Association between pulmonary vein stenosis and necrotizing enterocolitis or gastrointestinal pathology: A case-control study.

Objective: Pulmonary vein stenosis (PVS) is an emerging cause of pulmonary hypertension in preterm infants. It is an often lethal condition with poor long.term prognosis and high mortality. Previous work suggests an association between necrotizing enterocolitis (NEC) and PVS, supporting a possible role for inflammatory processes due to gastrointestinal (GI) pathology as an associated risk factor for PVS. Study Description: We performed a matched case-control study where infants with PVS were matched for gestational age with infants without PVS. Hospital records were reviewed for prior history of NEC or other gut pathology. Results: Twenty-four PVS patients were matched with 68 controls; 63% of patients (15/24) had prior GI pathology as opposed to 19% (13/68) of controls. The GI pathology group had a significantly higher growth restriction and C-reactive protein. The mean gradient across the pulmonary veins was higher in the gut pathology group versus controls, as was mortality (29% vs. 9%). Conclusions: The previously described association between PVS and intestinal pathology was further strengthened by this study. The presence of GI pathology should lead to early surveillance and intervention for PVS.

Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is an inflammatory disease affecting premature infants. Intestinal microbial composition may play a key role in determining which infants are predisposed to NEC and when infants are at highest risk of developing NEC. It is unclear how to optimize antibiotic therapy in preterm infants to prevent NEC and how to optimize antibiotic regimens to treat neonates with NEC. This article discusses risk factors for NEC, how dysbiosis in preterm infants plays a role in the pathogenesis of NEC, and how probiotic and antibiotic therapy may be used to prevent and/or treat NEC and its sequelae.

The Risks of Being Tiny: The Added Risk of Low Weight for Neonates Undergoing Congenital Heart Surgery.

The aims of this study were (1) to describe the additive risk of performing cardiac surgery in neonates born ≤ 2.0 kg, after accounting for the baseline risks of low birth weight, and (2) to describe the additive risk of being born ≤ 2.0 kg in neonates undergoing cardiac surgery. We used a risk difference analysis in a retrospective cohort, 2006-2016. Neonates born ≤ 2.0 kg undergoing congenital heart surgery during initial postnatal admission were included. Data were standardized alternatingly for birth weight and cardiac surgical risk using national population data to estimate the number of deaths expected had they not required cardiac surgery or were they of normal weight. Of 105 neonates ≤ 2 kg, median birth weight was 1.6 kg (IQR 1.3-1.8 kg). Median gestational age was 33 weeks (IQR 31-35 weeks). Observed operative mortality was 14.3%; 0% for neonates ≤ 1.0 kg (CI 0-33.6%), 20.6% for neonates > 1.0-1.5 kg (CI 8.7-37.9%), and 12.9% for neonates > 1.5-2.0 kg (CI 5.7-23.9%). Among neonates ≤ 2.0 kg not undergoing cardiac surgery, expected mortality was 4.8% (CI 1.6-10.8); cardiac surgery increased the risk of mortality 9.5% (CI 1.7-17.4%). Conversely, the expected risk for normal birth weight neonates undergoing cardiac surgery was 5.7% (CI 2.1-12.0%); low birth weight increased the risk of mortality 8.6% (CI 0.5-16.6%). To continue making advancements in cardiac surgery, we must understand that the rate of mortality observed in normal weight infants is not a realistic target and that, despite advances, the risk attributable to the surgery remains higher among low birth weight patients.

Safety and Varicella Outcomes in In Utero-Exposed Newborns and Preterm Infants Treated With Varicella Zoster Immune Globulin (VARIZIG): A Subgroup Analysis of an Expanded-Access Program.

BACKGROUND: Infants exposed to varicella zoster virus (VZV) in utero ≤5 days before or ≤48 hours after delivery and preterm infants are at high risk for varicella complications. An expanded-access program assessed varicella outcomes after administration of varicella zoster immune globulin (human) (VARIZIG) in a real-world setting. METHODS: In this open-label, expanded-access program, high-risk infants received ≤125 IU/10 kg of VARIZIG (NCT00338442). VZV outcomes and safety were assessed. RESULTS: There were 43 newborns exposed to VZV in utero and 80 preterm infants exposed to VZV; >80% received VARIZIG within 96 hours of reported exposure. When varicella outcomes were available, varicella occurred in 7 of 38 (18%) in utero-exposed newborns and zero of 65 preterm infants. Varicella-related complications were reported in 3 in utero-exposed newborns (3 with >100 lesions, 1 each with encephalitis and pneumonia). Adverse events were reported for 16% of in utero-exposed newborns and 25% of preterm infants, but few were considered related to VARIZIG. There were no deaths attributable to varicella or VARIZIG. CONCLUSIONS: Varicella incidence and morbidity were low in in utero-exposed infants and zero in preterm infants who received prophylactic VARIZIG. There were few VARIZIG-related safety concerns.

Varicella zoster immune globulin (VARIZIG) administration up to 10 days after varicella exposure in pregnant women, immunocompromised participants, and infants: Varicella outcomes and safety results from a large, open-label, expanded-access program.

INTRODUCTION: Despite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013-2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited. METHODS: This open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration. RESULTS: The varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG. CONCLUSION: Postexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants.

Expanding Existing Antimicrobial Stewardship Programs in Pediatrics: What Comes Next.

The prevalence of pediatric antimicrobial stewardship programs (ASPs) is increasing in acute care facilities across the United States. Over the past several years, the evidence base used to inform effective stewardship practices has expanded, and regulatory interest in stewardship programs has increased. Here, we review approaches for established, hospital-based pediatric ASPs to adapt and report standardized metrics, broaden their reach to specialized populations, expand to undertake novel stewardship initiatives, and implement rapid diagnostics to continue their evolution in improving antimicrobial use and patient outcomes.

NEC-zero recommendations from scoping review of evidence to prevent and foster timely recognition of necrotizing enterocolitis.

BACKGROUND: Although decades have focused on unraveling its etiology, necrotizing enterocolitis (NEC) remains a chief threat to the health of premature infants. Both modifiable and non-modifiable risk factors contribute to varying rates of disease across neonatal intensive care units (NICUs). PURPOSE: The purpose of this paper is to present a scoping review with two new meta-analyses, clinical recommendations, and implementation strategies to prevent and foster timely recognition of NEC. METHODS: Using the Translating Research into Practice (TRIP) framework, we conducted a stakeholder-engaged scoping review to classify strength of evidence and form implementation recommendations using GRADE criteria across subgroup areas: 1) promoting human milk, 2) feeding protocols and transfusion, 3) timely recognition strategies, and 4) medication stewardship. Sub-groups answered 5 key questions, reviewed 11 position statements and 71 research reports. Meta-analyses with random effects were conducted on effects of standardized feeding protocols and donor human milk derived fortifiers on NEC. RESULTS: Quality of evidence ranged from very low (timely recognition) to moderate (feeding protocols, prioritize human milk, limiting antibiotics and antacids). Prioritizing human milk, feeding protocols and avoiding antacids were strongly recommended. Weak recommendations (i.e. "probably do it") for limiting antibiotics and use of a standard timely recognition approach are presented. Meta-analysis of data from infants weighing <1250 g fed donor human milk based fortifier had reduced odds of NEC compared to those fed cow's milk based fortifier (OR = 0.36, 95% CI 0.13, 1.00; p = 0.05; 4 studies, N = 1164). Use of standardized feeding protocols for infants <1500 g reduced odds of NEC by 67% (OR = 0.33, 95% CI 0.17, 0.65, p = 0.001; 9 studies; N = 4755 infants). Parents recommended that NEC information be shared early in the NICU stay, when feedings were adjusted, or feeding intolerance occurred via print and video materials to supplement verbal instruction. DISCUSSION: Evidence for NEC prevention is of sufficient quality to implement. Implementation that addresses system-level interventions that engage the whole team, including parents, will yield the best impact to prevent NEC and foster its timely recognition.

The effects of postoperative hematocrit on shunt occlusion for neonates undergoing single ventricle palliation.

OBJECTIVES: Our primary objective was to test the effects of first postoperative hematocrit on early shunt occlusion for children undergoing systemic to pulmonary artery shunt placement. Because any intervention to reduce shunt occlusion is only beneficial if it reduces mortality or is, at least, mortality neutral, we also tested the effects of first postoperative hematocrit on in-hospital mortality. METHODS: We conducted a retrospective study on all neonates who underwent primary systemic to pulmonary artery shunt placement, with or without a Norwood/Damus-Kaye-Stansel procedure, at Columbia University Medical Center between January 2010 and July 2015. Univariable regression was used to test the effects of first postoperative hematocrit on early shunt occlusion and 30-day mortality, clustering standard errors by surgeon. In secondary analyses, we also tested associations between red blood cell transfusion volumes in the first 24 postoperative hours and first postoperative hematocrit, shunt occlusion, and mortality. RESULTS: Eighty infants met inclusion criteria. Median initial postoperative hematocrit was 41.7% (interquartile range, 37.9-46.0). Six infants (7.5%) died. Four infants (5.0%) died within the first 30 days. Five infants (6.3%) experienced early shunt occlusion. No children with early shunt occlusion died. In univariable models, for every 5 additional percentage points of hematocrit, an infant's odds of early shunt occlusion more than doubled (odds ratio, 2.70; P = .009). The odds of all-cause 30-day mortality remained unchanged. CONCLUSIONS: Higher postoperative hematocrit levels are associated with early shunt occlusions in infants undergoing primary systemic to pulmonary artery shunt placement. Multicenter investigations are warranted to validate these findings and to determine ideal postoperative hematocrit targets for this population.

Congenital Parvovirus B19 Infection: Persistent Viremia and Red Blood Cell Aplasia.

We describe a case of fetal parvovirus B19 infection resulting in preterm birth and leading to hydrops fetalis requiring multiple in utero transfusions. The infant developed chronic postnatal anemia responsive to intravenous immunoglobulin therapy. Serum viral load decreased after immunoglobulin treatment but remained detectable for over 1 year.

TORCH infections.

TORCH infections classically comprise toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus, hepatitis viruses, human immunodeficiency virus, and other infections, such as varicella, parvovirus B19, and enteroviruses. The epidemiology of these infections varies; in low-income and middle-income countries, TORCH infections are major contributors to prenatal, perinatal, and postnatal morbidity and mortality. Evidence of infection may be seen at birth, in infancy, or years later. For many of these pathogens, treatment or prevention strategies are available. Early recognition, including prenatal screening, is key. This article covers toxoplasmosis, parvovirus B19, syphilis, rubella, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus.

Heterotaxy syndrome infants are at risk for early shunt failure after Ladd procedure.

BACKGROUND: Cardiac-specific risks and complications after a Ladd procedure in patients with heterotaxy syndrome (HS) and intestinal rotational anomalies (IRA) are unknown. We sought to (1) describe rates of hospital mortality and early systemic-to-pulmonary (S-P) artery shunt failure after the Ladd procedure in patients with HS and (2) explore risk factors associated with early shunt failure in patients with HS with single ventricle (SV). METHODS: This retrospective study included all Ladd procedures performed from January 1999 to December 2012 in patients with HS at a single center. Risk factors investigated for early S-P artery shunt failure included birth weight, gestational age, sex, age at and timing of Ladd procedure relative to cardiac operations, and shunt type. RESULTS: Ladd procedure was performed on 54 infants with HS and congenital heart disease. Hospital mortality for the entire cohort was 5.6% (3 of 54 patients). Early shunt failure occurred in 19% (4 of 21) of HS infants with SV. Mean preoperative blood urea nitrogen (BUN) levels were higher in HS infants with early shunt failure (20 versus 12.5 mg/dL; p = 0.054). CONCLUSIONS: Patients with SV and HS with S-P artery shunts are at risk for early shunt failure after a Ladd procedure. A higher mean preoperative BUN level is noted in patients with HS and early shunt failure. Careful risk-benefit analysis is indicated before recommending routine elective Ladd procedures in patients with HS.

Outcomes of cardiac surgery in patients weighing <2.5 kg: affect of patient-dependent and -independent variables.

OBJECTIVE: A recent Society of Thoracic Surgeons database study showed that low weight (<2.5 kg) at surgery was associated with high operative mortality (16%). We sought to assess the outcomes after cardiac repair in patients weighing <2.5 kg versus 2.5 to 4.5 kg in an institution with a dedicated neonatal cardiac program and to determine the potential role played by prematurity, the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) risk categories, uni/biventricular pathway, and surgical timing. METHODS: We analyzed the outcomes (hospital mortality, early reintervention, postoperative length of stay, mortality [at the last follow-up point]) in patients weighing <2.5 kg at surgery (n = 146; group 1) and 2.5 to 4.5 kg (n = 622; group 2), who had undergone open or closed cardiac repairs from January 2006 to December 2012 at our institution. The statistical analysis was stratified by prematurity, STAT risk category, uni/biventricular pathway, and usual versus delayed surgical timing. Univariate versus multivariate risk analysis was performed. The mean follow-up was 21.6 ± 25.6 months. RESULTS: Hospital mortality in group 1 was 10.9% (n = 16) versus 4.8% (n = 30) in group 2 (P = .007). The postoperative length of stay and early unplanned reintervention rate were similar between the 2 groups. Late mortality in group 1 was 0.7% (n = 1). In group 1, early outcomes were independent of the STAT risk category, uni/biventricular pathway, or surgical timing compared with group 2. A lower gestational age at birth was an independent risk factor for early mortality in group 1. CONCLUSIONS: A dedicated multidisciplinary neonatal cardiac program can yield good outcomes for neonates and infants weighing <2.5 kg independently of the STAT risk category and uni/biventricular pathway. A lower gestational age at birth was an independent risk factor for hospital mortality.

Utility of surveillance cultures for antimicrobial resistant organisms in infants transferred to the neonatal intensive care unit.

BACKGROUND: Infections with antibiotic resistant organisms (AROs) are an important source of morbidity and mortality among infants hospitalized in the neonatal intensive care unit (NICU). To identify potential reservoirs of AROs in the NICU, active surveillance strategies have been adopted by many NICUs to detect infants colonized with AROs. However, the yield, risks, benefits and costs of different strategies have not been fully evaluated. METHODS: We conducted a retrospective study in 2 level III NICUs from 2004 to 2010 to investigate the yield of surveillance cultures obtained from infants transferred to the NICU from other hospitals. Cultures were processed for methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and antibiotic-resistant gram-negative rods. Risk factors, selected outcomes and laboratory costs associated with ARO colonization were assessed. RESULTS: Among 1751 infants studied, the rate of colonization for methicillin-resistant S. aureus, vancomycin-resistant enterococci and antibiotic-resistant gram-negative rods was 3%, 1.7% and 1%, respectively. Age at transfer was the strongest predictor of ARO colonization; infants transferred at ≥ 7 days of life had 5.8 increased odds of ARO colonization compared with infants <7 days of age. Transferred infants who were colonized had similar rates of mortality, ARO infection and duration of hospitalization compared with those who were not colonized. The laboratory cost of surveillance cultures during the study period was $58,425. CONCLUSIONS: The rate of colonization with AROs at transfer was low particularly in infants <7 days old. Future studies should examine the safety of targeted surveillance strategies focused on older infants.

Development of an antimicrobial stewardship intervention using a model of actionable feedback.

We describe the development of an audit and feedback intervention to improve antibiotic prescribing in the neonatal intensive care unit (NICU) using a theoretical framework. Participants included attending physicians, neonatal fellows, pediatric residents, and nurse practitioners. The intervention was based on the "model of actionable feedback" which emphasizes that feedback should be timely, individualized, nonpunitive, and customized to be effective. We found that real-time feedback could not be provided for the parameters established in this study, as we had to collect and analyze numerous data elements to assess appropriate initiation and continuation of antibiotics and required longer intervals to examine trends in antibiotic use. We learned during focus groups that NICU clinicians strongly resisted assigning individual responsibility for antibiotic prescribing as they viewed this as a shared responsibility informed by each patient's laboratory data and clinical course. We were able to create a non-punitive atmosphere thanks to written informed consent from NICU attendings and assurance from leadership that prescribing practices would not be used to assess job performance. We provided customized, meaningful feedback integrating input from the participants. Adapting the principles of the "model of actionable feedback" to provide feedback for antimicrobial prescribing practices proved challenging in the NICU setting.

Epidemiology of enterococci in a neonatal intensive care unit.

We performed an epidemiological investigation of a 62-bed neonatal intensive care unit in response to 2 infants with clinical cultures positive for vancomycin-resistant enterococci (VRE). Surveillance cultures detected 11 infants colonized with VRE. Surveillance triggered by even a single clinical culture positive for VRE may be justified in the neonatal intensive care unit, because a single culture result may represent a large hidden reservoir of VRE-colonized infants.