Necrotizing funisitis: A study of 45 cases

doi:10.1016/0046-8177(92)90296-F

Human Pathology

Volume 23, Issue 11, November 1992, Pages 1278-1283

https://doi.org/10.1016/0046-8177(92)90296-F Get rights and content

Abstract

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.

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Cited by (44)

Placental lesions associated with stillbirth by gestational age, according to feature importance: Results from the stillbirth collaborative research network
2023, Placenta
Previous studies have identified lesions commonly found in placentas associated with stillbirth but have not distinguished across a range of gestational ages (GAs). The objective of this study was to identify lesions associated with stillbirths at different GAs by adapting methods from the chemical machine learning field to assign lesion importance based on correlation with GA.
Placentas from the Stillbirth Collaborative Research Network were examined according to standard protocols. GAs at stillbirth were categorized as: <28 weeks (extreme preterm stillbirth [PTSB]), 28–33′6 weeks (early PTSB), 34–36′6 weeks (late PTSB), ≥37 weeks (term stillbirth). We identified and ranked the most discriminating placental features, as well as those that were similar across GA ranges, using Kernel Principal Covariates Regression (KPCovR).
These analyses included 210 (47.2%) extreme PTSB, 85 (19.1%) early PTSB, 62 (13.9%) late PTSB, and 88 (19.8%) term stillbirths. When we compute the KPCovR, the first principal covariate indicates that there are four lesions (acute funisitis & nucleated fetal red blood cells found in extreme PTSB; multifocal reactive amniocytes & multifocal meconium found in term stillbirth) that distinguish GA ranges among all stillbirths.
There are distinct placental lesions present across GA ranges in stillbirths; these lesions are identifiable using sophisticated feature selection. Further investigation may identify histologic changes across gestations that relate to fetal mortality.
Necrotizing funisitis associated with Ureaplasma urealyticum infection: A clinicopathologic analysis of 14 cases
2022, Placenta
Citation Excerpt :
Necrotizing funisitis is characterized as a distinct morphologic lesion with a crescent of necrosis, often calcified, between the surface of the umbilical cord and umbilical vessel walls that is not present in the usual funisitis (acute umbilical cord inflammation) [1–3].
Necrotizing funisitis is a distinct lesion of the umbilical cord associated with chorioamnionitis and bloodborne fetal infection. The lesion may be a response to microorganisms in Wharton's jelly. A common microorganism detected in chorioamnionitis is Ureaplasma urealyticum (U. urealyticum). This study hypothesizes that U. urealyticum DNA will be present in Wharton's jelly in necrotizing funisitis.
Necrotizing funisitis was identified retrospectively from a 2-year pathology database and confirmed in review. Paraffin fixed embedded tissue sections of the lesion were prepared for polymerase chain reaction (PCR) by using primers to identify U. urealyticum. Twenty matched controls without funisitis were similarly processed. Clinical data included serological tests of common bloodborne infections in the mothers and infants, and U. urealyticum PCR results in the urine of the neonates.
Fourteen cases of necrotizing funisitis were identified in 7,416 examined placentas. Nine of these umbilical cords were positive by PCR for U. urealyticum (64.3%). Nineteen of twenty control cases were negative. Eight of ten neonates (80%) also had positive urine PCR tests for U. urealyticum. No infants or mothers had evidence of bloodborne fetal infection.
U. urealyticum DNA was present in Wharton's jelly by PCR testing in the majority of the necrotizing funisitis lesions tested. This result supports a possible causative role for U. urealyticum in many cases of necrotizing funisitis.
Necrotizing funisitis is an indicator that intra-amniotic inflammatory response is more severe and amnionitis is more frequent in the context of the extension of inflammation into Wharton's jelly
2021, Taiwanese Journal of Obstetrics and Gynecology
Citation Excerpt :
Unfortunately, although previous several classifications [5,6,11,15] included NF, these studies had limitations in the classification for the progression of inflammation in UC as follows: 1) the presence or absence of inflammation in WJ was not considered [5,6]; and 2) only NF, but not inflammation in umbilical vessels and WJ, was focused [11,15]. In addition to these limitations, they did not examine IAIR [5,6,11,15]. Notably, our current study demonstrated that NF is the most advanced stage in the inflammation of UC based on the finding that the surrogate markers for FIR (i.e., IAIR and amnionitis) are continuously increased with the progression of inflammation in the whole subdivisions of UC (i.e., stage-1, umbilical phlebitis only; stage-2, involvement of at least one UA and either the other UA or UV without extension into WJ; stage-3, the extension of inflammation into WJ without NF; and stage-4, the extension of inflammation into WJ with NF).
Necrotizing funisitis (NF) is defined as the presence of an arc (i.e., crescent/band/ring/halos) of infiltrated neutrophils and/or associated debris in Wharton's jelly (WJ) of umbilical-cord (UC). However, no information exists about the comparison in intra-amniotic inflammatory-response (IAIR) and inflammation in extra-placental membranes between the presence and absence of NF in the context of inflammation in WJ among spontaneous preterm births (PTBs). The objective of current study is to examine this issue.
We examined IAIR and the frequency of amnionitis according to the progression of inflammation in UC (i.e. stage-1, umbilical phlebitis [inflammation in umbilical-vein(UV)] only; stage-2, involvement of at least one umbilical-artery[UA] and either the other UA or UV without extension into WJ; stage-3, the extension of inflammation into WJ without NF; stage-4, the extension of inflammation into WJ with NF) in 120singleton spontaneous PTBs (<37weeks). IAIR was gauged by AF MMP-8 (ng/ml) within 3days before birth.
1) Stage-1, stage-2, stage-3, and stage-4 were present in 20%(24/120), 6%(7/120), 61%(73/120), and 13%(16/120) of cases respectively; 2) AF MMP-8 continuously increased (stage-1 vs. stage-2 vs. stage-3 vs. stage-4; median[ng/ml], range[ng/ml]; 207.2[16.8–1196.5] vs. 444.1[8.5–2608.0] vs. 458.8[0.4–3116.7] vs. 1859.7[912.3–5304.8]; Spearman's rank correlation-test, α = 0.454, P = 0.006), and the frequency of increased AF MMP-8 (≥854.1 ng/ml) elevated (stage-1 vs. stage-2 vs. stage-3 vs. stage-4; 13%[1/8] vs. 33%[1/3] vs. 32%[6/19] vs. 100%[5/5]; Linear-by-linear-association, P = 0.012) with the progression of inflammation in UC; 3) Moreover, there was a stepwise increase in the frequency of amnionitis according to the progression of inflammation in UC (stage-1, 33%[8/24]; stage-2, 43%[3/7]; stage-3, 62%[45/73]; stage-4, 81%[13/16]; Linear-by-linear-association, P = 0.001).
NF is an indicator that IAIR is more severe and amnionitis is more frequent in the context of the extension of inflammation into WJ. Therefore, current study confirms that NF is the most advanced stage in the progression of inflammation within UC.
Clinically relevant umbilical cord inflammation identified based on CD15-associated vasculitis patterning
2021, Placenta
Citation Excerpt :
Staging is principally determined by the distribution of polymorphonuclear leukocytes. Stage 1 of the fetal inflammatory response includes chorionic vasculitis or umbilical phlebitis, stage 2 refers to umbilical phlebitis with one or more arteritis lesions, and stage 3 represents the so-called necrotizing funisitis [8,9]. In contrast, grading depends on the density of polymorphonuclear leukocytes.
Acute funisitis, a granulocyte-related inflammation of the umbilical cord, is associated with chorioamnionitis and perinatal adverse events. However, there is no efficient procedure for detecting clinically relevant umbilical cord inflammation. The objective of this study was to identify such inflammation, based on immunohistochemical assessment of umbilical cord vasculitis patterns.
Accordingly, 261 cases were retrieved from a single medical institute. Using the well-established granulocyte marker CD15, we developed a five-tier umbilical cord inflammation-scoring system. Additionally, previous morphological assessments from pathological reports were compared to the immunohistochemical findings.
Analysis of results based on our new scoring system revealed that severe umbilical phlebitis (score 3) was significantly associated with maternal inflammatory response and that severe umbilical arteriophlebitis (score 4) was correlated with low umbilical arterial blood pH, a feature linked to fetal mortality and morbidity. These results corresponded with and were validated by the morphology-based assessments. Additionally, immunohistochemical analysis revealed the clinical and pathological relevance of vitelline vasculitis, a recently proposed condition. We found that analyzing three umbilical cord sections enabled superior detection of severe umbilical vasculitis than analyzing two sections. However, whether these sections were sampled from multiple distant sites or a single localized site did not significantly affect the detection of clinically relevant inflammation.
CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation.
Perinatal Infections
2018, Diagnostic Pathology of Infectious Disease
Syphilis (Treponema pallidum)
2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases

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^☆: Presented in part at the American Society of Clinical Pathologists/College of American Pathologists Fall Meeting, New Orleans, LA, September 1991.

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Human Pathology

Abstract

References (24)

Subacute necrotizing funisitis: A variant of cord inflammation with a high rate of perinatal infection

J Pediatr

Placental inflammation and infection. A prospective bacteriologic and histologic study

Am J Obstet Gynecol

The value of umbilical cord histology in the management of potential perinatal infection

J Pediatr

Intrauterine bacterial infection of the newborn infant: Frozen sections of the cord as an aid to early detection

J Pediatr

Relative placental weight in congenital syphilis

Placenta

Congenital syphilis and necrotizing funisitis

JAMA

Necrotizing funisitis. 60 cases

Lab Invest

Pathologisch-anatomische Veränderungen in der Nachgeburt bei Syphilis

Beitr Pathol Anat

Die syphilitischen Veränderungen in der Nabelschnur

Arch Gynakol

Die Veränderungen an Placenta, Nabelschnur, und Eihäuten bei Syphilis und ihre Beziehungen zur Spirochäta pallida

Z Geburtschilfe Gynakol

Umbilical cord sclerosis as an indicator of congenital syphilis

J Clin Pathol

Degeneration and calcification of the umbilical cord

Obstet Gynecol

Cited by (44)

Placental lesions associated with stillbirth by gestational age, according to feature importance: Results from the stillbirth collaborative research network

Necrotizing funisitis associated with Ureaplasma urealyticum infection: A clinicopathologic analysis of 14 cases

Necrotizing funisitis is an indicator that intra-amniotic inflammatory response is more severe and amnionitis is more frequent in the context of the extension of inflammation into Wharton's jelly

Clinically relevant umbilical cord inflammation identified based on CD15-associated vasculitis patterning

Perinatal Infections

Syphilis (Treponema pallidum)

Original contributionNecrotizing funisitis: A study of 45 cases☆

Abstract

J Pediatr

Am J Obstet Gynecol

J Pediatr

J Pediatr

Placenta

Congenital syphilis and necrotizing funisitis

JAMA

Necrotizing funisitis. 60 cases

Lab Invest

Pathologisch-anatomische Veränderungen in der Nachgeburt bei Syphilis

Beitr Pathol Anat

Die syphilitischen Veränderungen in der Nabelschnur

Arch Gynakol

Die Veränderungen an Placenta, Nabelschnur, und Eihäuten bei Syphilis und ihre Beziehungen zur Spirochäta pallida

Z Geburtschilfe Gynakol

Umbilical cord sclerosis as an indicator of congenital syphilis

J Clin Pathol

Degeneration and calcification of the umbilical cord

Obstet Gynecol

Original contribution
Necrotizing funisitis: A study of 45 cases☆