Placenta
Volume 31, Issue 11 , Pages 1015-1018, November 2010

Pathological analysis of umbilical cord ulceration associated with fetal duodenal and jejunal atresia

  • M. Ichinose

      Affiliations

    • Department of Obstetrics and Gynecology, Japan Red Cross Medical Center, Tokyo, Japan
    • Corresponding Author InformationCorresponding author. Present address: University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: +81 338155411.
    • ,
  • T. Takemura

      Affiliations

    • Department of Pathology, Japan Red Cross Medical Center, Tokyo, Japan
    • ,
  • K. Andoh

      Affiliations

    • Department of Obstetrics and Gynecology, Japan Red Cross Medical Center, Tokyo, Japan
    • ,
  • M. Sugimoto

      Affiliations

    • Department of Obstetrics and Gynecology, Japan Red Cross Medical Center, Tokyo, Japan

Accepted 9 August 2010. published online 02 September 2010.

Article Outline

Abstract 

Umbilical cord ulceration is a serious complication of fetal intestinal atresia. To elucidate the relationship between fetal intestinal atresia and umbilical cord ulceration grade, we pathologically examined umbilical cords in 15 duodenal and 5 jejunal atresia cases and 28 control cases. Microscopic examination of the umbilical cords of patients with intestinal atresia revealed high-grade ulceration and a significant increase in macrophage numbers (P = 0.0087). Transudation of red blood cells was not associated with any specific clinical diagnosis, but was seen in all high-grade ulceration cases. It is suggested that clinical symptoms become apparent following gradual pathological changes.

Keywords: Umbilical cord ulceration, Intestinal atresia, Ulceration grade, Wharton’s jelly

 

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1. Introduction 

Congenital fetal duodenal or jejunal atresia often accompanies umbilical cord ulceration, which results in the rupture of umbilical cord vessels and massive intrauterine hemorrhage that might lead to fetal death [1], [2], [3], [4], [5], [6], [7]. The frequency of umbilical cord ulceration in congenital intestinal atresia cases has been reported to range from 6.5% [1] to 13.6% [2]. Three hypotheses for the cause of umbilical cord ulceration are vascular reactivity, gastric reflux, and epithelial abnormalities [3].

Although there are many case reports of the association between umbilical cord ulceration and fetal intestinal obstruction, no studies have reported on the umbilical cord ulceration grade. To elucidate the relationship between fetal intestinal atresia and umbilical cord ulceration grade, we pathologically analyzed the umbilical cords in 15 duodenal and 5 jejunal atresia cases and 28 control cases; we determined the ulceration grade and assessed the transudation of red blood cells and number of macrophages in the Wharton’s jelly.

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2. Materials and methods 

We analyzed the umbilical cord pathology of 15 duodenal atresia patients and 5 jejunal atresia patients born at the Japan Red Cross Medical Center from January 1997 to January 2010. Umbilical cord ulcerations were clinically diagnosed when the amniotic fluid was bloodstained, and exposed umbilical vessels and neonatal anemia were observed at birth. In cases of duodenal atresia, the location of the precise site of obstruction (oral or anal side of the major duodenal papilla) was determined on the basis of the operation or autopsy records, except in the case of 1 patient who died without both records. We also included 28 control infants without intestinal atresia born between 33 and 35 gestational weeks. The mean gestational week and the birth weight at the time of delivery were 34.8 weeks (range, 25–41 weeks) and 2044 g for the intestinal atresia cases and 34.5 weeks (range, 33–35 weeks) and 2018 g for the control cases, respectively.

Three different sections of each umbilical cord (2 cm from the placental end of the cord, approximately 2 cm from the fetal umbilicus, and the midportion of the cord) were pathologically examined to determine ulceration grade, transudation of red blood cells, and the number of macrophages in the Wharton’s jelly. Ulceration was graded using the original criteria (Fig. 1a): grade 1, desquamation of epithelium only; grade 2, detachment of basal lamina; grade 3, thinning of the Wharton’s jelly with widespread grade 2 change; and grade 4, exposed umbilical artery or vein. The grade of each specimen was determined by the grade of the most severe lesion. We examined the transudation of red blood cells from the umbilical artery or vein into the Wharton’s jelly. Macrophages in the Wharton’s jelly were immunohistochemically stained for CD68 (clone Kp-1, DAKO) (Fig. 2). The number of macrophages per 1 mm2 area in the 2 most crowded sites was calculated using a micrometer, and the mean was used as the number for each sample. We statistically analyzed the data by unpaired t-test. Cases with funisitis were excluded from macrophage counts to eliminate the influence of bacterial infection.

  • View full-size image.
  • Fig. 1. 

    (a)Original classification of ulceration grade, Hematoxylin and eosin stain, ×100, scale bar = 250 μm, (b)Distribution of ulceration grade in intestinal atresia cases, (c)Distribution of ulceration grade in cases of each precise part of obstruction clinically diagnosed umbilical cord ulceration cases, (d)Distribution of ulceration grade in cases in each gestational week at delivery.

  • View full-size image.
  • Fig. 2. 

    (a) Macrophage in Wharton's jelly CD68 immunohistochemical stain : ×200, scale bar = 100 μm : ×400, scale bar = 50 μm, (b)The number of macrophage in each group.

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3. Results 

Among 20 fetal patients with intestinal atresia, 3 were clinically diagnosed with umbilical cord ulceration. These 3 patients presented with nonreassuring fetal status during routine fetal heart rate monitoring, and emergency cesarean sections were performed; however, these patients died during the neonatal period.

The ulceration grades in the intestinal atresia cases and control cases are shown in Fig. 1b. Among the 20 intestinal atresia cases, the ulceration grade was 2–4 in 16 cases, whereas the ulceration grade was either 0 or 1 in all control cases. Of the 3 clinically diagnosed umbilical cord ulceration cases, 2 were assessed as grade 4 and 1 as grade 3. The distribution of ulceration grades in cases of duodenal atresia at the oral and anal sides of the major duodenal papilla and jejunal atresia is shown in Fig. 1c. The distribution of ulceration grades in each gestational week at delivery is shown in Fig. 1d. The mean gestational week at delivery in cases of intestinal atresia that presented with each ulceration grade was as follows: grade 0, 36.0 weeks (n = 1); grade 1, 34.7 weeks (n = 3); grade 2, 35.3 weeks (n = 7); grade 3, 34.9 weeks (n = 7); and grade 4, 32.5 weeks (n = 2).

Transudation of red blood cells was observed in 15 of 20 intestinal atresia cases and 12 of 28 control cases. The incidence of transudation of red blood cells for each ulceration grade in the atresia cases was as follows: grade 0, 0/1 case; grade 1, 2/3 cases; grade 2, 4/7 cases; grade 3, 7/7 cases; and grade 4, 2/2 cases.

We determined the number of CD68+ macrophages in the Wharton’s jelly in 12 intestinal atresia cases and 9 control cases, which did not have infectious funisitis (Fig. 2). The number of macrophages was significantly increased in the intestinal atresia cases (P = 0.0087) (Fig. 2b). The mean macrophage count for each ulceration grade in the intestinal atresia cases was as follows: grade 0, 19.5 (n = 1); grade 1, 34.8 (n = 2); grade 2, 27.0 (n = 4); grade 3, 23.5 (n = 4); and grade 4, 19.5 (n = 1).

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4. Discussion 

The pathologic findings of umbilical cords in clinically diagnosed umbilical cord ulceration cases have been precisely described in some reports [2], [3], [4]. Degeneration of the Wharton’s jelly and the existence of macrophages were common findings, and necrotic umbilical vessels were observed in many cases. Ohyama reported mild degenerative changes in 3 asymptomatic intestinal atresia cases [2]. In our study, the ulceration grade was determined to evaluate the pathological changes in the umbilical cord in asymptomatic intestinal atresia cases. The number of macrophages in the Wharton’s jelly was determined. Additionally, transudation of red blood cells was examined as pathological confirmation of bleeding from the umbilical cord.

Considering our results that the ulceration grade was higher in intestinal atresia cases, it is suggested that clinical symptoms become apparent following gradual pathological changes. The gradual changes did not seem to be correlated with gestational weeks.

Transudation of red blood cells was also observed in all cases in which the ulceration grade was higher than 3, but it was also observed in many control cases and was not specific to any clinical diagnosis. Transudation of red blood cells does not always indicate fetal anemia. In fact, other than the 3 clinically diagnosed umbilical cord ulceration cases, anemia was not observed in any other case at birth. Theoretically, the transudation of red blood cells along with the thinning of the Wharton’s jelly may result in fetal umbilical cord bleeding. Clinical signs such as umbilical cord bleeding or bloodstained amniotic fluid suggest the relationship between cord ulceration and anemia at birth.

Finally, although the number of macrophages was significantly increased in intestinal atresia cases as compared to the control cases, it did not increase with an increase in ulceration grade. The increase in macrophages may be a chronic reaction against some stimulus other than infection, such as the presence of a chemical substance in the amniotic fluid.

Bile acid and bilirubin concentrations in the amniotic fluid are reported to be considerably elevated in intestinal obstruction cases [8], [9]. A thick meconium can result in vascular necrosis and ulceration in the umbilical cord [10]. However, the substance in the regurgitated digestive juices that causes umbilical cord ulceration remains unknown. In our study, no significant differences were found between the sites of obstruction in the ulceration grades, and grade 3 umbilical cord ulcerations were observed in cases of duodenal atresia that presented with obstruction at the oral side of the major duodenal papilla. This suggests that gastric juice can cause umbilical cord ulceration and that multiple digestive enzymes such as pepsin, bile acid, bilirubin, and trypsin are related to umbilical cord ulceration. In patients without fetal anemia, no clinical signs predictive of umbilical cord ulceration, such as fetal heart rate abnormality or abnormal Doppler velocity, were observed. Prenatal diagnosis of umbilical cord ulceration may be possible by performing a thorough ultrasonographic examination of the umbilical cord.

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References 

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  2. Ohyama M, Itani Y, Yamanaka M, Imaizumi K, Nishi T, Ijiri R, et al. Umbilical cord ulcer: a serious in utero complication of intestinal atresia. Placenta. 2000;21:432–435
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PII: S0143-4004(10)00300-0

doi:10.1016/j.placenta.2010.08.005

Placenta
Volume 31, Issue 11 , Pages 1015-1018, November 2010

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