Resistance to activated protein C - a genetic risk factor for neonatal necrotizing enterocolitis?

Background: Recently the resistance to activated protein C(APC-resistance) was identified to be the most common risk factor for deep vein thrombosis in the Caucasian population. Reports on a high frequency of APC-resistance in children and newborns with venous or arterial thrombembolism(Nowak-Göttl, Br J Hämatol 1996;92:992-8) and a high prevalence of thrombi within the large mesenteric artery branches in patients autopsied because of NEC (Ballance, J Pediatr 1990;117:S6-13), raising the question if APC-resistance is a risk factor for the development of neonatal necrotizing enterocolitis. Study design: Retrospective case-control-study .Patients: All patients with NEC ≥ II according to Bell (n=30) or spontaneous gastrointestinal perforation (n=9) treated in our intensive care unit between January 1990 and December 1996. Controls matched by birth weight .Methods: DNA-extraction of dried filterpaper blood spots from the newborn screening program. polymerase chain reaction with primers specific for a 266 bp fragment of factor V and digestion with Mnl 1 (Bertina. Nature 1994:369:64-7). Results: DNA-extraction and PCR was successful in 87% of the children with NEC and 78% of children with spontaneous gastrointestinal perforation, including all children who died (n=5). No differences between patients and controls with regard to birth weight, gestational age. sex and number of children who need ventilatory support. In both groups one child (3%) was heterozygote APC-resistant (p=n.s.). Conclusion: Despite the limitations imposed by the retrospective study design, our data clearly indicate that APC-resistance is no risk factor for the development of NEC.