Misdiagnosis of Total Parental Nutrition-Related Riboflavin Deficiency: Three Case Reports of Diagnostic Error.

Total parental nutrition (TPN) is a critical component of neonatal intensive care. Supply shortages leading to deficiencies in TPN constituents can have devastating consequences for critically ill patients in the neonatal intensive care unit (NICU), who may be initially misdiagnosed as potential inborn errors of metabolism. Here, we present three cases of patients with prolonged TPN dependence due to intra-abdominal pathology who presented with signs and symptoms concerning for metabolic disorders and who were ultimately determined to be a result of vitamin deficiencies in the TPN after unnecessary testing and interventions had occurred. These diagnostic errors highlight the need for clinicians to maintain a high index of suspicion for nutritional deficiencies when treating patients in the NICU with potential metabolic disorders during times when TPN constituents are not available, as well as advocating to ensure that adequate supplies are maintained for this vulnerable population.

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial.

PURPOSE: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual's limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. METHODS: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. RESULTS: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. CONCLUSIONS: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

Birth Tourism and Neonatal Intensive Care: A Children's Hospital Experience.

Objective The aim of this article is to examine characteristics of birth tourism (BT) neonates admitted to a neonatal intensive care unit (NICU). Methods This was a retrospective review over 3 years; BT cases were identified, and relevant perinatal, medical, social, and financial data were collected and compared with 100 randomly selected non-birth tourism neonates. Results A total of 46 BT neonates were identified. They were more likely to be born to older women (34 vs. 29 years; p < 0.001), via cesarean delivery (72 vs. 48%; p = 0.007), and at a referral facility (80 vs. 32%; p < 0.001). BT group had longer hospital stay (15 vs. 7 days; p = 0.02), more surgical intervention (50 vs. 21%; p < 0.001), and higher hospital charges (median $287,501 vs. $103,105; p = 0.003). One-third of BT neonates were enrolled in public health insurance program and four BT neonates (10%) were placed for adoption. Conclusion Families of BT neonates admitted to the NICU face significant challenges. Larger studies are needed to better define impacts on families, health care system, and society.

A Multidisciplinary Quality Improvement Approach Increases Breastmilk Availability at Discharge from the Neonatal Intensive Care Unit for the Very-Low-Birth-Weight Infant.

BACKGROUND: Mothers of very-low-birth-weight (VLBW) infants often struggle to establish and maintain a milk supply. Children's Hospital of Orange County (CHOC Children's) data from 2005 to 2011 showed that while the total percentage of all neonatal intensive care unit (NICU) babies being discharged on breastmilk had remained stable, the percentage of VLBW babies with breastmilk at discharge had declined. This information resulted in a quality improvement initiative to remove barriers and implement programs shown to have the greatest impact on initiating and sustaining lactation in this patient subset. The objective of this initiative was to increase breastmilk availability at discharge for the VLBW population. MATERIALS AND METHODS: A multidisciplinary program was initiated, which included NICU parent and staff education, clarification of roles, and improved access to pumping supplies. Physicians and nurses completed online education. An algorithm defining roles in lactation support was developed, and a resource team of trained bedside nurses was formed. Lactation consultant time was then refocused on the VLBW population. In addition, "Lactation Support" was added to the physician daily documentation to bring the topic to daily bedside rounds. Twice weekly lactation rounds between the lactation consultant and neonatologist addressed lactation concerns for each dyad. To address pumping issues, the loaner pump program was enhanced. RESULTS: To assess the effectiveness of the initiative, breastmilk availability at discharge for the VLBW population at CHOC Children's was compared from baseline (2011) to the end of June 2015. VLBW breastmilk availability at discharge upon project initiation was 58.7% and increased by 36% to a final rate of 80% by 2013--a rate sustained through the first 6 months of 2015. CONCLUSIONS: The results of this initiative suggest that a multidisciplinary approach, including education, changes in workflow, and redefinition of roles, is effective in improving breastmilk rates at discharge in the VLBW patient population.

Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early Diagnosis of Intubation-related Subglottic Injury.

RATIONALE: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury. OBJECTIVES: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness. METHODS: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1-104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome. MEASUREMENTS AND MAIN RESULTS: Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P < 0.001; multiple r(2) = 0.44) and subglottic (P < 0.001; multiple r(2) = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure. CONCLUSIONS: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates. Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).

Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: a prospective, randomized, open-label, placebo-controlled pilot study.

OBJECTIVE: This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates. METHODS: This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality. RESULTS: Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality. CONCLUSIONS: L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.