Case Studies #1 & #2

Case Study #1: Recurrent umbilical cord torsion leading to fetal death in 3 subsequent pregnancies: a case report and review of the literature.

Bakotic BW, Boyd T, Poppiti R, Pflueger S.

The Arkadi M. Rywlyn, MD, Department of Pathology, Mount Sinai Medical Center, Miami Beach, FL, USA.

During a span of 3.5 years, a 30-year-old, gravida 9, para 3 woman experienced 3 pregnancies complicated by umbilical cord torsion and constriction. In each case, the complication resulted in acute vascular compromise and intrauterine fetal demise. Gross examination disclosed cord constriction and torsion at the fetal end of the cord in each instance. Histologic sections from the cord torsion sites demonstrated fibrosis and deficiencies in Wharton's jelly in each case. Cytogenetic studies prepared using fetal villous tissue demonstrated normal karyotypes in fetal cells from the first 2 pregnancies (46,XX and 46,XY, respectively). The karyotype from the third pregnancy showed a 46,XX,del(X)(q24) mutation in 3 of 15 cultured cells, while 12 of 15 cells possessed a normal 46,XX karyotype. This cytogenetic abnormality was not believed to represent the cause of fetal demise in this case. To our knowledge, this is the first report of umbilical cord torsion in 3 pregnancies within one family. The familial clustering observed in this report suggests that a genetic predisposition for umbilical cord torsion may exist in some cases.

REPORT OF A CASE

During a 7-year period, a 30-year-old, white, gravida 9, para 3 woman experienced 3 successful births resulting in healthy infants (1990, 1992 twins), 3 spontaneous abortions for unknown causes (1989, 1989, 1995), and 3 cases of intrauterine fetal demise secondary to umbilical cord torsion (1993, 1996, 1996). In each pregnancy complicated by cord torsion, the patient had received prenatal care, including ultrasound imaging studies, which initially confirmed the presence of healthy viable fetuses. The mother presented with symptoms of decreased fetal movements in the initial instance, whereas the second and third cases were discovered during routine prenatal examinations. Following fetal demise in each instance, delivery was medically induced, and a nonviable fetus was delivered without further complication. A fetopsy examination was performed in each case.

PATHOLOGIC FINDINGS

Gross Findings

The initial occurrence of umbilical cord torsion resulted in the death of a 19-week female fetus. The fetus weighed 164 g and had a crown-rump length of 15.5 cm, a crown-heel length of 21.9 cm, and a foot length of 2.3 cm. The external surface showed generalized moderate maceration. The phenotypically female fetus was without facial dysmorphology. Internal examination demonstrated normal organogenesis and moderate visceral autolysis. The umbilical cord measured 36.5 cm and disclosed extensive spiraling. A well-defined point of constriction and torsion was noted in association with focally deficient Wharton's jelly, located 1 cm from the fetal abdominal wall. The placental disk disclosed a 1.3-cm subchorionic thrombus. No further gross abnormalities were present.

The second pregnancy to be complicated by umbilical cord torsion resulted in the death of a 16-week, phenotypically male fetus. The fetus weighed 96 g and had a crown-rump length of 13.4 cm, a crown-heel length of 19.4 cm, and a foot length of 2.0 cm. The cutaneous surface was moderately macerated in a generalized distribution. The fetus was without facial dysmorphology. Internal examination disclosed normal organogenesis and severe visceral autolysis. The umbilical cord measured 33.0 cm in length and showed extensive spiraling. A well-defined site of marked attenuation and torsion was present at the umbilical cord insertion site, immediately adjacent to the fetal abdomen (Figure 1 ). The proximal cord was moderately edematous. The placenta was grossly unremarkable.

The third instance of cord torsion resulted in the delivery of a nonviable, 15.5-week, phenotypically female fetus. The fetus weighed 58 g and had a crown-rump length of 8.7 cm, a crown-heel length of 11.9 cm, and a foot length of 1.2 cm. The integument showed moderately severe maceration in a generalized distribution. No facial dysmorphology was present. Internal examination revealed moderate visceral autolysis and normal organogenesis with appropriate reproductive system development for gestational age. The umbilical cord measured 27.0 cm in length and was extensively spiraled. The umbilical cord was focally deficient of Wharton's jelly and showed stricture and mild torsion adjacent to the abdominal insertion site. Proximal to the primary constriction site, the umbilical cord was moderately edematous and disclosed additional, less pronounced foci of attenuation. The placenta was grossly unremarkable.

Microscopic Findings

In all cases, histologic examination revealed normal visceral development without microscopic evidence of chronic fetal stress. The region of cord constriction and torsion in each case was deficient in Wharton's jelly, most notably in the peripheral aspects of the umbilical cord. The paucity of Wharton's jelly at the torsion sites was further illustrated by pale staining with Alcian blue, pH 2.5 (Figure 2 ), and toluidine blue. All torsion sites were without significant inflammation. Microscopic analysis of each placenta disclosed slight variability in villous size and maturation, as well as patchy villous edema. Additionally, intravascular karyorrhexis, villous sclerosis, and villous edema were present in the placenta from the second case of cord torsion. These placental findings are consistent with the history of intrauterine fetal demise.

Cytogenetic Findings

An aliquot of fetal cells was obtained from fetal villous tissue in each case, and the samples were examined by cytogenetic techniques. To summarize, metaphase spreads were made from a 24-hour, unstimulated cell culture and were G-banded by the standard trypsin-Giemsa banding method. Analysis performed on a sample of metaphase chromosomes disclosed normal karyotypes (46,XX and 46,XY, respectively) in the initial and second case of fetal demise. In the third case, 3 of 15 scored cells disclosed a 46,XX,del(X)(q24) karyotype, while the remaining cells showed a normal 46,XX karyotype.

Umbilical cord torsion is now an accepted cause of intrauterine fetal demise. Until recently, the identification of umbilical cord constriction and torsion has been restricted to postmortem examinations, leaving room for much debate as to whether such findings represented actual causes of death or postmortem artifacts.1 It is now suspected that cord torsion may occasionally be associated with adverse fetal and placental changes prior to fetal demise. Investigators have suggested that cardiac arrhythmias, heart failure, nonimmune hydrops, intrauterine growth retardation, placental insufficiency, and oligohydramnios may all occur secondary to cord torsion.4,5 The antemortem findings associated with this gestational complication may now be better characterized, as it is becoming possible to identify cord torsion prenatally using ultrasonography.6

The mechanism and predisposing factors for umbilical cord torsion have not been completely elucidated. Previous authors have noted an increased propensity for occurrence in association with excessively long and spiraled umbilical cords, twin gestations, and following amniocentesis procedures.1,2,7–10 Additionally, focal deficiencies in Wharton's jelly may leave the cord without its structural integrity and predispose it to torsion and resultant vascular compromise.1,2,11,12 In the third pregnancy of this series, the primary constriction site lacked the profound spiraling observed in the previous 2 gestations. The affected region of the cord showed marked attenuation with fibrosis in association with mild spiraling. These findings suggest that cord stricture, in lieu of a significant torsion component, may have played a more significant role in the eventual demise of this fetus. Although cord constriction seems to be related and possibly predisposes to cord torsion in some cases, instances in which umbilical cord stricture has resulted in fetal death independent of umbilical cord torsion have been reported.8,13

From a histologic perspective, the umbilical cord torsion site is typically deficient in Wharton's jelly and shows stromal fibrosis. Wharton's jelly is comprised largely of mucopolysaccharides, specifically hyaluronic acid and chondroitin sulfate.12 For this reason, its absence may be easily demonstrated using Alcian blue (pH 2.5) or toluidine blue, both of which will highlight mucosubstances present within the cord. In some instances the Wharton's jelly is entirely replaced by fibrous tissue, although this change did not occur in our cases.1,2,9 Although usually not commented on, some reported cases have described a lack of inflammation at the torsion site, as noted in our case.2 This finding might be predicted when considering the acute setting in which the vascular compromise may occur and the avascular microenvironment produced at the constriction site by cord torsion. Many early reports emphasized the presence of intravascular thrombi as a defining characteristic for genuine umbilical cord torsion1; however, as in our cases, subsequent reports have not found intravascular thrombi to be a consistent finding.2,9

In a recent review of the literature regarding mosaicism found by fetal villous sampling, Phillips et al14 found only 10% of such cases harbored mosaicism within the fetal tissue proper. In our case, the presence of a 46,XX,del(X)(q24)/46,XX mosaic karyotype most likely represents contamination from a lost twin or a nondisjunctional event limited to extraembryonic tissue.15,16 In the low likelihood that this genetic abnormality was present in fetal cells, the mosaicism could be explained by maternal cell contamination, or more likely by its occurrence as a postzygotic event in embryological development. Although a Turner syndrome phenotype cannot be entirely ruled out, a recent study has suggested that this is unlikely in deletions occurring distal to Xq24.17 Because our cases demonstrated a distinct lack of facial and corporal dysmorphology and normal organogenesis, and cytogenetic studies showed a low number of cells expressing the 46,XX,del(X)(q24) mutation, we believe this genetic abnormality did not contribute to the cause of death in this fetus.

In summary, umbilical cord torsion is an uncommon cause of intrauterine fetal death. Although once thought to be an exclusively sporadic event, recent reports have shown familial clustering. In the present report, we describe 3 pregnancies complicated by umbilical cord stricture and torsion occurring in one family over a 3.5-year period. Such intrafamilial clustering suggests that a genetic predisposition for umbilical cord torsion may exist in some cases.



Case Study #2: One Woman Loses 3 of 4 Pregnancies to Umbilical Cord Stricture

Obstetrics & Gynecology 2005;105:1235-1239

CASE REPORTS

Umbilical Cord Stricture: A Cause of Recurrent Fetal Death

Amy E. French, MD, Vanessa H. Gregg, MD, Yvonne Newberry, NP and Theodore Parsons, MD

Departments of Obstetrics and Gynecology and Pathology, University of Virginia, Charlottesville, Virginia

BACKGROUND: Umbilical cord stricture is a recognized cause of fetal demise, but the exact etiology remains unknown. The risk of recurrence has generally been thought to be low.

CASE: Three of 4 fetuses of a single patient died between 28 and 30 weeks of gestation; all were found to have stricture of the umbilical cord at the fetal insertion. Her one surviving infant was delivered emergently at 25 weeks. All infants were growth restricted but had no anatomic abnormalities.

CONCLUSION: Umbilical cord stricture was diagnosed as the cause of all 3 fetal deaths. Patients with a demise attributed to umbilical cord stricture should be counseled that the risk of recurrent cord stricture is undetermined.