Fetal Inflammatory Response Of Umbilical And Chorionic Plate Vessels

Fetal response to infection occurs after the maternal response and usually suggests a more well-established infection. It may be attenuated or absent in midgestation, although I have seen significant funisitis as early as 18 weeks of gestation.

Funisitis and Vasculitis: Gross and Microscopic

Funisitis can rarely be grossly identified. The umbilical cord may be quite edematous. Within the extra fluid within the cord substance, large accumulations of neutrophils may be visible as white rings incompletely around the fetal vessels (Fig. 4). The fetal response to infection within the amniotic fluid is toward the amnion surface (amniotropic), similar to an Ochterlony reaction. Concentric inflammation may be the result of cord injury. Funisitis may be segmental because of positioning of the cord within the uterus (23); thus, the recommendation is for examination of two sections of umbilical cord.

An acute fetal inflammatory response is most often a response to ascending bacterial infection. Chronic vasculitis or funisitis is less common but may occur in cases of hematogenously acquired viral infection (58). In severely macerated fetuses, caution should be used in diagnosing funisitis as degeneration of the vascular smooth muscle may falsely give the impression of inflammation.

Acute inflammation of the chorionic plate vessels may precede inflammation of the umbilical vessels. Gross examination rarely demonstrates an amniotropic intravascular density. Inflammation of the chorionic plate vessels is usually obscured by the associated chorioamnionitis. Chronic fetal vasculitis is most often a nonspecific response associated with VUE. Inflammation of the chorionic plate may therefore be a combination of maternal and fetal inflammation. The fetal inflammatory response frequently includes eosinophils as an acute reaction, not only in the preterm (21), but also in the term baby. This may be caused by the small pool of neutrophils and the presence of large amounts of eosinophilic extramedullary hematopoiesis within the liver. The most severe consequence of inflammation of the chorionic plate vessels is thrombosis.

Grade of Fetal Vasculitis and Funisitis

As with chorioamnionitis, no uniform definition has been accepted, but van Hoeven defined funisitis as the presence of neutrophils within the vessel wall, with or without extension into the substance of Wharton's jelly. Simple margination of neutrophils was excluded from the definition (14,16,18).

Stage of Fetal Vasculitis and Funisitis

The umbilical vein becomes inflamed first, maybe beginning at the placental end of the cord (59). Inflammation begins as margination of neutrophils at the endothelium with progressive movement through the muscle into the cord substance (Fig. 5A-C).

Necrotizing or Sclerosing Funisitis

Necrotizing or sclerosing funisitis is evidence of a prolonged fetal inflammatory response. Fetal neutrophils that have migrated out of the umbilical vessels toward the amnion surface undergo degeneration, necrosis, and finally calcification (Fig. 6A). Lack of lymphatic drainage of the umbilical cord results in accumulation of debris (Fig. 6B). The etiology has been attributed to a number of organisms, which have in common the ability to result in prolonged infection without spontaneous uterine contractions. In many cases, no infectious cause is identified. The most common etiology is syphilis (60), but it has also been reported in HSV (61), and cultures have been positive with common organisms such as group B streptococcus and Gardnerella (62). There was no statistically significant correlation between the degree of necrotizing funisitis and fetal outcome; however, poorer fetal outcome is suggested with severe necrotizing funisitis, including a high rate of IUGR, stillbirth, necrotizing enterocolitis, and chronic lung disease (52,63).

Umbilical Cord Microabscesses (Candida Funisitis)

The most common congenital fungal infection is caused by Candida sp. Although Candida vaginitis is a very common complication of pregnancy, it rarely results in chorioamnionitis. The risk of Candida colonization is increased with cerclage or the presence of other foreign bodies and coexistent infection (64). Term infants may be colonized but are usually asymptomatic. Candida funisitis is life-threatening in a preterm infant.

The diagnosis of Candida infection is often made on the gross examination of the umbilical cord. The cord surface is studded with 0.05- to 0.2-cm yellow-white plaques that seem to be just under the amnion (Fig. 7A). Histological confirmation may be difficult if the exact area from the cord is not submitted. Acute inflammation from the cord vessels extends to the basement membrane of the amnion epithelium and forms a microabscess. The yeast and pseudohyphae are very difficult to see on routine stains and usually require a silver stain (Fig. 7B). Although chorioamnionitis often accompanies Candida funisitis, rarely are organisms seen within the membranes (65). Candida

Fetal Inflammatory ResponseNeutrophils Vue Microskopie
Fig. 6. (A) Cross section of umbilical cord with necrotizing funisitis. Note dense white band partially surrounding the umbilical vein. (B) Sclerosing funisitis with necrotic debris within the umbilical cord stroma caused by syphilis.

Fig. 5. (opposite page) (A) Umbilical vein with early phlebitis and margination of neutrophils. Neutrophils are seen beneath the endothelium and within the muscular wall. (B) Umbilical arteritis with extension of neutrophils into the muscular wall. (C) Funisitis with extension of neutrophils into Wharton's jelly in an amniotropic pattern around an umbilical artery.

Neutrophils Vue Microskopie

Fig. 7. (A) Candida albicans funisitis at term. Edema of umbilical cord, with 1- to 2-mm pinpoint yellow-white lesions on or just beneath the cord amnion epithelium. (B) Candida albicans pseudohyphae are very difficult to identify on H&E stains; all cases suspicious for Candida should be stained with a silver stain.

Fig. 7. (A) Candida albicans funisitis at term. Edema of umbilical cord, with 1- to 2-mm pinpoint yellow-white lesions on or just beneath the cord amnion epithelium. (B) Candida albicans pseudohyphae are very difficult to identify on H&E stains; all cases suspicious for Candida should be stained with a silver stain.

glabrata may also cause cord microabscesses but more often has widespread involvement of the membranes without production of pseudohyphae.

Funisitis Caused by Meconium Aspiration or Vascular Smooth Muscle Injury

Although acute chorioamnionitis is thought to be exclusively caused by infection, funisitis may be caused by other things. In the case of cord compression, inflammation may be secondary to tissue injury. Theoretically, the inflammatory cells should be evenly distributed around the injured vessel, not in the usual amniotropic pattern.

Meconium-laden macrophages have been identified within Wharton's jelly and are associated with smooth muscle injury and inflammation of the umbilical cord vessels (66). Meconium-associated inflammation is usually more severe in the cord than the membranes. This may be because of direct injury of the cord vessels by meconium. It has been postulated that the muscle injury is secondary injury caused by vasoconstriction. The presence of meconium within the fetal lung may also set up an inflammatory response, which is then manifest within the cord vessels (67).

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The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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  • Mara
    What is funisitis caused from?
    7 years ago

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