Concentration of novel urinary tract infection biomarkers in neonates.

Urinary tract infections (UTIs) are a common comorbidity in hospitalized neonates. The current UTI diagnostics have several limitations including invasive collection of urinary samples to ensure sterility, risk of contamination and lack of consensus definitions of UTI based on urine culture. Antimicrobial peptides (AMPs) have been recently utilized as novel biomarkers that can efficiently and accurately diagnose pediatric UTI. However, the concentration of AMPs in neonatal urine is not well-defined. Urine from neonates admitted to a single level IV neonatal intensive care unit was obtained to determine baseline concentration of two AMPs, Ribonuclease 7 (RNase 7) and Beta Defensin-1 (BD-1) and to define the relationship between AMP concentration and gestational age (GA). AMP levels were normalized to urine creatinine. RNase 7 and BD-1 were expressed in neonatal urine (n = 66) regardless of GA and as early as 22 weeks gestation. Urinary concentrations of both AMPs decreased as GA and birthweight increased. The overall median urinary RNase 7/UCr and BD-1/UCr values were 271 ng/mg, and 116 ng/mg, respectively. Median urinary concentrations of RNase 7/UCr for infants born at < 27, 27-32, 33-35 and ≥ 36 weeks were 569, 308, 254, and 124 ng/mg respectively. Similarly, the concentrations of BD-1/UCr at these GA were 166, 115, 108, and 14 ng/mg, respectively. Baseline neonatal urinary concentration of two AMPs (RNase 7 and BD-1) and the variation by GA were identified. This is an essential first step toward the potential utilization of AMPs in improving neonatal UTI diagnostics.

Multicentre study protocol comparing standard NRP to deveLoped Educational Modules for Resuscitation of Neonates in the Delivery Room with Congenital Heart Disease (LEARN-CHD).

INTRODUCTION: Infants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings. METHODS AND ANALYSIS: In a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations. ETHICS AND DISSEMINATION: This study protocol is approved by nine participating sites: the Boston Children's Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children's Wisconsin IRB (1760009-1), Nationwide Children's Hospital IRB (STUDY00001518), Milwaukee Children's IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children's Healthcare of Atlanta, Children's Hospital of Los Angeles and Children's Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.

Linking the Perinatal Environment to Neonatal Cardiovascular Outcomes.

Cases of high-risk pregnancies continue to rise throughout the United States and globally, increasing rates of maternal and neonatal morbidity. Common pregnancy complications and morbidities include preterm birth, hypertensive disorders, fetal growth restriction, diabetes mellitus, and chorioamnionitis. Exposure to these perinatal conditions contributes to cardiac morbidities in the fetus and neonate, including altered cardiac growth, congenital heart disease, and cardiac dysfunction. Significant research has demonstrated lasting effects of these pregnancy complications, with increased rates of cardiac morbidities seen in children and adults after these perinatal exposures. The link between the perinatal environment and long-term outcomes has not been fully elucidated. The aim of this review is to discuss the current understanding of the implications of a high-risk pregnancy on fetal and neonatal cardiac development.

Perspectives on developing and sustaining a small baby program.

The Small Baby Program at Nationwide Children's Hospital was launched in 2004 in response to a need for better care for infants born extremely preterm. Standardization of care, decreased variability, multidisciplinary support, and robust research and quality improvement have allowed us to greatly improve our outcomes. In addition to the numerous medical and technological advances during this time, a strong commitment to kangaroo care and family-centered care have been integral to the growth and success of our program. The following review of the program aims to highlight the above areas while detailing the specific processes that have contributed to its ongoing success. Key areas of focus have been on respiratory management, neurodevelopmental care, and nutritional optimization. The implementation and continued refinement of the Small Baby Program has allowed us to improve the survival of extremely preterm infants, decrease certain morbidities, and improve long-term neurodevelopmental outcomes.

Worsened short-term clinical outcomes in a cohort of patients with iNO-unresponsive PPHN: a case for improving iNO responsiveness.

OBJECTIVES: To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. STUDY DESIGN: Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. RESULTS: Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. CONCLUSION: Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.

Eligibility Criteria and Representativeness of Randomized Clinical Trials That Include Infants Born Extremely Premature: A Systematic Review.

OBJECTIVE: To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation). STUDY DESIGN: PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28 weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale. RESULTS: Among RCTs (n = 201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n = 301) of criteria. Fifty-five RCTs (27.4%) included infants <24 weeks of gestation; 454 (1.4%) infants were identified as <24 weeks of gestation. CONCLUSIONS: The present study identifies sources of variability across RCTs that included infants born extremely preterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.

Short-term complications and long-term morbidities associated with repeated unplanned extubations.

OBJECTIVE: To describe characteristics associated with repeated unplanned extubations, short-term complications and outcomes, and longer-term morbidities including acquired subglottic stenosis. STUDY DESIGN: Cohort study including neonates admitted to a tertiary care neonatal intensive care unit who experienced an unplanned extubation in a 5-year period. RESULTS: We reviewed 588 events involving 300 patients. Ten percent had airway trauma with reintubation, 42% required ≥2 reintubation attempts, and 39% led to increased baseline oxygen. Increased odds of repeated events were seen in patients with bronchopulmonary dysplasia and were associated with higher rates of tracheostomy and longer length of stay. The 9% of patients diagnosed with acquired subglottic stenosis had more unplanned extubations, higher rates of airway trauma and tracheitis, and were an older gestational age at birth. CONCLUSION: Unplanned extubations lead to short- and long-term morbidities. Certain patient characteristics are associated with increased odds of repeated events and the development of acquired subglottic stenosis.

MiR-29b is associated with perinatal inflammation in extremely preterm infants.

BACKGROUND: Inflammation is strongly associated with premature birth and neonatal morbidities. Increases in infant haptoglobin, haptoglobin-related protein (Hp&HpRP), and interleukin-6 (IL-6) levels are indicators of intra-amniotic inflammation (IAI) and have been linked to poor neonatal outcomes. Inflammation causes epigenetic changes, specifically suppression of miR-29 expression. The current study sought to determine whether miR-29b levels in cord blood or neonatal venous blood are associated with IAI, identified by elevated IL-6 and Hp, and subsequent clinical morbidities in the infant. METHODS: We tested 92 cord blood samples from premature newborns and 18 venous blood samples at 36 weeks corrected gestational age. MiR-29b, Hp&HpRP, and IL-6 were measured by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Decreased levels of miR-29b were observed in infants exposed to IAI with elevated Hp&HpRP and IL-6 levels and in infants delivered by spontaneous preterm birth. Lower miR-29 levels were also observed in women diagnosed with histological chorioamnionitis or funisitis and in infants with cerebral palsy. Higher levels of miR-29 were measured in infants small for gestational age and in venous samples from older infants. CONCLUSIONS: MiR-29 may be an additional biomarker of IAI and a potential therapeutic target for treating poor newborn outcomes resulting from antenatal exposure to IAI. IMPACT: Decreases in miR-29b are associated with intrauterine inflammation. Hp&HpRP increases are associated with decreased miR-29b. MiR-29b may be an additional biomarker for neonatal outcomes and a potential therapeutic target for intrauterine inflammation.

Near-Infrared Spectroscopy in Extremely Preterm Infants.

With advances in neonatal care, survival of premature infants at the limits of viability has improved significantly. Despite these improvement in mortality, infants born at 22-24 weeks gestation are at a very high risk for short- and long-term morbidities associated with prematurity. Many of these diseases have been attributed to abnormalities of tissue oxygenation and perfusion. Near-infrared spectroscopy utilizes the unique absorption properties of oxyhemoglobin and deoxyhemoglobin to provide an assessment of regional tissue oxygen saturation, which can be used to calculate the fractional tissue oxygen extraction. This allows for a non-invasive way to monitor tissue oxygen consumption and enables targeted hemodynamic management. This mini-review provides a brief and complete overview of the background and physiology of near-infrared spectroscopy, practical use in extremely preterm infants, and potential applications in the neonatal intensive care unit. In this mini-review, we aim to summarize the three primary application sites for near-infrared spectroscopy, disease-specific indications, and available literature regarding use in extremely preterm infants.

A Quality Improvement Approach to Reduce Unplanned Extubation in the NICU While Avoiding Sedation and Restraints.

The unplanned extubation (UE), a common adverse event in the neonatal intensive care unit (NICU), may result in airway trauma, cardiopulmonary resuscitation, and, in extreme cases, death. As part of the Nationwide Children's Hospital NICU's effort to optimize NICU graduates' neurodevelopmental outcomes, skin-to-skin care of intubated infants is encouraged, while sedation and restraints to prevent UE are strongly discouraged. This project aimed to decrease the UE rate from 1.85 to 1.5 per 100 endotracheal tube (ETT) days. METHODS: The project occurred in a 114-bed, level-IV NICU with approximately 850 admissions per year and 100% outborn infants. A multidisciplinary team began biweekly meetings to review all UE events, later separating these into preventable and nonpreventable. Important ongoing tests of change included assigning a single process owner for UE reporting, ensuring proper ETT securement, and using 2 clinical staff during patient and/or ETT manipulation. RESULTS: Early in the project, enhanced detection led to an increased rate from 1.85 to 3.26 per 100 ETT days. However, identifying preventable events empowered staff to decrease the frequency to 2.03 per 100 ETT days. In August 2017, an ETT taping method change produced an increase in special causes due to decreased compliance. However, when securement methods were enhanced, noncompliance reversed and is now trending favorably. CONCLUSIONS: Decreasing UE in a neurodevelopmentally friendly unit, which avoids sedation and restraints, is challenging. Using a multidisciplinary quality improvement approach and after appropriately capturing events, we reduced UE, with the highest impact of intervention being ETT securement standardization.

Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after Maternal Overdose.

Here, we review the case of a 26 1/7 weeks' gestation premature female infant born to a mother who intentionally ingested a large quantity of Tylenol, aspirin, quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated levels of both Tylenol and aspirin when checked on the first day of life. While overall clinically stable, the neonate did demonstrate coagulopathy as evidenced by abnormal coagulation studies. Both poison control and a pediatric gastroenterologist/hepatologist were consulted. She successfully tolerated a course of N-acetylcysteine; her subsequent Tylenol level was markedly decreased and the neonate exhibited no further effects of toxicity. The salicylate level decreased on its own accord. To our knowledge, this is the first report of a neonate at 26 weeks' gestation that has been successfully managed for supratherapeutic concentrations of acetaminophen and acetylsalicylic acid secondary to maternal ingestion. While rare, this case may serve as a reference for the effectiveness of N-acetylcysteine in premature infants in such instances.

Catheter-based closure of the patent ductus arteriosus in lower weight infants.

Risks associated with drug therapy and surgical ligation have led health care providers to consider alternative strategies for patent ductus arteriosus (PDA) closure. Catheter-based PDA closure is the procedure of choice for ductal closure in adults, children, and infants ≥6kg. Given evidence among older counterparts, interest in catheter-based closure of the PDA in lower weight (<6kg) infants is growing. Among these smaller infants, the goals of this review are to: (1) provide an overview of the procedure; (2) review the types of PDA closure devices; (3) review the technical success (feasibility); (4) review the risks (safety profile); (5) discuss the quality of evidence on procedural efficacy; (6) consider areas for future research. The review provided herein suggests that catheter-based PDA closure is technically feasible, but the lack of comparative trials precludes determination of the optimal strategy for ductal closure in this subgroup of infants.