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Background Bronchopulmonary dysplasia (BPD) is a disease that can affect preterm neonates. Infants with severe BPD may develop pulmonary hypertension (PHN) and may require chronic mechanical ventilation with tracheostomy. The outcomes of these infants have not been studied well. We proposed to review survival and outcomes of infants requiring tracheostomy secondary to severe BPD in our NICU at 24 months. Methods We reviewed infants’ charts who were diagnosed with BPD that underwent tracheostomy from January 2011 to May 2016 at our children’s hospital NICU. Data were recorded from hospital stay as well as from follow up clinics. Institutional review board approval was obtained prior to beginning of study. Results Forty-one babies (37 during initial hospitalization and 4 subsequently) requiring tracheostomy were identified from our database. Median gestational age at birth was 26 weeks (25–27 IQR), mean birthweight of 731 g (±245 SD) and 32% were small for gestational age (SGA). Median age of tracheostomy placement was 168 days (108–197 IQR), and median PMA 48 wks (40–56 IQR). 26% of infants requiring tracheostomy also had subglottic stenosis along with BPD. 34 infants (83%) survived to discharge from NICU. 66% (27/41) of our patients had a composite outcome of death, ventilator dependency and/or poor neurodevelopmental outcome at 2 years. We found that a higher respiratory severity score at the time of tracheostomy placement and later post-menstrual age at admission to level IV NICU was associated with a worse outcome. Small for gestational age infants were found to have worse outcomes as well. 41% (13/32) of infants had more than 3 hospital admissions after discharge. Conclusions In our cohort about 80% of infants with severe BPD and tracheostomy survived to discharge with need for prolonged home ventilation in more than half of the survivors. Later postmenstrual age at admission to level 4 NICU was associated with a worse outcome. Our retrospective data may be inadequate to determine the causal relationship between postmenstrual age at admission and outcome. These patients continue to have high morbidity and recurrent hospitalizations.

Objective We report here on the management and outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection. Study design In this prospective study, eligible neonates were enrolled in a database to track in-hospital outcomes and followed up outpatient periodically till 2 months of age to assess for late onset symptoms of infection. Results From April 2020 to February 2021, 67 mothers with perinatal SARS-CoV-2 infection and 70 at-risk neonates were included. Two neonates (3%) tested positive for SARS-CoV-2 within 48 h of life but remained asymptomatic during hospitalization and at all follow-up periods. Three infants were reported to have a febrile illness in 2 months follow up period, none of which was attributable to SARS-CoV-2. Conclusion Our data supports the emerging evidence which describes a probable low risk of vertical transmission of SARS-CoV-2. We also demonstrate a low risk of post-natal transmission or late-onset symptomatic infection with SARS-CoV-2.

Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

Background: Pulmonary hypertension (PH) is a common comorbidity in infants with bronchopulmonary dysplasia (BPD). Sildenafil is a widely recognized therapy for PH, but its efficacy in infants with BPD is questionable. We propose to assess the efficacy of sildenafil in BPD-associated PH as evaluated based on transthoracic echocardiography (TTE) changes and clinical measures. Methods: Data were retrospectively and prospectively collected. Inclusion criteria were gestational age (GA) < 32 weeks, birth weight (BW) < 1500 g with severe BPD, diagnosis of PH via TTE on sildenafil treatment. PH was evaluated via TTE, which was performed monthly after 36 weeks post-menstrual age (PMA) as a standard of care, and re-reviewed by a single pediatric cardiologist, who was blind to the initial reading. Results: In total, 19 patients were enrolled in the study, having a median GA of 24 3/7 weeks (IQR 23 5/7–25 5/7) and a median BW of 598 g (IQR 572–735). Sildenafil treatment was started at a median PMA of 40.4 weeks. The median respiratory severity score (RSS) at 28 d was 6.5, RSS and FiO2 showed improvement about 12 weeks after starting sildenafil treatment. Conclusions: Improvement in PH was noted via TTE, and patients had improvement in their RSS and FiO2 after prolonged therapy. However, TTE improvements did not correlate with clinical improvements.

Background: The most common cause of persistent hypoglycemia in infancy is hyperinsulinemic hypoglycemia. When conservative measures fail, providers often use medications to treat persistent hypoglycemia. Diazoxide is first-line therapy for neonatal hypoglycemia and works by inhibiting insulin secretion. Diazoxide is associated with fluid retention, and less commonly with respiratory decompensation and pulmonary hypertension. Case reports documenting these severe adverse events exist in the literature, although the overall incidence, risk factors, and timing for these effects in a newborn are not clearly defined. Methods: We performed a retrospective chart review of all infants admitted to the neonatal intensive care unit (NICU) at Regional One Health from 1 January 2013 until 15 August 2019, who received diazoxide as a treatment for persistent hypoglycemia secondary to hyperinsulinism. Patients were stratified as either having no adverse event or having an adverse outcome to the medication. A severe adverse outcome was defined as any known major side effect of the medication, which a patient developed within 2 weeks of medication initiation that led to medication discontinuation. Results: From our pharmacy database, we identified a total of 15 babies who received diazoxide for persistent hypoglycemia. Of these patients, eight (53%) were classified as having a complication requiring discontinuation of the medication. Six out of eight patients required intubation with mechanical ventilation and five out of eight patients developed pulmonary hypertension. All patients returned to their baseline respiratory support after drug discontinuation. Conclusions: A total of 53% of our study population had an adverse outcome to diazoxide. Previous studies suggest 5% of patients may have respiratory decompensation and require ventilatory support while on diazoxide; however, 40% of our patients deteriorated and then required mechanical ventilation. Based on our data, respiratory deterioration may be more likely to occur when diazoxide is used in preterm infants, those with lower birth weight and intrauterine growth restriction. Plain language summary The dangers in diazoxide Newborns could experience a transient period of low blood glucose levels soon after birth. However, some may progress to persistent low blood glucose levels that cannot be controlled with adequate glucose infusion and may require other ways of treatment. Diazoxide is the first-line drug approved by the US Food and Drug Administration (FDA) for this condition. However, certain cases have reported the development of respiratory deterioration, including increased blood pressure in lung circulation after its use. This prompted a black box warning in 2015 by the FDA. The incidence of neonatal low blood glucose levels seems to have increased and so has the use of this drug. Our study identifies 15 newborns who received diazoxide at Regional One Health neonatal intensive care unit in the past 6 years and reports a significantly higher rate of adverse events in our population leading to drug discontinuation in almost 53% of our cases.

Background The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown. Results Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models. Instead of fungal communities dominated by Candida and Saccharomyces , the first stool microbiomes of infants who developed BPD had less interconnected community architectures with a greater diversity of rarer fungi. After using a pseudohumanized model to show that transfer to the neonatal microbiome from infants with BPD increased the severity of lung injury, we used gain and loss of function approaches to demonstrate that modulating the extent of initial neonatal fungal colonization affected the extent of BPD-like lung injury in mice. We also identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. Conclusions These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in murine models, which suggests both causality and a potential therapeutic strategy. 7tBaiGhHzrwGBbT1j3n_5h Video Abstract

Background Invasive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of numerous neonatal intensive care unit (NICU) outbreaks. There have been increasing reports of MRSA outbreaks in various neonatal intensive care units (NICUs) over the last decade. Our objective was to review the experience of Staphylococcus aureus sepsis in our NICU in the last decade and describe the trends in the incidence of Staphylococcus aureus blood stream infections from 2000 to 2009. Methods A retrospective perinatal database review of all neonates admitted to our NICU with blood cultures positive for Staphylococcus aureus from (Jan 1 st 2000 to December 31 st 2009) was conducted. Infants were identified from the database and data were collected regarding their clinical characteristics and co-morbidities, including shock with sepsis and mortality. Period A represents patients admitted in 2000-2003. Period B represents patients seen in 2004-2009. Results During the study period, 156/11111 infants were identified with Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A and 115/6625 (1.73%) in Period B ( p  < 0.0004). Mean gestation at birth was 26 weeks for infants in both periods. There were more MRSA infections in Period B (24% vs. 55% p  < 0.05) and they were associated with more severe outcomes. In comparing the cases of MRSA infections observed in the two periods, infants in period B notably had significantly more pneumonia cases (2.4% vs. 27%, p  = 0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p  = 0.0038). The incidences of skin and soft tissue infections and of necrotizing enterocolitis were not significantly changed in the two periods. Conclusion There was an increase in the incidence of Staphylococcus aureus infection among neonates after 2004. Although MSSA continues to be a problem in the NICU, MRSA infections were more prevalent in the past 6 years in our NICU. Increased severity of staphylococcal infections and associated rising mortality are possibly related to the increasing MRSA infections with a more virulent community-associated strain.

ObjectiveWe report a statewide collaborative quality initiative to improve resuscitation and stabilization practices following introduction of the 6th edition of the Neonatal Resuscitation Program.MethodsParticipants drafted a consensus toolkit of interventions and corresponding measures. Hospital teams collected baseline data, and implemented changes using PDSA-cycles and statistical process control charts.ResultsNine Tennessee NICUs submitted data on 3771 resuscitations. “Special cause” improvements were achieved and sustained for pre-resuscitation checklists (77–90%) and team briefings (80–92%). Time to intravenous access (50–42 min), glucose infusion initiation (73–60 min), and antibiotic dosing (113–98 min) were also significantly reduced. Teams were unable to meet new NRP oxygen saturation targets. Improvements in post-resuscitation debriefing were not sustained, while communication with parents declined significantly (68–60%).ConclusionLarge-scale collaboration facilitated statewide implementation of new guidelines, while highlighting under-appreciated systems challenges among competing resource demands.

IntroductionIn the last 60 years, newborn bloodspot screening (NBS) has expanded as a public health intervention from a single severe childhood genetic disease (SCGD) to up to as many as 80 SCGD and testing of ~40 million newborns/year worldwide. However, the gap between current NBS and its potential to increase the efficiency, effectiveness and global equity of healthcare delivery for SCGD is large and rapidly growing. There are now effective therapeutic interventions—drugs, diets, devices and surgeries—for up to 2000 SCGD. Since almost all SCGD can be identified by bloodspot genome sequencing, it has been a longstanding goal to supplement current NBS with genome sequencing-based NBS (gNBS) for all eligible SCGD. We recently described a novel gNBS platform (named Begin Newborn Genome Sequencing (BeginNGS)) with the potential to overcome several major challenges to gNBS (cost, scalability, false positives and an unprepared healthcare workforce). A pilot clinical trial of BeginNGS for 412 SCGD in a level IV neonatal intensive care unit (NICU) had a true positive rate of 4.2%, sensitivity of 83%, positive predictive value of 100% and clinical utility rate of 4.2%, indicating readiness of the platform for use in a powered, multicentre study.Methods and analysisThe BeginNGS study is a single group, international, multicentre, adaptive clinical trial to compare utility, acceptability, feasibility and cost-effectiveness of BeginNGS gNBS (experimental intervention) with standard NBS (control). A minimum of 10 000 neonates (aged <28 days, maximum of 100 000) will be enrolled across 25 racial, ethnic and ancestry populations and five enrolment site types (high-risk obstetrician offices, labour induction office visits, newborn nurseries, NICUs and well-baby visits). BeginNGS is gNBS for circa 2000 SCGD (currently 508 SCGD). The primary objective of the trial is to generate equitable evidence to support broad implementation of gNBS. Enrolled newborns receive both interventions (BeginNGS and standard of care NBS). Newborns who screen positive receive confirmatory testing and medical follow-up for at least 1 year to obtain outcomes data. The primary outcome measure is clinical utility, defined as the proportion of diagnoses identified by BeginNGS and state NBS during infancy that are likely to benefit (likely to have an improved outcome) from treatment. We hypothesise that BeginNGS has a greater rate of clinical utility than standard NBS. An adaptive design was chosen rather than a traditional, fixed design to allow accumulating results to make the trial more efficient, informative, equitable and ethical by addition or removal of SCGD and genetic variants, population enrichment (for under-represented racial, ethnic and ancestral groups) and sample size re-estimation. Adaptive design will also facilitate meta-analysis with other clinical trials of gNBS, providing greater power to test utility in ultra-rare SCGD. Parents will be approached (in person, via phone or via electronic communication) to provide informed consent to enrol their newborns prenatally, postnatally in newborn nurseries or NICUs or at well baby outpatient visits. This study is part of phase III of the BeginNGS programme. Patient and public voices have been engaged in the design and execution of each BeginNGS phase through individuals and groups joining the BeginNGS consortium and participating in the family and community engagement work group. gNBS has the potential to transform the way we diagnose and treat childhood genetic diseases. Preliminary data suggest that national adoption of BeginNGS for all births has the potential to improve outcomes of >50 000 US children per year.Ethics and disseminationThis study was approved by the WCG Clinical institutional review board on 14 February 2024, and the most recent amendment approved on 7 October 2025 (approval number 20235517). Study findings will be shared through research consortium workshops, national and international conferences, community presentations and peer-reviewed journals.Trial registration numberNCT06306521.

Context Reports evaluating a possible association between necrotising enterocolitis (NEC) and blood transfusion have been predominantly case–control studies. As the possible associations of disease with any variable on which cases and controls have been matched cannot be explored, a cohort study would offer a solution to this problem. Objective Our objective was to evaluate the association between exposure to a packed red blood cell (PRBC) transfusion and development of NEC in a cohort where biases of matching are omitted. Design In a retrospective cohort, exposed infants were defined as those who received a transfusion and did not develop NEC or developed NEC within 48 h of the transfusion. All others were considered unexposed. Setting A single regional perinatal centre in Memphis, Tennessee, USA. Patients 3060 ≤1500 g birth weights (BW) were included. Outcome measures The relative risk of developing NEC after exposure to a PRBC transfusion was measured. Results 3060 infants were identified. 174 infants (5.7%) developed NEC; 116 of the 174 infants (67%) were exposed. NEC infants had a significantly lower BW (924 vs 1042 g) and required a longer stay on a ventilator (7 vs 2 days). Divided into groups, infants with BW ≤750 , 751–1000 , 1001–1250 g and 1251–1500 g (n=52, 51, 46 and 25, respectively) had a relative risk of 0.14, 0.46, 1.83 and 1.78 (p<0.01, 0.02, 0.07 and 0.17), respectively, to develop NEC after an exposure. Infants with longest ventilator days were also significantly less likely to develop NEC after an exposure; relative risk=0.11 (p<0.01). Conclusions Exposure to transfusions was less likely associated with NEC in ≤1000 g infants and remained a risk factor in 1001–1500 infants. BW has to be factored in any study evaluating the association between PRBC transfusions and NEC.