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Fetal Inflammatory Response (fetal + inflammatory_response)

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Medical Sciences	100%

Selected Abstracts

Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre-Labor Rupture of Membranes

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Daniel B. DiGiulio
Citation DiGiulio DB, Romero R, Kusanovic JP, Gómez R, Kim CJ, Seok K, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzún E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64: 38,57 Problem, The role played by microbial invasion of the amniotic cavity (MIAC) in preterm pre-labor rupture of membranes (pPROM) is inadequately characterized, in part because of reliance on cultivation-based methods. Method of study, Amniotic fluid from 204 subjects with pPROM was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad-range and group-specific polymerase chain reaction (PCR) assays targeted small subunit ribosomal DNA (rDNA), or other gene sequences, from bacteria, fungi, and archaea. Results were correlated with measurements of host inflammation, as well as pregnancy and perinatal outcomes. Results, The prevalence of MIAC was 34% (70/204) by culture, 45% (92/204) by PCR, and 50% (101/204) by both methods combined. The number of bacterial species revealed by PCR (44 species-level phylotypes) was greater than that by culture (14 species) and included as-yet uncultivated taxa. Some taxa detected by PCR have been previously associated with the gastrointestinal tract (e.g., Coprobacillus sp.), the mouth (e.g., Rothia dentocariosa), or the vagina in the setting of bacterial vaginosis (e.g., Atopobium vaginae). The relative risk for histologic chorioamnionitis was 2.1 for a positive PCR [95% confidence interval (CI), 1.4,3.0] and 2.0 for a positive culture (95% CI, 1.4,2.7). Bacterial rDNA abundance exhibited a dose relationship with gestational age at delivery (R2 = 0.26; P < 0.01). A positive PCR was associated with lower mean birthweight, and with higher rates of respiratory distress syndrome and necrotizing enterocolitis (P < 0.05 for each outcome). Conclusion, MIAC in pPROM is more common than previously recognized and is associated in some cases with uncultivated taxa, some of which are typically associated with the gastrointestinal tract. The detection of MIAC by molecular methods has clinical significance. [source]

Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2009
CS Buhimschi
Objective, To determine the relationship between presence of amniotic fluid (AF) biomarkers characteristic of inflammation (defensins 2 and 1 and calgranulins C and A) and fetal inflammatory status at birth. Design, Prospective observational cohort. Setting, Tertiary referral University hospital. Population, One hundred and thirty-two consecutive mothers (gestational age, median [interquartile range]: 29.6 [24.1,33.1] weeks) who had a clinically indicated amniocentesis to rule out infection and their newborns. Methods, Intra-amniotic inflammation was diagnosed by mass spectrometry surface-enhanced-laser-desorption-ionization time of flight (SELDI-TOF). The AF proteomic fingerprint (mass-restricted [MR] score) ranges from 0,4 (none to all biomarkers present). The intensity of intra-amniotic inflammation was graded based on the number of proteomic biomarkers: MR score 0: ,no' inflammation, MR score 1,2: ,minimal' inflammation and MR score 3,4: ,severe' inflammation. At birth, cord blood was obtained for all women. Severity of histological chorioamnionitis and early-onset neonatal sepsis (EONS) was based on established histological and haematological criteria. Interleukin-6 (IL-6) levels were measured by sensitive immunoassays. The cord blood-to-AF IL-6 ratio was used as an indicator of the differential inflammatory response in the fetal versus the AF compartment. Main outcome measures, To relate proteomic biomarkers of intra-amniotic infection to cord blood IL-6 and to use the latter as the primary marker of fetal inflammatory response. Results, Women with intra-amniotic inflammation delivered at an earlier gestational age (analysis of variance, P < 0.001) and had higher AF IL-6 levels (P < 0.001). At birth, neonates of women with severe intra-amniotic inflammation had higher cord blood IL-6 levels (P = 0.002) and a higher frequency of EONS (P = 0.002). EONS was characterised by significantly elevated cord blood IL-6 levels (P < 0.001). Of the 39 neonates delivered by mothers with minimal intra-amniotic inflammation, 15 (39%) neonates had umbilical cord blood IL-6 levels above the mean for the group and 2 neonates had confirmed sepsis. The severity of the neutrophilic infiltrate in the chorionic plate (P < 0.001), choriodecidua (P = 0.002), umbilical cord (P < 0.001) but not in the amnion (P > 0.05) was an independent predictor of the cord blood-to-AF IL-6 ratio. Relationships were maintained following correction for gestational age, birthweight, amniocentesis-to-delivery interval, caesarean delivery, status of the membranes, race, MR score and antibiotics and steroid exposure. Conclusions, We provide evidence that presence of proteomic biomarkers characteristic of inflammation in the AF is associated with an increased inflammatory status of the fetus at birth. Neonates mount an increased inflammatory status and have positive blood cultures even in the context of minimal intra-amniotic inflammation. [source]

Absence of pestivirus antigen in brains with white matter damage

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2006
Olaf Dammann
We previously suggested that antenatal pestivirus infection might play a role in the pathogenesis of perinatal brain white matter damage (WMD) in preterm infants. We have now examined 22 brains from stillborns and deceased newborns (both preterm and term) for the presence of bovine virus diarrhoea virus (BVDV) antigen. The brains of five females and five males with WMD (median gestational age 36.5wks), and nine female and three male controls (median gestational age 36.5wks) were used in the study. No BVDV antigen was detected in any of the 22 brains. We conclude that brain infection with BVDV is unlikely to play a role in WMD pathogenesis among preterm or term newborns. Further research is needed to test the hypothesis that intrauterine exposure to pestivirus antigen elicits a fetal inflammatory response which then contributes to WMD. [source]

Comparison of markers for fetal inflammatory response syndrome: Fetal blood interleukin-6 and neonatal urinary ,2 -microglobulin

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2009
Shigeru Nishimaki
Abstract Aim:, Chronic lung disease (CLD) is a major component in the morbidity of premature infants suffering from fetal inflammatory response (FIRS). The aim of the present study was to compare the value of measuring neonatal urinary ,2 -microglobulin (,2 -MG) levels with fetal blood interleukin (IL)-6 levels in premature infants at risk of developing CLD. Methods:, Premature infants (gestational age <30 weeks) without CLD (n = 19) and with CLD (n = 10) were enrolled. We measured IL-6 levels in umbilical cord blood and ,2 -MG levels in urine obtained within 48 h after birth. Results:, IL-6 and ,2 -MG levels were significantly higher in infants who developed CLD than in those who did not (median IL-6, 54.7 vs 7.6 pg/mL; P < 0.005; ,2 -MG 17.7 vs 9.3 × 104 µg/gCr; P < 0.05). The sensitivity and negative predictive value of ,2 -MG at the cut-off value at 10.0 × 104 µg/gCr (0.90 and 0.92) were comparable to IL-6 at 16 pg/mL (0.90 and 0.94). Conclusion:, We suggest that measuring urinary ,2 -MG in premature infants soon after birth can monitor FIRS and may provide information on the risk of subsequent CLD development that is as clinically important as information derived from umbilical cord blood IL-6. [source]

Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre-Labor Rupture of Membranes

Genetic susceptibility to viral exposure may increase the risk of cerebral palsy

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2009
Michael DJUKIC
Aim: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples. Results: At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50,0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05,1.83). For infants born 32,36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34,80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21,14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13,0.76). Conclusion: Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection. [source]

Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth

Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: Results of a multicenter, prospective, open-label clinical trial,

ARTHRITIS & RHEUMATISM, Issue 4 2010
Deborah M. Friedman
Objective The recurrence rate of anti-SSA/Ro,associated congenital heart block (CHB) is 17%. Sustained reversal of third-degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, intravenous immunoglobulin (IVIG) was evaluated as preventive therapy for CHB. Methods A multicenter, prospective, open-label study based on Simon's 2-stage optimal design was initiated. Enrollment criteria included the presence of anti-SSA/Ro antibodies in the mother, birth of a previous child with CHB/neonatal lupus rash, current treatment with ,20 mg/day of prednisone, and <12 weeks pregnant. IVIG (400 mg/kg) was given every 3 weeks from week 12 to week 24 of gestation. The primary outcome was the development of second-degree or third-degree CHB. Results Twenty mothers completed the IVIG protocol before the predetermined stopping rule of 3 cases of advanced CHB in the study was reached. CHB was detected at 19, 20, and 25 weeks; none of the cases occurred following the finding of an abnormal PR interval on fetal Doppler monitoring. One of these mothers had 2 previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal titers of antibody to SSA/Ro, SSB/La, or Ro 52 kd were detected over the course of therapy or at delivery. There were no safety issues. Conclusion This study establishes the safety of IVIG and the feasibility of recruiting pregnant women who have previously had a child with CHB. However, IVIG at low doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers. [source]