Gastroschisis and low incidence of early-onset infection: a case for antimicrobial stewardship.

OBJECTIVE: Early onset infection (EOI) in gastroschisis is rare. Excess antibiotic exposure in neonates increases necrotizing enterocolitis and mortality. We evaluated antibiotic exposure and EOI in gastroschisis. STUDY DESIGN: Retrospective cohort analysis between 2010-2016 in the Children's Hospital Neonatal Database. Included: Infants ≥32 weeks with gastroschisis admitted <48 h. Excluded: major anomalies or surgical intervention prior to admission. PRIMARY OUTCOME: EOI diagnosis (<72 h). RESULTS: In 2021 patients with gastroschisis, median gestational age was 36 weeks (IQR 35, 37). 93.9% patients received empiric antibiotics after delivery, with median 7 days duration (IQR 3, 9). Only 13 patients (0.64%) had early positive blood culture. The rate of late onset blood stream infection (7.08%) was higher, and higher in complex (18%) than simple gastroschisis (4.8%, p < 0.001). CONCLUSION: Despite low incidence of EOI and risks of excess antibiotic exposure, neonates with gastroschisis are exposed to long courses of empiric antibiotics. These data should stimulate interinstitution work to improve antibiotic prescribing.

Gestational Age at Delivery and Neonatal Outcomes among Infants with Gastroschisis in the Children's Hospitals Neonatal Consortium (CHNC).

OBJECTIVE: The effect of gestational age (GA) on gastroschisis outcomes is unclear and delivery timing varies in practice. We aimed to correlate clinical outcomes of infants with gastroschisis and GA at delivery in the Children's Hospitals Neonatal Consortium (CHNC). STUDY DESIGN: This was a retrospective multicenter cohort study of infants with gastroschisis admitted to CHNC neonatal intensive care units (NICUs) from 2010 to 2016. Patients were categorized by GA: 32 to 346/7, 35 to 366/7, and ≥37 weeks. Respiratory and feeding interventions, mortality, length of stay, and common complications were compared. RESULTS: In 2021 for patients with gastroschisis, median GA at delivery was 36.3 weeks (interquartile range [IQR] 35.1, 37.3) and mean birth weight 2,425 g (IQR 2,100, 2,766). Overall mortality was low and there was no difference across GA groups. Infants <35 weeks' gestation had the greatest need for respiratory and feeding interventions. Complications such as medical necrotizing enterocolitis (NEC), cholestasis, and central line-associated blood stream infection were less common in infants ≥37 weeks. Feeding initiation and full feeds were earliest in term infants, compared with infants between 35 and 366/7 weeks, and longest in infants <35 weeks. Prematurity had a significant negative association with breast milk exposure. Enteral feeding tube support at discharge increased with prematurity. Compared with term, infants born between 35 and 366/7 weeks' gestation had a higher incidence of medical NEC and lower exposure to mother's milk at discharge but the need for respiratory interventions or tube feeding at discharge was similar. CONCLUSION: Premature infants with gastroschisis had more neonatal complications including respiratory interventions, longer NICU stay, longer time to full enteral feeds, and higher need for tube feeds at discharge as compared with those delivered at term. Differences were greatest for those <35 weeks GA. While overall mortality remains low, these results provide additional information about GA at birth in gastroschisis, with no evidence of benefit from preterm delivery. KEY POINTS: · Respiratory support was greatest for those with <35 weeks gestation.. · NEC and cholestasis increase with prematurity.. · Term infants have better feeding outcomes..

Gastroschisis with intestinal atresia leads to longer hospitalization and poor feeding outcomes.

OBJECTIVE: Compare in-hospital outcomes in gastroschisis with intestinal atresia versus simple gastroschisis (GS) using a national database. STUDY DESIGN: The Children's Hospitals Neonatal Database identified infants with gastroschisis from 2010 to 2016. RESULTS: 2078 patients with gastroschisis were included: 183 (8.8%) with co-existing intestinal atresia, 1713 (82.4%) with simple gastroschisis, the remainder with complex gastroschisis without atresia. Length of hospitalization was longer for those with atresia, and yielded higher rates of mortality, medical NEC, and intestinal perforation. They began enteral feedings later, were less likely to initiate feeds orally, and reached full feedings later. They were less likely to be receiving any maternal breast milk or breastfeeding at discharge and more likely than simple gastroschisis to be discharged with a feeding tube. CONCLUSION: A large multicenter cohort showed gastroschisis with atresia results in worse outcomes and complications, including necrotizing enterocolitis, feeding delays, and enteral feeding tube dependence.

The role of feeding advancement strategy on length of stay and hospital costs in newborns with gastroschisis.

BACKGROUND: Infants with gastroschisis require prolonged hospitalization for surgical repair and gradual advancement of feeds. The present study explores the effect of a change in a protocolized enteral feeding regimen with length of hospital stay (LOS) and total costs in newborns with gastroschisis. METHODS: A retrospective review was performed in neonates with uncomplicated gastroschisis at a free-standing pediatric institution from 2012 to 2020. The effect of two different enteral feed advancement protocols on clinical outcomes and hospital costs was analyzed. RESULTS: Seventy-four patients were identified, of which 50 (68%) underwent 10 ml/kg/day feeding advancements, and 24 (32%) underwent 20 ml/kg/day feeding advancements. Compared to neonates who underwent 10 ml/kg/day enteral advancements, neonates receiving 20 ml/kg/day advancements reached goal feeds faster (14 vs 20 days, p<0.001), were younger at goal feeds (26 vs 34 days, p = 0.001), required fewer days of parenteral nutrition (22 vs 29 days, p = 0.001), and had shorter LOS (30 vs 36 days, p = 0.001). On multivariable analysis, total costs decreased by 9.77% in the 20 ml/kg/day advancement cohort (p = 0.071). CONCLUSION: In neonates with uncomplicated gastroschisis who underwent primary repair, a nutritional protocol that incorporated 20 ml/kg/day feeding advancements was safe and resulted in faster attainment of goal feeds and shorter LOS. LEVEL OF EVIDENCE: II/III.

Hepatitis B Vaccination of Low Birth Weight Infants in Washington State.

OBJECTIVE: The U.S. Advisory Committee on Immunization Practices (ACIP) recommends that infants born weighing less than 2,000 g receive the hepatitis B (HepB) vaccine at hospital discharge or 30 days of age. This study aimed to assess timely HepB vaccination among low birth weight infants. We hypothesized that many of these vulnerable infants would fail to receive their HepB birth dose on time. STUDY DESIGN: This retrospective cohort study included Washington State infants born weighing less than 2,000 g at an academic medical center between 2008 and 2013. Data were abstracted from electronic health records and linked to vaccine data from the Washington State Immunization Information System. Multivariable logistic regression was used to examine the associations between sociodemographic, clinical, and visit characteristics and HepB vaccination by birth hospitalization discharge or 30 days of age. RESULTS: Among 976 study infants, 58.4% received their HepB vaccine by birth hospitalization discharge or 30 days of age. Infants had higher odds of timely HepB vaccination if they were Hispanic (adjusted odds ratio [AOR] = 1.80, 95% confidence interval [CI]: 1.10-2.95) or non-Hispanic black (AOR = 2.28, 95% CI: 1.36-3.80) versus non-Hispanic white or if they were hospitalized 14 days or longer versus less than 14 days (AOR = 2.43, 95% CI: 1.66-3.54). Infants had lower odds of timely HepB vaccination if they were born before 34 weeks versus on or after 34 weeks of gestational age (AOR = 0.41, 95% CI: 0.27-0.63) or if they had an estimated household income less than $50,845 versus 50,845 or greater (AOR = 0.64, 95% CI: 0.48-0.86). CONCLUSION: Many infants born weighing less than 2,000 g did not receive their first HepB birth dose according to ACIP recommendations. Strategies are needed to improve timely HepB vaccination in this high-risk population. KEY POINTS: · Low birth weight infants are at increased risk for vaccine preventable diseases.. · Many of these vulnerable infants failed to receive their first hepatitis B vaccine on time.. · This study identified key factors associated with timely hepatitis B vaccination..

Hepatitis B Birth Dose: First Shot at Timely Early Childhood Vaccination.

INTRODUCTION: Current U.S. recommendations state that newborns weighing ≥2,000 grams should receive a birth dose of hepatitis B vaccine, yet approximately one quarter do not receive this first dose as scheduled. The relationship between timely receipt of the first hepatitis B vaccine and other early childhood vaccines remains unclear. METHODS: Washington State newborns (birth weight ≥2,000 grams) who received birth hospitalization care at an urban academic medical center between 2008 and 2013 were included. Multivariable logistic regression was used to assess whether hepatitis B vaccine receipt during the birth hospitalization was associated with completing the seven-vaccine series by 19 months, adjusting for select sociodemographic, clinical, and birth hospitalization characteristics. Analyses were conducted in 2017-2018. RESULTS: Of the 9,080 study participants, 75.5% received hepatitis B vaccine during the birth hospitalization, and 53.6% completed the seven-vaccine series by 19 months. Overall, 60.0% of infants vaccinated against hepatitis B during the birth hospitalization completed the seven-vaccine series by 19 months compared with 33.8% of those who were unvaccinated at discharge (p<0.001). The odds of series completion were nearly 3 times higher among infants who received versus did not receive hepatitis B vaccine during the birth hospitalization (AOR=2.92, 95% CI=2.61, 3.26). CONCLUSIONS: Infants who received hepatitis B vaccine during their birth hospitalization had higher odds of receiving all recommended vaccines by 19 months independent of other factors associated with vaccine receipt. Understanding the factors that influence this first parental vaccine decision and how hepatitis B vaccine delay or declination may affect subsequent vaccination requires further research.

Early Childhood Vaccination Status of Preterm Infants.

BACKGROUND: Preterm infants are at increased risk for vaccine-preventable infections and associated complications. Limited studies describe timely vaccination of these vulnerable infants. METHODS: This retrospective cohort study included Washington State infants with birth hospitalizations at an urban academic medical center between 2008 and 2013. Demographic, clinical, and visit data from electronic health records were linked to vaccine data from the Washington State Immunization Information System. Completion of the recommended 7-vaccine series by 19 months of age was compared between preterm infants (born at <37 weeks' gestation) and term/postterm infants (born at 37-43 weeks' gestation) by using Pearson's χ2 test and multivariable logistic regression. Secondary outcomes included 7-vaccine series completion by 36 months of age and receipt of individual vaccines in the series. Rotavirus, hepatitis A, and influenza vaccination was also assessed. RESULTS: Of study infants (n = 10 367), 19.3% were born prematurely. Preterm infants had lower 7-vaccine series completion compared with term/postterm infants by 19 months (47.5% vs 54.0%; adjusted odds ratio 0.77 [95% confidence interval 0.65-0.90]) and 36 months (63.6% vs 71.3%; adjusted odds ratio 0.73 [95% confidence interval 0.61-0.87]). Early preterm (23-33 weeks' gestation) and late preterm (34-36 weeks' gestation) infants had a lower rate of 7-vaccine series completion compared with term/postterm infants. Full influenza vaccination coverage by 19 months also differed between groups (early preterm: 47.7%; late preterm: 41.5%; term/postterm: 44.7%; P = .02). CONCLUSIONS: Over half of preterm infants were undervaccinated at 19 months; one-third failed to catch up by 36 months. Strategies to improve vaccination of these high-risk infants are needed.

Sociodemographic, clinical and birth hospitalization characteristics and infant Hepatitis B vaccination in Washington State.

OBJECTIVE: Hepatitis B (HepB) vaccine is recommended at birth; however, national coverage estimates fall far below target levels. Studies describing the factors associated with infant HepB vaccination are lacking. This study aimed to identify the sociodemographic, clinical and birth hospitalization factors associated with timely receipt of the first HepB vaccine dose. STUDY DESIGN: This retrospective cohort study included Washington State infants born weighing ≥2000 g who received birth hospitalization care at an urban academic medical center between January 2008-December 2013. Multivariable logistic regression was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI) for associations between maternal and infant characteristics and HepB vaccine receipt during the birth hospitalization. RESULTS: Of the 9080 study infants, 75.5% received HepB vaccine during the birth hospitalization. Infants had higher odds of being vaccinated during the birth hospitalization if they were Hispanic (AOR 2.08; CI: 1.63, 2.65), non-Hispanic black (AOR 2.34; CI: 1.93, 2.84) or Asian (AOR 2.70; CI: 2.22, 3.28) compared to non-Hispanic white. Infants with a Spanish- vs. English-speaking mother (AOR 1.97; CI: 1.46, 2.68), public vs. private insurance (AOR 2.01; CI: 1.78, 2.29), and those hospitalized ≥96 h vs. 24 to <48 h (AOR 1.67; CI: 1.34, 2.09) also had higher odds of vaccination. CONCLUSIONS: Populations that are typically underserved (e.g., publicly insured, racial/ethnic minorities) had higher odds of receiving HepB vaccine during the birth hospitalization. These findings may aid in identifying high-risk infants who could benefit from targeted interventions to increase initial HepB vaccination.

A Real Human Umbilical Cord Simulator Model for Emergency Umbilical Venous Catheter Placement Training.

Emergency umbilical venous catheter placement is a critical procedure during newborn resuscitation. Providing training in this high-acuity and low-frequency procedure is important to optimize the skills of newborn resuscitation teams. Available simulators use simulated umbilical cords which are lower in fidelity than real human umbilical cords and may not provide optimal training. This technical report describes the creation and use of a real human umbilical cord simulator model for emergency umbilical venous catheter placement training. This low-cost model provides learners the opportunity to experience placing an emergency umbilical venous catheter in a real umbilical cord, providing a more realistic training model than currently available commercial simulators.

Changes in uptake and cost of long-acting reversible contraceptive devices following the introduction of a new low-cost levonorgestrel IUD in Utah's Title X clinics: a retrospective review.

OBJECTIVE: The objective was to assess changes in long-acting reversible contraceptive (LARC) method uptake at Utah's Title X clinics before and after introduction of a new, low-cost levonorgestrel (LNG) 52mg IUD (Liletta®). STUDY DESIGN: We conducted a retrospective medical record review of LARC visits occurring at seven Title-X family planning clinics in Utah before the introduction of the low-cost LNG IUD (preintroduction period: 01/01/2014-04/30/2015) and after (postintroduction period: 05/01/2015-03/31/2016). We ran segmented, interrupted time series ordinary least squares regression models using Newey-West standard errors to assess both the change in numbers of women initiating any LARC method and the average payment amount per LARC method. We evaluated both the low-cost LNG IUD and all LARC methods. RESULTS: At the outset of preintroduction period, there were 29.2 [95% confidence interval (CI): 20.1-38.4] monthly LNG IUD insertions. Immediately postintroduction, there was a significant level of increase of 14.4 LNG IUD insertions the first month (95% CI: 2.0-26.8) followed by a significant trend increase each month of 2.4 additional LNG IUD insertions (95% CI: 0.32-4.47). Postintroduction, there was a significant level of remitted-payment decrease from all sources of -$240.43 per LNG IUD (95% CI: -311.02 to 168.87) followed by a significant monthly trend decrease of -$23.01 per LNG IUD (95% CI: -32.02 to -13.98). There were minimal changes in uptake and payment of other LARC methods following the introduction of the low-cost LNG IUD. CONCLUSIONS: Following introduction of a low-cost LNG IUD at Title X clinics, LNG IUD initiation increased and average payment for the method decreased. IMPLICATIONS: Reducing the cost of LARC methods, both to clinics and to patients, is essential to expanding access. Additional efforts to develop and provide access to low-cost copper IUDs and subdermal implants as well as novel LARC methods should be continued.

Risk of Rotavirus Nosocomial Spread After Inpatient Pentavalent Rotavirus Vaccination.

BACKGROUND: Infants born prematurely or with underlying conditions are at increased risk of severe rotavirus disease and associated complications. Given the theoretical risk of nosocomial transmission of vaccine-type rotavirus, rotavirus vaccination is recommended for infants at or after discharge from neonatal care settings. Because the first dose should be administered by 104 days of age, some infants may be age-ineligible for vaccination if delayed until discharge. METHODS: This prospective cohort included infants admitted to an urban academic medical center between birth and 104 days who received care in intensive care settings. Pentavalent human-bovine reassortant rotavirus vaccine (RV5) was used, per routine clinical care. Stool specimens were collected weekly (February 2013-April 2014) and analyzed for rotavirus strains using real-time reverse transcription-polymerase chain reaction. Demographic and vaccine data were collected. RV5 safety was not assessed. RESULTS: Of 385 study infants, 127 were age-eligible for routine vaccinations during hospitalization. At discharge, 32.7% were up-to-date for rotavirus vaccination, compared with 82.7% for other vaccinations. Of rotavirus-unvaccinated infants, 42.6% were discharged at age >104 days and thus vaccination-ineligible. Of 1192 stool specimens collected, rotavirus was detected in 13 (1.1%): 1 wild-type strain from an unvaccinated infant; 12 vaccine-type strains from 9 RV5-vaccinated infants. No vaccine-type rotavirus cases were observed among unvaccinated infants (incidence rate: 0.0 [95% confidence interval: 0.0-1.5] cases per 1000 patient days at risk). CONCLUSIONS: These data suggest that delaying rotavirus vaccination until discharge from the hospital could lead to missed vaccination opportunities and may be unnecessary in institutions using RV5 with comparable infection control standards.

Distinctive clinical presentation of a NF-1 patient with loss of heterozygosity of PTCH in his epithelial tumors.

Although patients with neurofibromatosis (NF) have an increased incidence of tumors, there is only one study that suggests that NF1 patients may have an increased risk for epithelial malignancies. We present a patient with known NF1 who had developed multiple epithelial tumors since early in his life. All but one of these tumors were morphologically most consistent with trichoepitheliomas. Loss of heterozygosity (LOH) for Patched 1 gene (PTCH) was demonstrated within two of the trichoepitheloma-like tumors and one tumor diagnosed as basal cell carcinoma, and the patient was show to have a PTCH gene deletion. To our knowledge, a patient presenting with both NF1 and multiple trichoepitheliomas (MTE) has not previously been reported. The dysregulation in cellular proliferation and signaling induced by decreased NF1 along with the PTCH gene mutation may explain the pattern of immunohistochemical staining within these tumors, and the rare association of NF1 with epithelial neoplasms.

Pilot study of low-dose interleukin-2, pegylated interferon-alpha 2b, and ribavirin for the treatment of hepatitis C virus infection in patients with HIV infection.

BACKGROUND: Patients infected with hepatitis C virus (HCV) and human immunodeficiency virus have a diminished HCV virologic response to standard interferon (IFN)-based therapies. We explored the strategy of initial immunostimulatory therapy with interleukin (IL)-2, followed by the addition of specific anti-HCV therapy, as a possible synergistic approach to treatment. METHODS: Coinfected subjects (n=23) with CD4 cell counts >300 cells/ micro L received low-dose IL-2 daily for 12 weeks, followed by pegylated IFN- alpha 2b and ribavirin for an additional 48 weeks. The primary end point was permanent discontinuation of treatment before week 24 due to toxicity or intolerance. RESULTS: Six subjects (26.1%) discontinued treatment before week 24, and 11 (47.8%) discontinued treatment before week 60. Overall, 4 subjects discontinued because of adverse events. Four of 23 (17%; 95% confidence interval [CI], 5%-39%) had sustained virologic responses. Of 17 subjects with increased levels of alanine aminotransferase at baseline, 13 had follow-up measurements at week 60, of which 6 (46%) were normal. CONCLUSIONS: Low-dose IL-2 plus PEG-IFN and ribavirin was associated with a high discontinuation rate. Although the study was not powered for efficacy, CIs surrounding the treatment response rate suggest that this strategy should not be pursued in larger trials.

Unexplained hypereosinophilia and the need for cytogenetic and molecular genetic analyses.

BACKGROUND: Idiopathic hypereosinophilic syndrome (HES) is a diagnosis made after the exclusion of other causes of eosinophilia. However, differentiation of idiopathic HES from eosinophilic leukemia is sometimes difficult. In some cases, these diagnoses can be differentiated by cytogenetic or molecular findings, as illustrated in the patients described herein. OBSERVATIONS: We describe 3 patients with HES and associated pruritus; 1 patient also had recurrent lesions of eosinophilic cellulitis. All 3 patients were initially diagnosed as having idiopathic HES, but after evaluation and demonstration of molecular abnormalities, they were classified as having eosinophilic leukemia. CONCLUSIONS: Patients with a diagnosis of idiopathic HES should be evaluated for cytogenetic or molecular genetic abnormalities. These abnormalities can establish a diagnosis of chronic eosinophilic leukemia and may provide clues for emerging therapies.

Probabilistic capture zone delineation based on an analytic solution.

A major tool used in the design of wellhead protection areas is the delineation of a capture zone for a pumping well by use of a simple, steady-state analytic solution. This simple approach has been useful for many small municipalities because of the high costs associated with obtaining the hydrogeologic information needed for detailed numerical modeling. This analytic solution, however, is deterministic, and uncertainty in the mean value estimates of the hydraulic parameters used in this model can be a major source of error in predicting capture zones. To address this problem, a statistical theory was developed for including the uncertainty in the transmissivity and the magnitude and direction of the hydraulic head gradient in the analytic solution for both the ultimate and time-dependent capture zone for an arbitrary reliability level. To demonstrate the method and investigate the effect of varying magnitudes of uncertainty on time-dependent capture zones, the method is applied to three synthetic data sets based on data from the Borden Aquifer in Ontario, Canada. In general, the results show that uncertainty in the length of the time-dependent capture zone at a given reliability level is dependent on the uncertainty in the magnitude of the mean regional flow, which is equal to the transmissivity multiplied by the hydraulic head gradient; uncertainty in the maximum width of the capture zone is dependent primarily on the uncertainty in the mean direction of the regional flow.