cultured for Ureaplasma. Each case was evaluated histologically for four features of inflammation and one feature of degeneration. For comparison, 32 selected placentas from third trimester preterm deliveries (11 with positive Ureaplasma cultures) were examined histologically for umbilical vasculitis and acute chorioamnionitis. In abortion specimens, Ureaplasma cultures were positive in 11 of 42 early spontaneous abortions (26%) versus 0 of 21 elective abortions (EABs). None of the five histologic features correlated with positive Ureaplasma cultures in early spontaneous abortions. In contrast, in preterm placentas, umbilical vasculitis, and acute chorioamnionitis correlated strongly with positive Ureaplasma cultures. The authors conclude that in premature delivery, U urealyticum chorionic culture positivity is associated with histologic chorioamnionitis; and in abortions, Ureaplasma chorionic culture positivity correlates with early spontaneous abortions (vs elective abortions), but not with histologic inflammation. This suggests that mechanisms of Ureaplasma pathogenesis other than acute inflammation should be considered in future studies of early spontaneous abortions.

Abortion, Spontaneous↗

PubMed1993

Ureaplasma urealyticum and premature birth.

Evidence related to the association of Ureaplasma urealyticum with premature birth is reviewed. U. urealyticum is a common inhabitant in the vagina of pregnant women. It is recovered from the vaginas of approximately 70% of pregnant women. The presence of U. urealyticum in the vagina is not associated with premature birth. Therapy to eradicate U. urealyticum from the vagina during pregnancy does not reduce the incidence of premature birth. Recovery of U. urealyticum from the amniotic fluid has not been associated with prematurity. However, in three of six reports, the recovery of U. urealyticum from the chorioamnion has been associated with prematurity, and U. urealyticum is rather consistently associated with histological chorioamnionitis. This review suggests that U. urealyticum in the lower genital tract is not associated with premature birth but that its presence in the chorioamnion is weakly associated with prematurity and strongly associated with histological chorioamnionitis.

Amniotic Fluid↗

PubMed2002

Placental inflammation and perinatal transmission of HIV-1.

The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported. Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya. Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks. The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

Chorioamnionitis↗

PubMed2004

Lipopolysaccharide increases alveolar type II cell number in fetal mouse lungs through Toll-like receptor 4 and NF-kappaB.

Chorioamnionitis is a major cause of preterm delivery. Infants exposed to inflammation in utero and then born preterm may have improved lung function in the immediate postnatal period. We developed a mouse model of chorioamnionitis to study the inflammatory signaling mechanisms that might influence fetal lung maturation. With this in vivo model, we found that Escherichia coli lipopolysaccharide (LPS) increased the number of alveolar type II cells in the fetal mouse lung. LPS also increased type II cell number in cultured fetal lung explants, suggesting that LPS could directly signal the fetal lung in the absence of maternal influences. Using immunostaining, we localized cells within the fetal mouse lung expressing the LPS receptor molecule Toll-like receptor 4 (TLR4). Similar to the signaling pathways in inflammatory cells, LPS activated NF-kappaB in fetal lung explants. Activation of the TLR4/NF-kappaB pathway appeared to be required, as LPS did not increase the number of type II cells in C.C3H-Tlr4(Lps-d) mice, a congenic strain containing a loss of function mutation in tlr4. In addition, the sesquiterpene lactone parthenolide inhibited NF-kappaB activation following LPS exposure and blocked the LPS-induced increase in type II cells. On the basis of these data from our mouse model of chorioamnionitis, it appears that LPS specifically activated the TLR4/NF-kappaB pathway, leading to increased type II cell maturation. These data implicate an important signaling mechanism in chorioamnionitis and suggest the TLR4/NF-kappaB pathway can influence lung development.

Animals↗

PubMed2001

Dose and time response after intraamniotic endotoxin in preterm lambs.

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.

Amniotic Fluid↗