Neonatal Risk Factors for Pulmonary Vein Stenosis in Infants Born Preterm with Severe Bronchopulmonary Dysplasia.

OBJECTIVE: To evaluate associations between neonatal risk factors and pulmonary vein stenosis (PVS) among infants born preterm with severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: We performed a case-control study of infants born from 2010 to 2022 at <32 weeks' gestation with sBPD among 46 neonatal intensive care units in the Children's Hospitals Neonatal Consortium. Cases with PVS were matched to controls using epoch of diagnosis (2010-2016; 2017-2022) and hospital. Multivariable logistic regression analyses were utilized to evaluate PVS association with neonatal risk factors. RESULTS: From 10 171 preterm infants with sBPD, we identified 109 cases with PVS and matched those to 327 controls. The prevalence of PVS (1.07%) rose between epochs (0.8% in 2010-2016 to 1.2% in 2017-2022). Relative to controls, infants with PVS were more likely to be <500 g at birth, to be small for gestational age <10th%ile, or have surgical necrotizing enterocolitis, atrial septal defects, or pulmonary hypertension. In multivariable models, these associations persisted, and small for gestational age, surgical necrotizing enterocolitis, atrial septal defects, and pulmonary hypertension were each independently associated with PVS. Among infants on respiratory support at 36 weeks' postmenstrual age, infants with PVS had 4.3-fold higher odds of receiving mechanical ventilation at 36 weeks' postmenstrual age. Infants with PVS also had 3.6-fold higher odds of in-hospital mortality relative to controls. CONCLUSIONS: In a large cohort of preterm infants with sBPD, multiple independent, neonatal risk factors are associated with PVS. These results lay important groundwork for the development of targeted screening to guide the diagnosis and management of PVS in preterm infants with sBPD.

ADVANCE: a biomedical informatics approach to investigate acute kidney injury in infants.

BACKGROUND: Acute kidney injury (AKI) occurs in up to half of infants admitted to the neonatal intensive care unit (NICU) and is associated with increased risks of death and more days of mechanical ventilation, hospitalization, and vasopressor drug support. Our objective was to build a granular relational database to study the impact that AKI has on infants admitted to Level-IV NICUs. METHODS: A relational database was created by linking data from the Children's Hospitals Neonatal Database with AKI-focused data from electronic health records from 9 centers. RESULTS: The current cohort consists of 24,870 infants with a median (IQR) gestational age of birth of 37 weeks (32 weeks, 39 weeks), and a median birth weight of 2.720 kg (1.750 kg, 3.310 kg). There was a male predominance with 14,214 (57%) males. In all, 2434 (9.8%) of the mothers were of Hispanic ethnicity. The maternal race breakdown of the cohort was as follows: 741 (3.0%) Asian, 5911 (24%) Black, and 14,945 (60%) White. Overall mortality was 5.8%. CONCLUSION: The ADVANCE relational database is an innovative research tool to rigorously study the epidemiology of AKI in a large national cohort of infants admitted to Level-IV NICUs involved in the Children's Hospital Neonatal Consortium. IMPACT: We used a biomedical informatics approach to build a relational database to study acute kidney injury in infants. We highlight our methodology linking Children's Hospital Neonatal Consortium and electronic health record data from nine neonatal intensive care units. The ADVANCE relational database is a granular and innovative research tool to study risk factors and in-hospital outcomes of acute kidney injury and mortality in a vulnerable patient population.

Provision and availability of genomic medicine services in Level IV neonatal intensive care units.

PURPOSE: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada. METHODS: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services. RESULTS: Overall response rate was 74% (32/43). Although chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites), and pre- and post-test counseling practices varied widely. CONCLUSION: We observed large inter-center variation in genomic medicine services across level IV NICUs: most notably, access to rapid, comprehensive genetic testing in time frames relevant to critical care decision making was limited at many level IV Children's Hospitals Neonatal Consortium NICUs despite a significant burden of genetic disease. Further efforts are needed to improve access to neonatal genomic medicine services.

Variability for Age at Successful Extubation in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: The objective of this study was to characterize clinical factors associated with successful extubation in infants with congenital diaphragmatic hernia. STUDY DESIGN: Using the Children's Hospitals Neonatal Database, we identified infants with congenital diaphragmatic hernia from 2017 to 2020 at 32 centers. The main outcome was age in days at the time of successful extubation, defined as the patient remaining extubated for 7 consecutive days. Unadjusted Kaplan-Meier and multivariable Cox proportional hazards ratio equations were used to estimate associations between clinical factors and the main outcome. Observations occurred through 180 days after birth. RESULTS: There were 840 eligible neonates with a median gestational age of 38 weeks and birth weight of 3.0 kg. Among survivors (n = 693), the median age at successful extubation was 15 days (interquartile range [IQR]: 8-29 days, 95th percentile: 71 days). For nonsurvivors (n = 147), the median age at death was 21 days (IQR: 11-39 days, 95th percentile: 110 days). Center (adjusted hazards ratio: 0.22-15, P < .01), low birth weight, intrathoracic liver position, congenital heart disease, lower 5-minute Apgar score, lower pH upon admission to Children's Hospitals Neonatal Database center, and use of extracorporeal support were independently associated with older age at successful extubation. Tracheostomy was associated with multiple failed extubations. CONCLUSION: Our findings suggest that infants who have not successfully extubated by about 3 months of age may be candidates for tracheostomy with chronic mechanical ventilation or palliation. The variability of timing of successful extubation among our centers supports the development of practice guidelines after validating clinical criteria.

Analgesia, Sedation, and Neuromuscular Blockade in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: The aim of this study was to describe the use, duration, and intercenter variation of analgesia and sedation in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: This is a retrospective analysis of analgesia, sedation, and neuromuscular blockade use in neonates with CDH. Patient data from 2010 to 2016 were abstracted from the Children's Hospitals Neonatal Database and linked to the Pediatric Health Information System. Patients were excluded if they also had non-CDH conditions likely to affect the use of the study medications. RESULTS: A total of 1,063 patients were identified, 81% survived, and 30% were treated with extracorporeal membrane oxygenation (ECMO). Opioid (99.8%), sedative (93.4%), and neuromuscular blockade (87.9%) use was common. Frequency of use was higher and duration was longer among CDH patients treated with ECMO. Unadjusted duration of use varied 5.6-fold for benzodiazepines (median: 14 days) and 7.4-fold for opioids (median: 16 days). Risk-adjusted duration of use varied among centers, and prolonged use of both opioids and benzodiazepines ≥5 days was associated with increased mortality (p < 0.001) and longer length of stay (p < 0.001). Use of sedation or neuromuscular blockade prior to or after surgery was each associated with increased mortality (p ≤ 0.01). CONCLUSION: Opioids, sedatives, and neuromuscular blockade were used commonly in infants with CDH with variable duration across centers. Prolonged combined use ≥5 days is associated with mortality. KEY POINTS: · Use of analgesia and sedation varies across children's hospital NICUs.. · Prolonged opioid and benzodiazepine use is associated with increased mortality.. · Postsurgery sedation and neuromuscular blockade are associated with mortality..

A Qualitative Study of Nurses' Perspectives on Neonatologist Continuity of Care.

BACKGROUND: Families and staff in neonatal intensive care units (NICUs) value continuity of care (COC), though definitions, delivery, and impacts of COC are incompletely described. Previously, we used parental perspectives to define and build a conceptual model of COC provided by neonatologists. Nursing perspectives about COC remain unclear. PURPOSE: To describe nursing perspectives on neonatologist COC and revise our conceptual model with neonatal nurse input. METHODS: This was a qualitative study interviewing NICU nurses. The investigators analyzed transcripts with directed content analysis guided by an existing framework of neonatologist COC. Codes were categorized according to previously described COC components, impact on infants and families, and improvements for neonatologist COC. New codes were identified, including impact on nurses, and codes were classified into themes. RESULTS: From 15 nurses, 5 themes emerged: (1) nurses validated parental definitions and benefits of COC; (2) communication is nurses' most valued component of COC; (3) neonatologist COC impact on nurses; (4) factors that modulate the delivery of and need for COC; (5) conflict between the need for COC and the need for change. Suggested improvement strategies included optimizing staffing and transition processes, utilizing clinical guidelines, and enhancing communication at all levels. Our adapted conceptual model describes variables associated with COC. IMPLICATIONS FOR PRACTICE AND RESEARCH: Interdisciplinary NICU teams need to develop systematic strategies tailored to their unit's and patients' needs that promote COC, focused to improve parent-clinician communication and among clinicians. Our conceptual model can help future investigators develop targeted interventions to improve COC.

Central Line Utilization and Complications in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: Infants with congenital diaphragmatic hernia (CDH) require multiple invasive interventions carrying inherent risks, including central venous and arterial line placement. We hypothesized that specific clinical or catheter characteristics are associated with higher risk of nonelective removal (NER) due to complications and may be amenable to efforts to reduce patient harm. STUDY DESIGN: Infants with CDH were identified in the Children's Hospital's Neonatal Database (CHND) from 2010 to 2016. Central line use, duration, and complications resulting in NER are described and analyzed by extracorporeal membrane oxygenation (ECMO) use. RESULTS: A total of 1,106 CDH infants were included; nearly all (98%) had a central line placed, (average of three central lines) with a total dwell time of 22 days (interquartile range [IQR]: 14-39). Umbilical arterial and venous lines were most common, followed by extremity peripherally inserted central catheters (PICCs); 12% (361/3,027 central lines) were removed secondary to complications. Malposition was the most frequent indication for NER and was twice as likely in infants with intrathoracic liver position. One quarter of central lines in those receiving ECMO was placed while receiving this therapy. CONCLUSION: Central lines are an important component of intensive care for infants with CDH. Careful selection of line type and location and understanding of common complications may attenuate the need for early removal and reduce risk of infection, obstruction, and malposition in this high-risk group of patients. KEY POINTS: · Central line placement near universal in congenital diaphragmatic hernia infants.. · Mean of three lines placed per patient; total duration 22 days.. · Clinical patient characteristics affect risk..

Parental Perspectives on Neonatologist Continuity of Care.

BACKGROUND: Continuity of care (COC) is highly regarded; however, data about benefits are mixed. Little is known about components, parental views, or the value COC may provide to neonatal intensive care unit (NICU) infants and families. PURPOSE: To describe parents' perspectives on definitions, reasons they value, and suggested improvements regarding COC provided by neonatologists. METHODS: We performed a qualitative study of in-person, semistructured interviews with parents of NICU infants hospitalized for 28 days or more. We analyzed interview transcripts using content analysis, identifying codes of parental experiences, expressed value, and improvement ideas related to neonatologist COC, and categorizing emerging themes. RESULTS: Fifteen families (15 mothers and 2 fathers) described 4 themes about COC: (1) longitudinal neonatologists: gaining experience with infants and building relationships with parents over time; (2) background knowledge: knowing infants' clinical history and current condition; (3) care plans: establishing patient-centered goals and management plans; and (4) communication: demonstrating consistent communication and messaging. Parents described benefits of COC as decreasing knowledge gaps, advancing clinical progress, and decreasing parental stress. Suggested improvement strategies included optimizing staffing and sign-out/transition processes, utilizing clinical guidelines, and enhancing communication. Using parent input and existing literature, we developed a definition and conceptual framework of COC. IMPLICATIONS FOR PRACTICE: NICUs should promote practices that enhance COC. Parental suggestions can help direct improvement efforts. IMPLICATIONS FOR RESEARCH: Our COC definition and conceptual framework can guide development of research and quality improvement projects. Future studies should investigate nursing perspectives on NICU COC and the impact of COC on infant and family outcomes.

Home Oxygen Use and 1-Year Readmission among Infants Born Preterm with Bronchopulmonary Dysplasia Discharged from Children's Hospital Neonatal Intensive Care Units.

OBJECTIVE: To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units. STUDY DESIGN: We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission. RESULTS: Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission. CONCLUSIONS: Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD.

Center, Gestational Age, and Race Impact End-of-Life Care Practices at Regional Neonatal Intensive Care Units.

OBJECTIVE: To assess the impact of intercenter variation and patient factors on end-of-life care practices for infants who die in regional neonatal intensive care units (NICUs). STUDY DESIGN: We conducted a retrospective cohort analysis using the Children's Hospital Neonatal Database during 2010-2016. A total of 6299 nonsurviving infants cared for in 32 participating regional NICUs were included to examine intercenter variation and the effects of gestational age, race, and cause of death on 3 end-of-life care practices: do not attempt resuscitation orders (DNR), cardiopulmonary resuscitation within 6 hours of death (CPR), and withdrawal of life-sustaining therapies (WLST). Factors associated with these practices were used to develop a multivariable equation. RESULTS: Dying infants in the cohort underwent DNR (55%), CPR (21%), and WLST (73%). Gestational age, cause of death, and race were significantly and differently associated with each practice: younger gestational age (<28 weeks) was associated with CPR (OR 1.7, 95% CI 1.5-2.1) but not with DNR or WLST, and central nervous system injury was associated with DNR (1.6, 1.3-1.9) and WLST (4.8, 3.7-6.2). Black race was associated with decreased odds of WLST (0.7, 0.6-0.8). Between centers, practices varied widely at different gestational ages, race, and causes of death. CONCLUSIONS: From the available data on end-of-life care practices for regional NICU patients, variability appears to be either individualized or without consistency.

Machine learning mortality classification in clinical documentation with increased accuracy in visual-based analyses.

AIM: The role of machine learning on clinical documentation for predictive outcomes remains undefined. We aimed to compare three neural networks on inpatient providers' notes to predict mortality in neonatal hypoxic-ischaemic encephalopathy (HIE). METHODS: Using Children's Hospitals Neonatal Database, non-anomalous neonates with HIE treated with therapeutic hypothermia were identified at a single-centre. Data were linked with the initial seven days of documentation. Exposures were derived using the databases and applying convolutional and two recurrent neural networks. The primary outcome was mortality. The predictive accuracy and performance measures for models were determined. RESULTS: The cohort included 52 eligible infants. Most infants survived (n = 36, 69%) and 23 had severe HIE (44%). Neural networks performed above baseline and differed in their median accuracy for predicting mortality (P = .0001): recurrent models with long short-term memory 69% (25th , 75th percentile 65, 73%) and gated-recurrent model units 65% (62, 69%) and convolutional 72% (64, 96%). Convolutional networks' median specificity was 81% (72, 97%). CONCLUSION: The neural network models demonstrated fundamental validity in predicting mortality using inpatient provider documentation. Convolutional models had high specificity for (excluding) mortality in neonatal HIE. These findings provide a platform for future model training and ultimately tool development to assist clinicians in patient assessments and risk stratifications.

Small-for-Gestational Age Birth Confers Similar Educational Performance through Middle School.

OBJECTIVE: To estimate the association between small for gestational age (SGA) at birth and educational performance on standardized testing and disability prevalence in elementary and middle school. STUDY DESIGN: Through linked birth certificates and school records, surviving infants born at 23-41 weeks of gestation who entered Florida's public schools 1998-2009 were identified. Twenty-three SGA definitions (3rd-25th percentile) were derived. Outcomes were scores on Florida Comprehensive Assessment Test (FCAT) and students' disability classification in grades 3 through 8. A "sibling cohort" subsample included families with at least 2 siblings from the same mother in the study period. Multivariable models estimated independent relationships between SGA and outcomes. RESULTS: Birth certificates for 80.2% of singleton infants were matched to Florida public school records (N = 1 254 390). Unadjusted mean FCAT scores were 0.236 SD lower among <10th percentile SGA infants compared with non-SGA infants; this difference declined to -0.086 SD after adjusting for maternal and infant characteristics. When siblings discordant in SGA status were compared within individual families, the association declined to -0.056 SD. For SGA <10th percentile infants, the observed prevalence of school-age disability was 15.0%, 7.7%, and 6.3% for unadjusted, demographics-adjusted, and sibling analyses, respectively. No inflection or discontinuity was detected across SGA definitions from 3rd to 25th percentile in either outcome, and the associations were qualitatively similar. CONCLUSIONS: The associations between SGA birth and students' standardized test scores and well-being were quantitatively small but persisted through elementary and middle school. The observed deficits were largely mitigated by demographic and familial factors.

Association of Neonatologist Continuity of Care and Short-Term Patient Outcomes.

OBJECTIVES: To describe neonatologist continuity of care and estimate the association between these transitions and selected patient outcomes. STUDY DESIGN: We linked Children's Hospitals Neonatal Database records with masked neonatologist daily schedules at 4 centers, which use 2- and 3-week and 1-month "on service" blocks to provide care. After describing the neonatologist transitions, we estimated associations between these transitions and selected short-term patient outcomes using multivariable Poisson, logistic, and linear regression analyses, independent of length of stay (LOS) and case-mix. We also completed analyses after stratifying the cohort by LOS, birthweight, age at admission categories, and selected diagnoses. RESULTS: Stratified by LOS, patient transitions varied between centers in both unadjusted (P < .001) and multivariable analyses (adjusted incidence rate ratio; 95% CI for center B = 3.98 (3.81-4.15), center C = 4.92 (4.71-5.13), center D = 4.2 (4.0-4.4), P < .001), independent of LOS, gestational age, birthweight, surgical intervention, ventilator duration, and mortality. Only central venous line duration (adjusted incidence rate ratio 1.015, 95% CI 1.01-1.02) was minimally and independently associated with the number of transitions. No differences were observed in ventilator duration, oxygen use at neonatal intensive care unit discharge, bloodstream infections, or urinary tract infections. Surviving infants with meconium aspiration, hypoxic ischemic encephalopathy, cerebral infarction, bronchopulmonary dysplasia, and diaphragmatic hernia demonstrated similar findings. CONCLUSIONS: Transitions in neonatologists are frequent in regional neonatal intensive care units but appear unrelated to short-term patient outcomes. Future work to define continuity of care and develop effective strategies that promote longitudinal inpatient management is needed.

Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs.

BACKGROUND: The incidence of the neonatal abstinence syndrome, a drug-withdrawal syndrome that most commonly occurs after in utero exposure to opioids, is known to have increased during the past decade. However, recent trends in the incidence of the syndrome and changes in demographic characteristics and hospital treatment of these infants have not been well characterized. METHODS: Using multiple cross-sectional analyses and a deidentified data set, we analyzed data from infants with the neonatal abstinence syndrome from 2004 through 2013 in 299 neonatal intensive care units (NICUs) across the United States. We evaluated trends in incidence and health care utilization and changes in infant and maternal clinical characteristics. RESULTS: Among 674,845 infants admitted to NICUs, we identified 10,327 with the neonatal abstinence syndrome. From 2004 through 2013, the rate of NICU admissions for the neonatal abstinence syndrome increased from 7 cases per 1000 admissions to 27 cases per 1000 admissions; the median length of stay increased from 13 days to 19 days (P<0.001 for both trends). The total percentage of NICU days nationwide that were attributed to the neonatal abstinence syndrome increased from 0.6% to 4.0% (P<0.001 for trend), with eight centers reporting that more than 20% of all NICU days were attributed to the care of these infants in 2013. Infants increasingly received pharmacotherapy (74% in 2004-2005 vs. 87% in 2012-2013, P<0.001 for trend), with morphine the most commonly used drug (49% in 2004 vs. 72% in 2013, P<0.001 for trend). CONCLUSIONS: From 2004 through 2013, the neonatal abstinence syndrome was responsible for a substantial and growing portion of resources dedicated to critically ill neonates in NICUs nationwide.

Risk Factors for Neonatal Venous and Arterial Thromboembolism in the Neonatal Intensive Care Unit-A Case Control Study.

OBJECTIVE: To identify risk factors associated with venous and arterial thrombosis in sick neonates admitted to the neonatal intensive care unit. STUDY DESIGN: A case-control study was conducted at 2 centers between January 2010 and March 2014 using the Children's Hospital Neonatal Database dataset. Cases were neonates diagnosed with either arterial or venous thrombosis during their neonatal intensive care unit stay; controls were matched in a 1:4 ratio by gestational age and presence or absence of central access devices. Bivariable and conditional logistic regression analyses for venous and arterial thrombosis were performed separately. RESULTS: The overall incidence of neonatal thrombosis was 15.0 per 1000 admissions. A higher proportion of neonates with thrombosis had presence of central vascular access devices (75% vs 49%; P < .01) were of extremely preterm gestational age (22-27 weeks; 26% vs 15.0%; P <.05) and stayed ≥31 days in the neonatal intensive care unit (53% vs 32.9%; P <.01), when compared with neonates without thrombosis. A final group of 64 eligible patients with thrombosis and 4623 controls were analyzed. In a conditional multivariable logistic regression model, venous thrombosis was significantly associated with male sex (AOR, 2.12; 95% CI, 1.03-4.35; P = .04) and blood stream infection (AOR, 3.47; 95% CI, 1.30-9.24; P = .01). CONCLUSIONS: The incidence of thrombosis was higher in our neonatal population than in previous reports. After matching for central vascular access device and gestational age, male sex and blood stream infection represent independent risk factors of neonatal venous thrombosis. A larger cohort gleaned from multicenter data should be used to confirm the study results and to develop thrombosis prevention strategies.

Energy and Protein Intake During the Transition from Parenteral to Enteral Nutrition in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the association between nutrition delivery practices and energy and protein intake during the transition from parenteral to enteral nutrition in infants of very low birth weight (VLBW). STUDY DESIGN: This was a retrospective analysis of 115 infants who were VLBW from a regional neonatal intensive care unit. Changes in energy and protein intake were estimated during transition phase 1 (0% enteral); phase 2 (>0, ≤33.3% enteral); phase 3 (>33.3, ≤66.7% enteral); phase 4 (>66.7, <100% enteral); and phase 5 (100% enteral). Associations between energy and protein intake were determined for each phase for parenteral nutrition, intravenous lipids, central line, feeding fortification, fluid restriction, and excess non-nutritive fluid intake. RESULTS: In phases 2 and 3, infants receiving feeding fortification received less protein than infants who were unfortified (-1.1 and -0.3 g/kg/d, respectively; P < .001). However, this negative association was not observed after adjusting for relevant nutrition delivery practices. Despite greater enteral protein intake during phases 2 and 3 (0.3 and 0.8 g/kg/d, respectively; P < .001), infants with early fortification received less parenteral protein than infants who were unfortified (-1.4 and -1.1 g/kg/d, respectively; P < .001). Similar patterns were observed for energy intake. Protein intake declined during phases 3 and 4. CONCLUSIONS: Infants paradoxically received less protein and energy on days with early fortification, suggesting that clinicians may lack easily accessible data to detect the association between nutrition delivery practices and overall nutrition in infants who are VLBW.

Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome.

OBJECTIVE: To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: From the Pediatrix Clinical Data Warehouse database, we identified all infants born at ≥36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS (International Classification of Diseases, Ninth Revision code 779.5) and treated with methadone or morphine in the first 7 days of life. We used multivariable Cox proportional hazards regression analysis to quantify the association between initial treatment and LOS after adjusting for maternal age, maternal race/ethnicity, maternal drug use, maternal smoking, gestational age, small for gestational age status, inborn status, and discharge year. RESULTS: We identified a total of 7667 eligible infants, including 1187 treated with methadone (15%) and 6480 treated with morphine (85%). Birth weight, gestational age, and sex were similar in the 2 groups. Methadone treatment was associated with a 22% shorter median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P < .001) and a 19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36 days]; P < .001). After adjustment, methadone was associated with a shorter LOS (hazard ratio for discharge, 1.24; 95% CI, 1.11-1.37; P < .001) CONCLUSION: Among infants born at ≥36 weeks of gestation with NAS, initial methadone treatment was associated with a shorter LOS compared with morphine treatment. Future prospective comparative effectiveness trials to treat infants with NAS are needed to verify this observation.

Predicting Risk of Infection in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: To predict incident bloodstream infection and urinary tract infection (UTI) in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010-2016. Infants with CDH admitted at 22 participating regional neonatal intensive care units were included; patients repaired or discharged to home prior to admission/referral were excluded. The primary outcome was death or the occurrence of bloodstream infection or UTI prior to discharge. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: Median gestation and postnatal age at referral in this cohort (n = 1085) were 38 weeks and 3.1 hours, respectively. The primary outcome occurred in 395 patients (36%); and was associated with low birth weight, low Apgar, low admission pH, renal and associated anomalies, patch repair, and extracorporeal membrane oxygenation (P < .001 for all; area under receiver operating curve = 0.824; goodness of fit χ2 = 0.52). After omitting death from the outcome measure, admission pH, patch repair of CDH, and duration of central line placement were significantly associated with incident bloodstream infection or UTI. CONCLUSIONS: Infants with CDH are at high risk of infection which was predicted by clinical factors. Early identification and low threshold for sepsis evaluations in high-risk infants may attenuate acquisition and the consequences of these infections.

The Impact of Pulmonary Hypertension in Preterm Infants with Severe Bronchopulmonary Dysplasia through 1 Year.

OBJECTIVES: To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe bronchopulmonary dysplasia. STUDY DESIGN: This was a multicenter, retrospective cohort study of 1677 infants born <32 weeks of gestation with severe bronchopulmonary dysplasia enrolled in the Children's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System. RESULTS: Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio [IRR] = 1.38, 95% CI 1.18-1.63, P < .001). CONCLUSIONS: Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through 1 year of corrected age. This highlights the need for improved diagnostic practices and prospective studies evaluating treatments for this high-risk population.

Nutritional Practices and Growth in Premature Infants After Surgical Necrotizing Enterocolitis.

OBJECTIVE: The aim of the study was to describe the nutritional provisions received by infants with surgical necrotizing enterocolitis (NEC) and the associated effects on short-term growth. METHODS: Through the Children's Hospitals Neonatal Database, we identified infants born ≤32 weeks' gestation with surgical NEC from 5 regional neonatal intensive care units for 4 years. Excluded infants had isolated intestinal perforation and died <14 days postoperatively. Infants were stratified by their median parenteral protein dose (low [LP] or high [HP] protein) for the first postoperative week. The primary outcome was postoperative weight growth velocity. Growth (weight, length, and head circumference [HC]) was measured and the effects related to protein dose were estimated using multivariable analyses. RESULTS: There were 103 infants included; the median parenteral protein dose received was 3.27 g ·â€Škg ·â€Šday (LP: 2.80 g ·â€Škg ·â€Šday; HP: 3.87 g ·â€Škg ·â€Šday). Postoperative weight (11.5 ±â€Š6.5 g ·â€Škg ·â€Šday) and linear growth (0.9 ±â€Š0.2 cm/wk) were similar regardless of dose (P > 0.3 between groups for weight and length). Unadjusted and independent associations were identified with HC changes and HP dose (ß = 0.1 cm/wk, P = 0.03) after adjusting for gestational age, the presence of severe bronchopulmonary dysplasia, short bowel syndrome, blood stream infection, severe intraventricular hemorrhage, small for gestational age, and calorie intake. Eventual nonsurvivors received 18% less protein and 14% fewer calories over the first postoperative month. CONCLUSIONS: Postoperative protein doses in infants with surgical NEC appear related to increases in HC. The influence of postoperative nutritional support on risk of adverse outcomes deserves further attention.