Spectrum of Disease in Hospitalized Newborns with Congenital Micrognathia: A Cohort of 3,236 Infants at North American Tertiary-Care Intensive Care Units.

OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers. STUDY DESIGN: The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge. RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both). CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.

Survey of Quaternary Neonatal Management of Posthemorrhagic Hydrocephalus.

OBJECTIVE: This study aimed to determine clinical care practices for infants at risk for posthemorrhagic hydrocephalus (PHH) across level IV neonatal intensive care units (NICUs). STUDY DESIGN: Cross-sectional survey that addressed center-specific surveillance, neurosurgical intervention, and follow-up practices within the Children's Hospitals Neonatal Consortium. RESULTS: We had a 59% (20/34 sites) response rate, with 10 sites having at least two participants. Respondents included neonatologists (53%) and neurosurgeons (35%). Most participants stated having a standard guideline for PHH (79%). Despite this, 42% of respondents perceive inconsistencies in management. Eight same-center pairs of neonatologists and neurosurgeons were used to determine response agreement. Half of these pairs disagreed on nearly all aspects of care. The greatest agreement pertained to a willingness to adopt a consensus-based protocol. CONCLUSION: Practice variation in the management of infants at risk of PHH in level IV NICUs exists despite the perception that a common practice is available and used. KEY POINTS: · Practice variation exists despite the perception that common practices are available/used for PHH.. · Our survey had same-center pairs of neonatologist and neurosurgeons to determine response agreement.. · The greatest agreement pertained to a willingness to adopt a consensus-based protocol..

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.

Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): Reduction of Nephrotoxic Medication-Associated Acute Kidney Injury in the Neonatal Intensive Care Unit.

OBJECTIVE(S): To test if acute kidney injury (AKI) is preventable in patients in the neonatal intensive care unit and if infants at high-risk of nephrotoxic medication-induced AKI can be identified using a systematic surveillance program previously used in the pediatric non-intensive care unit setting. STUDY DESIGN: Quality improvement project that occurred between March 2015 and September 2017 in a single center, level IV neonatal intensive care unit. Infants were screened for high-risk nephrotoxic medication exposure (≥3 nephrotoxic medication within 24 hours or ≥4 calendar days of an intravenous [IV] aminoglycoside). If infants met criteria, a daily serum creatinine (SCr) was obtained until 2 days after end of exposure or end of AKI, whichever occurred last. The study was divided into 3 eras: pre-Nephrotoxic Injury Negated by Just-in-time Action (NINJA), initiation, and sustainability. Differences for 5 metrics across 3 eras were compared: SCr surveillance, high nephrotoxic medication exposure rate (per 1000 patient-days), AKI rate (per 1000 patient-days), nephrotoxin-AKI percentage, and AKI intensity (number of AKI days per 100 susceptible patient-days). RESULTS: Comparing the initiation with sustainability era, there was a reduction in high nephrotoxic medication exposures from 16.4 to 9.6 per 1000 patient-days (P = .03), reduction in percentage of nephrotoxic medication-AKI from 30.9% to 11.0% (P < .001), and reduction in AKI intensity from 9.1 to 2.9 per 100 susceptible patient-days (P < .001) while maintaining a high SCr surveillance rate. This prevented 100 AKI episodes during the 18-month sustainability era. CONCLUSION(S): A systematic surveillance program to identify high-risk infants can prevent nephrotoxic-induced AKI and has the potential to prevent short and long-term consequences of AKI in critically ill infants.

Smaller circuits for smaller patients: improving renal support therapy with Aquadex™.

BACKGROUND: Providing renal support for small children is very challenging using the machinery currently available in the United States. As the extracorporeal volume (ECV) relative to blood volume increases and the state of critical illness worsens, the chance for instability during continuous renal replacement therapy (CRRT) initiation also increases. CRRT machines with smaller ECV could reduce the risks and improve outcomes. METHODS: We present a case series of small children (n = 12) who received continuous venovenous hemofiltration (CVVH) via an Aquadex™ machine (ECV = 33 ml) with 30 ml/kg/h of prereplacement fluids at Children's of Alabama between December 2013 and April 2015. We assessed in vitro fluid precision using the adapted continuous veno-venous hemofiltration (CVVH) system. RESULTS: We used 101 circuits over 261 days to provide CVVH for 12 children (median age 30 days; median weight 3.4 kg). Median CVVH duration was 14.5 days [interquartile range (IQR) = 10; 22.8 days]. Most circuits were routinely changed after 72 h. Five of 101 (5 %) initiations were associated with mild transient change in vital signs. Complications were infrequent (three transient cases of hypothermia, three puncture-site bleedings, one systemic bleed, and one right atrial thrombus). Most patients (7/12, 58 %) were discharged from the intensive care unit; six of them (50 %) were discharged home. CONCLUSIONS: CRRT machines with low ECV can enable clinicians to provide adequate, timely, safe, and efficient renal support to small, critically ill infants.

Survival of Infants With Severe Congenital Kidney Disease After ECMO and Kidney Support Therapy.

Congenital kidney failure not only affects the homeostatic functions of the kidney, but also affects neonatal respiratory integrity. Until recently, extracorporeal membrane oxygenation (ECMO) support was not used in this population because the need for ECMO clearly established nonviability. Since 2016, 31 neonates have been admitted to the NICU at Children's of Alabama with congenital kidney failure. Five patients were placed on ECMO for severe respiratory distress unresponsive to conventional interventions. We evaluated neonates with congenital kidney failure and pulmonary hypoplasia/hypertension refractory to conventional therapies who received ECMO support within the first 9 postnatal days. We describe the pre and postnatal diagnoses, ECMO course details, dialysis modalities, complications, procedures, and long-term outcomes of these patients. All 5 patients received kidney support therapy by postnatal day 7. Diagnoses included posterior urethral valves, bilateral renal dysplasia, and autosomal recessive polycystic kidney disease. Gestational age ranged from 35.6 to 37.1 weeks. Birth weight ranged from 2740 to 3140 g. Days on ECMO ranged from 4 to 23. Four survived and are living today. Pulmonary hypertension resolved in surviving patients. Three surviving patients require no oxygen support, and 1 patient requires nocturnal oxygen. Three survivors received a kidney transplant, and 1 awaits transplant evaluation. Patients with congenital kidney failure with severe pulmonary hypoplasia/pulmonary hypertension no longer warrant a reflexive assignment of nonviability. Meticulous ECMO, respiratory, nutritional, and kidney support therapies may achieve a favorable long-term outcome. Further investigation of strategies for optimal outcome is needed.

Interdisciplinary clinical bronchopulmonary dysplasia programs: development, evolution, and maturation.

Multidisciplinary bronchopulmonary dysplasia (BPD) programs provide improved and consistent medical management, care of the developing infant, family support, and smoother transitions in care resulting in improved survival, pulmonary, and extra-pulmonary outcomes. This review summarizes the benefits of interdisciplinary BPD management, as well as strategies for initial programmatic development, program growth, and maintenance at centers across the United States factoring in institutional, provider, and parent reported goals that were derived from a consensus conference on BPD management.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Surgical outcome and treatment trends in 1289 infants with micrognathia: a multicenter cohort.

BACKGROUND: Studies of infants with micrognathia, especially Robin Sequence (RS), are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this condition is sourced from small, single-institution samples. METHODS: This is a cross-sectional study including infants with micrognathia admitted to 38 Children's Hospital Neonatal Consortium centers from 2010-2020. Predictor variables included demographic data, birth characteristics, cleft and syndrome status. Outcome variables included length of stay (LOS), death, feeding or respiratory support, and secondary airway operations. RESULTS: 1289 infants with micrognathia had a surgery to correct upper airway obstruction. Mean age and weight at operation were 34.8±1.8 weeks and 3515.4±42 grams, respectively. A syndromic diagnosis was made in 150 (11.6%) patients, with Stickler (5.4%) and Treacher Collins Syndromes (2.2%) most common. Operations included: mandibular distraction osteogenesis (MDO), 66.3%; tracheostomy, 25.4%; and tongue-lip adhesion (TLA), 8.3%. Tracheostomy patients had a lower birth weight, head circumference, gestational age, and APGAR scores. MDO patients were less likely to need a second airway operation compared to TLA patients (3.5%vs17.8%,p<0.001). The proportion of infants feeding exclusively orally at hospital discharge differed significantly, from most to least: MDO, TLA, tracheostomy. Hospital LOS was not statistically different for patients that had MDO and TLA, but was longer for those with primary tracheostomy. Mortality was low for all operations (0.5%). CONCLUSION: In this 1289 surgical patient cohort, MDO was associated with shorter hospital stay, improved oral feeding, and lower rates of secondary airway operations. Prospective multi-center studies are necessary to support these conclusions.

An intronic ABCA3 mutation that is responsible for respiratory disease.

INTRODUCTION: Member A3 of the ATP-binding cassette family of transporters (ABCA3) is essential for surfactant metabolism. Nonsense, missense, frameshift, and splice-site mutations in the ABCA3 gene (ABCA3) have been reported as causes of neonatal respiratory failure (NRF) and interstitial lung disease. We tested the hypothesis that mutations in noncoding regions of ABCA3 may cause lung disease. METHODS: ABCA3-specific cDNA was generated and sequenced from frozen lung tissue from a child with fatal lung disease with only one identified ABCA3 mutation. ABCA3 was sequenced from genomic DNA prepared from blood samples obtained from the proband, parents, and other children with NRF. RESULTS: ABCA3 cDNA from the proband contained sequences derived from intron 25 that would be predicted to alter the structure and function of the ABCA3 protein. Genomic DNA sequencing revealed a heterozygous C>T transition in intron 25 trans to the known mutation, creating a new donor splice site. Seven additional infants with an ABCA3-deficient phenotype and inconclusive genetic findings had this same variant, which was not found in 2,132 control chromosomes. DISCUSSION: These findings support that this variant is a disease-causing mutation that may account for additional cases of ABCA3 deficiency with negative genetic studies.

Reduction of Central-line-Associated Bloodstream Infections in a Tertiary Neonatal Intensive Care Unit through Simulation Education.

Introduction: Critically ill neonates and those with complex medical conditions frequently require the use of central venous lines. Unfortunately, central line-associated bloodstream infections (CLABSIs) result in significant morbidity and mortality, and the cost and increased length of stay burden the healthcare system. Previous studies have demonstrated that standardized care bundles can decrease CLABSI rates, but achieving sustained improvement has proven difficult. Methods: All patients admitted to the Neonatal Intensive Care Unit between 2014 and 2020 who had a CVL were included in this study. First, we recorded all CLABSI events and total CVL days according to defined criteria. Then, in late 2016, we instituted simulation-based nursing training for CVL care. Results: Job Instruction Sheets were initially introduced to Neonatal Intensive Care Unit nursing staff simultaneously with one-on-one teaching sessions between instructors and bedside nurses. Intermittent performance audits and re-education for identified deficiencies did not improve the CLABSI rate per 1000 line days. After instituting simulation-based CVL training in 2016, there was a decreased rate of CLABSI events per 1000 line days sustained over time (x = 0.692). Conclusions: Standardized care bundles and Hospital-acquired Condition interactor audits were insufficient to reduce the CLABSI rate. However, combining care bundles and education with simulation-based training significantly decreased CLABSI rates. One-on-one intensive training and continued ongoing monitoring were critical to producing a sustained reduction. This experience demonstrates that supervised, interactive education combined with simulation can significantly impact patient outcomes.

Chronic lung disease in full-term infants: Characteristics and neonatal intensive care outcomes in infants referred to children's hospitals.

OBJECTIVE: To describe characteristics, outcomes, and risk factors for death or tracheostomy with home mechanical ventilation in full-term infants with chronic lung disease (CLD) admitted to regional neonatal intensive care units. STUDY DESIGN: This was a multicenter, retrospective cohort study of infants born ≥37 weeks of gestation in the Children's Hospitals Neonatal Consortium. RESULTS: Out of 67,367 full-term infants admitted in 2010-2016, 4886 (7%) had CLD based on receiving respiratory support at either 28 days of life or discharge. 3286 (67%) were still hospitalized at 28 days receiving respiratory support, with higher mortality risk than those without CLD (10% vs. 2%, p < 0.001). A higher proportion received tracheostomy (13% vs. 0.3% vs. 0.4%, p < 0.001) and gastrostomy (30% vs. 1.7% vs. 3.7%, p < 0.001) compared to infants with CLD discharged home before 28 days and infants without CLD, respectively. The diagnoses and surgical procedures differed significantly between the two CLD subgroups. Small for gestational age, congenital pulmonary, airway, and cardiac anomalies and bloodstream infections were more common among infants with CLD who died or required tracheostomy with home ventilation (p < 0.001). Invasive ventilation at 28 days was independently associated with death or tracheostomy and home mechanical ventilation (odds ratio 7.6, 95% confidence interval 5.9-9.6, p < 0.0001). CONCLUSION: Full-term infants with CLD are at increased risk for morbidity and mortality. We propose a severity-based classification for CLD in full-term infants. Future work to validate this classification and its association with early childhood outcomes is necessary.

A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children's Hospitals Neonatal Consortium Severe BPD Group.

OBJECTIVE: To compare three bronchopulmonary dysplasia (BPD) definitions against hospital outcomes in a referral-based population. STUDY DESIGN: Data from the Children's Hospitals Neonatal Consortium were classified by 2018 NICHD, 2019 NRN, and Canadian Neonatal Network (CNN) BPD definitions. Multivariable models evaluated the associations between BPD severity and death, tracheostomy, or length of stay, relative to No BPD references. RESULTS: Mortality was highest in 2019 NRN Grade 3 infants (aOR 225), followed by 2018 NICHD Grade 3 (aOR 145). Infants with lower BPD grades rarely died (<1%), but Grade 2 infants had aOR 7-21-fold higher for death and 23-56-fold higher for tracheostomy. CONCLUSIONS: Definitions with 3 BPD grades had better discrimination and Grade 3 2019 NRN had the strongest association with outcomes. No/Grade 1 infants rarely had severe outcomes, but Grade 2 infants were at risk. These data may be useful for counseling families and determining therapies for infants with BPD.

Achieving Vancomycin Troughs Within Goal Range in Low Birth Weight Neonates.

OBJECTIVE: Vancomycin is commonly used in the neonatal population to treat Gram-positive bacterial infections. Despite frequent use, consensus on the ideal dosing regimen in low birth weight (LBW) neonates is lacking. The objective of this research is to determine how frequently vancomycin troughs within goal range (10-20 mg/L) are achieved with empiric dosing in critically ill neonates and infants weighing less than 2500 g. METHODS: This retrospective review evaluated LBW infants who were admitted to a level IV NICU from January 2015 to December 2016. Patients were included if they had a vancomycin trough sample collected at steady state (after at least 3 doses). Three trough cohorts (subtherapeutic: <10 mg/L, therapeutic: 10-20 mg/L, and supratherapeutic: >20 mg/L) were compared with 1-way ANOVA for continuous data and a chi-square analysis for categorical data. RESULTS: A total of 74 patients were included, with a mean birth weight (BW) of 819.7 ± 355.4 g and a mean gestational age (GA) of 26.4 ± 3.7 weeks. Only 27 patients (36.5%) had therapeutic vancomycin trough concentrations. Subtherapeutic troughs were recorded in 40 patients (54.1%), while supratherapeutic troughs were recorded in 7 patients (9.5%). Although there was no difference between the initial dose, initial frequency was significantly different between cohorts (p = 0.04). CONCLUSION: Empiric dosing regimens do not produce vancomycin troughs within the goal range in most LBW patients.

Inter-center variation in autopsy practices among regional neonatal intensive care units (NICUs).

OBJECTIVE: To characterize infants who underwent autopsy in regional neonatal intensive care units (NICUs) and examine inter-center variability in autopsy completion. STUDY DESIGN: Retrospective cohort study of infants who died between 2010 and 2016 from 32 participating hospitals in the Children's Hospital Neonatal Database (CHND). Maternal/infant demographics and hospital stay data were collected, along with autopsy rates by center, year, and region. Data analysis utilized bivariate and multivariable statistics. RESULT: Of 6299 deaths, 1742 (27.7%) completed autopsy. Infants who underwent autopsy had higher median birth weight (2 124 g vs. 1 655 g) and gestational age (34 vs. 32 weeks). No differences were seen in sex, length of stay, or primary cause of death. Marked inter-center variability was observed, with 17-fold adjusted difference (p < 0.001) in autopsy rates. CONCLUSION: Patient characteristics do not account for variability in autopsy practices across regional NICUs. Factors such as provider practices and parental preferences should be investigated.

Medical and surgical interventions and outcomes for infants with trisomy 18 (T18) or trisomy 13 (T13) at children's hospitals neonatal intensive care units (NICUs).

OBJECTIVES: To examine characteristics and outcomes of T18 and T13 infants receiving intensive surgical and medical treatment compared to those receiving non-intensive treatment in NICUs. STUDY DESIGN: Retrospective cohort of infants in the Children's Hospitals National Consortium (CHNC) from 2010 to 2016 categorized into three groups by treatment received: surgical, intensive medical, or non-intensive. RESULTS: Among 467 infants admitted, 62% received intensive medical treatment; 27% received surgical treatment. The most common surgery was a gastrostomy tube. Survival in infants who received surgeries was 51%; intensive medical treatment was 30%, and non-intensive treatment was 72%. Infants receiving surgeries spent more time in the NICU and were more likely to receive oxygen and feeding support at discharge. CONCLUSIONS: Infants with T13 or T18 at CHNC NICUs represent a select group for whom parents may have desired more intensive treatment. Survival to NICU discharge was possible, and surviving infants had a longer hospital stay and needed more discharge supports.