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Objective: We determined the effect of preterm delivery on the course of neonatal abstinence syndrome (NAS) in infants born to mothers participating in a methadone maintenance program. Study design: A retrospective cohort study was conducted in which infant and maternal data were collected from the medical records of 53 preterm and 66 term infants. Infants were selected from all infants admitted to Thomas Jefferson University hospital born between 1998 and 2002 whose mothers were enrolled in the methadone maintenance program. All infants were managed by a standard protocol utilizing the Neonatal Abstinence Scoring System (NASS) and neonatal opiate solution (NOS). Preterm and term infants were compared. Results: Preterm infants had shorter lengths of stay, treatment courses and required less medication than did term infants during the same time period. Conclusion: These data indicate that following exposure to maternal methadone, preterm infants have a different neonatal course than do infants born at term. [ABSTRACT FROM AUTHOR]

Background: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 24 0/7 -27 6/7  weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation., Methods: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-27 6/7  weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO 2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO 2  ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer., Discussion: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites., Trial Registration: www., Clinicaltrials: gov , trial identifier NCT05446272 , registered July 6, 2022., (© 2024. The Author(s).)

Introduction: The early acute phase of the coronavirus disease 2019 pandemic created rapid adaptation in health care delivery. Methods: Using electronic medical record data from two different institutions located in two different states, we examined how telemedicine was integrated into obstetric care. Results: With no telemedicine use prior, both institutions rapidly incorporated telemedicine into prenatal care (PNC). There were significant patient-level and institutional-level differences in telemedicine use. Telemedicine users initiated PNC earlier and had more total visits, earlier timing of ultrasounds, and earlier diabetes screening during pregnancy compared with nonusers. There were no significant differences in delivery mode or stillbirth associated with telemedicine use at either institution. Conclusions: Rapid adoption of obstetric telemedicine maintained adequate prenatal care provision during the early pandemic, but implementation varied across institutions.

Objective: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare delivery, including prenatal care. The study objective was to assess if timing of routine prenatal testing changed during the COVID-19 pandemic., Methods: Retrospective observational cohort study using claims data from a regional insurer (Highmark) and electronic health record data from two academic health systems (Penn Medicine and Yale New Haven) to compare prenatal testing timing in the pre-pandemic (03/10/2018-12/31/2018 and 03/10/2019-12/31/2019) and early COVID-19 pandemic (03/10/2020-12/31/2020) periods. Primary outcomes were second trimester fetal anatomy ultrasounds and gestational diabetes (GDM) testing. A secondary analysis examined first trimester ultrasounds., Results: The three datasets included 31,474 pregnant patients. Mean gestational age for second trimester anatomy ultrasounds increased from the pre-pandemic to COVID-19 period (Highmark 19.4 vs. 19.6 weeks; Penn: 20.1 vs. 20.4 weeks; Yale: 18.8 vs. 19.2 weeks, all p  < 0.001). There was a detectable decrease in the proportion of patients who completed the anatomy survey <20 weeks' gestation across datasets, which did not persist at <23 weeks' gestation. There were no consistent changes in timing of GDM screening. There were significant reductions in the proportion of patients with first trimester ultrasounds in the academic institutions (Penn: 57.7% vs. 40.6% and Yale: 78.7% vs. 65.5%, both p  < 0.001) but not Highmark. Findings were similar with multivariable adjustment., Conclusion: While some prenatal testing happened later in pregnancy during the pandemic, pregnant patients continued to receive appropriately timed testing. Despite disruptions in care delivery, prenatal screening remained a priority for patients and providers during the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Handley, Ledyard, Lundsberg, Passarella, Yang, Son, Mckenney, Greenspan, Dysart, Culhane and Burris.)

Objective: We aimed to determine whether coronavirus-disease-2019 (COVID-19) pandemic exposure duration was associated with PTB and if the pandemic modified racial disparities., Study Design: We analyzed Philadelphia births and replicated in New Haven. Compared to matched months in two prior years, we analyzed overall PTB, specific PTB phenotypes, and stillbirth., Results: Overall, PTB was similar between periods with the following exceptions. Compared to pre-pandemic, early pregnancy (&lt;14 weeks') pandemic exposure was associated with lower risk of PTB &lt; 28 weeks' (aRR 0.60 [0.30-1.10]) and later exposure with higher risk (aRR 1.77 [0.78-3.97]) (interaction p = 0.04). PTB &lt; 32 weeks' among White patients decreased during the pandemic, resulting in non-significant widening of the Black-White disparity from aRR 2.51 (95%CI: 1.53-4.16) to aRR 4.07 (95%CI: 1.56-12.01) (interaction P = 0.41). No findings replicated in New Haven., Conclusion: We detected no overall pandemic effects on PTB, but potential indirect benefits for some patients which could widen disparities remains possible., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Timely central venous access is essential in the care of critically ill neonates. Peripherally inserted central catheters (PICCs) are the preferred form of central venous access when umbilical venous catheters cannot be placed or are discontinued. However, time delays increase risk for injury from peripheral intravenous lines and may contribute to inconsistent delivery of necessary fluids and medications., Purpose: The aim of this quality improvement project was to decrease wait times for PICC placement in the neonatal intensive care unit (NICU)., Methods: A unit-based PICC team was developed consisting of NICU nurses and attending neonatologists and implemented in 2 phases. Data were collected from chart reviews before, during, and after implementation of the team. We tracked time between PICC order and placement and number of attempts. Hospital metrics on peripheral intravenous line infiltrations and central line-associated blood stream infection were also monitored. At the end of the project, we continued tracking outcomes to determine whether gains would be sustained past the project period., Results: Implementation of a unit-based interdisciplinary specialty team led to a 50% reduction in mean PICC wait times from 1.2 days to 0.58 days. Benefits of the initiative were sustained past the initial project period., Implications for Practice: The development of a dedicated, local team played a key role in improving vascular access in the NICU., Implications for Research: Proximity of specialized teams provides a solution to address gaps in care in the NICU., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 by The National Association of Neonatal Nurses.)

Purpose of Review: Neonatal lymphatic disorders (NLDs) are conditions that are relatively rare and difficult to treat. The recent development of lymphatic imaging, such as Dynamic Contrast-Enhanced MR Lymphangiography and Intranodal Lymphangiography has led to a new, better understanding of the anatomical substrate and pathophysiological mechanisms of the diseases. Consequently, this has allowed the development of new targeted therapeutic interventions as well as prognostication for this population with lymphatic flow disorders., Recent Findings: The underlying causes of all NLD is an obstruction or altered flow of the central lymphatic flow. Two types of NLD have been described: isolated neonatal chylothorax and central lymphatic flow disorder (CLFD). Isolated neonatal chylothorax can be treated successfully with oil-based contrast (lipiodol) embolization. CLFD secondary to obstruction of the thoraco-venous junction can be successfully treated with surgical thoracic duct-venous anastomosis. CLFD caused by elevated central pressure and/or thoracic duct dysplasia can be treated medically, including with new systemic therapies such as mammalian target of rapamycin inhibitors., Summary: New diagnostic and interventional tools have recently allowed for classification, prognostication, and targeted interventions for neonatal patients with lymphatic flow disorders. Further research will build on these discoveries., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE)., Study Design: Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months., Results: Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09-2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54-16.6) and 6.92 in the first 48 h (95% CI 2.20-21.8) of TH., Conclusions: Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To determine if birth hospitalization length of stay (LOS) and infant rehospitalization changed during the coronavirus disease 2019 (COVID-19) era among healthy, term infants., Methods: Retrospective cohort study using Epic's Cosmos data from 35 health systems of term infants discharged ≤5 days of birth. Short birth hospitalization LOS (vaginal birth <2 midnights; cesarean birth <3 midnights) and, secondarily, infant rehospitalization ≤7 days after birth hospitalization discharge were compared between the COVID-19 (March 1 to August 31, 2020) and prepandemic eras (March 1 to August 31, 2017, 2018, 2019). Mixed-effects models were used to estimate adjusted odds ratios (aORs) comparing the eras., Results: Among 202 385 infants (57 110 from the COVID-19 era), short birth hospitalization LOS increased from 28.5% to 43.0% for all births (vaginal: 25.6% to 39.3%, cesarean: 40.1% to 61.0%) during the pandemic and persisted after multivariable adjustment (all: aOR 2.30, 95% confidence interval [CI] 2.25-2.36; vaginal: aOR 2.12, 95% CI 2.06-2.18; cesarean: aOR 3.01, 95% CI 2.87-3.15). Despite shorter LOS, infant rehospitalizations decreased slightly during the pandemic (1.2% to 1.1%); results were similar in adjusted analysis (all: aOR 0.83, 95% CI 0.76-0.92; vaginal: aOR 0.82, 95% CI 0.74-0.91; cesarean: aOR 0.87, 95% CI 0.69-1.10). There was no change in the proportion of rehospitalization diagnoses between eras., Conclusions: Short infant LOS was 51% more common in the COVID-19 era, yet infant rehospitalization within a week did not increase. This natural experiment suggests shorter birth hospitalization LOS among family- and clinician-selected, healthy term infants may be safe with respect to infant rehospitalization, although examination of additional outcomes is needed., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: The RAM cannula (Neotech, Valencia, CA) has become a commonly used interface for CPAP in neonatal intensive care. Performance characteristics of this interface used with a critical care ventilator are not well described., Methods: This was a bench study utilizing a lung simulator configured as an actively breathing infant (weights of 800 g, 1.5 kg, and 3 kg) with moderate lung disease and a critical care ventilator in CPAP mode with leak compensation on. Three sizes of the RAM cannulae (preemie, newborn, and infant) were compared to 3 BabyFlow nasal prongs (Dräger Medical, Lübeck, Germany) (medium, large, and extra-large). Fabricated nasal models produced a 70% occlusive fit for the RAM cannula and an occlusive fit with the Dräger prongs. Delivered flow and pressure levels were recorded at 9 CPAP levels between 5 and 20 cm H 2 O., Results: The Dräger prongs produced a mean airway pressure ([Formula: see text]) within 0.20 cm H 2 O (range -0.10 to 0.35) of the set CPAP across all evaluated prong sizes and CPAP levels. In contrast, the RAM cannula produced [Formula: see text] values that averaged 8.5 cm H 2 O (range -15 to -3.5) below the set CPAP levels. The deficit in delivered versus target CPAP level for the RAM cannula increased with greater set CPAP. Set CPAP of 5 cm H 2 O delivered [Formula: see text] values that ranged from 0.6 to 1.5 cm H 2 O (difference of 3.5-4.4 cm H 2 O). Set CPAP of 20 cm H 2 O delivered [Formula: see text] values that ranged from 5.0 to 8.4 cm H 2 O (difference of 11.7-15 cm H 2 O). Inspiratory flow required to achieve set CPAP levels did not differ between interfaces, suggesting high resistance in the RAM cannula device masks the delivered CPAP levels., Conclusions: Use of the RAM cannula with a 30% leak on a critical care ventilator delivered [Formula: see text] values lower than set CPAP. This may be clinically meaningful and should be considered when choosing a nasal interface., Competing Interests: Ms Napolitano has disclosed relationships with Aerogen, Dräger Medical, Vero-Biotech, Smiths Medical, and Philips/Respironics. Ms Nickel has disclosed a relationship with Nihon Kohden. The remaining authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Objective: To examine whether the coronavirus disease 2019 (COVID-19) pandemic altered risk of adverse pregnancy-related outcomes and whether there were differences by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status among pregnant women., Methods: In this retrospective cohort study using Epic's Cosmos research platform, women who delivered during the pandemic (March-December 2020) were compared with those who delivered prepandemic (matched months 2017-2019). Within the pandemic epoch, those who tested positive for SARS-CoV-2 infection were compared with those with negative test results or no SARS-CoV-2 diagnosis. Comparisons were performed using standardized differences, with a value greater than 0.1 indicating meaningful differences between groups., Results: Among 838,489 women (225,225 who delivered during the pandemic), baseline characteristics were similar between epochs. There were no significant differences in adverse pregnancy outcomes between epochs (standardized difference<0.10). In the pandemic epoch, 108,067 (48.0%) women had SARS-CoV-2 testing available; of those, 7,432 (6.9%) had positive test results. Compared with women classified as negative for SARS-CoV-2 infection, those who tested positive for SARS-CoV-2 infection were less likely to be non-Hispanic White or Asian or to reside in the Midwest and more likely to be Hispanic, have public insurance, be obese, and reside in the South or in high social vulnerability ZIP codes. There were no significant differences in the frequency of preterm birth (8.5% vs 7.6%, standardized difference=0.032), stillbirth (0.4% vs 0.4%, standardized difference=-0.002), small for gestational age (6.4% vs 6.5%, standardized difference=-0.002), large for gestational age (7.7% vs 7.7%, standardized difference=-0.001), hypertensive disorders of pregnancy (16.3% vs 15.8%, standardized difference=0.014), placental abruption (0.5% vs 0.4%, standardized difference=0.007), cesarean birth (31.2% vs 29.4%, standardized difference=0.039), or postpartum hemorrhage (3.4% vs 3.1%, standardized difference=0.019) between those who tested positive for SARS-CoV-2 infection and those classified as testing negative., Conclusion: In a geographically diverse U.S. cohort, the frequency of adverse pregnancy-related outcomes did not differ between those delivering before compared with during the pandemic, nor between those classified as positive compared with negative for SARS-CoV-2 infection during pregnancy., Competing Interests: Financial Disclosure Eric Lindgren, Kieran Gallagher, and Justin Y. Lo disclosed that they are employees of Epic Systems Corporation, a health IT software company that provides Cosmos, a research platform containing data from Epic's health care provider customer organizations. Epic licenses electronic health record software and provides related services to health care organizations that pay Epic for such software and services. The authors and Epic and have no conflicts of interest with respect to the subject matter of this study but would like to clarify that insights gleaned from this research may inform Epic's software design and development activities. Heather H. Burris disclosed that money was paid to her institution from Highmark Blue Cross Blue Shield Delaware's donor-advised fund (foundation grant), BluePrints for the Community, and Independence Blue Cross. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The antibiotic use rate (AUR) has emerged as a potential metric for neonatal antibiotic use, but reported center-level AURs are limited by differences in case mix. The objective of this study was to identify patient characteristics associated with AUR among a large cohort of preterm infants., Methods: Retrospective observational study using the Optum Neonatal Database, including infants born from January 1, 2010 through November 30, 2016 with gestational age 23-34 weeks admitted to neonatal units across the United States. Exposures were patient-level characteristics including length of stay, gestational age, sex, race/ethnicity, bacterial sepsis, necrotizing enterocolitis, and survival status. The primary outcome was AUR, defined as days with ≥ 1 systemic antibiotic administered divided by length of stay. Descriptive statistics, univariable comparative analyses, and generalized linear models were utilized., Results: Of 17 910 eligible infants, 17 836 infants (99.6%) from 1090 centers were included. Median gestation was 32.9 (interquartile range [IQR], 30.3-34) weeks. Median length of stay was 25 (IQR, 15-46) days and varied by gestation. Overall median AUR was 0.13 (IQR, 0-0.26) and decreased over time. Gestational age, sex, and race/ethnicity were independently associated with AUR (P < .01). AUR and gestational age had an unexpected inverse parabolic relationship, which persisted when only surviving infants without bacterial sepsis or necrotizing enterocolitis were analyzed., Conclusions: Neonatal AURs are influenced by patient-level characteristics besides infection and survival status, including gestational age, sex, and race/ethnicity. Neonatal antibiotic use metrics that account for patient-level characteristics as well as morbidity case mix may allow for more accurate comparisons and better inform neonatal antibiotic stewardship efforts., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Aerosolized albuterol is widely used, but its tolerability and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established., Objectives: To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD., Methods: Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25 mg, 2.5 mg) and 3 ml of normal saline were administered every 4 h during separate 24-h treatment periods assigned in random order with a 6-h washout phase between periods. The primary outcome was the absolute change (post and pretherapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia., Results: Average within subject EF75 values improved with each therapy: saline placebo ( + 0.45 L/min ± 2.5, p = .04), 1.25 mg of albuterol ( + 0.70 L/min ± 2.4, p < .001), and 2.5 mg of albuterol ( + 0.38 L/min ± 2.4, p = .06). However, 1.25 mg of albuterol (0.26 L/min; 95% CI -0.19, 0.72) and 2.5 mg (-0.10 L/min; 95% CI -0.77, 0.57) produced similar changes in EF75 when compared to saline. All secondary outcomes were similar between saline and 1.25 mg of albuterol. Peak inspiratory pressure needed to deliver goal tidal volumes (7.5% relative decrease, 95% CI 2.6, 12.3) and heart rate (6.5% increase, 95% CI 2.2, 10.8) differed significantly between albuterol 2.5 mg and saline., Conclusion: Albuterol at 1.25 mg and 2.5 mg, compared to aerosolized saline, did not affect EF75 in infants with sBPD receiving invasive ventilation. Greater improvement in peak inspiratory pressures with albuterol 2.5 mg suggests benefit, but close heart monitoring may be indicated., (© 2020 Wiley Periodicals LLC.)

Objective: Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia., Design: N-of-1 multiple crossover trials with individual patient and pooled data analyses., Setting: Level IV intensive care nursery., Patients: Infants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014-July 2016., Intervention: N-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order., Main Outcome Measures: The primary outcome was the frequency of daily intermittent hypoxaemic events (SpO 2 ≤80% lasting 10-180 s). Secondary outcomes included the daily proportion of time with an SpO 2 ≤80% and mean daily fraction of inspired oxygen., Results: Of 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1-23.5) vs 3/day (1-11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1-2.3) vs 0.4% (0.07-1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5)., Conclusions: Transpyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants., Trial Registration Number: NCT02142621., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity. Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age. Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Measurements and Main Results: Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks' postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support ( n  = 773); grade 1, nasal cannula ≤2 L/min ( n  = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure ( n  = 617); and grade 3, invasive mechanical ventilation ( n  = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment. Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.

Objective: To determine differences in severe intraventricular hemorrhage (IVH) between very-low-birth-weight (≤1500 g, VLBW) infants born to mothers with and without hypertensive disorders (HD)., Design/methods: Retrospective analysis from the Optum Neonatal Database. The primary outcome of interest was severe IVH (grade 3 or 4). Secondary outcomes included other neonatal morbidities, mortality, and length of hospitalization. Outcomes were compared between VLBW infants born to mothers with and without HD., Results: A total of 5456 infants met inclusion criteria. After multivariable regression analysis, risks of severe IVH and bronchopulmonary dysplasia (BPD) were lower ([OR 0.42, 95% CI 0.33-0.89, p = 0.01] and [OR 0.75, 95% CI 0.58-0.97, p = 0.03], respectively) and median length of hospitalization was decreased in the HD group (49 versus 61 days, p < 0.001)., Conclusions: VLBW infants born to mothers with HD have a decreased risk of severe IVH, BPD, and a shorter duration of hospitalization.

Objective: The objective of this study is to assess whether infants with neonatal abstinence syndrome (NAS), who receive maternal breast milk (BM), have shorter pharmacological treatment durations and lengths of stay compared with formula-fed infants., Study Design: Retrospective data analysis from Optum Neonatal Database for infants born between 1 January 2010 and 21 November 2016, who received treatment for NAS. Clinical characteristics and outcomes were compared between infants who received any amount of BM and those exclusively formula-fed., Result: Infants (1738) were analyzed. Median length of pharmacological treatment was significantly lower in infants who received any BM (14 days) compared with "no BM" group (17 days, p = 0.04). Similarly, median length of hospitalization was significantly reduced in "any BM" group (19 days vs. 20 days), which remained significant after adjustment for confounders (p = 0.01). There was no difference in hospital re-admission rates., Conclusion: Feeding any BM to infants with NAS was associated with both decreased lengths of pharmacological treatment and hospital stay compared with exclusively formula-fed infants.

Objectives: This study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18-22 months., Methods: Retrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at <27 weeks gestational age with birth weights of 401-1000 g. Respiratory support received during initial hospitalization from birth was characterized as follows: no support, only invasive support, only non-invasive support or mixed invasive, and non-invasive support. The primary outcome was death after 24 h of life or NDI at 18-22 months corrected age., Results: In a cohort of 3651 infants, 1494 (40.9%) died or had NDI. Cumulative respiratory support of any type beyond 60 days was associated with the likelihood of death or NDI. Infants who only received invasive support had the highest rate (89.1%), followed by those received mixed support (26.1%). Infants who received only non-invasive support had the lowest rate (7.7%). When compared to the only non-invasive support group, both invasive [OR 62.7 (95%CI 25.7, 152.6)] and mixed [OR 6.1 (95%CI 2.6, 14.4)] support groups were significantly more likely to die or have NDI., Conclusion: Prolonged respiratory support, whether invasive or non-invasive, is associated with increased odds of a poor outcome. The proportion of infants with a poor outcome increased in a dose dependent manner by two factors: the cumulative duration of respiratory support beyond 60 days, and the extent to which invasive support is provided., (© 2018 Wiley Periodicals, Inc.)

Objective: To characterize the independent association between antibiotic exposure in the first week of life and the risk of bronchopulmonary dysplasia (BPD) or death among very preterm infants without culture-confirmed sepsis., Methods: Retrospective cohort study using the Optum Neonatal Database. Infants without culture-confirmed sepsis born less than 1500 g and less than 32 weeks gestation between 1/2010 and 11/2016 were included. The independent association between antibiotic therapy during the first week of life and BPD or death prior to 36 weeks postmenstrual age (PMA) was assessed by multivariable logistic regression., Results: Of 4950 infants, 3946 (79.7%) received antibiotics during the first week of life. Rates of BPD or death (41.5% vs. 31.1%, p < 0.001) and the two individual outcomes were significantly higher among antibiotic treated infants. After adjusting for potential confounding variables, antibiotic use in the first week of life was not associated with increased risk of BPD or death (OR 0.96, 95% CI [0.76,1.21]) or BPD among survivors (OR 0.86, 95% CI [0.67,1.09]). Antibiotic use was associated with increased risk of death prior to 36 weeks PMA (OR 3.01, 95% CI [1.59,5.71]), however, secondary analyses suggested this association may be confounded by unmeasured illness severity., Conclusions: Antibiotic exposure in the first week of life among preterm infants without culture-confirmed sepsis was not independently associated with increased risk of BPD or death.

Background: Pregnant women with sickle cell disease (SCD) are at increased risk of maternal and fetal complications. There are limited data on the outcome of the treatment of VOCs with opioids in relation to neonatal complications during pregnancy., Methods: This is a retrospective cohort study of women with SCD from January 1999 to December 2008. Women with SCD were identified by ICD-9 codes and matched 2:1 to a control group of women on methadone for opioid dependence. The primary outcome was the rate of neonatal abstinence syndrome (NAS). Secondary outcomes included the mean NAS score prior to treatment and the length of treatment. Statistical analysis was performed using SPSS., Results: Twenty-one women with SCD who delivered a total of 23 neonates were included. The rate of NAS among infants born to women with SCD who were treated with opioids at any time was 22% compared to 54% in the methadone controls (p = .010). The rate of NAS was 27% among infants born to women taking opioids daily compared to 54% in the methadone control group (p = .062)., Conclusions: Neonates born to women with SCD who are treated with daily opioids are at a similar risk for developing NAS as those born to mothers on methadone for opioid dependence. Neonates born to women with SCD treated with episodic opioids are at a significantly lower risk for developing NAS than those born to women on methadone for opioid dependence., (Copyright © 2018 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective The objective of this study was to determine differences in the incidence of bronchopulmonary dysplasia (BPD) or death in very low-birth-weight (VLBW) infants managed successfully on continuous positive airway pressure (CPAP) versus mechanical ventilation on the first day of life (DOL). Study Design This is a retrospective analysis of the Alere neonatal database for infants born between January 2009 and December 2014, weighing ≤ 1,500 g. Baseline demographics, clinical characteristics, and outcomes were compared between the two groups. Multivariable regression analysis was performed to control the variables that differ in bivariate analysis. Results In this study, 4,629 infants (birth weight 1,034 ± 290 g, gestational age 28.1 ± 2.5 weeks) met the inclusion criteria. The successful use of early CPAP was associated with a significant reduction in BPD or death (p < 0.001), as well as days to room air, decreased oxygen use at discharge, lower risk for severe intraventricular hemorrhage, and patent ductus arteriosus requiring surgical ligation (p < 0.001 for all outcomes). Conclusion Successful use of early CPAP on the first DOL in VLBW infants is associated with a reduced risk of BPD or death., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Randomized clinical trials are the best method to assess the safety and efficacy of therapeutic interventions. However, it is not always clear how much evidence from randomized trials is required to change clinical practice. Throughout the history of neonatal medicine, some therapies were subject to excessive and unnecessary testing through replication of clinical trials. Other therapies were adopted into clinical practice with insufficient evidence. In only a few cases was the right amount of evidence accumulated to drive a change in practice. Here we present a case history for each of these three scenarios. Arising from these, we suggest principles to identify when enough evidence exists for a therapy to become standard practice., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: High flow nasal cannula therapy (HFT) has been shown to be similar to nasal continuous positive airway pressure (nCPAP) in neonates with respect to avoiding intubation. The objective of the current study is to determine if there are trends for adverse safety and long-term respiratory outcomes in very low birth weight infants (<1500 g) from centers using HFT as their primary mode of non-invasive respiratory support compared to data from the largest neonatal outcomes database (Vermont Oxford Network; VON)., Methods: A multicenter, retrospective analysis of pulmonary outcomes data was performed for the calendar years 2009, 2010 and 2011. Performance of five HFT centers was compared with population outcomes from the VON database. The five HFT centers routinely use flow rates between 4-8 L/min as described by the mechanistic literature. Weighted average percentages from the five HFT centers were calculated, along with the 95% confidence intervals (CI) to allow for comparison to the VON means., Results: Patient characteristics between the HFT centers and the VON were not different in any meaningful way, despite the HFT having a greater percentage of smaller infants. The average VON center primarily used nCPAP (69% of all infants) whereas the HFT centers primarily used HFT (73%). A lesser percentage of VLBW infants in the HFT cohort experienced mortality and nosocomial infection. Compared to VON data, an appreciably lesser percent of the HFT cohort were receiving oxygen at 36 weeks and less went home on oxygen., Conclusions: Considering there was no trend for adverse events, and there was a trend for better outcomes pertaining to long-term oxygen use, these data support claims of safety for HFT as a routine respiratory management strategy in the NICU.

The Apgar score is a standardized tool for evaluating newborns in the delivery room. Despite its long history and widespread use, debate remains over its reliability of predicting neonatal outcomes, especially in extremely low-birth-weight premature infants. The aim of the study was to examine the relationship between the 5-minute Apgar score of extremely low-birth-weight infants, as it relates to survival and morbidities associated with prematurity and length of hospital stay. A retrospective query of the Alere neonatal database from 2001 to 2011 examined all infants less than 32 weeks' gestation and less than 1000-g birth weight. The 5-minute Apgar score was divided into 2 groups, score of 4 or greater or less than 4. The study compared results of the 5-minute Apgar score and associated morbidities in surviving infants. Statistical analyses included chi-square, Fisher exact test, t test, and multivariate regression. The sample consisted of 3898 infants with an 86.4% (n = 3366) survival rate. Controlling for gestational age and birth weight, surviving infants with a 5-minute Apgar score of less than 4 were more likely to demonstrate nonintact survival. Infants with a low 5-minute Apgar score have greater risk for mortality and morbidities associated with prematurity.

Aims: More than half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacological therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS., Design: Randomized, Phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine., Setting: Large, urban, tertiary care hospital., Participants: Twenty-four term infants requiring pharmacological treatment for NAS., Measurements: Outcomes were neonatal safety, length of treatment and length of hospitalization., Findings: Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (P = 0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (P = 0.05)., Conclusions: Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

We compared survival and outcomes in process of care in female versus male infants born ≤32 weeks gestational age (GA). Data were obtained from the Alere database for infants born ≤32 weeks GA. Females were compared with males for demographics, complications, and care processes. Univariate and multivariate analysis was conducted using chi-square analysis, analysis of variance, or logistic regression. Of the infants included, 6086 female and 6721 males were included. Mean GA did not differ, males were born larger than females, and females were more likely to be born SGA. Males received more surfactant, developed more CLD, received more steroids, and more often required oxygen at discharge. Females were more likely to develop a patent ductus arteriosus. After controlling for body weight, GA, and small-for-GA status, females were more likely to survive (95.4% versus 93.6%, odds ratio 1.63, P < 0.01). Male sex did not play a role in other processes of care except for weaning to a crib. Male infants born ≤32 weeks GA have a decreased rate of survival and an increased rate of respiratory morbidity in spite of higher birth weight distributions. Sex did not play a role in other processes of care., (© Thieme Medical Publishers.)

Introduction: High-flow nasal cannula therapy (HFNC) has been shown to be more effective than continuous positive airway pressure (CPAP) in reducing intubations and ventilator days. HFNC likely provides mechanisms to support respiratory efficiency beyond application of distending pressure. We reason that HFNC washout of nasopharyngeal dead space impacts CO(2) removal along with oxygenation. The aim of this study was to demonstrate the flow dependence of CO(2) reduction and improved oxygenation during HFNC and the dependence on leak around the nasal prongs., Materials and Methods: Neonatal piglets (n=13; 2-6 kg) were injured with IV oleic acid and supported with HFNC at 2 through 8 L/min. High and low leak around the nasal prongs was accomplished by using single and double prong cannulae, respectively. Measurement of hemodynamic, respiratory and blood gas parameters were made at each setting following 10 min for physiologic equilibration. Tracheal pressures were recorded by transmural catheters., Results: With HFNC, CO(2) trended downward in a flow-dependent manner independent of leak. Oxygenation and tracheal pressures increased in a flow-dependent manner with the greatest effect during double prong. At 8 L/min, tracheal pressures did not exceed 6 ± 1 cmH(2) O., Conclusions: HFNC improves gas exchange in a flow-dependent manner; double prong had greater impact on O(2;) single prong had greater impact on CO(2) elimination., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: To characterize physical and inflammatory injury that may result from repeated intubation, independent of positive-pressure ventilation; and to determine whether corticosteroids can attenuate injury and or inflammation that may result from repeated intubation., Design: A 4-hr animal protocol., Setting: All work was done in the animal laboratory at the Alfred I. DuPont Hospital for Children., Subjects: Neonatal piglets (2-8 days old; 2.5 ± 0.4 kg) were intubated and randomized to four groups (n = 8 each) to be followed over 4 hrs. Groups were control (not reintubated), injured (reintubated every 0.5 hr), intratracheal pretreatment with 1 mg of nebulized budesonide (intratracheal pretreated), or intravenous pretreatment with 0.3 mg/kg of dexamethasone (intravenous pretreated)., Intervention: Each pig was sedated for the duration of study and had a 3.5F catheter inserted in the femoral artery for blood sampling and blood pressure measurement every hour. After 4 hrs, each pig was killed, and tissue was harvested for histology and interleukin-6 assays., Measurements and Main Results: Laryngeal tissue interleukin-6 content was greater in the injured group compared with the control group (p < .05). In the intratracheal pretreated group, the interleukin-6 content of laryngeal tissue was greater compared with the control group (p < .05), whereas the intravenous pretreated group was not different from the control group. The reintubation injury resulted in plasma interleukin-6 levels that, compared with control, were greater in the injured and intratracheal pretreated groups (p < .05). Quantitative histology showed that the degree of tracheal injury was higher in injured and intratracheal pretreated groups compared with the control group (p < .05)., Conclusions: Repeated intubation alone results in significant tracheal trauma and systemic inflammation. Intravenous but not inhaled steroids attenuated the injury.

We examined if very low-birth-weight (VLBW) infants of multiple gestation pregnancies experience more complications and take longer to achieve clinical milestones compared with similar singletons. We performed a retrospective analysis of all infants less than 1500 g at birth in a large neonatal database. Singletons were compared with twins and higher-order multiples for demographic, morbidities, and process milestones including feeding, respiratory, thermoregulation, and length of stay. Multivariable regression analyses were performed to control for potential confounding variables. A total of 5507 infants were included: 3792 singletons, 1391 twins, and 324 higher-order multiples. There were no differences in Apgar scores, small for gestational age status, and incidence of necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, or the need for surgery. Multiples had higher rates of apnea and patent ductus arteriosus than singletons. VLBW multiples achieved milestones at similar rates in most areas compared with singletons except for the achievement of full oral feedings. Length of stay, after controlling for confounding variables, did not differ between the groups. Compared with singletons, VLBW multiples had similar morbidity and achieved most feeding and thermoregulation milestones at similar rates., (Thieme Medical Publishers.)

Recently, heater/humidifier devices that use novel methods to condition breathing gases from an external source have been introduced. The addition of sufficient warmth and high levels of humidification to breathing gas has allowed for higher flow rates from nasal cannula devices to be applied to patients (i.e., high flow therapy). This article provides a review of the proposed mechanisms behind the efficacy of high flow therapy via nasal cannula, which include washout of nasopharyngeal dead space, attenuation of the inspiratory resistance associated with the nasopharynx, improvement in conductance and pulmonary compliance, mild distending pressure and reduction in energy expenditure for gas conditioning.

Objective: In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered., Methods: We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 mug/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system., Results: Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated., Conclusions: Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.

Objective: To estimate if exposure to antenatal corticosteroids was associated with decreased rate of death in neonates born at 23 weeks of gestation., Methods: This is a retrospective cohort study performed at three tertiary centers of neonates born at 23 weeks of gestation between 1998 and 2007. Stillbirths, voluntary terminations, or parental elected nonresuscitations were excluded. Clinical and demographic variables were examined to determine possible confounding variables. A multivariable logistic regression model was used to assess the effect of steroids on the odds of death after adjustment for these confounders., Results: The sample included 181 neonates. Of the multiple variables examined (institution, race, diagnosis, illicit drug use, antibiotics, assisted reproduction, birth weight, gender, and route of delivery), only multiple gestations were significantly associated (P

Unlabelled: Alterations in neonatal airway mechanics resulting from ventilatory therapies are implicated in airway collapse and chronic disease. Quantifying the functional impact of mechanical ventilation (MV) on the neonatal airway and elucidating the time course of these changes will support development of protective therapies. The objective of this study was to test the hypothesis that conventional MV would result in decreased static and dynamic elastance of an isolated tracheal segment and thinning of the muscle (trachealis) region of the tracheal wall in a time dependent manner. Tracheal segments were isolated in newborn lambs spontaneously breathing through the distal trachea; segments were MV (n = 7; PIP/PEEP = 35/5 cmH2O; 40 breaths/min) or instrumented, non-ventilated (SHAM; n = 7; PIP/PEEP = 0/0 cmH2O) for 4 hr. At baseline and hourly, tracheal segments were filled with saline, and static pressure-volume curves were constructed as the pressure response to stepwise volume infusions. Then, cross-sectional ultrasound images were captured at 0 cmH2O on SHAM, and at 0 cmH2O, peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP), on MV tracheae for subsequent dimensional analysis. Tracheal elasticity indices were derived from static pressure-volume data, and during dynamic ventilation using ultrasound images to calculate the stress-strain relationships. Over 4 hr of MV, tracheal internal diameter (ID) increased (14%; P < 0.05). Markers of tracheal mechanical properties indicated a decrease in elasticity under both static (bulk modulus; 28%; P < 0.05) and dynamic (elastic modulus; 282 %; P < 0.05) conditions, indicating a significant alteration in elastic components. No time dependent changes were identified in dimensions or mechanical properties in the SHAM group., Conclusions: MV results in dimensional alterations that increased anatomical dead space and reduced static and dynamic elastance of the neonatal trachea., ((c) 2006 Wiley-Liss, Inc.)