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Due to the changing complex healthcare environment, educational innovation is essential to meet the needs of current and future neonatal-perinatal medicine (NPM) leaders. Greater clinical demands, decreased academic funding, and expanded graduate medical education program requirements have negatively impacted time for teaching and educational scholarship potentially limiting innovation in the field. By focusing on adult learning principles, embracing technology, and promoting collaboration, today's educators are preparing the next generation of neonatologists. Current innovations include regionalizing simulation boot camps, leveraging virtual learning to increase accessibility, developing niche training opportunities, and incorporating population health principles within existing quality initiatives. Areas in need of additional innovation include faculty and fellow development for teaching skills, expansion of educational networks, and dissemination and financial support of educational scholarship. These efforts and future innovations will require medical institutions and national NPM organizations to further invest in the medical educator as part of their missions.

Objectives To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age. Study design The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models. Results One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age. Conclusions Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

Background Symptomatic patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. In these infants, prophylactic use of indomethacin, a non-selective cyclooxygenase inhibitor, has demonstrated short-term clinical benefits. The effect of indomethacin in preterm infants with a symptomatic PDA remains unexplored. Objectives To determine the effectiveness and safety of indomethacin (given by any route) compared to placebo or no treatment in reducing mortality and morbidity in preterm infants with a symptomatic PDA. Search methods We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 31 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. Selection criteria We included RCTs and quasi-RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants. Data collection and analysis We used the standard methods of Cochrane Neonatal, with separate evaluation of trial quality and data extraction by at least two review authors. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of PDA closure within one week of administration of the first dose of indomethacin; bronchopulmonary dysplasia (BPD) at 28 days' postnatal age and at 36 weeks' postmenstrual age; proportion of infants requiring surgical ligation or transcatheter occlusion; all-cause neonatal mortality; necrotizing enterocolitis (NEC) (≥ Bell stage 2); and mucocutaneous or gastrointestinal bleeding. Main results We included 14 RCTs (880 preterm infants). Four out of the 14 included studies were judged to have high risk of bias in one or more domains. Indomethacin administration was associated with a large reduction in failure of PDA closure within one week of administration of the first dose (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.23 to 0.38; risk difference (RD) -0.52, 95% CI -0.58 to -0.45; 10 studies, 654 infants; high-certainty evidence). There may be little to no difference in the incidence of BPD (BPD defined as supplemental oxygen need at 28 days' postnatal age: RR 1.45, 95% CI 0.60 to 3.51; 1 study, 55 infants; low-certainty evidence; BPD defined as supplemental oxygen need at 36 weeks' postmenstrual age: RR 0.80, 95% CI 0.41 to 1.55; 1 study, 92 infants; low-certainty evidence) and probably little to no difference in mortality (RR 0.78, 95% CI 0.46 to 1.33; 8 studies, 314 infants; moderate-certainty evidence) with use of indomethacin for symptomatic PDA. No differences were demonstrated in the need for surgical PDA ligation (RR 0.66, 95% CI 0.33 to 1.29; 7 studies, 275 infants; moderate-certainty evidence), in NEC (RR 1.27, 95% CI 0.36 to 4.55; 2 studies, 147 infants; low-certainty evidence), or in mucocutaneous or gastrointestinal bleeding (RR 0.33, 95% CI 0.01 to 7.58; 2 studies, 119 infants; low-certainty evidence) with use of indomethacin compared to placebo or no treatment. Certainty of evidence for BPD, surgical PDA ligation, NEC, and mucocutaneous or gastrointestinal bleeding was downgraded for very serious or serious imprecision. Authors' conclusions High-certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication-related adverse effects.

Due to the changing complex healthcare environment, educational innovation is essential to meet the needs of current and future neonatal-perinatal medicine (NPM) leaders. Greater clinical demands, decreased academic funding, and expanded graduate medical education program requirements have negatively impacted time for teaching and educational scholarship potentially limiting innovation in the field. By focusing on adult learning principles, embracing technology, and promoting collaboration, today's educators are preparing the next generation of neonatologists. Current innovations include regionalizing simulation boot camps, leveraging virtual learning to increase accessibility, developing niche training opportunities, and incorporating population health principles within existing quality initiatives. Areas in need of additional innovation include faculty and fellow development for teaching skills, expansion of educational networks, and dissemination and financial support of educational scholarship. These efforts and future innovations will require medical institutions and national NPM organizations to further invest in the medical educator as part of their missions.

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22–26 months corrected gestational age (cGA) compared with those randomized to placebo. STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs. placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine [SCr]/ cystatin C values at days 0, 7, 9 and 14). At 22–26 months cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95(th) percentile for age, and 40% had a diastolic blood pressure (DBP) >95(th) percentile for age. SBP >90(th) percentile occurred less often among recipients of erythropoietin (p95(th) percentile or DBP >90(th) or >95(th) percentiles. CONCLUSIONS: ELGANs have high rates of in-hospital AKI and kidney-related problems at 22–26 months cGA. Recombinant erythropoietin (rhEpo) may protect ELGANs against long-term elevated SBP, but does not appear to protect from AKI, low eGFR, albuminuria or elevated DBP at 22–26 months cGA.

Supplemental Digital Content is available in the text., Objectives: To establish the first regional quality improvement collaborative solely dedicated to follow-through care of high-risk infants after Neonatal intensive care unit (NICU) discharge and to characterize extremely low birth weight (ELBW) follow-up in New England. Methods: Eleven of 14 follow-up programs in New England partnered with the Vermont Oxford Network (VON) ELBW project for an initial data collection project. We collected information about the health status and developmental outcomes of infants born ≤1,000 g or younger than 28 weeks 2014–2016 at the 18–24 months corrected for gestational age (CGA) follow-up visit. VON collected and compiled the data. Results: Of 993 eligible infants, 516 (52.0%) had follow-up visits. The rehospitalization rate was 33.9%, mostly respiratory illness. Ninety-six children (19.3%) had weight less than 10th percentile and 44 (8.9%) had weight less than third percentile at 18–24 months. Only 170 (61.4%) children had recommended hearing screening after NICU discharge. Forty-six (9.1%) had cerebral palsy; 81 of the 441 infants that completed all 3 sections of the Bayley Scales of Infant Development, third edition (18.4%) had any composite score less than 70. Over half of the social and demographic data were missing. Conclusion: Most quality initiatives in neonatology stop at NICU discharge. This first project by the New England Follow-up Network showed a low rate for clinical follow-up. It demonstrated many opportunities to improve postdischarge follow-through specific to NICU-based care. Future projects will aim to improve the quality of follow-through services through collaborative learning, data sharing, and comparative outcomes.

OBJECTIVE In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group. METHODS A randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the United States. Despite medical advances in diagnostics and thromboprophylaxis, the incidence of VTE has not substantially decreased over time. Furthermore, many patients are diagnosed with VTE without an identifiable cause. Objectives: We sought to investigate the prevalence of idiopathic VTE and risk factors associated with this diagnosis. Methods: Patients diagnosed with deep vein thrombosis (DVT) or pulmonary embolism (PE) were enrolled into a prospective venous thromboembolic center (VTEC) registry at a large tertiary medical center from 7/2015-12/2015. VTE events were considered to be idiopathic if none of the following criteria were met: current pregnancy; current use of hormonal therapy or oral contraceptives, active malignancy; diagnosed thrombophilia; major surgery within 90 days; bed rest, restricted mobility, cast or mold, or serious trauma within 30 days. Patient demographics, comorbidities, social history, family history, laboratory and clinical data were analyzed and compared between groups. Multivariable logistic regression analysis was used to estimate odds of idiopathic VTE. Results: Of 223 patients with VTE, 93 (41.7%) were determined to be idiopathic. Patients with idiopathic and non-idiopathic VTE were of similar age, race/ethnicity, level of education, type of insurance, and type of VTE (DVT or PE). Patients with idiopathic VTE were more frequently female (68.8% vs. 46.4%; p < 0.01), more likely to have a history of COPD (8.6% vs. 1.1%, p = 0.03), hyperlipidemia (33.6% vs. 18.3%, p = 0.02), and less likely to be on a statin at the time of diagnosis (17.2% vs. 29.3%, p = 0.05) than non-idiopathic VTE. After multivariable adjustment, female sex (OR: 2.47, 95% CI 1.35-4.64) and history of varicose veins (OR 2.67, 95% CI 1.15-6.37) were significantly associated with the prevalence of idiopathic VTE. Conclusions: In a large tertiary medical center, idiopathic VTE occurred in more than 40% of all VTEs. Female sex and history of varicose veins were independently associated with having an idiopathic VTE. These data provide a basis for future investigation into this high-risk population and for further development of prediction models.

To evaluate the efficacy and safety of passive cooling during transport of asphyxiated newborns.Retrospective medical record review of newborns with perinatal asphyxia transported for hypothermia between July 2007 and June 2010.Of 43 newborns transported, 27 were passively cooled without significant adverse events. Twenty (74%) passively cooled newborns arrived with temperature between 32.5 and 34.5 °C. One newborn arrived with a temperature32.5, and 6 (22%) had temperatures34.5 °C. Time from birth to hypothermia was significantly shorter among passively cooled newborns compared with newborns not cooled (215 vs 327 min, P0.01), even though time from birth to admission to Boston Children's Hospital was similar (252 vs 259 min, P=0.77). Time from birth to admission was the only significant predictor of increased time to reach target temperature (P=0.001).Exclusive passive cooling achieves significantly earlier initiation of effective hypothermia for asphyxiated newborns but should not delay transport for active cooling.

To assess the strength of association between alternative measures of electroencephalographic (EEG) signal peak-to-peak amplitude (ppA) and postmenstrual age (PMA) among a cohort of extremely premature infants.177 Two-channel EEG recordings 3-6h long were collected from 26 infants born before 29weeks of gestation. The raw EEG was converted into four different continuous measures of ppA: amplitude-integrated EEG (aEEG), range-EEG (rEEG), Gotman and Gloor's half-wave decomposition (HWD), and root of mean squares (RMS). For each ppA-measure EEG indices including mean, median, and 5% margins; indices of spread (width, standard deviation, coefficient of variation), and asymmetry were calculated for each 1min epoch. The medians of each index for the entire recording were tested for association with PMA using linear mixed models.The log-transformed values of aEEG and rEEG indices of spread were highly associated with PMA (fixed effects R(β)(2)=0.84-0.89).Indices of spread by aEEG or rEEG can be used as indicators of neonatal brain maturation. However, rEEG produces the absolute values that most closely approximate the raw EEG amplitudes.The indices of spread and rEEG as a measure of ppA provide a basis for improvements in neonatal EEG monitoring.

Venous thromboembolism (VTE), comprised of deep vein thrombosis and pulmonary embolism, is a common health problem both in the United States and worldwide, with significant associated morbidity and mortality. Despite multiple known genetic and situational risk factors, an estimated 30% of all events remain classified as idiopathic, demonstrating a significant knowledge gap in the pathophysiology VTE. While platelets are well established as an essential contributor to thrombus formation and there has been recent interest in the role of neutrophil extracellular traps, specific cell types and pathways involved in the pathogenesis of VTE remain uncertain. In this study, our primary aims were to define a unique transcriptional signature for VTE and to identify the types of cells and specific pathways involved in development of VTE. Whole blood was collected in PAX gene tubes and RNA sequencing for coding mRNA was performed in an unbiased manner in 201 patients with prevalent VTE as well as 43 healthy controls. We used a bioinformatics approach to develop a unique signature for VTE by identifying differentially expressed genes, developing cell-type modules, and ascertaining pathways driving differentially expressed transcripts. We performed additional analyses on subgroups of patients with idiopathic VTE, patients with incident VTE, and VTE patients matched to healthy controls by age and sex. We went on to use machine learning methods to learn models that best differentiate VTE patients from healthy controls and validated it on a left out test set within our VTE population. Genes specific to neutrophils, erythrocytes, and platelets, in that order, were most significantly upregulated in patients with VTE compared to healthy controls. Genes related to T-cells were downregulated. Pathway analysis revealed upregulated neutrophil activation and degranulation, erythrocyte differentiation and homeostasis, and platelet degranulation. A gene signature of 217 transcripts was outstanding at differentiating patients with VTE versus healthy controls (AUC 0.94). Following adjustment for age, sex, and race/ethnicity our genetic signature remained significantly robust at differentiating patients with VTE versus controls (AUC 0.83). Our expression signature remained stable across patients with idiopathic VTE (AUC 0.93), and in patients who went on to develop future VTE events (AUC 0.95). In summary, we have demonstrated a whole blood transcriptional signature for prevalent and incident VTE. Genes related to neutrophils, erythrocytes, and platelets are upregulated in patients with VTE and genes related to T-cells were downregulated. These findings suggest an active role of cell types once thought to be passively entrapped within thrombus and provide new areas of study to establish the pathophysiology of VTE. Disclosures No relevant conflicts of interest to declare.

To document one centre's experience with a multimodal analgesic approach, with or without low dose intrathecal morphine (ITM), in facilitating "fast-track" recovery in patients undergoing cardiac surgery.Records of 131 consecutive patients who underwent first time elective cardiac surgery during a four-month period in 2000 were reviewed. Patients were divided into two groups: those receiving and those not receiving preoperative low dose ITM (5 microgxkg(-1)) as part of a multimodal analgesic technique. Demographic and surgical characteristics, postoperative morphine use, time to extubation and requirement for antiemetics were recorded.Overall, 75% of patients were extubated within two hours, and 93% within six hours. Fifty-five patients received, and 76 did not receive, ITM (mean +/- SD 259 +/- 53 microg) along with a multimodal analgesic technique (parasternal infiltration, acetaminophen and indomethacin, and postoperative i.v. morphine). Anesthetic technique involved modest dose opioids, volatile agent and propofol infusion. The groups were similar with respect to preoperative, intraoperative and anesthetic characteristics. Mean extubation time for fast-track patients receiving vs not receiving ITM was 75 +/- 65 vs 117 +/- 85 min (P = 0.003). Intravenous morphine use for the first 12 hr after surgery was also reduced in the ITM group (4.6 +/- 4.1 vs 10.0 +/- 14.8 mg, P = 0.009). There was no difference in rescue antiemetic or antipruritic requirements, failed fast-tracking, or serious adverse events.Multimodal postoperative analgesia allowed for uneventful early extubation and low opioid requirements. Low dose ITM further facilitated early extubation, and reduced postoperative analgesic requirements.

Objective To explore the direct measure of EEG amplitude (range EEG, rEEG) for detection of interburst intervals (IBIs) and bursts in neonates. Methods Previously described 177 two-channel EEG recordings 3–6 h long from 26 preterm infants (median gestational age of 26 weeks) at 23–38 weeks post-menstrual age (PMA) without major abnormalities were used to test four definitions of IBI detection algorithms with various settings of the parameters. Results As the basis for all four algorithms we developed the aggregation of rEEG signal over the channels by taking its maximum, and method of EEG trace selection at different phases of sleep–wake cycle (with different degree of discontinuity). The two less restrictive algorithms – with one and two amplitude thresholds - turned to be the most promising definitions. There were enough IBI detections for analysis, with no substantial difference in mean and maximum values of intervals. The longest IBI were measured at the location of greater discontinuity. Values of bursts and IBI indices as well as association with PMA were close to the published normative values derived manually. Conclusions rEEG as a direct measure of EEG amplitude can be used for detection of bursts and IBI. Significance The automatic measurement of IBI based on rEEG provides a basis for improvements in neonatal brain monitoring.

This conference paper reports on a national survey conducted in the summer of 2010 which sought to identify programs and gather information on their operations, programming and challenges. This research project was a joint initiative of the Nova Scotia Read to Me! early literacy program and Dalhousie University’s School of Information Management.Cette communication porte sur un sondage national effectué au cours de l’été 2010 et dont l’objectif était d’identifier les programmes d’alphabétisation et d’obtenir de l’information quant à leur opération, aux activités et aux défis. Ce projet de recherche est une initiative conjointe du programme d’alphabétisation chez les jeunes enfants Nova Scotia Read to Me! et de la School of Information Management de l’Université Dalhousie.

To determine whether low doses of droperidol mixed with morphine in patient-controlled analgesia (PCA) would extend the duration of prophylaxis against postoperative nausea and vomiting.Healthy women having elective open-abdominal gynaecological surgery consented to this double-blind, placebo-controlled study. Subjects were randomized to receive placebo, or 1 mg droperidol before induction followed by droperidol 0.0 (bolus group), 0.02 (0.02 group), or 0.04 (0.04 group) mg.mg-1 of PCA morphine. Study endpoints included severity of nausea, episodes of vomiting and rescue antiemetic doses, pain, and sedation and were assessed at 1, 2, 4, 8, 12, 16, 20 and 24 hr postoperatively.Seventy-one subjects completed the study. The groups were similar in age, weight, surgical time, pain scores, and morphine used. The 0.04 group had lower mean visual analogue scale scores for nausea (P0.05 vs all other groups). The incidence of vomiting was lower in all treatment groups (P0.05 for all groups vs placebo). The 0.04 group had lower rescue antiemetic requirements than the bolus group (P0.03). Mean sedation scores were low in all groups but were increased with PCA droperidol (P0.02).Droperidol 1 mg before induction of anaesthesia reduces postoperative vomiting. The addition of droperidol 0.04 mg.mg-1 of PCA morphine further reduces (i) severity of nausea and (ii) rescue antiemetic requirements postoperatively. No clinically significant side-effects were attributed to this regimen.

Objective.To describe health and neurodevelopmental outcomes and parental satisfaction with hospital care among surviving intervention and control enrollees in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn (PPHN).Methods.All surviving enrollees 1 to 4 years of age were eligible for follow-up. Outcomes were assessed by telephone using a trained interviewer and standardized instruments. Domains assessed included parental report of specific conditions and hospital use, rating of general health, cognitive and motor development, behavior problems, temperament, and satisfaction with the hospital stay. Fisher's exact test and the Wilcoxon rank sum test assessed differences between intervention and control infants.Results.Interviews were completed on 60 of 83 survivors (72%). Eighteen families (22%) could not be located, 2 (2%) were non-English-speaking, and 3 (4%) declined participation. No postdischarge deaths were ascertained. Among those interviewed, race, income, and education of parents of intervention and controls were comparable, as were entry oxygenation index, extracorporeal oxygenation utilization, and days of hospitalization. No differences were found in pulmonary, neurologic, cognitive, behavioral, or neurosensory outcomes; hospital readmission rates; or parental ratings of child's health. The overall neurologic handicap rate was 15%. The rate of hearing deficit was 7%. The rate of significant behavioral problems was 26%. Levels of satisfaction expressed were high for each group. No differences in parental ratings were found between the 2 groups.Conclusions.No adverse health or neurodevelopmental outcomes have been observed among infants treated with nitric oxide for PPHN. The parents of the critically ill infants enrolled in our clinical trial welcomed their child's inclusion and all expressed satisfaction with the care that their child received while at a tertiary care hospital. Enrollment in either arm of this randomized, controlled trial did not seem to affect parental satisfaction with the hospital care that their child received.

Introduction Data on chronic hepatitis C (HCV) infection prevalence in European prisons are incomplete and impact the public health opportunity that incarceration provides. Aims We aimed to estimate the seroprevalence of untreated chronic HCV infection and to identify associated risk factors in an Irish male prison. Methods We conducted a cross-sectional study involving a researcher-administered questionnaire, review of medical records and HCV serology. Results Of 422 prisoners (78.0% of the study population) who participated in the study, 298 (70.6%) completed the questionnaire and 403 (95.5%) were tested for HCV antibodies. Of those tested, 92 (22.8%) were HCV antibody-positive, and of those, 53 (57.6%) were HCV RNA-positive, 23 (25.0%) had spontaneous clearance, 16 (17.4%) had a sustained viral response, 10 (11.0%) were co-infected with HIV and six (6.0%) with HBV. The untreated chronic HCV seroprevalence estimate was 13.1% and the seroprevalence of HCV among prisoners with a history of injecting drug use (IDU) was 79.7%. Risk factors significantly associated with past HCV infection were IDU (p Conclusion The level of untreated chronic HCV infection in Irish prisons is high, with IDU the main associated risk.