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Updated: Aug 11, 2026

An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance
Published on: December 3, 2020
New insights into spontaneous intestinal perforation using a national data set: (2) two populations of patients with
J T Attridge1, R Clark, M W Walker
1University of Virginia Children's Hospital, Charlottesville, VA 22908, USA.
Insights
Spontaneous intestinal perforation (SIP) in premature infants presents two distinct patterns: early-onset SIP in less premature infants and late-onset SIP in extremely low birth weight (ELBW) infants linked to postnatal treatments.
Area of Science:
- Neonatalogy
- Pediatric Surgery
- Gastroenterology
Background:
- Spontaneous intestinal perforation (SIP) is a growing concern in premature infants.
- Historically, SIP was considered congenital, but recent observations link it to postnatal treatments like glucocorticoids and indomethacin.
- These differing etiological views have not been reconciled.
Purpose of the Study:
- To create a national cohort of SIP patients.
- To differentiate SIP cases based on diagnosis timing, distinguishing those susceptible to postnatal factors from those diagnosed at or near birth.
Main Methods:
- A national dataset was retrospectively analyzed for SIP diagnosis timing.
- The cohort was divided into early (0-3 days) and late (4-14 days) diagnosis groups.
- Univariate analysis compared demographics between early and late SIP subcohorts.
Main Results:
- 633 SIP patients were identified.
- Early SIP (n=116, median BW 1.401 kg) differed significantly from late SIP (n=386, median BW 775 g).
- Infants with early SIP were more likely to be male, have higher Apgar scores, and less likely to receive antenatal steroids, surfactant, or mechanical ventilation.
Conclusions:
- Two distinct infant populations develop SIP.
- Extremely low birth weight (ELBW) infants develop SIP later (7-10 days) after exposure to indomethacin and glucocorticoids.
- Infants with early SIP (0-3 days) are less premature and less exposed to postnatal risk factors.
Background:
Spontaneous intestinal perforation (SIP) is increasingly common in the premature infant and has been demonstrated to be associated with early postnatal administration of glucocorticoids and indomethacin. Before survival of the extremely low birth weight (ELBW) infant, SIP was thought to be a rare, congenitally acquired disease sporadically affecting the muscularis of the distal intestine. These disparate views of etiology have not been previously reconciled in the literature.
Objectives:
(1) To establish a cohort of SIP patients in a national data set. (2) To use timing of diagnosis as a unique data element and thereby differentiate between SIP cases which are susceptible to postnatal risk factors versus those occurring at or immediately after birth (and therefore not exposed to postnatal risk factors).
Methods:
A large identified national data set was used to retrospectively look at timing of diagnosis and then the cohort was divided into postnatal treatment groups for further subanalyses. This analysis resulted in the division of the cohort into early and late diagnosis SIP subcohorts. These were then queried retrospectively by univariate analysis to look for differences in demographics between the two (using a P-value < 0.05).
Results:
There were 633 patients with SIP evaluated in this data set. The early SIP cohort (0-3 days) was made up of 116 infants with a median BW of 1.401 kg, whereas the late cohort (4-14 days) held 386 infants with a median BW of 775 g. Infants with early SIP were significantly more likely to: be male, have higher Apgar scores, have not received antenatal steroids, surfactant or required mechanical ventilation.
Conclusions:
Two populations of infants acquire SIP: ELBW infants acquire SIP on average between 7 and 10 days of life after exposure to indomethacin and glucocorticoids (either endogenous or exogenous), and infants with early SIP (0-3 days) who are significantly less likely to have been exposed to postnatal risk factors and are less premature.
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