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PubMed2001

New insights into the pathogenesis of pulmonary inflammation in preterm infants.

Chronic lung disease (CLD) and bronchopulmonary dysplasia are associated with a significant inflammatory response of the airways and the interstitium of the lungs. Besides inflammatory cells, various cytokines, lipid mediators, proteolytic enzymes and toxic oxygen radicals may play an essential role in the pathogenesis of this disease. Intrauterine exposure to chorioamnionitis or proinflammatory cytokines has been shown to induce a pulmonary and systemic inflammatory response in the fetus. In this subgroup, antenatal infection may prime the lung such that minimally injurious postnatal events provoke an excessive inflammatory response in the airways and the pulmonary tissue. Inflammation and lung injury most certainly affect normal alveolization and pulmonary vascular development in preterm infants with CLD.

Bronchopulmonary Dysplasia↗
PubMedDate not supplied

Effects of urinary trypsin inhibitor in patients at risk for premature labor with a bulging fetal membrane.

OBJECTIVE: To investigate the effect of urinary trypsin inhibitor (UTI) in patients at risk for premature labor with bulging membrane. METHODS: Patients who had developed a bulging membrane from 22 to 27 weeks and 6 days of gestation were studied. These cases were divided into two types based on the severity: those with a moderately developed bulging membrane like a 'dome' (dome type), and those with a membrane prolapsed into the vagina, resulting in an 'hourglass' shape (hourglass type). We compared the outcomes of treatment with or without UTI (UTI group versus non-UTI group) in each type. Gestational age at delivery, birth weight, prolongation time from admission to delivery, and neonatal mortality rate were examined in each group. RESULTS: A total of 43 patients with a bulging membrane were analyzed. In 21 patients with the dome type, gestational age at delivery (the UTI group versus the non-UTI group; 30.4 +/- 5.0 versus 26.4 +/- 1.9 weeks, p < 0.05), birth weight (1,436.8 +/- 708.3 versus 882.8 +/- 261.6 g, p < 0.05) and neonatal mortality rate (0/13 versus 3/8, p < 0.05) were all significantly improved by the use of UTI. On the other hand, in 22 patients with the hourglass type, there was no significant difference between the UTI group and the non-UTI group. The overall prevalence of histological chorioamnionitis was 60%. CONCLUSION: These results suggest that UTI therapy is very effective in patients at risk for premature labor with a moderately developed bulging membrane during the second trimester.

Adult↗
PubMedDate not supplied

Effect of pathological perinatal conditions on the maternofetal transfer of mononuclear cells.

OBJECTIVE: It is known that mononuclear cells can cross the placenta in both directions: from mother to fetus and the other way. In addition, it has been shown that perinatal pathological conditions can affect the fetomaternal cell transfer. This study has focused on the question whether perinatal conditions will also support the transfer of maternal cells in the fetus. METHODS: Minisatellite polymerase chain reaction (PCR) with a sensitivity of 1:100 was used to examine blood samples of 36 mother-child pairs for transplacental mononuclear cell transfer (group 1). Furthermore, 28 blood samples of mother-child pairs were examined by allele-specific PCR (sensitivity 1:1,000) for maternofetal mononuclear cell transfer; only 9 of these mother-child pairs were informative (group 2). RESULTS: Three cases of maternofetal and 2 additional cases of fetomaternal mononuclear cell transfer could be documented in group 1; 2 of the 9 informative samples in group 2 showed a maternofetal mononuclear cell transfer. In conclusion, 9 of 40 cases lacking maternofetal cell transfer and 4 of 5 cases with maternofetal cell transfer were high-risk deliveries (p < 0.01). CONCLUSION: The current study shows that certain ante-partum conditions like placental insufficiency or chorioamnionitis increase significantly the chance that maternal cells enter the fetus.

Alleles↗
PubMedDate not supplied

Sepsis due to Clostridium perfringens after pregnancy termination with feticide by cordocentesis: a case report.

We report a case of sepsis due to Clostridium perfringens after termination of pregnancy at 22 weeks with feticide by cordocentesis. Three weeks earlier, the 41-year-old patient had undergone an amniocentesis and a full trisomy 13 karyotype had been discovered. Feticide was performed by injection of thiopental and potassium chloride after percutaneous umbilical foetal blood sampling through the same needle. The patient delivered vaginally with signs of chorioamnionitis and septicaemia. She recovered under broad-spectrum antibiotherapy. C. perfringens was present in maternal blood cultures, placental smears and foetal organs. We discuss the possible mechanisms of infection by C. perfringens, including inoculation of intestinal germs.

Abortion, Induced↗
PubMed2004

[Prognosis of preterm infants with a birth weight <1,501 g].

The prognosis of very low birth weight infants (birth weight <1,501 g) is correlated with gestational age. Mortality is between 10 and 16%, showing high numbers in infants < or = 26 weeks of gestation. Looking at the low-term outcome, cerebral palsy is the most prevalent major disability with an incidence of 8%. Similar to mortality, the incidence of cerebral palsy is inversely proportional to gestational age. A clinically verified chorioamnionitis increases the risk of developing cerebral palsy by a factor of up to 4.

Bronchopulmonary Dysplasia↗
PubMed2005

Effect of bacterial vaginosis on premature rupture of membranes and related complications in pregnant women with a gestational age of 37-42 weeks.

BACKGROUND: The most serious outcome of term, premature rupture of membrane and chorioamnionitis is often associated with adverse maternal and infant outcomes related to infection. This study was undertaken to determine the prevalence of bacterial vaginosis (BV) at 37-42 gestational weeks and its relationship to premature rupture of membranes. METHOD: During an analytical descriptive prospective study, 425 pregnant women with a gestational age of 37-42 weeks were studied for prevalence of BV. Then, 304 women on the basis of having BV or not were followed up until 48 h after delivery for premature rupture of membranes. RESULT: The rate of BV in this population was 30.5%. No significant association was found between BV and premature rupture of membranes (odds ratio 1.6, 95% CI 0.9-2.8). CONCLUSION: BV is a common vaginitis in term pregnancy, but we could not find any relationship between BV and premature rupture of membranes at term.

Adult↗
PubMed2006

Intrauterine inflammation and the onset of peri-intraventricular hemorrhage in premature infants.

BACKGROUND: Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants. METHODS: A prospective study included 125 infants with gestational age 23-29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late. RESULTS: Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH. CONCLUSIONS: These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.

Cerebral Hemorrhage↗
PubMed2006

Antibiotic treatment of intra-amniotic infection with Ureaplasma urealyticum. A case report and literature review.

BACKGROUND: Ureaplasma urealyticum is the most common pathogen cultured from the amniotic cavity of women with preterm labor and intact membranes. However, experience with antibiotic eradication of the pathogen in this setting is limited. CASE: We report a case of U. urealyticum isolation from the amniotic cavity of a woman with preterm labor at 27 weeks gestation. The patient was treated with erythromycin base for 1 week, followed by fluoroquinolones and clindamycin for 10 days. A healthy neonate was delivered after spontaneous labor began at 33 weeks. The cultures obtained from the placenta and membranes were sterile, but the histopathology of the placenta revealed acute chorioamnionitis with acute funisitis. CONCLUSION: We suggest that intra-amniotic colonization with Mycoplasma spp. remote from term may be managed expectantly, and that therapy with fluoroquinolones and/or clindamycin may be an appropriate choice.

Acute Disease↗
PubMed1991

Perinatal hematological profile of newborn infants with candida antenatal infections.

We serially studied hematological profiles of 8 newborns with proven antenatal candida chorioamnionitis and funisitis. Candida albicans was cultured from various sources in the infants; blood and CSF cultures were all negative. Seven of the 8 were premature; 5 were sick. We statistically compared hematological data of the 'well' and 'sick' babies. The latter showed neutrophilia (mean 52,381 vs. 11,326/microliters, p less than 0.01) accompanied by significant elevation of nonsegmented granulocytes (NSG) and a NSG/neutrophil ratio greater than 0.3. Significant monocytosis (mean 7,836 vs. 2,869/microliters, p less than 0.01) and eosinophilia (mean 4,723 vs. 782/microliters, p less than 0.05) were also noted. Remarkable toxic granulations, vacuolization, and Döhle bodies were found in the neutrophils of the 'sick' newborns. Hematological profiles correlated with the infants' clinical condition.

Blood Cell Count↗
PubMed1997

[Amnionic infection syndrome by retro-amniotic uterine abscess: false-negative bacteriological diagnostic amniocentesis].

UNLABELLED: In general intra-amniotic infection causes severe fetal compromise. Prematurity resulting from preterm labor, premature rupture of membranes, maternal fever, maternal or fetal septicemia and fetal tachycardia is the major problem of this clinical syndrome. Therefore early detection of chorioamnionitis gains high prospective value. Gram's staining method from amniotic fluid provides a quick and reliable diagnostic tool (sensitivity 63.8%, specificity 97.7%). A localized extra-amniotic abscess demonstrates the special case of a false negative amniocentesis performed for bacteriological reasons. CONCLUSION: In suspected amniotic infection the obstetrical management has always to take into account all different parameters--clinical symptoms, chemistry and microbiological analysis. Nevertheless Gram's stain is a reliable and quick method to verify amniotic infection syndrome.

Abdominal Abscess↗
PubMed1995

Low birth weight and genital infections. An incident case-referent study.

In an attempt to elucidate the potential association between genital infections and low birth weight (LBW) births, 51 women with LBW neonates were identified and compared to 51 women with normal birthweight (NBW) neonates. Both groups were matched according to age and parity. All women were subjected to interviews regarding socioeconomic background and obstetric history. The were examined clinical and tested regarding serum haemoglobin, malaria parasitaemia, syphilis and HIV serology. Cultures were taken from the vagina, endocervix, amniotic fluid and from various sites of newborn, including the conjunctivae and the stomach and from the interior of the placenta. Whilst socioeconomic background factors did not differ among cases and referents, previous neonatal death did. Significant differences were also found in mid-upper-arm circumference (OR 3.08) and body mass index (OR 6.00). The prevalence of alleged risk factors according to the antenatal card was similar among cases and referents. Birthweight < 2,000 g was significantly more often associated with chorioamnionitis than birthweight between 2,000 and 2,499 g (OR 5.46). Bacteriological findings did not show significant differences in cases and referents. Haemoglobin values and prevalence of malaria parasitaemia were similar as was the neonatal mortality. It is concluded that LBW births is difficult to predict by use of alleged risk factors in existing antenatal cards.

Adolescent↗
PubMed2003

Increased IP-10 and MIG expression after intra-amniotic endotoxin in preterm lamb lung.

Subtraction hybridization was performed to explore changes in gene expression in the fetal lung after 20 mg of intra-amniotic (IA) endotoxin. Interferon-gamma-inducible 10-kd protein (IP-10) and monokine induced by interferon-gamma (MIG) constituted 20% of 102 endotoxin-induced clones identified in the preterm lamb lung. IP-10 (CXCL10) and MIG (CXCL9) are T-cell chemoattractants that have angiostatic properties. Both IP-10 and MIG mRNA were induced 30- to 40-fold in the fetal lung at 1 to 2 days after IA endotoxin. Intense IP-10 mRNA expression was detected by in situ hybridization in the bronchiolar and peribronchiolar areas and the vascular endothelium after IA endotoxin at all time points tested. MIG mRNA expression was detected initially focally in infiltrating neutrophils (15 hours after IA endotoxin) and later in the bronchiolar and peribronchiolar areas and vascular endothelium (1 day after IA endotoxin). In contrast to endotoxin, IA tumor necrosis factor-alpha or interleukin-1 alpha did not induce IP-10 or MIG mRNA in the lung. IA endotoxin also caused a modest induction of IP-10 and MIG mRNA in the jejunum, liver, and spleen. The IP-10 and MIG receptor CXCR3 was detected in the bronchiolar epithelium of preterm lambs by immunostaining. IP-10 and MIG are potent angiostatic chemokines that may contribute to lung injury and altered pulmonary vascular development in the preterm exposed to chorioamnionitis.

Amnion↗
PubMed1985

Significance of placental findings in early-onset group B streptococcal neonatal sepsis.

Assessment of placental pathology and its relationship to historical data, initial laboratory parameters, and outcome was undertaken in 22 cases of early-onset group B streptococcal sepsis of the neonate. Fourteen (64%) of the placentas demonstrated chorioamnionitis, six (27%) funisitis, and in nine (41%) gram stain demonstrated organisms within the membranes. Focal villous edema was observed in five (23%) cases and diffuse villous edema in four (18%). No placenta demonstrated chorangiosis. Placental inflammation was significantly (p less than 0.05) associated with prematurity, prolonged rupture of membranes, and onset of symptoms at less than 3 hours of age. No placental change was significantly associated with outcome or with neutropenia, which was the only parameter assessed that appeared to have prognostic value.

Chorioamnionitis↗
PubMed1993

Some placental considerations related to neurodevelopmental and other disorders.

Many newborns who appear normal at birth later manifest substantial neurologic and other disease. Pathologists are able to explain some of that sad enigma. Placental pathology frequently reveals the pathogenesis of cerebral palsy, mental retardation, and other neurodevelopmental disorders. This requires recognition of gross placental abnormalities and insightful light microscopic examination. Chorioamnionitis is now proven to be the major cause of premature onset of labor and prematurity. There is important need for investigation of pathogenetic processes associated with ascending intrauterine infection. Major complications therein include bacterially mediated fetal hypoperfusion resulting from placental and umbilical vasocontraction. Placentas of 10% of newborns have villitis of unknown etiology. The importance of villitis is incompletely known. The fetus may discharge meconium on more than one occasion, particularly so when the fetus is postmature. Clinicians may not recognize that fetal discharge has occurred if the event occurred 4 days or more prior to delivery. Intra-amniotic meconium associated with oligohydramnios probably causes placental and umbilical vasocontraction. Meconium probably thus contributes to the pathogenesis of pulmonary vasoconstriction, persistent fetal circulation, necrotizing enterocolitis, and damage of the fetal brain, liver, and kidneys. Fetal hypoxia and asphyxia may be acutely or chronically acquired. Major placental lesions associated with neonatal asphyxia include chronic ischemic change, nucleated red blood cells, intravillous hemorrhages, intimal vascular fibrin cushions, meconium staining, and intervillous fibrin.

Brain Damage, Chronic↗
PubMed2006

Joint distribution approaches to simultaneously quantifying benefit and risk.

BACKGROUND: The benefit-risk ratio has been proposed to measure the tradeoff between benefits and risks of two therapies for a single binary measure of efficacy and a single adverse event. The ratio is calculated from the difference in risk and difference in benefit between therapies. Small sample sizes or expected differences in benefit or risk can lead to no solution or problematic solutions for confidence intervals. METHODS: Alternatively, using the joint distribution of benefit and risk, confidence regions for the differences in risk and benefit can be constructed in the benefit-risk plane. The information in the joint distribution can be summarized by choosing regions of interest in this plane. Using Bayesian methodology provides a very flexible framework for summarizing information in the joint distribution. RESULTS: Data from a National Institute of Child Health & Human Development trial of hydrocortisone illustrate the construction of confidence regions and regions of interest in the benefit-risk plane, where benefit is survival without supplemental oxygen at 36 weeks postmenstrual age, and risk is gastrointestinal perforation. For the subgroup of infants exposed to chorioamnionitis the confidence interval based on the benefit-risk ratio is wide (Benefit-risk ratio: 1.52; 90% confidence interval: 0.23 to 5.25). Choosing regions of appreciable risk and acceptable risk in the benefit-risk plane confirms the uncertainty seen in the wide confidence interval for the benefit-risk ratio--there is a greater than 50% chance of falling into the region of acceptable risk--while visually allowing the uncertainty in risk and benefit to be shown separately. Applying Bayesian methodology, an incremental net health benefit analysis shows there is a 72% chance of having a positive incremental net benefit if hydrocortisone is used in place of placebo if one is willing to incur at most one gastrointestinal perforation for each additional infant that survives without supplemental oxygen. CONCLUSION: If the benefit-risk ratio is presented, the joint distribution of benefit and risk also should be shown. These regions avoid the ambiguity associated with collapsing benefit and risk to a single dimension. Bayesian methods allow even greater flexibility in simultaneously quantifying benefit and risk.

Anti-Inflammatory Agents↗
PubMed2004

Oral mucosal microvascular abnormalities: an early marker of bronchopulmonary dysplasia.

An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 +/- 2.0 wk; birth weight 850 +/- 125 g) and 15 sex- and gestational age-matched infants (nine boys and six girls; gestational age 27.6 +/- 2.6 wk; birth weight 865 +/- 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.

Adult↗
PubMed2005

Relationship between antenatal inflammation and antenatal infection identified by detection of microbial genes by polymerase chain reaction.

Although antenatal infection is thought to play an important role in the pathogenesis of preterm labor and neonatal diseases, the exact mechanisms are largely unknown. We sought to clarify the relationship between antenatal infection and intrauterine and neonatal inflammation. Samples were obtained from 41 preterm infants of <33 wk gestation delivered to 36 mothers and analyzed for the presence of 16s ribosomal RNA (16s rRNA) genes using PCR and for the proinflammatory cytokines IL-6 and IL-8. In 16 (44%) mother-baby pairings, at least one sample was found to be positive for the presence of 16s rRNA genes. All but one of the positive samples were from mothers presenting with preterm prelabor rupture of membranes (pPROM) or in spontaneous idiopathic preterm labor. A strong association was found between the presence of 16s rRNA genes and chorioamnionitis and with funisitis. A marked increase in IL-6 and IL-8 was noted in all tissues positive for 16s rRNA genes, including placenta, fetal membranes, cord blood serum, and, where samples were available, in bronchoalveolar lavage fluid (BAL) and in amniotic fluid. Interestingly, gastric fluid was always positive for 16s rRNA genes if any other intrauterine or BAL sample was positive, suggesting that this sample may provide an alternative to amniotic fluid to identify antenatal infection. In conclusion, we have found that microbial genes are particularly prevalent in pPROM and spontaneous preterm labor groups and that their presence is strongly associated with a marked intrauterine inflammatory response.

Amniotic Fluid↗
PubMed2003

Differential expression and regulation of microsomal prostaglandin E(2) synthase in human fetal membranes and placenta with infection and in cultured trophoblast cells.

We have evaluated the effect of chorioamnionitis on the protein expression of microsomal and cytosolic prostaglandin E(2) synthases (mPGES and cPGES) in preterm human placentae (PL) and fetal membranes (FM), by Western blot and immunohistochemistry, as well as the regulatory effect of IL-1beta and TNF-alpha on mPGES, cPGES, and cyclooxygenase (COX)-2 expression in villous trophoblast (VT) and chorion trophoblast (CT) cell cultures. mPGES localized to the syncytiotrophoblast and vascular endothelium in PL and to the amnion epithelium, CT, and decidual cells in FM. cPGES protein was localized only to the syncytiotrophoblast in PL and had the same profile of expression as mPGES in FM. With infection, there was an increase in mPGES expression in PL and a decrease in the expression in FM. cPGES protein did not change in either PL or FM with infection. In VT cells in culture, IL-1beta up-regulated COX-2 protein expression but did not affect mPGES. However, TNF-alpha increased both mPGES and COX-2 protein expression in these cells. In CT cells in culture, IL-1beta and TNF-alpha increased both mPGES and COX-2 protein levels. Neither IL-1beta nor TNF-alpha affected cPGES in either VT or CT cells. We conclude that protein levels of mPGES, as well as COX-2, can be stimulated by cytokines, potentially contributing to the increased prostaglandin production at the time of infection-driven preterm labor. However, multiple mechanisms, which apparently are inductor- and cell-type-specific, exist for the regulation of these enzymes.

Bacterial Infections↗