Umbilical cord ulceration-intestinal atresia syndrome (ORPHA:3405)
A rare syndromic intestinal malformation characterized by ulcer formation in the umbilical cord associated with congenital upper-intestinal atresia, typically presenting with intra-uterine hemorrhaging from the ulcer site and subsequent fetal bradycardia.
Epidemiology
Whilst about 66 cases have been described to date in the medical and scientific literature, the entity is probably grossly under-reported due to lack of awareness.
Clinical description
Umbilical cord ulceration (UCU) occurs in the context of duodenal or jejunal intestinal atresia, developing in 6.5-13.6% of infants with a prenatal diagnosis of congenital upper intestinal atresia (CUIA). Onset of the UCU typically occurs from gestational week 30 onwards. Symptoms of UCU usually begin with the onset of premature labor or rupture of membranes, where the increased intra-uterine pressure causes rupture of the umbilical vessel into the amniotic cavity, triggering massive fetal hemorrhage and subsequent bradycardia. Severe anemia is typically present at birth. The degree of ulceration ranges from only desquamation of the epithelium to exposure of the umbilical artery or vein. Cases that do not significantly hemorrhage, especially lower grade lesions, may go undiagnosed.
Etiology
Whilst the exact mechanism of pathogenesis is unclear, it is suspected that UCU is closely related to in-utero regurgitation of bile. Other mechanisms proposed include vascular hyper-reactivity and secondary ischemia, causing simultaneous occurrence of both UCU and CUIA, due to an epithelial abnormality (similar to the association of epidermolysis bullosa with intestinal atresia).
Diagnostic methods
Prenatal ultrasound findings of CUIA with polyhydramnios should raise suspicion of associated UCU. However, in these cases, confirmation of diagnosis is most often done postnatally upon examination of umbilical cord.
Differential diagnosis
Differential diagnoses include absence of Wharton's jelly, omphalomesenteric duct with gastric mucosa, umbilical cord hemangioma, and umbilical hematoma.
Antenatal diagnosis
Suggestive ultrasound (US) findings include signs of CUIA and polyhydramnios. Whilst there is an increased risk of UCU in cases of CUIA, prenatal detection of UCU is challenging. In high-risk cases, increased frequency of ultrasound monitoring with a meticulous evaluation of the umbilical cord, especially at the fetal end, is advisable but technically difficult. Findings suspicious of blood in amniotic fluid include observations of bleeding from the umbilical cord by color Doppler or changes in the luminosity of the amniotic fluid indicating the presence of blood. Measurement of bile acid concentration in amniotic fluid can further help in segregation of high-risk cases.
Management and treatment
It is currently difficult to present a method by which sudden fetal death can be prevented. The risk of UCU must be explained elaborately to the parents of fetuses with CUIA. Daily monitoring of high risk cases with fetal kick chart and non‐stress test (NST) is advisable for early detection of UCU. Termination of pregnancy may be considered when hemorrhage is confirmed via amniocentesis or ultrasound findings are suggestive of blood in amniotic fluid. In cases of polyhydramnios with CUIA, continuous fetal heart monitoring at the onset of premature labor or premature rupture of membranes has been found to improve outcome. Awareness of this association and immediate delivery of fetus at first signs of hemorrhage or hypoxia will help prevent stillbirths and poor neonatal outcomes.
Prognosis
Prognosis of Umbilical cord ulceration-intestinal atresia syndrome is poor, with intra-uterine fetal or neonatal death occurring in the majority of cases. Prompt intervention, initiated with immediate delivery at the first signs of fetal hemorrhage/hypoxia, may improve the outcome.

                            Last update: 
                            March 2019


                            - Expert reviewer(s): 
                            Dr Sangeeta GUPTA