Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Implementing Standardized Feeding Guidelines, Challenges, and Results.

PURPOSE: The purpose of this article was to develop standardized nutritional guidelines that would promote increased growth velocity (GV) in premature infants. DESIGN: Evidence-based standardized nutritional guidelines were developed. Guidelines included total parenteral nutrition advancement; enteral feeding advancement; and a bedside nurse gastric residual management algorithm. Staff education was given. Guideline compliance was measured. Nutritional intake and daily weights were recorded. SAMPLE: Infants of birth weight <1,500 grams who were admitted to the NICU before day of life four. MAIN OUTCOME VARIABLE: Increase in GV from 12 to 15 g/kg/d. RESULTS: Growth velocity was unchanged. Compliance to the nutritional guidelines was 70 percent. No difference was seen in length of stay. Rate of necrotizing enterocolitis was decreased.

Just-in-Time Training: A Novel Approach to Quality Improvement Education.

Just-in-time training (JITT) is accepted in medical education as a training method for newer concepts or seldom-performed procedures. Providing JITT to a large nursing staff may be an effective method to teach quality improvement (QI) initiatives. We sought to determine if JITT could increase knowledge of a specific nutrition QI initiative. Members of the nutrition QI team interviewed staff using the Frontline Contextual Inquiry to assess knowledge regarding the specific QI project. The inquiry was completed pre- and post-JITT. A JITT educational cart was created, which allowed trainers to bring the educational information to the bedside for a short, small group educational session. The results demonstrated a marked improvement in the knowledge of the frontline staff regarding our Vermont Oxford Network involvement and the specifics of the nutrition QI project. Just-in-time training can be a valuable and effective method to disseminate QI principles to a large audience of staff members.

Behavioral economics in neonatology-balancing provider wellness and departmental finances.

High work relative value units (wRVU) per clinical full-time-equivalent (cFTE) productivity by Neonatologists have played a key role in enhancing departmental revenue in Pediatrics. However, such high productivity is not sustainable due to recent changes in trainee schedules and global daily codes and is likely to impact physician morale and wellness. Incentives based on wRVU benchmarks have the capacity to promote desirable behavior such as better documentation and in-person attendance in delivery room resuscitation and consults but comes at a cost of physician time providing care. An alternate method of funding academic Pediatric departments using time- or point-based staffing models, a reduction in productivity benchmarks for academic neonatologists through more accurate reporting of effort and physician leadership that promotes transparency and mutual respect are warranted to improve neonatologist well-being and morale.

Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants.

OBJECTIVE: The influence of post-ligation cardiac syndrome (PLCS), a complication of patent ductus arteriosus (PDA) ligations, on neonatal outcomes is unknown. The purpose of this study was to determine the risks of PLCS on severe pulmonary morbidity and severe retinopathy of prematurity (ROP). STUDY DESIGN: Retrospective cohort study of infants who underwent a PDA ligation between 2006 and 2015. Data were collected on patients with and without PLCS. The primary outcome was the difference in severe bronchopulmonary dysplasia (BPD) between groups. Secondary outcomes included discharge with home oxygen and severe ROP. RESULT: A total of 100 infants that underwent PDA ligation during the study period were included in the study; 31 (31%) neonates developed PLCS. In adjusted analysis, PLCS was associated with increased risk for severe BPD (RR 1.67, 95% CI: 1.15-2.42) and home oxygen therapy (RR: 1.47, 95% CI: 1.09-1.99) only. No association with severe ROP was seen (RR: 1.48; 95% CI: 0.87-2.52). CONCLUSION: PLCS is associated with severe neonatal pulmonary morbidity, but not with severe ROP. Further investigation is warranted to validate these results.

Platelet endothelial cell adhesion molecule-1 and capillary loading in premature infants with and without chronic lung disease.

It was our objective to quantify platelet endothelial cell adhesion molecule-1 (PECAM-1) by immunohistochemistry in control infants of 22-50 weeks postconceptual age, and to correlate it with varying degrees of neonatal chronic lung disease (CLD). We tested the hypothesis that the density of PECAM-1 staining will positively correlate with increasing gestational age (GA) and the inflammatory process in CLD. A library of postmortem lung tissue of infants receiving ventilator care was accessed. The population consisted of 35 control infants exposed briefly to oxygen and positive pressure ventilation, and 31 infants who were 23-30 weeks GA with mild to severe CLD. A monoclonal anti-human PECAM-1 antibody was used to stain 5-microm paraffin sections. The slides were viewed at a magnification of x 40 by a blinded examiner. Twenty consecutive fields from standardly expanded tissue samples were viewed, and the volume density of PECAM-1 (V(V PECAM)) per parenchyma was measured, using point counting. In addition, 1-microm sections from 15 controls and 5 infants with CLD were stained with Toluidine blue and viewed under oil at a magnification of x 100, and the volume density of capillaries (V(V CAP)) and capillary load (CL) were calculated. The V(V PECAM) increased significantly with GA in controls (r = 0.72, P < 0.001). There was no relationship between V(V PECAM) and severity of CLD. Both V(V CAP) and CL increased significantly with GA (r = 0.93, P < 0.001; r = 0.94, P < 0.001, respectively). The infants with CLD had a normal or increased V(V CAP) and CL compared to controls. In summary, V(V PECAM), V(V CAP), and CL increased significantly with gestational age in control infants, but the postconceptional age range in CLD infants was too short to determine whether the V(V PECAM) changed. Infants with CLD had normal or increased V(V CAP) and CL compared to controls. The PECAM-1 immunostain does not appear to be a sensitive method for assessing capillary density in infants with CLD. These findings of normal or increased capillary load may represent a vascular adaptation for the lack of secondary septation and decreased surface area in CLD.

Exhaled nitric oxide and tracheal endothelin-1 in preterm infants with and without RDS.

We measured exhaled nitric oxide and tracheal aspirate endothelin-1 to determine relationships between these substances and alterations in pulmonary gas exchange during respiratory distress syndrome (RDS) in comparison to those obtained from control preterm infants without RDS. Eight infants with RDS had measurements made at 24 hr and again at 48-72 hr. Eight control infants were studied once at 24-48 hr of life. Exhaled gas was analyzed on-line, and minute excretion of NO (V(NO)) was calculated. ET-1 was determined by immunoassay. Median V(NO) at 24 hr in RDS was 0.405 nl/min/kg (range, 0.30 -0.79), which subsequently declined by 48-72 hr to 0.166 nl/min/kg (P < 0.01). The V(NO) in RDS infants was significantly higher than time-matched V(NO) in controls, with a median of 0.099 nl/min/kg (range, 0.03-0.27; P < 0.001). ET-1 was not correlated with initial V(NO) in the RDS or control patients. In conclusion, in RDS, V(NO) decreases as gas exchange improves. ET-1 is detectable in tracheal aspirate samples in both groups of infants.

Crossover trial comparing pressure support with synchronized intermittent mandatory ventilation.

OBJECTIVE: To compare pressure support ventilation (PSV) with volume guarantee (VG) to synchronized intermittent mandatory ventilation (SIMV) in infants with respiratory distress syndrome (RDS). STUDY DESIGN: A randomized, crossover study design was used. We enrolled 14 infants [BW (mean+/-SD) 2.5+/-0.7 kg, GA 34+/-2 weeks, age 49+/-26 hours]. Subjects received 4 hours of each mode of ventilation, with the first mode selected randomly. End expiratory volume (EEV) was measured during both ventilatory modes. RESULTS: Minute ventilation was greater with PSV+VG than with SIMV (p=0.012). This occurred despite no difference in p(a)CO(2). Mean airway pressure was higher during PSV+VG (p=0.023). There was no difference in the arterial/alveolar oxygen tension (a/A) ratio or in the specific dynamic compliance (sCdyn). CONCLUSION: Because of an increase in V(E) with PSV+VG, and no difference in the a/A ratio or sCdyn, we do not recommend the routine use of PSV+VG for this population.

Optimizing therapeutic hypothermia for neonatal encephalopathy.

OBJECTIVE: Therapeutic hypothermia (TH) for neonatal encephalopathy is becoming widely available in clinical practice. The goal of this collaborative was to create and implement an evidence-based standard-of-care approach to neonatal encephalopathy, deliver consistent care, and optimize outcomes. METHODS: The quality improvement process identified and used the Model for Improvement as a framework for improvement efforts. This was a Vermont Oxford Network Collaborative focused on optimizing TH in the treatment of neonatal encephalopathy. By using an evidence-based approach, Potentially Better Practices were developed by the topic expert, modified by the collaborative, and implemented at each hospital. These included the following: timely identification of at-risk infants, coordination with referring hospitals to ensure TH was available within 6 hours after birth, staff education for both local and referring hospitals, nonsedated MRI, incorporating amplitude-integrated EEG into a TH protocol, and ensuring standard neurodevelopmental follow-up of infants. Each center used these practices to develop a matrix for implementation. RESULTS: Local self-assessments directed the implementation and adaptation of the Potentially Better Practices at each center. Resources, based on common identified barriers, were developed and shared among the group. CONCLUSIONS: The implementation of a TH program to improve the consistency of care for patients in NICUs is feasible using standard-quality improvement methodology. The successful introduction of new interventions such as TH to the NICU culture requires a collaborative multidisciplinary team, use of a systematic quality improvement process, and perseverance.