BACKGROUND:Prior studies have identified individual risk factors that are associated with necrotizing enterocolitis (NEC); however, the small sample sizes of these previous studies have not allowed the analysis of potential interaction between multiple variables and NEC. Our purpose was to describe the incidence and risk factors for NEC in premature neonates admitted for intensive care. METHODS:We identified neonates as having NEC if they met accepted diagnostic criterion for necrotizing enterocolitis. Using a national database, we assessed the association between NEC and a battery of risk factors previously reported in peer-reviewed literature. RESULTS:There were 15,072 neonates that met inclusion criteria; 14,682 did not have NEC, while 390 (2.6%) met criterion for NEC. Multivariate analysis showed that low birth weight was the most important risk factor for NEC. Other factors that were associated with an increased risk of NEC were exposure to antenatal glucocorticoids, vaginal delivery, need for mechanical ventilator support, exposure to both glucocorticoids and indomethacin during the first week of life, absence of an umbilical arterial catheter, and low Apgar score at 5 minutes. Length of hospital stay and mortality were higher in neonates with NEC than in neonates without NEC. CONCLUSIONS:NEC remains an important cause of morbidity and mortality in prematurely born neonates. In contrast to previous studies, we found that exposure to antenatal glucocorticoids was associated with an increased risk for NEC independent of birth weight.

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 postnatal 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 ¼ 581), those with SIP without report of NEC (n ¼ 633) and those with NEC requiring surgery (n ¼ 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.

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...

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Objective:Necrotizing enterocolitis (NEC) is associated with high morbidity and mortality among infants admitted for intensive care. The factors associated with mortality and catastrophic presentation remain poorly understood. Our objective was to describe the factors associated with mortality in infants with NEC and to quantify the degree to which catastrophic presentation contributes to mortality in infants with NEC. Catastrophic NEC was defined before data analysis as NEC that led to death within 7 days of diagnosis.Study Design:We performed a retrospective review of the Pediatrix's Clinical Data Warehouse (1997 to 2009, n=560,227) to compare the demographic, therapeutic and outcome characteristics of infants who survived NEC vs those who died. Associations were tested by bivariate and multivariate analysis.Result:We compared the 5594 infants diagnosed with NEC and who were discharged home with 1505 infants diagnosed with NEC who died. In multivariate analysis, the factors associated with death (P<0.01 in analysis) were lower estimated gestational age, lower birth weight, treatment with assisted ventilation on the day of diagnosis of NEC, treatment with vasopressors at the time of diagnosis, and Black race. Patients who received only ampicillin and gentamicin on the day of diagnosis were less likely to die. Two-thirds of NEC deaths occurred quickly (<7 days from diagnosis), with a median time of death of one day from time of diagnosis. Infants who died within 7 days of diagnosis had a higher birth weight, more often were on vasopressors and high frequency ventilation at the time of diagnosis compared with patients who died at 7 or more days. Although mortality decreased with increasing gestational age, the proportion of deaths that occurred within 7 days was relatively consistent (65 to 75% of the patients who died) across all gestational ages.Conclusion:Mortality among infants who have NEC remains high and infants who die of NEC commonly (66%) die quickly. Most of the factors associated with mortality are related to immaturity, low birth weight and severity of illness.