A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

Trends in Neonatal Extracorporeal Membrane Oxygenation During a Venovenous Cannula Shortage.

OBJECTIVES: To report temporal trends in venovenous extracorporeal membrane oxygenation (ECMO) use for neonatal respiratory failure in U.S. centers before and after functional venovenous cannula shortage due to withdrawal of one dual lumen venovenous cannula from the market in 2018. DESIGN: Retrospective cohort study. SETTING: ECMO registry of the Extracorporeal Life Support Organization. PATIENTS: Infants who received neonatal (cannulated prior to 29 d of age) respiratory ECMO at a U.S. center and had a record available in the ECMO registry from January 1, 2010 to July 20, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was receipt of venovenous ECMO (vs venoarterial or other), and secondary outcomes were survival to hospital discharge and adverse neurologic outcomes. Using an interrupted time series design, we fit multivariable mixed effects logistic regression models with receipt of venovenous ECMO as the dependent variable, treatment year modeled as a piecewise linear variable using three linear splines (pre shortage: 2010-2014, 2014-2018; shortage: 2018-2021), and adjusted for center clustering and multiple covariates. We evaluated trends in venovenous ECMO use by primary diagnosis including congenital diaphragmatic hernia, meconium aspiration, pulmonary hypertension, and other. Annual neonatal venovenous ECMO rates decreased after 2018: from 2010 to 2014, adjusted odds ratio (aOR) for yearly trend 0.98 (95% CI 0.92-1.04), from 2014 to 2018, aOR for yearly trend 0.90 (95% CI 0.80-1.01), and after 2018, aOR for yearly trend 0.46 (95% CI 0.37-0.57). We identified decreased venovenous ECMO use after 2018 in all diagnoses evaluated, and we failed to identify differences in temporal trends between diagnoses. Survival and adverse neurologic outcomes were unchanged across the study periods. CONCLUSIONS: Venovenous ECMO for neonatal respiratory failure in U.S. centers decreased after 2018 even after accounting for temporal trends, coincident with withdrawal of one of two venovenous cannulas from the market.

The association of inborn status and resource utilization among neonates who received extracorporeal membrane oxygenation.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997-2012. Neonates (infants, <28 days) placed on ECMO were categorized as either inborn or outborn. Salient clinical characteristics were compared between groups. A multivariable analysis was performed to identify the factors associated with length of stay (LOS), total hospital costs, and mortality in these two patient populations. RESULTS: Of 5,152 neonates receiving ECMO, 800 were inborn and 4,352 were outborn. Inborn neonates were more frequently diagnosed with cardiac-related diagnoses (70.5% vs 62.1%, p < 0.001). After adjusting for demographics and hospital-level factors, inborn neonates had longer hospital LOS (13.2 days, 95% CI, 8.7-18.7; p < 0.001), higher total encounter costs ($62,000, 95% CI, 40,000-85,000; p < 0.001) and higher mortality (OR 2.4, 95% CI 1.9-2.9; p < 0.001) compared to outborn neonates. CONCLUSIONS: Inborn neonates placed on ECMO were more frequently diagnosed with cardiac-related diseases or congenital diaphragmatic hernia, had longer LOS, higher total encounter costs, and higher mortality rates relative to their outborn counterparts, and likely represent a higher risk population. These two populations of infants may be inherently different and their differences should be further explored to inform decision making about optimal site of delivery.

Development and Validation of the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support.

OBJECTIVE: To develop and validate the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support, which estimates the risk of in-hospital death for neonates prior to receiving respiratory extracorporeal membrane oxygenation (ECMO) support. STUDY DESIGN: We used an international ECMO registry (2008-2013); neonates receiving ECMO for respiratory support were included. We divided the registry into a derivation sample and internal validation sample, by calendar date. We chose candidate variables a priori based on published evidence of association with mortality; variables independently associated with mortality in logistic regression were included in this parsimonious model of risk adjustment. We evaluated model discrimination with the area under the receiver operating characteristic curve (AUC), and we evaluated calibration with the Hosmer-Lemeshow goodness-of-fit test. RESULTS: During 2008-2013, 4592 neonates received ECMO respiratory support with mortality of 31%. The development dataset contained 3139 patients treated in 2008-2011. The Neo-RESCUERS measure had an AUC of 0.78 (95% CI 0.76-0.79). The validation cohort had an AUC = 0.77 (0.75-0.80). Patients in the lowest risk decile had an observed mortality of 7.0% and a predicted mortality of 4.4%, and those in the highest risk decile had an observed mortality of 65.6% and a predicted mortality of 67.5%. CONCLUSIONS: Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support offers severity-of-illness adjustment for neonatal patients with respiratory failure receiving ECMO. This score may be used to adjust patient survival to assess hospital-level performance in ECMO-based care.

Evaluation of Heart Rate Assessment Timing, Communication, Accuracy, and Clinical Decision-Making during High Fidelity Simulation of Neonatal Resuscitation.

Objective. Accurate heart rate (HR) determination during neonatal resuscitation (NR) informs subsequent NR actions. This study's objective was to evaluate HR determination timeliness, communication, and accuracy during high fidelity NR simulations that house officers completed during neonatal intensive care unit (NICU) rotations. Methods. In 2010, house officers in NICU rotations completed high fidelity NR simulation. We reviewed 80 house officers' videotaped performance on their initial high fidelity simulation session, prior to training and performance debriefing. We calculated the proportion of cases congruent with NR guidelines, using chi square analysis to evaluate performance across HR ranges relevant to NR decision-making: <60, 60-99, and ≥100 beats per minute (bpm). Results. 87% used umbilical cord palpation, 57% initiated HR assessment within 30 seconds, 70% were accurate, and 74% were communicated appropriately. HR determination accuracy varied significantly across HR ranges, with 87%, 57%, and 68% for HR <60, 60-99, and ≥100 bpm, respectively (P < 0.001). Conclusions. Timeliness, communication, and accuracy of house officers' HR determination are suboptimal, particularly for HR 60-100 bpm, which might lead to inappropriate decision-making and NR care. Training implications include emphasizing more accurate HR determination methods, better communication, and improved HR interpretation during NR.

Neonatal candidiasis: epidemiology, risk factors, and clinical judgment.

OBJECTIVE: Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (<1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis. METHODS: The study involved a prospective observational cohort of infants≤1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis. RESULTS: Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from ≥1 of these sources: blood (n=96); cerebrospinal fluid (n=9); urine obtained by catheterization (n=52); or other sterile body fluid (n=10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled≥50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis. CONCLUSION: Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.

Prevention and treatment of Candida infections in neonates.

Invasive Candia infections have become the third most common cause of late-onset infection among very low birth weight infants in most neonatal intensive care units. Significant risk factors include birth weight less than 1000 g, exposure to more than two antibiotics, third generation cephalosporin exposure, parenteral nutrition including lipid emulsion, central venous catheter, and abdominal surgery. The majority of neonatal Candida infections are caused by C. albicans and C. parapsilosis, although other nonalbicans species are being reported more frequently. Standard therapy has been amphotericin B; however, successful use of fluconazole as a single agent has also been reported and a small comparison trial demonstrated similar efficacy. The addition of new antifungal agents, including voriconazole and the echinocandins may further improve our ability to effectively treat these infections and possibly reduce the development of complications. Antifungal chemoprophylaxis has been studied in single-center and cohort studies, primarily using fluconazole. Although it is clear that fluconazole prophylaxis decreases the risk of fungal colonization and infection, identification of potential harm, particularly the development of or selection for resistant strains, requires further investigation with multicenter trials before widespread use is recommended outside of the clinical trial setting.

Invasive neonatal candidiasis: an overview.

Until the 1980s, recovery of Candida species from normally sterile body sites in high-risk infants was often dismissed as contamination. Such delay in diagnosis often resulted in death, multifocal disease, or significant morbidity, outcomes that still occur today. Problems establishing the diagnosis of invasive candidiasis persist, while the frequency of this infection in increasingly fragile and smaller premature infants appears to be increasing. Standard culture techniques have limited sensitivity and often take several days for recovery of Candida when positive. Heightened suspicion and improved diagnostic tools are needed. Less toxic antifungal agents with better tissue penetration profiles will help. Better understanding of risk factors and pathogenesis may permit more effective strategies for prophylaxis and appropriately targeted empiric antifungal therapy.

Central nervous system candidiasis in the high-risk neonate.

Central nervous system involvement in neonatal candidiasis is not rare, although possibly less frequent than in previous decades. In addition to increasing the potential for neurodevelopmental morbidity, this infection poses major challenges in establishing diagnosis and assuring adequate treatment. In the setting of candidemia or other severe invasive candida disease, suggestive imaging studies or inflammatory changes in cerebrospinal fluid should prompt careful consideration of central nervous system candidiasis even if culture of the fluid is negative. Although delivery of amphotericin to cerebrospinal fluid appears much better in premature infants than in older individuals, the availability of other agents with superior delivery to the central nervous system suggests that strong consideration be given to their use as alternative or adjunct therapy if central nervous system involvement appears likely. Careful surveillance for neurodevelopmental sequelae may permit early detection, timely rehabilitative intervention, and potentially better long-term functional outcomes.

Candida infections in the neonate.

Candida infections have become an increasingly frequent problem in neonatal intensive care units, particularly among extremely low birth weight infants. Transmission occurs both vertically and horizontally, with Candida albicans and C. parapsilosis as the predominant species. Multiple risk factors have been identified with prior antibiotic exposure, presence of a central line, endotracheal intubation, and prior fungal colonization reported most frequently. The primary site of infection can involve the bloodstream, meninges, or urinary tract, but disease is frequently disseminated to multiple organ systems. Amphotericin is the most commonly used antifungal agent, although fluconazole is being used more frequently. The potential role of antifungal prophylaxis is not yet clearly defined, but has been the topic of recent investigative efforts. The crude mortality rate among neonates with systemic candidiasis remains approximately 30%.

Persistent bacteremia and outcome in late onset infection among infants in a neonatal intensive care unit.

BACKGROUND: Persistent bacteremia despite antibiotic therapy has been correlated with adverse outcomes, including focal suppurative complications and death. Coagulase-negative staphylococci (CONS) are the most common cause of nosocomial infection in infants requiring neonatal intensive care and might yield more substantial pathology if infection were persistent. METHODS: To compare the severity and features of persistent infection by CONS with those of other bacteria, we reviewed infants admitted to our neonatal intensive care unit from 1990 through 2001 who developed bacteremia at >5 days of age with recovery of the same bacterial species from blood for >24 h after initiation of antibiotic therapy to which the organism was susceptible. Cases were excluded if a focal complication was already present with the initial positive culture or if the medical record was unavailable. Outcomes of interest included focal suppurative complications, death attributable to infection and duration of hospitalization among survivors. RESULTS: We identified 62 infants with sustained infection, caused by CONS in 30 and by other organisms in 32 [10 Gram-negative, 22 Gram-positive (16 Staphylococcus aureus)]. Infants with persistent CONS had significantly lower birth weight and gestational age, but no difference was found for multiple other clinical and demographic risk factors. Indwelling vascular catheters were present at diagnosis in 85% of the infants (CONS 26 of 30, non-CONS 27 of 32). Responses of bacteremia to catheter removal vs. in situ treatment did not differ between the groups. No differences were observed for death from all causes (27 vs. 34%), death attributable to infection (6 vs. 12%) or duration of hospitalization among survivors [median (interquartile range): 102 (73 to 167) 107.5 (89 to 130) days]. Focal suppurative complications were significantly more frequent in infants persistently infected with non-CONS (28 vs. 3%; P = 0.01). Duration of persistence correlated with focal complication in non-CONS infants (r = 0.988; P < 0.001). CONCLUSIONS: Although persistent infection with CONS occurs in significantly smaller and less mature infants than with non-CONS, death is no more frequent and focal complications are significantly less frequent. Infants with persistent infection should undergo aggressive evaluation for focal complications, with the yield expected to be higher in those with non-CONS.