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Chronic viral funisitis.

Four cases chronic funisitis, a rare variant of umbilical cord inflammation, are presented and compared with the acute and subacute forms. The distinctive findings are a predominantly lymphoplasmocytic infiltration, coagulative necorsis of the vascular media with secondary calcification, and the unusual association of chronic funisitis with chronic chorioamnionitis and chronic villitis. One fetus was stillborn, another was aborted, and two were live-born. Two fetuses were growth retarded and three had evidence of infection. Viral inclusions were identified in three placentas. The data strongly suggest that lymphoplasmocytic funisitis in these cases is the result of chronic intrauterine viral infection.

Amnion↗

Meconium-stained amniotic fluid and neonatal morbidity in near-term and term deliveries with acute histologic chorioamnionitis and/or funisitis.

OBJECTIVE: To determine the incidence of meconium-stained amniotic fluid (MSAF) and neonatal morbidity in near-term and term deliveries with histologic acute chorioamnionitis and/or funisitis compared to those with normal placental histology. STUDY DESIGN: In a retrospective case-control design, we compared the incidence of MSAF and neonatal outcome in 45 cases of acute histologic chorioamnionitis and/or funisitis with 89 cases of normal placental histology. We reviewed the obstetric and neonatal records for perinatal complications and neonatal morbidity. RESULTS: Mean birthweights (3372+/-473 vs 3287+/-518 g) were similar in infants born to mothers with histologic chorioamnionitis and/or funisitis compared to infants born to mothers with normal placental histology. The incidence of MSAF was significantly higher in the group with acute chorioamnionitis/funisitis (p<0.05). Similarly, the incidence of admissions to newborn intensive care unit, respiratory distress, meconium aspiration syndrome, and presumed sepsis was also significantly higher (p<0.05) in this group. CONCLUSION: The incidence of MSAF and neonatal morbidity is higher in the presence of acute inflammation of placental membranes. The presence of meconium in the amniotic fluid should alert the physician to the potential for infection and increased neonatal morbidity.

Acute Disease↗

Necrotizing funisitis: a study of 45 cases.

Necrotizing funisitis (NF) is a distinctive inflammatory condition of the umbilical cord, characterized by perivascular concentric rings of inflammatory cells, necrotic debris, or calcium deposits. Necrotizing funisitis has been strongly associated with syphilis by some investigators, while others have failed to link NF with any consistent infectious agents. We examined 45 cases of NF to determine its relationship with syphilis. Five (11%) mothers had syphilis as confirmed by a positive rapid plasma reagin test and a positive fluorescent antibody absorbed test, 31 (69%) had a negative rapid plasma reagin test or venereal disease research laboratory test, and test results were not available for the remaining nine (20%). There was no record of syphilis in those babies born to mothers without confirmed syphilis. Estimated gestational age at the time of delivery ranged from 18 to 40 weeks (mean, 28 weeks). Prolonged rupture of membranes was present in 28 (62%) of the mothers, and ranged from 1 to 51 days (mean, 9 days); this was the most frequently seen maternal factor in connection with NF. Fourteen (31%) of the babies were stillborn or nonviable, including three (60%) of the five born to mothers with syphilis. Maternal and fetal cultures revealed no consistent microorganisms. Placental histology was significant for chronic villitis in 26 (58%) cases, including all five (100%) with maternal syphilis. Acute chorioamnionitis was present in each case (100%) and varied from mild to severe. We conclude that (1) NF has a polymicrobial etiology, (2) in the absence of other placental findings associated with syphilis NF should not be considered presumptive of this disease, and (3) factors leading to NF may also contribute to acute chorioamnionitis, premature rupture of membranes, and stillbirth.

Female↗

Necrotizing funisitis and herpes simplex infection of placental and decidual tissues: study of four cases.

Necrotizing funisitis (NF) is a macroscopically and microscopically distinctive pattern of umbilical cord inflammation recently heralded as presumptive of congenital syphilis. Four nonsyphilitic cases are presented in which herpes simplex virus (HSV) 2 antigen was demonstrated in the placenta by immunohistochemistry. The clinicopathologic findings in one case, including HSV 2 antigen in amniotic epithelium, subamniotic chorion, and Wharton jelly, indicate that NF was caused by chronic ascending primary HSV 2 infection, whereas those of the other three cases with HSV 2 Ag confined to decidual cell clusters suggest that NF was caused by chronic ascending bacterial infection and that latent endometrial HSV 2 infection was fortuitous. We conclude that (1) NF is caused by protracted inflammation of a structure whose normal anatomy precludes removal of inflammatory debris; (2) no single pathogen causes NF; and (3) NF is strongly associated with latent endometrial HSV 2 infection, which should be sought in all instances. Although latent HSV 2 endometrial infection may be more prevalent than currently recognized, we speculate that its strong association with NF may be more than causal; whereas the usual ascending bacterial infection leads to labor before NF has had sufficient time to develop, latent endometrial HSV 2 infection may alter local paracrine factors and delay parturition for the time sufficient to permit NF, a morphological hallmark of chronicity, to become apparent.

Adolescent↗

The pathophysiology of acute syphilitic funisitis.

There is an increase in the number of cases of syphilis in pregnancy in the United States. Fetal death may occur in syphilis from acute or chronic infections. A case is presented in which an acute fetal infection occurred. The patient presented at 31 weeks' gestation, with a decrease in fetal movements and non-reactive cardiotocography. Ultrasound and Doppler analysis of the fetal heart, cerebral and umbilical arteries, aorta and umbilical vein led to the suspicion of acute cardiac failure. An amniocentesis yielded a white cell count of 1122 white blood cells, with 91% polymorphs, but the Gram stain was negative. The fetus developed a persistent bradycardia and was delivered. The diagnosis of acute severe syphilitic funisitis was suspected from histological sections of the cord. Diagnosis was established from maternal and fetal blood. Modern ultrasound techniques, including imaging, Doppler and cardiotocography, can lead to the analysis of the pathophysiology of disease states. An acute syphilitic infection should be suspected when this constellation of findings is found.

Journal Article↗

Re-evaluation of chorioamnionitis and funisitis with a special reference to subacute chorioamnionitis.

Our purpose is to prove that prolonged inflammation of the chorionic plate, which we have termed subacute chorioamnionitis (SCAM), is a distinctive entity and should be differentiated from acute chorioamnionitis (ACAM) because it is an excellent prognostic indicator of chronic lung disease (CLD), including Wilson-Mikity syndrome (WMS). Ninety singleton placentas with stage-3 chorioamnionitis were delivered at 23 to 32 weeks of gestation during 1993 to 1996, and the infants survived more than 28 days. There were 49 placentas with stage 3 SCAM, 33 placentas with stage 3 ACAM, and 8 placentas with subacute necrotizing funisitis (SNF) and without inflammation of the chorionic plate. Fifty-three of gestation- and birthweight-matched placentas without chorioamnionitis were selected as control. To determine the risk factors for CLD, 27 clinical and 6 histological variables were analyzed. Logistic regression analysis showed that amniotic necrosis (AN) (P =.0168) and low birthweight (P =.0341) were the major contributing risk factors for CLD. SNF was not significantly related to CLD. Patients with SCAM (AN+, SNF-) were highly susceptible to CLD. In conclusion, SCAM, especially when associated with AN, seems to be a unique prognostic indicator of CLD.

Amnion↗

Chorioamnionitis with or without funisitis increases the risk of hypotension in very low birthweight infants on the first postnatal day but not later.

OBJECTIVE: To evaluate the relation between chorioamnionitis and hypotension in very low birthweight infants. METHODS: Retrospective cohort study in infants with a birth weight of <1500 g born between January 2002 and September 2004. The placentas were examined for evidence of chorioamnionitis and funisitis. Hypotension was defined by the use of vasopressors. RESULTS: Of 105 infants, 37 (35%) were chorioamnionitis positive. The onset of hypotension had a skewed distribution: day 1 for 30 episodes and scattered from day 2 to day 19 for the remaining 22. Of the 30 infants who developed hypotension on day 1, 17 (57%) were chorioamnionitis positive. The mean maturity of the chorioamnionitis positive group was 27.91 weeks, marginally less than the mean maturity of 29.05 weeks of the chorioamnionitis negative group (p = 0.05). After adjustment of the effects for confounding variables (birth weight, gestation, surfactant therapy, mechanical ventilation on day 1, high frequency oscillatory ventilation, patent ductus arteriosus), chorioamnionitis was the significant factor in line with hypotension developing on day 1 (adjusted odds ratio 5.14, 95% confidence interval 1.51 to 17.50). There was no evidence that hypotension developing after day 1 was associated with chorioamnionitis. CONCLUSIONS: There is a strong association between chorioamnionitis and hypotension developing on day 1 in very low birthweight infants.

Age Factors↗

[Necrotic funisitis].

The authors report eighty eight cases of a perticular type of funisitis characterized by perivascular necrosis of Wharton's jelly. The accompanying leucocyte reaction is weak, and sometimes nil, and the inflammatory lesions of the placenta are also moderate, and sometimes absent. The necrosis of the cord is, however, sufficiently pronounced to be visible to the naked eye. The neonate is often--but not always--very premature, but rarely shows clinical signs of infection (only one case in five). It nonetheless presents with hyperleucocytosis from birth, often severely, but this clears up within a few days, even in the absence of antibiotherapy. A very high rate of blood IgM is also often observed in these infants, on the day of birth. Immediate survival and postnatal development often present no problems. The etiology is not known. There are indirect arguments in favor of a rare germ which cannot be visualized by routine techniques, or possibly a virus. But this remains to be proved. Some observers have suggested that it is the fruit of a particular diathesis, with a tissular reaction to a non-infectious aggression by some modification of the amniotic fluid but this too remains to be established.

Humans↗

Chorioamnionitis and funisitis due to Corynebacterium kutscheri.

When isolated from the female genital tract, diphtheroids are usually regarded as commensal organisms. Corynebacterium kutscheri however is a pathogen in laboratory rodents. We report a case in which C. kutscheri was isolated as a pure culture from the umbilical cord and from other surface sites in an infant. Histological examination of the cord and membranes demonstrated the organisms within these fetal tissues. The organisms evoked a fetal cellular response. The importance of recognising commensals as potential pathogens in states of altered host resistance in stressed.

Corynebacterium↗

Histo-topographic distribution of acute inflammation of the human umbilical cord.

Acute inflammation of the umbilical cord, acute funisitis, is a sign of fetal inflammatory response, and the clinicopathological need for its identification is increasing. This study was conducted in order to describe the topographic distribution of acute funisitis, and thereby to provide more information on the intrinsic nature of acute funisitis and find a better way of pathologically examining the umbilical cord. A total of 10 umbilical cords affected by acute funisitis were histopathologically examined throughout their entire lengths at 1 mm intervals. Pathological examination was done to characterize the extent of the funisitis, the involvement of the vein (phlebitis) or of one or both arteries (arteritis), and the presence of inflammation in Wharton's jelly. Umbilical cord plasma interleukin (IL)-6 was measured by specific immunoassay to assess whether or not the severity of acute funisitis correlates with fetal cytokine response. It would appear that the inflammatory reaction begins as a discrete, multifocal process which eventually becomes contiguous as the inflammatory reaction proceeds. Umbilical cord plasma IL-6 concentrations tended to correlate with the extent of umbilical cord inflammation. The initial phase of acute funisitis involves discrete and multiple foci along the length of the umbilical cord. Moreover, the extent of acute funisitis reflects the severity of systemic fetal cytokine response. Therefore, adequate sampling using multiple sections would facilitate the identification of acute funisitis. We propose a standard sampling procedure taking one section from each third of the umbilical cord.

Acute Disease↗

Maternal serum cytokines in preterm premature rupture of membranes.

OBJECTIVE: To estimate whether maternal serum interleukin (IL)-6 or granulocyte colony-stimulating factor (G-CSF) obtained daily are elevated in women with preterm premature rupture of membranes who develop funisitis. METHODS: Daily blood samples were obtained from women with preterm premature rupture of membranes and analyzed for IL-6 and G-CSF by enzyme-linked immunosorbent assay. Funisitis was determined by placental examination. Observations were stratified based on the presence or absence of funisitis and analyzed. Proportional hazards models were used to evaluate time-to-delivery on the basis of diagnostic IL-6 and G-CSF levels, determined by receiver operating characteristic curve analysis. RESULTS: Of the 107 patients available for analysis, 54 (50%) had evidence of funisitis after delivery. Patients with funisitis were more likely to deliver at an earlier gestational age (28.5 weeks compared with 31.5 weeks, P<.001) and have Medicaid insurance (57% compared with 39%, P=.04). Serum IL-6 and G-CSF were elevated 24 to 48 hours before delivery in women with preterm premature rupture of membranes with funisitis compared with those without funisitis (IL-6, 7.5 compared with 2.8 pg/mL, P<.001; G-CSF, 121.7 compared with 56.9 pg/mL, P=.002). Using values identified by the receiver operating characteristic curve, elevated serum IL-6 in the interval 24-72 hours before delivery was significantly associated with funisitis (P<.03), even after controlling for gestational age and insurance status. CONCLUSION: Maternal serum IL-6 and G-CSF appear to be biomarkers in the identification of women with preterm premature rupture of membranes likely to develop funisitis. LEVEL OF EVIDENCE: II.

Adult↗