Iron Deficiency Prior to Discharge in Very Low Birth Weight Infants: Screening with Reticulocyte Hemoglobin Content.

OBJECTIVE: This study aimed to assess the iron status prior to discharge in very low birth weight (VLBW) infants utilizing reticulocyte hemoglobin content (CHr) and evaluate the impact of delayed cord clamping (DCC) on iron status. STUDY DESIGN: This is a retrospective analysis of VLBW infants from two tertiary level of care Neonatal Intensive Care Units. The primary outcome was the proportion of VLBW infants with low CHr (<29 pg) prior to discharge. Hematologic parameters were also compared between infants who received or did not receive DCC. Infants with a positive newborn screen for hemoglobin Bart's were excluded. RESULTS: Among the 315 infants included, 99 infants (31.4%) had low CHr prior to discharge. The median (interquartile range) CHr prior to discharge was 30.8 pg (28.4-39 pg). DCC was performed in 46.7% of infants. Hemoglobin at birth, discharge, and CHr prior to discharge were higher and the need for blood transfusion and the number of infants with low CHr prior to discharge were lower in the DCC group. CONCLUSION: Approximately 31.4% of VLBW infants had low CHr near the time of discharge suggesting they were iron deficient. DCC improved hematological parameters prior to discharge in VLBW infants. CHr content can be used to guide iron supplementation in VLBW infants to potentially improve their iron status and long-term neurocognitive outcomes. KEY POINTS: · DCC was associated with an improved hemoglobin and iron status at discharge in VLBW infants.. · CHr is an early and reliable marker for iron deficiency.. · Approximately one in three VLBW infants can be iron deficient at the time of discharge..

Acute Kidney Injury and Abnormalities on Brain Magnetic Resonance Imaging or Death in Infants with Hypoxic-Ischemic Encephalopathy: A Case-Control Study.

OBJECTIVE: This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This is a retrospective case-control analysis of 380 neonates born at ≥35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI. RESULTS: A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI. CONCLUSION: AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment. KEY POINTS: · Neonates with HIE are at increased risk for AKI.. · AKI is associated with hypoxic-ischemic injury on brain MRI or death among neonates with HIE.. · Identification of AKI in infants with HIE may help predict neurodevelopmental impairment..

Delayed Cord Clamping for 45 Seconds in Very Low Birth Weight Infants: Impact on Hemoglobin at Birth and Close to Discharge.

OBJECTIVE: To assess the impact of delayed cord clamping (DCC) for 45 seconds on hemoglobin at birth and close to discharge in very low birth weight (VLBW) infants and to compare modes of delivery in infants who received DCC. STUDY DESIGN: In a retrospective study, 888 VLBW infants (≤1,500 g) who survived to discharge and received immediate cord clamping (ICC) were compared with infants who received DCC. Infants who received DCC and born via Cesarean section (C-section) were compared with those born via vaginal birth. RESULTS: A total of 555 infants received ICC and 333 DCC. Only 188 out of 333 VLBW infants (56.5%) born during the DCC period received DCC. DCC was associated with higher hemoglobin at birth (15.9 vs. 14.9 g/dL, p = 0.001) and close to discharge (10.7 vs. 10.1 g/dL, p < 0.001) and reduced need for blood transfusion (39.4 vs. 54.9%, p < 0.001). In the DCC group, hemoglobin at birth and close to discharge was similar in infants born via C-section and vaginal birth. CONCLUSION: DCC for 45 seconds increased hemoglobin at birth and close to discharge and reduced need for blood transfusion in VLBW infants. DCC for 45 seconds was equally effective for infants born by C-section and vaginal delivery. Approximately 44% of VLBW infants did not receive DCC even after implementing DCC guidelines. KEY POINTS: · Studies to date have shown that DCC improves mortality and short- and long-term outcomes in VLBW infants.. · No consistent guidelines for the duration of DCC in preterm and term neonates.. · DCC for 45 seconds increased hemoglobin at birth and close to discharge in VLBW infants..

Is Maternal Methadone Dose Associated with the Severity of Neonatal Abstinence Syndrome?

OBJECTIVE: The aim of the study is to assess the correlation between maternal methadone dose and severity of neonatal abstinence syndrome (NAS) in infants that required pharmacological treatment for NAS. STUDY DESIGN: This is a retrospective analysis of 574 infants ≥35 weeks' gestation exposed to methadone in utero, born between August 2006 and May 2018, and who required pharmacological therapy for NAS. Indicators of NAS severity (duration of morphine treatment, maximum morphine dose, use of phenobarbital, and length of hospitalization) were compared between infants exposed to high (≥200 mg), intermediate (100-199 mg), and low doses (<100 mg) of methadone. Logistic and linear regression models were used to adjust for the covariates. RESULTS: Median (interquartile range) duration of medical treatment with morphine was higher in infants exposed to higher doses of methadone (low dose 23 [14-37] days, intermediate dose 31 [18-45] days, and high dose 35 [20-48] days, p < 0.001). Higher methadone doses were also predictive of longer duration of hospitalization, higher maximum morphine dose, and increased likelihood of treatment with phenobarbital. The association between maternal methadone dose and the severity of NAS persisted in multivariable regression models. CONCLUSION: Infants exposed to higher methadone doses displayed more severe NAS, as indicated by longer durations of treatment, higher maximum morphine dose, longer duration of hospitalization, and increased likelihood of phenobarbital use. KEY POINTS: · Methadone maintenance therapy is used during pregnancy to control maternal withdrawal symptoms.. · Relationship between maternal methadone dose and severity of NAS is not adequately investigated.. · Increased doses of methadone during pregnancy correlate with increased severity of NAS..

Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia.

BACKGROUND: Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. METHODS: We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed a global transcriptome analysis of all resident pulmonary immune cells. RESULTS: We show significant up-regulation of genes involved in chemokine-mediated signaling and immune cell chemotaxis, and down-regulation of genes involved in multiple T lymphocyte functions. Multiple genes involved in T cell receptor signaling are downregulated and Cd8a gene expression remains downregulated at 2 months of age in spite of recovery in normoxia for 6 weeks. Furthermore, the proportion of CD8a+CD3+ pulmonary immune cells is decreased. CONCLUSIONS: Our study has highlighted that perinatal lung inflammation in a double-hit model of BPD results in short- and long-term dysregulation of genes associated with the pulmonary T cell receptor signaling pathway, which may contribute to increased environmental pathogen-associated respiratory morbidities seen in children and adults with BPD. IMPACT: In a translationally relevant double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia, we identified pulmonary immune cell-specific transcriptomic changes and showed that T cell receptor signaling genes are downregulated in short term and long term. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD. Our study identifies novel resident pulmonary immune cell-specific targets for potential therapeutic modulation to improve short- and long-term respiratory health of preterm infants with BPD.

Prevalence and Utility of Low Mean Corpuscular Volume in Infants Admitted to the Neonatal Intensive Care Unit.

OBJECTIVE: To determine the prevalence of low mean corpuscular volume (MCV) in newborn infants admitted to the neonatal intensive care unit and to assess low MCV as a diagnostic test for alpha thalassemia. STUDY DESIGN: Retrospective analysis of all infants admitted to the neonatal intensive care unit between January 2010 and October 2018 for which a complete blood count was performed during the first 3 postnatal days. Infants with a low MCV were compared with those with a normal MCV. Infants with positive hemoglobin Bart (Hb Bart) were compared with those withnegative Hb Bart. Low MCV was also evaluated as a diagnostic test for alpha thalassemia. RESULTS: A total of 3851 infants (1386 preterm, 2465 term) met the inclusion criteria and 853 (22.2%) had a low MCV. A low MCV was more common in term (25%) compared with preterm infants (17.1%, P < .001). Hb Bart positive newborn screening was identified in 133 infants (3.5%). Hb Bart was positive in 11.1% of infants with low MCV compared with 1.3% with normal MCV (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of low MCV for the diagnosis of alpha thalassemia were 71.4%, 79.6%, 11.3%, and 98.7%, respectively. CONCLUSIONS: As Hb Bart positive newborn screens were seen in only 11.1% of infants with microcytosis, further diagnostic investigation may be warranted in individual infants. Further research to correlate microcytosis with iron status in infants and mothers is needed as well as studies using DNA analysis for the evaluation of alpha thalassemia variants.

Gender variations in neonatal and early infant mortality in India and Pakistan: a secondary analysis from the Global Network Maternal Newborn Health Registry.

BACKGROUND: To determine the gender differences in neonatal mortality, stillbirths, and perinatal mortality in south Asia using the Global Network data from the Maternal Newborn Health Registry. METHODS: This study is a secondary analysis of prospectively collected data from the three south Asian sites of the Global Network. The maternal and neonatal demographic, clinical characteristics, rates of stillbirths, early neonatal mortality (1-7 days), late neonatal mortality (8-28 days), mortality between 29-42 days and the number of infants hospitalized after birth were compared between the male and female infants. RESULTS: Between 2010 and 2018, 297,509 births [154,790 males (52.03%) and 142,719 females (47.97%)] from two Indian sites and one Pakistani site were included in the analysis [288,859 live births (97.1%) and 8,648 stillbirths (2.9%)]. The neonatal mortality rate was significantly higher in male infants (33.2/1,000 live births) compared to their female counterparts (27.4/1,000, p < 0.001). The rates of stillbirths (31.0 vs. 26.9/1000 births) and early neonatal mortality (27.1 vs 21.6/1000 live births) were also higher in males. However, there were no significant differences in late neonatal mortality (6.3 vs. 5.9/1000 live births) and mortality between 29-42 days (2.1 vs. 1.9/1000 live births) between the two groups. More male infants were hospitalized within 42 days after birth (1.8/1000 vs. 1.3/1000 live births, p < 0.001) than females. CONCLUSION: The risks of stillbirths, and early neonatal mortality were higher among male infants than their female counterparts. However, there was no gender difference in mortality after 7 days of age. Our results highlight the importance of stratifying neonatal mortality into early and late neonatal period to better understand the impact of gender on neonatal mortality. The information from this study will help in developing strategies and identifying measures that can reduce differences in sex-specific mortality.

Use of a Modified Early-Onset Sepsis Risk Calculator for Neonates Exposed to Chorioamnionitis.

OBJECTIVE: To validate the recently modified Kaiser Permanente early-onset sepsis (EOS) calculator with a higher baseline incidence in chorioamnionitis exposed neonates. STUDY DESIGN: This is a retrospective study of chorioamnionitis-exposed neonates born at ≥35 weeks of gestation with a known EOS incidence of 4.3/1000. The risk and management categories were calculated using the calculator with an incidence of 4/1000. The results were compared with a previous analysis of the same cohort that used an EOS incidence of 0.5/1000. RESULTS: In our sample, the EOS calculator recommends at least a blood culture in 834 of 896 (93.1%) and empiric antibiotics in 533 of 896 (59.5%) chorioamnionitis-exposed neonates when using an EOS incidence of 4/1000. This captures 5 of 5 neonates (100%) with EOS. When using a baseline EOS incidence of 0.5/1000, the calculator recommends at least a blood culture in only 289 of 896 (32.2%) and empiric antibiotics in only 209 of 896 (23.3%) neonates, but fails to recommend empiric antibiotics in 2 of 5 neonates with EOS (40%). CONCLUSIONS: When using an EOS risk of 4 of 1000 in infants exposed to mothers with chorioamnionitis, the EOS calculator has the ability to capture an increased number of neonates with culture-positive EOS. However, this change also leads to nearly a 3-fold increase in the use of empiric antibiotics and an evaluation with blood culture in almost all infants born to mothers with chorioamnionitis.

Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.

OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates. STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis. RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA < 27 weeks). CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.

Hyperoxia causes miR199a-5p-mediated injury in the developing lung.

BACKGROUND: Hyperoxia-induced acute lung injury (HALI) is characterized by increased permeability and infiltration of inflammatory cells, impairment of alveolar development, and compromised lung function. Recent evidence has determined that microRNAs (miRs) are implicated in hyperoxia-induced lung injury, including bronchopulmonary dysplasia (BPD). However, the expression profile and functional role of miR199a-5p in developing lungs have not been reported. METHODS: The present study was undertaken to explore the role of miR199a-5p in developing mice lungs and human neonates. We exposed neonatal mice for 7 days, mouse lung epithelial cells (MLE12), mouse lung endothelial cells (MLECs), and macrophages (RAW246.7), to hyperoxia at different time points. RESULTS: Our results demonstrated enhanced miR199a-5p expression in hyperoxia-exposed mice lungs and cells, as well as in tracheal aspirates of infants developing BPD, with significant reduction in the expression of its target, caveolin-1. Next, we observed that miR199a-5p-mimic worsens HALI as evidenced by increased inflammatory cells, cytokines, and lung vascular markers. Conversely, miR199a-5p-inhibitor treatment attenuated HALI. CONCLUSION: Thus, our findings suggest that miR199a-5p is a potential target for attenuating HALI pathophysiology in the developing lung. Moreover, miR199a-5p-inhibitor could be part of a novel therapeutic strategy for improving BPD in preterm neonates.

Infants Born to Mothers with Clinical Chorioamnionitis: A Cross-Sectional Survey on the Use of Early-Onset Sepsis Risk Calculator and Prolonged Use of Antibiotics.

OBJECTIVE: To evaluate variations in practice for the management of neonates born to mothers with clinical chorioamnionitis. METHODS: This was a prospective cross-sectional survey consisting of 10 multiple choice questionnaires distributed to 2,900 members of the Perinatal Section of American Academy of Pediatrics. Variations in responses were assessed and compared between the various groups. RESULTS: A total of 682 members (23.5%) completed the survey; 169 (24.8%) indicated that they use the neonatal early-onset sepsis (EOS) risk calculator for the management of neonates born to mothers with clinical chorioamnionitis. More respondents from the western region of United States and level III units are using the EOS risk calculator compared with the south and level II units. Approximately 44% of the respondents indicated that they will not stop antibiotics at 48 to 72 hours in asymptomatic neonates born to mothers with chorioamnionitis with negative blood culture if the complete blood count (CBC) and C-reactive protein (CRP) are abnormal. CONCLUSION: A large number of practitioners are using the neonatal EOS risk calculator for neonates born to mothers with chorioamnionitis. Despite a clear guideline from the Committee on Fetus and Newborn, almost 44% will treat healthy-appearing neonates born to mothers with chorioamnionitis with a prolonged course of antibiotics solely for abnormal CBC or CRP.

Apgar Scores at 10 Minutes and Outcomes in Term and Late Preterm Neonates with Hypoxic-Ischemic Encephalopathy in the Cooling Era.

OBJECTIVE: To determine the short-term outcomes (abnormal brain magnetic resonance imaging [MRI]/death) in infants born with a 10-minute Apgar score of 0 who received therapeutic hypothermia and compare them with infants with higher scores. STUDY DESIGN: This is a retrospective review of 293 neonates (gestational age ≥ 35 weeks) born between November 2006 and October 2015 admitted with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. Results of brain MRIs were assessed by the basal ganglia/watershed scoring system. Short-term outcomes were compared between infants with Apgar scores of 0, 1 to 4, and ≥5 at 10 minutes. RESULTS: Eight of 17 infants (47%) with an Apgar of 0 at 10 minutes survived, having 4 (24%) without abnormalities on the brain MRI and 7 (41%) without severe abnormalities. There was no significant difference in the combined outcomes of "death/abnormal MRI" and "death/severe abnormalities on the MRI" between infants with Apgar scores of 0 and 1 to 4. Follow-up data were available for six of eight surviving infants, and none had moderate or severe neurodevelopmental impairment. CONCLUSION: In the cooling era, 47% of infants with no audible heart rate at 10 minutes and who were admitted to the neonatal intensive care unit survived; 24% without abnormalities on the brain MRI and 41% without severe abnormalities.

Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia.

The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.

Utility of Early-Onset Sepsis Risk Calculator for Neonates Born to Mothers with Chorioamnionitis.

OBJECTIVES: To evaluate the performance of the early-onset sepsis (EOS) risk calculator in a cohort of neonates born to mothers with clinical chorioamnionitis, and to compare the diagnostic utility of the EOS calculator, clinical signs, and laboratory evaluations for correctly identifying EOS in this cohort. STUDY DESIGN: This was a retrospective study of neonates born at ≥35 weeks of gestation to mothers with chorioamnionitis. The risk and management categories for all neonates were calculated using the EOS calculator, and these results were analyzed and compared with laboratory data and clinical signs. RESULTS: Of the 1159 neonates born to mothers with chorioamnionitis, 5 (0.43%) had culture-proven EOS. Data for calculation of EOS risk were available for 896 neonates, including the 5 neonates with culture-proven EOS. The management recommendation based on the calculator was no empiric antibiotic treatment for 67% of the neonates, including 2 of the 5 with EOS. All neonates with culture-proven EOS had abnormal complete blood counts and C-reactive protein levels at 6-12 hours. Three of the 5 neonates with EOS had clinical signs of sepsis. CONCLUSIONS: The risk of EOS in neonates born to mothers with chorioamnionitis is low. The use of an EOS calculator may reduce the use of empiric antibiotics in chorioamnionitis-exposed neonates, but in our cohort, some neonates with culture-confirmed EOS would have been missed. A larger study is needed to evaluate whether limiting antibiotics to chorioamnionitis-exposed neonates with clinical and/or laboratory signs of infection can safely decrease antibiotic use.

Car Seat Tolerance Screening in the Neonatal Intensive Care Unit: Failure Rates, Risk Factors, and Adverse Outcomes.

OBJECTIVE: To characterize the epidemiology of Car Seat Tolerance Screening (CSTS) failure and the association between test failure and all-cause 30-day postdischarge mortality or hospital readmission in a large, multicenter cohort of preterm infants receiving neonatal intensive care. STUDY DESIGN: This retrospective cohort study used the prospectively collected Optum Neonatal Database. Study infants were born at <37 weeks of gestation between 2010 and 2016. We identified independent predictors of CSTS failure and calculated the risk-adjusted odds of all-cause 30-day mortality or hospital readmission associated with test failure. RESULTS: Of 7899 infants cared for in 788 hospitals, 334 (4.2%) failed initial CSTS. Greater postmenstrual age at testing and African American race were independently associated with decreased failure risk. Any treatment with an antacid medication, concurrent use of caffeine or supplemental oxygen, and a history of failing a trial off respiratory support were associated with increased failure risk. The mean adjusted post-CSTS duration of hospitalization was 3.1 days longer (95% CI, 2.7-3.6) among the infants who failed the initial screening. Rates of 30-day all-cause mortality or readmission were higher among infants who failed the CSTS (2.4% vs 1.0%; P = .03); however, the difference was not significant after confounder adjustment (OR, 0.38; 95% CI, 0.11-1.31). CONCLUSION: CSTS failure was associated with longer post-test hospitalization but no difference in the risk-adjusted odds for 30-day mortality or hospital readmission. Whether CSTS failure unnecessarily prolongs hospitalization or results in appropriate care that prevents adverse postdischarge outcomes is unknown. Further research is needed to address this knowledge gap.

Nasogastric Feeding Tubes May Not Contribute to Gastroesophageal Reflux in Preterm Infants.

OBJECTIVE: The objective was to determine if the presence of a nasogastric (NG) feeding tube is associated with increased gastroesophageal reflux (GER) and acid exposure in preterm infants. STUDY DESIGN: This is a retrospective study on preterm infants [gestational age (GA) <37 weeks] who were evaluated by multichannel intraluminal impedance and pH monitoring (MII-pH) between October 2009 and March 2016. Infants were divided into two groups, NG tube present and no feeding tube. GER events per hour and the percent of time with pH <4 during a 24-hour period were then compared. RESULTS: Eighty-three infants were included, 41 had an NG tube present and 42 did not. The group without an NG tube had significantly more reflux events per hour (2.3 ± 2.9 vs. 1.3 ± 0.8, p < 0.05) even after adjusting for differences in birth weight, GA, corrected GA, and total fluid intake. There was no significant difference in acidic events per hour and acid exposure time between the two groups. CONCLUSION: The presence of a 5-French NG tube is not associated with an increase in GER or acid exposure in preterm infants. In fact, it appears that infants fed through an NG tube have fewer episodes of GER.

Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure-Practice Variations and Outcomes.

OBJECTIVE: Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High frequency ventilation was associated with an increased mean (SEM) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and an increased mean (SEM) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted.

High Flow Nasal Cannula Use Is Associated with Increased Morbidity and Length of Hospitalization in Extremely Low Birth Weight Infants.

OBJECTIVE: To determine differences in the incidence of bronchopulmonary dysplasia (BPD) or death in extremely low birth weight infants managed on high flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP). STUDY DESIGN: This is a retrospective data analysis from the Alere Neonatal Database for infants born between January 2008 and July 2013, weighing ≤1000 g at birth, and received HFNC or CPAP. Baseline demographics, clinical characteristics, and neonatal outcomes were compared between the infants who received CPAP and HFNC, or HFNC ± CPAP. Multivariable regression analysis was performed to control for the variables that differ in bivariate analysis. RESULTS: A total of 2487 infants met the inclusion criteria (941 CPAP group, 333 HFNC group, and 1546 HFNC ± CPAP group). The primary outcome of BPD or death was significantly higher in the HFNC group (56.8%) compared with the CPAP group (50.4%, P < .05). Similarly, adjusted odds of developing BPD or death was greater in the HFNC ± CPAP group compared with the CPAP group (OR 1.085, 95% CI 1.035-1.137, P = .001). The number of ventilator days, postnatal steroid use, days to room air, days to initiate or reach full oral feeds, and length of hospitalization were significantly higher in the HFNC and HFNC ± CPAP groups compared with the CPAP group. CONCLUSIONS: In this retrospective study, use of HFNC in extremely low birth weight infants is associated with a higher risk of death or BPD, increased respiratory morbidities, delayed oral feeding, and prolonged hospitalization. A large clinical trial is needed to evaluate long-term safety and efficacy of HFNC in preterm infants.

Temporal Association Between Reflux-like Behaviors and Gastroesophageal Reflux in Preterm and Term Infants.

OBJECTIVES: Multichannel intraluminal impedance studies (MII-pH) have become the criterion standard for the diagnosis of gastroesophageal reflux (GER). Several clinical signs and symptoms that are attributed to GER during infancy may not be related to true reflux. Our objective was to correlate the observed reflux-like behaviors to reflux events on MII-pH studies. METHODS: This is a retrospective study on infants being evaluated for GER with MII. During the MII-pH study, the infants were observed for clinical behaviors. Symptom Index (SI), symptom sensitivity index (SSI), and symptom association probability were used to correlate symptoms with reflux events. RESULTS: Of 58 infants (40 preterm, 18 term) included in the study, only 6 infants (10%) had an abnormal MII-pH study. Irritability (32 infants), bradycardia (20), and desaturation (18) were the common signs and symptoms. A total of 2142 (755 acidic and 1386 nonacidic) reflux episodes and 953 clinical reflux behaviors were recorded. The incidence and pattern of GER was similar in preterm and term infants. There was no significant difference in GER episodes and acid exposure in preterm infants fed orally or via nasogastric tube. The symptom association probability was abnormal in only 6 (19%), 1 (5%), and 5 (28%) infants with irritability, bradycardia, and desaturation, respectively. CONCLUSIONS: The prevalence of GER as detected by MII-pH was low (10%) in symptomatic preterm and term infants. The incidence and pattern of GER was similar in preterm and term infants. The majority of suspected clinical reflux behaviors did not correlate with reflux events.