Pattern of cardiovascular anomalies associated with esophageal atresia: Support for a caudal pharyngeal arch neurocristopathy

Patients with cephalic neurocristopathy (an abnormality of neural crest differentiation) present a striking pattern of associated cardiovascular anomalies (CVA). Therefore, to support the hypothesis that esophageal atresia (EA) may be related to a defective contribution from the cephalic neural crest, we studied the pattern of CVA associated with EA. Medical records of 99 patients with isolated EA, 101 with isolated anorectal malformations (ARM) and 15 with both EA and ARM, consecutively admitted to our unit, were reviewed. The prevalence and pattern of CVA associated with isolated EA or isolated ARM were compared on the assumption that the cranial or caudal location of a major malformation is related to a different regional patterning of associated anomalies. The prevalence of CVA was 39% in patients with isolated EA and 7% in those with isolated ARM (p < 0.01). Neural crest-related CVA (aortic arch anomalies, conotruncal defects, and superior vena cava malformations) accounted for 72% of all CVA in patients with isolated EA versus 14% in those with isolated ARM (p < 0.02). In patients with isolated EA, anomalies of the fourth and sixth aortic arch derivatives accounted for 75% of all neural crest related CVA. The present pattern of CVA in infants with EA supports the concept that EA may be related to an abnormal contribution from caudal portion of cephalic neural crest.