New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure

Abstract

Background: Spontaneous intestinal perforation (SIP) is increasingly common in the premature infant and is associated with significant morbidity. Indomethacin use has been implicated as a co-risk factor for SIP when combined with glucocorticoids, but previous evidence argued against indomethacin being an independent risk factor when used prophylactically.

Objectives: (1) To establish a homogeneous cohort of SIP patients in a national data set and to contrast them to patients with surgical necrotizing enterocolitis (NEC). (2) To test the hypothesis that early post-natal indomethacin is independently associated with SIP.

Methods: A large de-identified data set was retrospectively queried by diagnosis, and then multiple antenatal and post-natal variables were tested by both univariate and multivariate analysis to identify associations with SIP. Sub-analyses were also performed to look at the timing of drug administration.

Results: There were 2105 patients evaluated in the data set. Patients were divided into matched controls (n = 581), those with SIP without report of NEC (n = 633) and those with NEC requiring surgery (n = 891). Infants with SIP were more likely to have a patent ductus arteriosus and more likely to be treated with vasopressors than either control or NEC patients. Compared to infants with NEC, patients with SIP were smaller, less mature and required more support. SIP was also diagnosed earlier than NEC (median of 7 vs 15 days). Patients with SIP were more likely to be treated with indomethacin, hydrocortisone or both on days of life 0-3 than controls.

Conclusions: (1) Surgical NEC and SIP have significant differences in presentation, demographics and morbidity. (2) A detailed look at drug timing revealed that early post-natal indomethacin is independently associated with SIP.