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ObjectiveTo investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease.Study designSixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 10(9) colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease.ResultsHealthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1β levels were transiently higher in the probiotic group.ConclusionCongenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent.

ObjectiveTo determine whether an association exists between antenatal antibiotic exposure and incidence of necrotizing enterocolitis (NEC) in low birth weight infants.Study designA retrospective case-control study was performed on all infants with a diagnosis of NEC born at our institition between 1988 and 2006. Medical histories of all infants with a diagnosis of NEC ≥Bell's stage IIA and matched controls without NEC were reviewed. Maternal and neonatal characteristics were compared using the Mantel-Haenszel chi-square procedure, and logistic regression models were constructed to account for confounding.ResultClinical data for 97 matched pairs were analyzed. The adjusted odds ratio (OR) for antenatal exposure to ampicillin was significantly greater for infants who developed NEC (OR 2.3, 95% confidence interval 1.1, 4.8, P=0.003) than for control infants.ConclusionInfants who developed NEC were more likely to have a history of in utero exposure to ampicillin in the immediate antepartum period than infants who did not develop NEC.

OBJECTIVE: To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18-22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation. STUDY DESIGN: Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center.RESULT: Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively). CONCLUSION: Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18-22 months corrected age. [ABSTRACT FROM AUTHOR]

Objective:Pasteurized, donated milk is increasingly provided to preterm infants in the absence of mother's own milk. The aim of this study was to determine the effect of pasteurization on the concentration of selected components in donated human breast milk.Study Design:Donated milk from 34 mothers was pooled into 17 distinct batches (4 mothers per batch). Aliquots of each batch were then Holder pasteurized (62.5 °C for 30 min). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70 and IL-13 were measured in a multiplex enzyme-linked immunosorbent assay (ELISA). Granulocyte colony-stimulating factor (G-CSF), heparin-binding epidermal-like growth factor (HB-EGF) and hepatocyte growth factor (HGF) were measured by ELISA. Lipids were assessed by gas chromatography and gangliosides by the resorcinol-HCl reaction.Result:IFN-γ, TNF-α, IL-1β, IL-10 and HGF were significantly reduced by pasteurization (P<0.05). Gangliosides were not affected, but the proportion of medium-chain saturated fats was increased (P<0.05) with a trend towards a decreased proportion of oleic acid (P=0.057).Conclusion:Pasteurization significantly reduced the concentration of several immunoactive compounds present in breast milk, but did not have an impact on others. [ABSTRACT FROM AUTHOR]

The intestinal microbiota normally exists in a commensal and/or symbiotic relationship with the host. In the past few years, emerging technologies derived largely from the Human Genome Project have been applied to evaluating the intestinal microbiota and new discoveries using these techniques have prompted new initiatives such as the Human Microbiome Roadmap designed to evaluate the role of the intestinal microbiome in health and disease. In this review, we wish to focus on some new developments in this area and discuss some of the effects of medical manipulations such as antibiotics, probiotics, prebiotics and C-section versus vaginal delivery on the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Objective:The objective of this study was to evaluate the impact of a standardized enteral feeding protocol for very low birth weight (VLBW) infants on nutritional, clinical and growth outcomes.Study Design:Retrospective analysis of VLBW cohorts 9 months before and after initiation of a standardized feeding protocol consisting of 6-8 days of trophic feedings, followed by an increase of 20 ml/kg/day. The primary outcome was days to reach full enteral feeds defined as 160 ml/kg/day. Secondary outcomes included rates of necrotizing enterocolitis and culture-proven sepsis, days of parenteral nutrition and growth end points.Result:Data were analyzed on 147 VLBW infants who received enteral feedings, 83 before ('Before') and 64 subsequent to ('After') feeding protocol initiation. Extremely low birth weight (ELBW) infants in the After group attained enteral volumes of 120 ml/kg/day (43.9 days Before vs 32.8 days After, P=0.02) and 160 ml/kg/day (48.5 days Before vs 35.8 days After, P=0.02) significantly faster and received significantly fewer days of parenteral nutrition (46.2 days Before vs 31.3 days After, P=0.01). Necrotizing enterocolitis decreased in the After group among VLBW (15/83, 18% Before vs 2/64, 3% After, P=0.005) and ELBW infants (11/31, 35% Before vs 2/26, 8% After, P=0.01). Late-onset sepsis decreased significantly in the After group (26/83, 31% Before vs 6/64, 9% After, P=0.001). Excluding those with weight <3rd percentile at birth, the proportion with weight <3rd percentile at discharge decreased significantly after protocol initiation (35% Before vs 17% After, P=0.03).Conclusion:These data suggest that implementation of a standardized feeding protocol for VLBW infants results in earlier successful enteral feeding without increased rates of major morbidities. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis is the most common and fulminant gastrointestinal disease affecting neonates. Its pathogenesis is heterogeneous and not clearly understood. Early detection could prevent some of the devastating consequences of this disease, but currently there is no noninvasive method of reliable early-stage detection. Here, we review various noninvasive monitoring technologies that have already been employed or show promise for early detection. Each method may have an important role after its technical difficulties are resolved. These are discussed in detail as they relate to various aspects of the putative pathophysiology of this devastating disease. [ABSTRACT FROM AUTHOR]

Objective:New biopharmaceuticals hold promise for preventing or treating necrotizing enterocolitis. However, it is unclear whether any such biopharmaceutical that requires enteral administration could be administered using an ‘early-treatment’ paradigm. This study was undertaken to assess this issue based on data from every case of Bell stage III NEC cared for during the past 7 years at Intermountain Healthcare.Study Design:Patients with Bell stage III NEC were identified from electronic medical record repositories and the diagnosis was validated using operative reports. Electronic and paper records of each patient were then used to identify potential clinical and laboratory antecedents occurring within the 48 h period preceding the diagnosis of NEC.Result:One hundred eighteen patients had Stage III NEC. The earliest recognized antecedents were nonspecific for NEC (apnea/bradycardia, skin mottling and irritability). These were recorded at 2.8±2.1, 4.5±3.1 and 5.4±3.7 (mean±s.d.) hours, respectively, before NEC was diagnosed. The most commonly identified gastrointestinal antecedents were blood in the stools, increased abdominal girth and elevated pre-feeding gastric residuals or emesis. These were identified 2.0±1.9, 2.8±3.1 and 4.9±4.0 h before NEC was recognized. Thirty-eight percent had a blood transfusion (18±12 h) preceding the NEC. Tachycardia, tachypnea, hypotension and diarrhea were rarely identified as antecedents and no consistent laboratory antecedents were discovered.Conclusion:We judge that an ‘early treatment of NEC’ paradigm testing any pharmacological agent that must be administered enterally is not feasible. The first recognized antecedents of Bell stage III NEC are nonspecific for gastrointestinal pathology and insufficient time exists for dosing between the first gastrointestinal signs and placement of the gastric decompression tube. [ABSTRACT FROM AUTHOR]

The pathophysiology of necrotizing enterocolitis (NEC) has not been clearly elucidated, but recent studies support the role of unbalanced pro-inflammatory signaling, leading to intestinal necrosis in premature infants. Although breast milk feeding is thought to reduce the risk of this condition, there are no preventive or therapeutic approaches that have consistently shown to be effective for this common and devastating disease. Recent studies show that probiotic colonization is abnormal in preterm neonates, and enteral supplementation with a variety of probiotic organisms can reduce the risk of disease. This chapter summarizes the current state-of-the-art regarding probiotics and NEC, but suggests caution until appropriately regulated products are available for use in this high-risk population.Journal of Perinatology (2009) 29, S2–S6; doi:10.1038/jp.2009.21 [ABSTRACT FROM AUTHOR]

Objective:To determine the association between human milk (HM) intake and risk of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth weight.Study Design:Analysis of 1272 infants in the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial was performed to determine if increasing HM intake was associated with decreased risk of NEC or death. HM intake was defined as the proportion of HM to total intake, to enteral intake and total volume over the first 14 days. Known NEC risk factors were included as covariates in Cox proportional hazard analyses for duration of survival time free of NEC.Result:Among study infants, 13.6% died or developed NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase in the proportion of total intake as HM. Each 100 ml kg−1 increase in HM intake during the first 14 days was associated with decreased risk of NEC or death (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards a decreased risk of NEC or death among infants who received 100% HM as a proportion to total enteral intake (HM plus formula), although this finding was not statistically significant (HR 0.85 (95% CI 0.60, 1.19)).Conclusion:These data suggest a dose-related association of HM feeding with a reduction of risk of NEC or death after the first 2 weeks of life among extremely low birth weight infants.Journal of Perinatology (2009) 29, 57–62; doi:10.1038/jp.2008.117; published online 21 August 2008 [ABSTRACT FROM AUTHOR]

Objective:Necrotizing enterocolitis (NEC) remains a major cause of neonatal morbidity and mortality. Some infants recover uneventfully with medical therapy whereas others develop severe disease (that is, NEC requiring surgery or resulting in death). Repeated attempts to identify clinical parameters that would reliably identify infants with NEC most likely to progress to severe disease have been unsuccessful. We hypothesized that comprehensive prospective data collection at multiple centers would allow us to develop a model which would identify those babies at risk for progressive NEC.Study Design:This prospective, observational study was conducted at six university children's hospitals. Study subjects were neonates with suspected or confirmed NEC. Comprehensive maternal and newborn histories were collected at the time of enrollment, and newborn clinical data were collected prospectively, thereafter. Multivariate logistic regression analysis was used to develop a predictive model of risk factors for progression.Result:Of 455 neonates analyzed, 192 (42%) progressed to severe disease, and 263 (58%) advanced to full feedings without operation. The vast majority of the variables studied proved not to be associated with progression to severe disease. A total of 12 independent predictors for progression were identified, including only 3 not previously described: having a teenaged mother (odds ratio, OR, 3.14; 95% confidence interval, CI, 1.45 to 6.96), receiving cardiac compressions and/or resuscitative drugs at birth (OR, 2.51; 95% CI, 1.17 to 5.48), and having never received enteral feeding before diagnosis (OR, 2.41; 95% CI, 1.08 to 5.52).Conclusion:Our hypothesis proved false. Rigorous prospective data collection of a sufficient number of patients did not allow us to create a model sufficiently predictive of progressive NEC to be clinically useful. It appears increasingly likely that further analysis of clinical parameters alone will not lead to a significant improvement in our understanding of NEC. We believe that future studies must focus on advanced biologic parameters in conjunction with clinical findings.Journal of Perinatology (2008) 28, 665–674; doi:10.1038/jp.2008.119; published online 11 September 2008 [ABSTRACT FROM AUTHOR]

Introduction:Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are neonatal intestinal emergencies that affect premature infants. Although most cases of early NEC can be successfully managed with medical therapy, prompt surgical intervention is often required for advanced or perforated NEC and FIP.Methods:The surgical management and treatment of FIP and NEC are discussed on the basis of literature review and our personal experience.Results:Surgical options are diverse, and include peritoneal drainage, laparotomy with diverting ostomy alone, laparotomy with intestinal resection and primary anastomosis or stoma creation, with or without second-look procedures.Conclusions:The optimal surgical therapy for FIP and NEC begins with prompt diagnosis and adequate fluid resuscitation. It appears that there is no significant difference in patient outcome based on surgical management alone. However, the infant's weight, comorbidities, surgeon preference and timing of intervention should be taken into account before operative intervention.Journal of Perinatology (2008) 28, S14–S17; doi:10.1038/jp.2008.44 [ABSTRACT FROM AUTHOR]

Introduction:Necrotizing enterocolitis (NEC) has been recognized for over 40 years as a cause of inflammation and necrosis of the small and large intestine of infants born at less than 36 weeks of gestation. NEC remains a significant health problem for infants born prematurely and may become the leading cause of morbidity and mortality among these infants worldwide. The sequence of events leading to NEC is complex and multifactorial, although damage to the intestinal epithelium and invasion by bacteria are known to play central roles in disease pathogenesis.Study Design:Bacteria initiate a cascade of inflammation that may progress to intestinal necrosis and perforation with sepsis and death.Result:Treatment of infants at risk for NEC with probiotic bacteria may be an area of great potential, as probiotic bacteria may promote maturation of the epithelial barrier and function to exclude bacterial pathogens from critical niches in the intestine, thereby disrupting a primary pathway in disease pathogenesis.Conclusion:Understanding how probiotic bacteria, or other novel therapies, prevent or limit disease propagation in NEC will be paramount in limiting the impact of disease in a growing population of premature newborns.Journal of Perinatology (2008) 28, S9–S13; doi:10.1038/jp.2008.43 [ABSTRACT FROM AUTHOR]

In the last decade, it has become increasingly clear that necrotizing enterocolitis (NEC) is neither a uniform nor a well-defined disease entity. There are many factors that are forcing this unwelcome realization upon the neonatal and pediatric surgery communities. In the course of this manuscript we will review the history and the physical findings of the disparate etiologies of acquired neonatal intestinal diseases (ANIDs), some which do lead to the common final pathology of NEC and some which do not. New guidelines for distinguishing between ANIDs will also be suggested.Journal of Perinatology (2007) 27, 661–671; doi:10.1038/sj.jp.7211782; published online 5 July 2007 [ABSTRACT FROM AUTHOR]

Objective:To describe the current use of treatments to prevent or treat patent ductus arteriosus (PDA) in preterm infants, examine the association between different treatment strategies and neonatal outcomes and review the variation in these practices between centers.Study design:Cohort study of infants born between 23 and 30 weeks gestation managed by the Pediatrix Medical Group from 1997 to 2004. We collected data on demographics, indomethacin and ligation, and outcomes of the following five groups: prophylactic indomethacin treatment: infants treated with indomethacin on day of life (DOL) 0 or 1; indicated indomethacin treatment: infants treated with indomethacin after DOL 1; PDA without treatment: infants with a PDA without report of treatment; ligation only: infants with a PDA ligation without use of indomethacin and no PDA: infants without a PDA and without treatment.Results:There were 6189 (18%) patients who received prophylactic indomethacin, 5690 (16%) patients received indicated treatment, 3886 (11%) patients had a PDA without treatment, 702 (2%) patients received ligation only and 18 136 (52%) patients had no PDA. In multivariate analysis, mortality among survivors to 2 days of age was lower (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.5 to 0.7, P<0.01) and chronic lung disease, isolated intestinal perforation and severe retinopathy of prematurity (stages 3 and 4) were higher (OR 1.5, 95% CI 1.3 to 1.6, P<0.01; OR 1.5, 95% CI 1.1 to 2.0, P<0.01 and 1.4, 95% CI 1.2 to 1.6, P<0.01, respectively) in the indicated treatment group compared with the PDA without treatment group. The proportion of infants receiving prophylactic indomethacin among all infants and infants receiving indicated treatment among neonates with a report of a PDA varied by site from 0 to 59% (median 9.5%) and 0 to 100% (median 62%), respectively.Conclusions:Indomethacin use for intraventricular hemorrhage prevention and/or treatment of a PDA is common, but the selection of infants for treatment, and the decision of when and how to treat vary widely between centers. Our findings suggest the need for randomized, placebo-controlled trials of the effect of treatment of the PDA in preterm infants.Journal of Perinatology (2007) 27, 164–170. doi:10.1038/sj.jp.7211662; published online 25 January 2007 [ABSTRACT FROM AUTHOR]

Objectives:To evaluate the effectiveness of low-dose oral erythromycin to treat feeding intolerance in preterm infants.Design:This study was a prospective, double-blind, randomized, placebo-controlled trial on 60 premature infants suffering from feeding intolerance. Thirty infants were given oral erythromycin 1 mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization was stratified on enrollment according to gestational age whether >32 weeks or 32 weeks. The primary end point was the length of time taken to establish full enteral feeding since enrollment. Potential adverse effects associated with erythromycin were also monitored. Groups of each corresponding stratum were compared using two-tail t-test and Mann–Whitney for continuous variables, and χ2 and Fisher's exact for categorical variables.Results:For infants with gestational age >32 weeks, the erythromycin group achieved full enteral feeding earlier than placebo group (10.5±4.1 vs 16.3±5.7 days, respectively; P=0.01) had fewer episodes of gastric residuals (P<0.05) and shorter duration of parenteral nutrition (PN) (P<0.05). On the other hand, in infants with gestational age 32 weeks, there were no significant differences between erythromycin and placebo groups regarding any of these variables.Conclusion:Low-dose enteral erythromycin is associated with better tolerance of feeding and shorter duration of PN in infants >32 weeks gestation. A similar effect on younger preterm infants was not demonstrable.Journal of Perinatology (2007) 27, 39–43. doi:10.1038/sj.jp.7211618; published online 12 October 2006 [ABSTRACT FROM AUTHOR]

Objective:To evaluate the relationship between enteral water infusion for hypernatremia and significant intestinal morbidity in infants 1000 grams.Study design:This is a retrospective study of 321 infants 1000 g birth weight. Infants were grouped by the highest serum sodium (mmol/l) during the first 14 days of life as follows: <150 (normal control), 150 (high sodium control), 150 and treated with sterile water (study group). Significant intestinal morbidity was defined as probable or proven necrotizing enterocolitis or spontaneous intestinal perforation. Statistical analysis included Student's t test for continuous variables and χ2 with Yeats correction for frequency variables. Multivariate logistic regression analysis was then performed to evaluate confounding variables among groups.Results:The incidence of intestinal morbidity was significantly higher in the high sodium-water treated group compared to each of the other groups (13/33 (38%) for high sodium-water versus 16/100 (16%) for high sodium control and 18/188 (10%) for normal sodium control, P<0.01 χ2). Logistic regression analysis indicated that enteral water and hydrocortisone were risk factors for significant intestinal morbidity.Conclusions:Enteral sterile water for hypernatremia appears to be associated with significant intestinal morbidity in infants 1000 g. Hydrocortisone is also a risk factor.Journal of Perinatology (2007) 27, 32–38. doi:10.1038/sj.jp.7211622 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of initiating early nasal continuous positive airway pressure (ENCPAP) on the length of hospital stay (LOS) for the very low birth weight (VLBW) infants. Study design: LOS at the George Washington University Hospital (GW) after the institution of ENCPAP policy was compared to benchmark values using two-tail t-tests. The incidence of neonatal morbidity was calculated using Bonferroni corrected 95% confidence interval as compared to benchmark rates (α=0.001). Comparisons were repeated after stratification of the population into four birth weight subcategories: group A (GrpA) (501 to 750 g), GrpB (751 to 1000 g), GrpC (1001 to 1250 g) and GrpD (1251 to 1500 g). Results: We studied 228 consecutive VLBW infants (birth weight: 995±294 g and gestational age: 27.7±2.7 weeks). Compared to benchmark values, the GW experience was associated with a significant reduction of 5.1 days in LOS (55.9±25.2 vs 61±32 days; P=0.04). The decrease in LOS was consistent in all subgroups, but was most noticeable in infants of the smallest weight subcategory (LOS in GrpA=86±21 vs 104±32, P=0.004; in GrpB=69.9±16.7 vs 79±27, P=0.018; in GrpC=48.2±13 vs 56±22, P<0.001 and in GrpD=31.7±12.5 vs 40±19, P=0.003). In the overall population, a lower incidence of chronic lung disease (CLD) (17.8 vs 29%, P<0.001) was also noted. There were no differences in mortality rates (9 vs 14%), or the incidence of necrotizing enterocolitis (NEC) (8 vs 6%) or intraventricular hemorrhage (6.2 vs 9%) between GW and the established benchmark rates. Conclusion: ENCPAP may reduce LOS in VLBW infants in our study population. This relatively shorter LOS was associated with a lower incidence of CLD, which may be a contributing factor. [ABSTRACT FROM AUTHOR]

Objective:This investigation tests the hypothesis that the clinical presentation and the outcome of necrotizing enterocolitis (NEC) vary with gestational age (GA).Methods:All infants admitted to our center between October 1991 and September 2003 were evaluated weekly to identify confirmed cases of NEC. Based upon GA, these infants were divided into five groups: Extremely premature (EP, 23 to 26 weeks), very premature (VP, 27 to 29 weeks), moderately premature (MP, 30 to 34 weeks), near-term (NT, 35 to 36 weeks), and term (T, 37 to 42 weeks).Results:A total of 202 infants developed NEC. The most common sign of NEC among EP infants was ileus (77%), followed by abdominal distention (71%), emesis (58%), pneumoperitoneum (54%), fixed intestinal loop (52%), gasless abdomen (42%) and bloody stools (17%). Intramural gas was detected in 100% of T but was present in only 29% of EP infants (P<0.0001). Similarly, portal venous gas was common in T but infrequent in the EP infants (47 vs 10%, P<0.0001). Despite a higher peritoneal drain insertion rate (31 vs 5%, P<0.001) and a higher mortality rate (33 vs 10%, P=0.05) in EP compared to T infants, other clinical outcomes were not different.Conclusions:The clinical presentation of NEC is different in EP compared to more mature infants; however, outcome among NEC survivors is similar across all GA. Reliance solely on observation of intramural or on portal venous gas in EP infants may lead to a delay or failure in the diagnosis.Journal of Perinatology (2006) 26, 342–347. doi:10.1038/sj.jp.7211510 [ABSTRACT FROM AUTHOR]

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.Journal of Perinatology (2006) 26, 93–99. doi:10.1038/sj.jp.7211429; published online 1 December 2005 [ABSTRACT FROM AUTHOR]