Localized intestinal perforations after enteral administration of indomethacin in premature infants

Alpan, Gad; Eyal, Fabian; Vinograd, Itzhak; Udassin, Raphael; Amir, Gail; Mogle, P; Glick, Benjamin S.

doi:10.1016/s0022-3476(85)80305-x

Cited by 119 publications

(47 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is often clinically mistaken for perforation secondary to necrotizing enterocolitis (NEC). 1 Case reports of FSBP have associated this disorder with hypoxic-ischemic injury, 2,3 congenital absence of the muscularis externa, 4 -6 indomethacin, 7,8 dexamethasone, 9,10 and candidal infection. 11 Risk factors for FSBP have also been postulated to be multifactorial.…”

Section: Discussionmentioning

confidence: 99%

“…Previous case reports have associated FSBP with obstructive-ischemic injury, 2,3 congenital absence of the muscularis externa, 4 -6 candidal infection, 11 indomethacin, 7,8 and dexamethasone. 9,10 Several of these possibilities were excluded in our patient group.…”

Section: Discussionmentioning

confidence: 99%

“…From the list of risk factors derived from case reports of FSBP above, only indomethacin and dexamethasone could not be excluded by intraoperative, microbiologic, or pathologic findings. Indomethacin is the only agent implicated in the genesis of FSBP 7,8 that also has been proven to cause intestinal injury in animal models. 12,13 Despite this, we were unable to demonstrate an increased risk for FSBP in infants treated with indomethacin.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Early Postnatal Dexamethasone Increases the Risk of Focal Small Bowel Perforation in Extremely Low Birth Weight Infants

et al. 1999

View full text Add to dashboard Cite

OBJECTIVE:We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants. METHODS:A case-controlled analysis was performed using all infants born weighing Ͻ1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study. RESULTS:Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens. CONCLUSION:These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.Focal small bowel perforation (FSBP) is a sporadic problem occurring in premature infants. It is often clinically mistaken for perforation secondary to necrotizing enterocolitis (NEC). 1 Case reports of FSBP have associated this disorder with hypoxic-ischemic injury, 2,3 congenital absence of the muscularis externa, 4 -6 indomethacin, 7,8 dexamethasone, 9,10 and candidal infection. 11 Risk factors for FSBP have also been postulated to be multifactorial. 1 Unfortunately, evidencebased research on FSBP is scant.In late 1996 and mid 1997, two clusters of FSBP occurred in extremely low birth weight (ELBW) infants at the University of Washington Medical Center (UWMC) neonatal intensive care unit (NICU). These clusters coincided with the onset of a standardized protocol for early dexamethasone prophylaxis (EDP) in premature infants at risk for bronchopulmonary dysplasia. During the first month, four infants who received EDP required urgent surgery for pneumoperitoneum and were found to have FSBP. The EDP protocol was suspended pending review of the cases and literature.Review of the literature failed to find any reports of FSBP occurring in clusters. Review of all neonatal surgical cases in the previous 6 months revealed two more infants with FSBP who also weighed Ͻ1001 gm. Indomethacin proph...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Early Postnatal Dexamethasone Increases the Risk of Focal Small Bowel Perforation in Extremely Low Birth Weight Infants

et al. 1999

View full text Add to dashboard Cite

show abstract

“…2 In 1985, with improving survival of low birth weight (LBW) neonates, four SIP case reports suggested the possibility of an acquired pathology secondary to perturbed intestinal development by indomethacin. 3 In 1988, Aschner et al 4 described a case series of SIP in LBW infants and was the first to demonstrate SIP as a prevalent diagnosis in this emerging patient population. At the end of the decade, Gordon et al 5 and Garland et al 6 demonstrated that early postnatal steroid (EPS) exposure was associated with increased prevalence of SIP in extremely LBW (ELBW) infants.…”

Section: Introductionmentioning

confidence: 99%

Discharge outcomes of extremely low birth weight infants with spontaneous intestinal perforations

et al. 2005

View full text Add to dashboard Cite

Objective: To examine discharge outcomes of extremely low birth weight infants (ELBW) with spontaneous intestinal perforation (SIP).Study design: A single-center retrospective cohort study of all ELBW infants admitted to the University of Virginia neonatal intensive care unit between July 1996 and June 2004. Results:We found 35 patients with SIP (incidence 8.4%). The median gestational age was 25 weeks, median birth weight was 722 g, and 71% of the infants were male. Most infants (n ¼ 28) with SIP were diagnosed secondary to pneumoperitoneum; however, one-third (7) of infants <25 weeks had occult presentations without pneumoperitoneum. When controlled for gestational age, gender, multiple gestation, indomethacin, and glucocorticoid exposure, infants with SIP have a higher risk of PVL and death than infants without perforation.Summary: Periventricular leukomalacia and death are significantly associated with SIP in ELBW after adjusting for gestational age, multiple gestation, indomethacin, and glucocorticoid exposure.

show abstract

“…Ibuprofen in comparison to indomethacin has been shown to have milder effects on cerebral, renal and mesenteric blood flow. 7,8,9 Impaired mesenteric circulation due to a 'diastolic steal' from a hemodynamically significant PDA, vasoconstrictive effects and local prostaglandin inhibition by indomethacin have been suggested as risk factors for the development of spontaneous intestinal perforation (SIP) and NEC; 10,11 gastrointestinal complications associated with indomethacin treatment.…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

Rao

Bryowsky

Mao³

et al. 2011

J Perinatol

View full text Add to dashboard Cite

Objective: To review intestinal complications associated with ibuprofen treatment of patent ductus arteriosus (PDA).Study Design: Data from preterm infants treated with ibuprofen were retrospectively reviewed. w 2 test and Fischer's exact test were used for univariate analyses. Multivariate analyses with logistic regression modeling were used to identify risk factors.Result: One hundred and two infants were treated with ibuprofen for PDA. Nine (9/102, 8.8%) infants developed spontaneous intestinal perforation (SIP), whereas 93/102 (91.2%) did not. The mean (±s.d.) gestational age (GA) at birth in infants with and without SIP was 25.2 ( ± 1.3) vs 27.6 ( ± 2.4) weeks (P ¼ 0.02) and the median (interquartile) length of stay (LOS) was 109.5 (91.0 to 116.5) vs 75.0 (53.0 to 94.5) days (P ¼ 0.002), respectively. The mean ( ± s.d.) age at starting ibuprofen was 3.3 ( ± 1.3) vs 5.8 (±3.5) days in infants with and without SIP, respectively (P ¼ 0.03). In logistic regression analyses, increasing GA and later initiation of ibuprofen treatment were protective against risk of SIP; odds ratio, 95% confidence interval (OR, 95% CI) ¼ 0.26 (0.09 to 0.75), P ¼ 0.01 and 0.63 (0.41 to 0.95), P ¼ 0.03, respectively.Conclusion: Infants at lower GA are at risk of SIP when treated early with ibuprofen for symptomatic PDA.

show abstract

Localized intestinal perforations after enteral administration of indomethacin in premature infants

Cited by 119 publications

References 21 publications

Early Postnatal Dexamethasone Increases the Risk of Focal Small Bowel Perforation in Extremely Low Birth Weight Infants

Early Postnatal Dexamethasone Increases the Risk of Focal Small Bowel Perforation in Extremely Low Birth Weight Infants

Discharge outcomes of extremely low birth weight infants with spontaneous intestinal perforations

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

Contact Info

Product

Resources

About