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Decreased expression of angiogenic factors in placentas with chorioamnionitis after preterm birth.

Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-kappaB, hypoxia-inducible factor-1alpha, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis ("funisitis"), chorioamnionitis without funisitis ("chorioamnionitis"), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-kappaB-positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1alpha expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs.

Angiogenesis Inducing Agents↗

Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years.

OBJECTIVE: The aim of this study was to determine whether fetal exposure to intra-amniotic inflammation and a systemic fetal inflammatory response (funisitis) are associated with the development of cerebral palsy at the age of 3 years. STUDY DESIGN: This cohort study included 123 preterm singleton newborns (gestational age at birth, </=35 weeks) born to mothers who underwent amniocentesis and were followed up for >/=3 years. The presence of intra-amniotic inflammation was determined by elevated amniotic fluid concentrations of proinflammatory cytokines such as interleukins 6 and 8 and by amniotic fluid white blood cell count. Cytokine concentrations were measured with sensitive and specific immunoassays. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Cerebral palsy was diagnosed by neurologic examination at the age of 3 years. RESULTS: Newborns with subsequent development of cerebral palsy had a higher rate of funisitis and were born to mothers with higher median concentrations of interleukins 6 and 8 and higher white blood cell counts in the amniotic fluid compared with newborns without subsequent development of cerebral palsy (funisitis: 75% [9/12] vs 23% [24/105]; interleukin 6: median, 18.9 ng/mL; range, 0. 02-92.5 ng/mL; vs median, 1.0 ng/mL; range, 0.01-115.2 ng/mL; interleukin 8: median, 13.0 ng/mL; range, 0.1-294.5 ng/mL; vs median, 1.2 ng/mL; range, 0.05-285.0 ng/mL; white blood cell count: median, 198 cells/mm(3); range, 0->1000 cells/mm(3); vs median, 3 cells/mm(3); range, 0-19,764 cells/mm(3); P <.01 for each). After adjustment for the gestational age at birth, the presence of funisitis and elevated concentrations of interleukins 6 and 8 in amniotic fluid significantly increased the odds of development of cerebral palsy (funisitis: odds ratio, 5.5; 95% confidence interval, 1.2-24.5; interleukin 6: odds ratio, 6.4; 95% confidence interval, 1. 3-33.0; interleukin 8: odds ratio, 5.9; 95% confidence interval, 1. 1-30.7; P <.05 for each). CONCLUSION: Antenatal exposure to intra-amniotic inflammation and evidence of a systemic fetal inflammatory response (funisitis) are strong and independent risk factors for the subsequent development of cerebral palsy at the age of 3 years.

Amniotic Fluid↗

Components of the systemic fetal inflammatory response syndrome as predictors of impaired neurologic outcomes in children.

OBJECTIVE: The purpose of this study was to compare interleukin-6 and funisitis as predictors of impaired neurologic outcomes in children by performing a secondary analysis on data that were collected prospectively for another purpose. STUDY DESIGN: We examined umbilical cords for funisitis and obtained cord blood for interleukin-6 levels. A psychomotor developmental index score was determined for each child at age 18 months. RESULTS: The prevalence (46%) of elevated interleukin-6 levels (> or = 10 pg/mL) among children with low psychomotor developmental index scores (<100) was not significantly different from that of children with normal scores (47%). Among children with funisitis (n = 21), the median psychomotor developmental index score was 94; for children without funisitis (n = 92), it was 99 (P <.02). When the data were regressed for confounding, funisitis remained significant (adjusted odds ratio, 1.3; 95% CI, 1.1-1.9). Furthermore, funisitis was a more specific predictor of low psychomotor developmental index scores (P <.001), although elevated interleukin-6 levels were more sensitive. CONCLUSION: When used for the prediction of impaired neurologic outcomes in children, funisitis has better specificity and thus a better positive predictive value than does interleukin-6.

Adult↗

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia.

OBJECTIVE: To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. METHODS: Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. RESULTS: Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. CONCLUSION: The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.

Betamethasone↗

C-reactive protein in vaginal fluid of patients with preterm premature rupture of membranes.

OBJECTIVE: To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation. METHODS: Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis. RESULTS: A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p < 0.001) and umbilical cord levels (r = 0.47, p < 0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p < 0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p < 0.01]. After adjustment for gestational age, vaginal fluid CRP concentration > 800 ng/mL remained a predictor of intraamniotic infection and funisitis. CONCLUSIONS: Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.

Adult↗

Umbilical vein interleukin-6 levels correlate with the severity of placental inflammation and gestational age.

Interleukin-6 (IL6) and suppurating placental inflammation are markers of neonatal sepsis. The purpose of this study was to define a relationship between IL6 and acute chorioamnionitis and funisitis of the placenta, and to compare IL6 levels in term and preterm neonates. Umbilical venous IL6 was measured in 137 term and 110 preterm neonates. Acute chorioamnionitis was graded as none, mild, moderate, severe, and necrotizing. Funisitis was graded as none, 1 vessel, 2 vessels, 3 vessels, or necrotizing. A 2-way analysis of variance with interaction was used to compare the IL6 levels. There was a stepwise progression of IL6 levels with increasing severity of acute chorioamnionitis and funisitis. Term neonates showed an IL6 elevation with mild acute chorioamnionitis and single-vessel vasculitis, which increased progressively until the inflammation became severe. In contrast, IL6 levels in preterm neonates did not increase significantly until severe acute chorioamnionitis or 3-vessel vasculitis was seen. Statistically significant differences in IL6 levels were seen in term versus preterm infants when the acute chorioamnionitis was mild or moderate or when the funisitis involved either 1 or 2 vessels (P < 0.05). The difference may be related to the relative immaturity of the preterm immune system, as has been demonstrated in vivo and in vitro. However, differences in management could be confounding factors. In conclusion, umbilical venous IL6 levels correlate with the severity of acute placental inflammation, with greater IL6 elevations in term infants compared to preterm infants until the inflammation becomes severe.

Acute Disease↗

Antibiotic administration in patients with preterm premature rupture of membranes reduces the rate of histological chorioamnionitis: a prospective, randomized, controlled study.

OBJECTIVE: To determine whether antibiotic administration in patients with preterm premature rupture of membranes is associated with a reduction in the rate of histological chorioamnionitis and funisitis. METHODS: One hundred consecutive patients with preterm premature rupture of membranes and no labor between 24 and 34 weeks were invited to participate in this study. Eligible patients randomly received either clindamycin-gentamicin for 7 days or placebo, and were managed expectantly until 35 weeks unless fetal or maternal indications developed. Microbial invasion of the amniotic cavity was defined as the presence of a positive amniotic fluid culture obtained by transabdominal amniocentesis. Cervicovaginal infection was diagnosed when bacterial vaginosis or a positive culture for cervicovaginal pathogens or facultative bacteria associated with a significant increase in the white blood cell count were found. Histological chorioamnionitis was based on the observation of polymorphonuclear leukocyte infiltration of the chorionic plate or the extraplacental fetal membranes. Funisitis was diagnosed in the presence of polymorphonuclear leukocyte infiltration into the umbilical vessel walls or Wharton jelly. Statistics were performed using contingency tables. RESULTS: Seventy-one patients with available histological study of the placenta were included. Thirty-five women received antibiotics and 36 were given placebo. Patients who received antibiotics had a significantly lower rate of histological chorioamnionitis than patients who received placebo (46% (16/35) vs. 69% (25/36), respectively; p < 0.05). This effect was more pronounced among women with microbial invasion of the amniotic cavity and/or cervicovaginal infection (58% vs. 89%, respectively; p < 0.01). Antibiotic therapy was associated with an increase in the frequency of placentas without histological abnormalities (29% vs. 6%; p < 0.01). The frequency of funisitis was not different between groups. CONCLUSION: Administration of antibiotics in patients with preterm premature rupture of membranes is associated with a significant reduction in the incidence of histological chorioamnionitis but it does not modify the frequency of funisitis.

Adolescent↗

The significance of different forms of placentitis.

A blind histological examination of placentae, with regard to placentitis, was carried out of 2 prospective, selected materials. The first consisted of 283 placentae, which were selected with regard to optimal obstetric outcome. The second consisted of 160 placentae, randomized from all premature and low birth weight infants in the local area. Placentitis was sub-divided into: funisitis, chorionitis, villitis and hypercellular villi. Funisitis was found in premature infants only. Villitis resulted in the birth of significantly smaller infants and placentae, and must therefore, in contrast to funisitis and chorionitis, be considered chronic. Hypercellular villi are found to have no importance. Funisitis, chorionitis and villitis could possibly be explained by an infection in 10 of a total of 15 cases of placentitis.

Birth Weight↗

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

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

Bacterial Infections↗

Management of premature rupture of membranes at term: randomized trial.

OBJECTIVE: We hypothesize that expectant management in the presence of premature rupture of membranes at term would result in a lower cesarean birth rate with no increase in maternal, fetal, or neonatal infection. STUDY DESIGN: Term patients who consented to the study were randomly allocated either to expectant management for 48 hours or to induction of labor 8 hours after premature rupture of membranes. Premature rupture of membranes was confirmed by sterile speculum examination of the vagina. Patients randomized to expectant management were transferred to antenatal care and were not examined vaginally until they went into labor. Patients randomized to induction of labor had induction with oxytocin 8 hours after premature rupture of membranes. RESULTS: Two hundred sixty-two patients were randomized to the expectant management and induction of labor groups. The cesarean birth rate and the clinical diagnosis of postpartum endometritis was not significantly different in the two groups. Pathologic diagnosis of chorioamnionitis and funisitis, however, was significantly greater in the expectant management group (p < 0.05). Eight of the 15 babies with funisitis were admitted to the neonatal intensive care unit for therapy (two in the induction of labor group and six in the expectant management group, p < 0.05). CONCLUSION: Expectant management did not reduce the incidence of cesarean birth and increased the pathologic diagnosis of funisitis and newborn requirements for neonatal intensive care.

Cesarean Section↗

Histologic chorioamnionitis: an occult marker of severe pulmonary hypertension in the term newborn.

OBJECTIVE: To determine whether the presence of histologic chorioamnionitis is associated with the severity of Persistent Pulmonary Hypertension of the Newborn (PPHN) as evidenced by the use of exogenous nitric oxide (iNO), high-frequency oscillatory ventilation (HFOV), extra-corporeal membrane oxygenation (ECMO) and/or death. METHODS: Retrospective chart review of term neonates > or =37 weeks gestation with PPHN. Placental pathology was reviewed. Primary outcome is the use of iNO. Secondary outcomes include the use of HFOV, ECMO and death. RESULTS: Over 2 years, 29 neonates fulfilled the entry criteria for the study. Interventions included iNO use n=14 (48%), HFOV n=7 (24%) and ECMO n=3 (10%); two neonates died. Histologic chorioamnionitis and/or funisitis was noted in 16 (55%) neonates. The presence of chorioamnionitis and/or funisitis (n=16) versus neither (n=13) was significantly associated with iNO use 11/16 (78%) versus 3/13 (22%) (p=0.02) and HFOV 7/16 (43%) versus 0/13 (0%) (p=0.008) but not to ECMO or death. CONCLUSION: The presence of histologic chorioamnionitis and/or funisitis is associated with more severe PPHN as indicated by the use of iNO as well as an increased requirement for more advanced respiratory support, that is, HFOV. The mechanism/s contributing to these findings are unclear.

Chorioamnionitis↗

The Northwestern Twin Chorionicity Study: I. Discordant inflammatory findings that are related to chorionicity in presenting versus nonpresenting twins.

OBJECTIVE: The purpose of this study was to evaluate the association between chorionicity and discordant chorioamnionitis and funisitis in twin gestations. STUDY DESIGN: This was a retrospective analysis of 1156 twin placentas with a standardized diagnosis of chorionicity, chorioamnionitis, and funisitis for comparison between presenting and nonpresenting twins with dichorionic-separate, dichorionic-fused, and monochorionic placentas. RESULTS: Frequencies of chorioamnionitis in the nonpresenting twin were significantly lower in dichorionic placentas (odds ratio, 0.4; 95% CI, 0.3, 0.6, in dichorionic-separate placentas; odds ratio, 0.5; 95% CI, 0.3, 0.8, in dichorionic-fused placentas) compared with monochorionic placentas. The frequency of advanced inflammation (ie, chorioamnionitis with funisitis) was significantly lower in the nonpresenting twin than in the presenting twin, but only in dichorionic-separate placentas (odds ratio, 0.2; 95% CI, 0.1, 0.4). CONCLUSION: Dichorionic placentas confer significant protection against the spread of chorioamnionitis from the presenting to the nonpresenting gestational sac. In the more advanced process that involves the umbilical cord, only the subset of separate dichorionic placentas confers this protective effect against the spread of inflammation.

Adult↗

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↗

Clinical significance of increasing histologic severity of acute inflammation in the fetal membranes and umbilical cord.

The purpose of this study was to determine the importance of varying histologic stages of inflammation in the placental membranes and cord. Acute inflammation was histologically staged in fetal membranes and umbilical cord sections from 2899 placentas received from consecutive singleton deliveries. Then clinical data were collected for a subset of randomly selected placentas with stage 1 through stage 4 membrane inflammation (n = 212) and without significant inflammation (stage 0, n = 216). Statistical analyses revealed that increasing stage of membrane inflammation was associated with an increasing rate of funisitis, perinatal death, and preterm birth (P < .05). Inflammation permeating the entire trophoblastic layer of the chorion (stage 1) was associated with clinical symptoms of intrauterine infection and thus was an important pathologic finding. Acute necrotizing chorioamnionitis was very strongly associated with perinatal death and preterm birth. Acute funisitis was a more specific but less sensitive marker for perinatal complications than inflammation in the membranes. With increasing stage of funisitis, there was an increased incidence of clinical symptoms of intrauterine infection, preterm birth, and perinatal death. Almost three-fourths of the cases with histologic evidence of membrane inflammation were clinically silent. In conclusion, increasing histologic stages of inflammation of the membranes and cord are associated with an increased rate of perinatal morbidity and mortality. Stage I membrane inflammation provides a clinically acceptable minimum threshold for the reporting of pathologic changes.

Biomarkers↗

[Placental histopathology in premature rupture of membranes. Its relationship with microbiological findings, maternal, and neonatal outcome].

BACKGROUND: There is a close relationship between premature membrane rupture, bacterial infections and premature labor. AIM: To study placental histological changes in patients with preterm membrane rupture. To establish a relationship between pathological findings, amniotic fluid and lower genital tract microbiological studies, maternal and neonatal outcome. PATIENTS AND METHODS: Patients with premature membrane rupture of membranes between 24 and 34 weeks of gestation participated in this study. On admission, patients had no evidence of clinical chorioamnionitis, labor or fetal distress. Microbiological studies of the amniotic fluid and cervicovaginal secretions were performed and the placenta was sent for pathological study. RESULTS: Seventy one placentas were available for the study. The main pathological findings were acute chorioamnionitis in 58%, trophoblastic proliferation in 38%, funisitis in 37%, villitis in 16%, fetal vascular lesions in 14% and no findings in 17%. Microbial invasion of amniotic cavity was present in 89% of acute chorioamnionitis. Sixty one percent of trophoblastic proliferation and all fetal vascular lesions were associated with negative amniotic and cervical cultures. Newborns with acute funisitis had a higher frequency of neonatal death (29%), severe asphyxia (42%) and neonatal infections (29%). CONCLUSIONS: Acute chorioamnionitis is the most frequent finding in patients with preterm membrane rupture and microbial invasion of amniotic cavity. In the absence of intra amniotic infection, proliferation of the trophoblast and the presence of fetal vascular lesions predominate. Acute funisitis is strongly associated with adverse fetal outcome.

Amniotic Fluid↗

Pathology of the placenta and cord in ascending and in haematogenous infection.

The two main patterns of inflammatory response in the placenta and its adnexae are: (1) amniotic infection, usually bacterial ascending, with acute chorioamnionitis and funisitis; (2) haematogenous villitis, usually viral, with early necrotizing lesions and vasculitis and, later, chronic infiltrates and obliterative vasculitis. In amniotic infection most cells in the exudate are maternal. These leucocytes participate in antibacterial defence of the amniotic cavity in conjunction with substances such as zinc polypeptide and lysozyme and may contribute directly to fetal defence. Immunoglobulins may be produced in the cord of placenta only in protracted lesions such as 'healed' funisitis. Individual variations in the resistance of the membranes to bacterial penetration are possible. In viral infections a massive multifocal production by plasmacytes of immunoglobulins M, G and A is seen in affected villi. The secretion of non-specific antiviral substances in the infected placenta is possible. In all affected villi there is an activation of fixed macrophages (Hofbauer cells) that remain partly 'immature', i.e. are lysozyme-negative. Multifocal lymphoplasmacytic villitis is uncommon and has helped to focus the diagnosis on prenatal infection. In contrast, non-specific lymphocytic villitis is common; since there is no morphological difference between cases known to be associated with an infection, e.g. varicella, and the others, many cases may well be due to silent infection, although a graft-versus-host reactions remains a distinct possibility.

Amnion↗

Pathology of the umbilical cord in congenital syphilis: analysis of 25 specimens using histochemistry and immunofluorescent antibody to Treponema pallidum.

Identification of Treponema pallidum in the placenta is important for diagnosis of congenital syphilis; however, spirochetes are difficult to observe in chorionic villi. To determine the sensitivity of umbilical cord examination for T pallidum, and the association of spirochetes with cord pathology, placentas were prospectively obtained from 25 women with untreated syphilis. The most common finding using hematoxylin-eosin staining was a normal-appearing umbilical cord (48%); necrotizing funisitis was the most frequent pathological lesion (36%). Spirochetes were detected using silver and immunofluorescent staining in 89% of cords, including 92% of histologically normal and 84% of abnormal cords. Three specimens showed subamnionic aggregates of spirochetes, consistent with amniotic fluid infection. Necrotizing funisitis was strongly associated with umbilical artery infection by spirochetes (P = .008). There was a 100% correlation between results of silver and immunofluorescent staining. The umbilical cord is a sensitive site for morphological confirmation of T pallidum; it is significant for the pathologist that spirochetes may often be detected in the absence of overt tissue inflammation or necrosis.

Antibodies, Bacterial↗

Risk factors associated with early-onset sepsis in premature infants.

OBJECTIVE: To define perinatal factors associated with early-onset neonatal sepsis. STUDY DESIGN: Maternal and neonatal variables were analysed retrospectively in 343 infants born before 35 weeks using univariate and multivariate statistical analysis. RESULTS: Logistic regression analysis identified risk factors for probable neonatal sepsis: gestational age at delivery (odds ratio 0.9, 95% confidence interval (CI) 0.91-0.96), premature rupture of the membranes (odds ratio 2.9, 95% CI 1.004-8.56), Apgar score after 1 min (odds ratio 0.7, 95% CI 0.53-0.96), and histological chorioamnionitis and/or funisitis (odds ratio 4.1, 95% CI 1.36-12.12). There was a strong association between probable sepsis and intracranial haemorrhage of the infant (odds ratio 4.3, 95% CI 1.07-17.40). Funisitis had a high specificity (91%) and positive predictive value (82%) for the detection of neonatal sepsis < or =32 weeks. CONCLUSIONS: Independent obstetrical risk factors for early-onset neonatal sepsis in premature infants may help to identify newborns who benefit from maternal antibiotic prophylaxis before birth. The histological examination of the umbilical cord can be used as an additional diagnostic test to detect newborns at risk of infection.

Antibiotic Prophylaxis↗