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

Abstract

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...

Necrotizing Enterocolitis Among Neonates in the United States

“…As previously described, breast milk appeared to reduce the severity of NEC. 2,6,26,27 Our multivariate analysis showed that in neonates who developed NEC, the reported use of breast milk decreased the likelihood that a neonate would require surgical treatment.…”

“…This is a dilemma that likely plagues all recent studies of NEC, since the diagnostic criteria for ileal perforations are not standardized and only one study has used histological criteria for the diagnosis of perforations in a clinical cohort. 2 In addition, proxies may not adequately reflect the true severity of illness or the therapeutic approach. Retrospective studies are also limited by incomplete data, and evaluation of interactions between drugs (like steroids and indocin) is better done prospectively.…”

“…In the last decade, there has been a gradual realization that not all clinically diagnosed cases of NEC fit the classic pathological description. 2 For example, isolated small bowel perforation may be diagnosed as a form of NEC even though there is little bowel necrosis. 2 Furthermore, not all types of NEC carry the same morbidity or mortality risks.…”

“…2 For example, isolated small bowel perforation may be diagnosed as a form of NEC even though there is little bowel necrosis. 2 Furthermore, not all types of NEC carry the same morbidity or mortality risks.…”

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

“…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. Since that time, two NICHD randomized controlled, multicenter trials involving EPS in ELBW infants have been halted by their safety review committees because of perforations in the treated cohorts.…”