Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Chronic lung disease in full-term infants: Characteristics and neonatal intensive care outcomes in infants referred to children's hospitals.

OBJECTIVE: To describe characteristics, outcomes, and risk factors for death or tracheostomy with home mechanical ventilation in full-term infants with chronic lung disease (CLD) admitted to regional neonatal intensive care units. STUDY DESIGN: This was a multicenter, retrospective cohort study of infants born ≥37 weeks of gestation in the Children's Hospitals Neonatal Consortium. RESULTS: Out of 67,367 full-term infants admitted in 2010-2016, 4886 (7%) had CLD based on receiving respiratory support at either 28 days of life or discharge. 3286 (67%) were still hospitalized at 28 days receiving respiratory support, with higher mortality risk than those without CLD (10% vs. 2%, p < 0.001). A higher proportion received tracheostomy (13% vs. 0.3% vs. 0.4%, p < 0.001) and gastrostomy (30% vs. 1.7% vs. 3.7%, p < 0.001) compared to infants with CLD discharged home before 28 days and infants without CLD, respectively. The diagnoses and surgical procedures differed significantly between the two CLD subgroups. Small for gestational age, congenital pulmonary, airway, and cardiac anomalies and bloodstream infections were more common among infants with CLD who died or required tracheostomy with home ventilation (p < 0.001). Invasive ventilation at 28 days was independently associated with death or tracheostomy and home mechanical ventilation (odds ratio 7.6, 95% confidence interval 5.9-9.6, p < 0.0001). CONCLUSION: Full-term infants with CLD are at increased risk for morbidity and mortality. We propose a severity-based classification for CLD in full-term infants. Future work to validate this classification and its association with early childhood outcomes is necessary.

Cardiac Interventions for Patients With Trisomy 13 and Trisomy 18: Experience, Ethical Issues, Communication, and the Case for Individualized Family-Centered Care.

This report is informed by the themes of the session Trisomy 13/18, Exploring the Changing Landscape of Interventions at NeoHeart 2020-The Fifth International Conference of the Neonatal Heart Society. The faculty reviewed the present evidence in the management of patients and the support of families in the setting of trisomy 13 and trisomy 18 with congenital heart disease. Until recently medical professionals were taught that T13 and 18 were "lethal conditions" that were "incompatible with life" for which measures to prolong life are therefore ethically questionable and likely futile. While the medical literature painted one picture, family support groups shared stories of the long-term survival of children who displayed happiness and brought joy along with challenges to families. Data generated from such care shows that surgery can, in some cases, prolong survival and increase the likelihood of time at home. The authors caution against a change from never performing heart surgery to always-we suggest that the pendulum of intervention find a balanced position where all therapies including comfort care and surgery can be reviewed. Families and clinicians should typically be supported and empowered to define the best care for their children and patients. Key concepts in communication and case vignettes are reviewed including the importance of supportive relationships and the fact that palliative care may serve as an additional layer of support for decision-making and quality of life interventions. While cardiac surgery may be beneficial in some cases, surgery should not be the primary focus of initial family education and support.

Venovenous versus venoarterial extracorporeal membrane oxygenation among infants with hypoxic-ischemic encephalopathy: is there a difference in outcome?

OBJECTIVE: Our hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH). DESIGN/METHODS: Retrospective cohort analysis of infants in the Children's Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation <7 days of age. The primary outcome was mortality or ICH. RESULTS: Severe HIE was more common in the VA ECMO group (n = 57), compared to the VV ECMO group (n = 53) (47.4% vs. 26.4%, P = 0.02). VA ECMO was associated with a significantly higher risk of death or ICH [57.9% vs. 34.0%, aOR 2.39 (1.08-5.28)] and mortality [31.6% vs. 11.3%, aOR 3.06 (1.08-8.68)], after adjusting for HIE severity. CONCLUSIONS: In HIE, VA ECMO was associated with a higher incidence of mortality or ICH. VV ECMO may be beneficial in this population.

Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program.

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.

Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation.

Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq). Aq-NF-κB is most similar to NF-κB p100/p105 among vertebrate proteins, with an N-terminal DNA-binding domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile akin to human NF-κB proteins. Like mammalian NF-κB p100, C-terminal truncation allows nuclear translocation of Aq-NF-κB and increases its transcriptional activation activity. Expression of IκB kinases (IKKs) induces proteasome-dependent C-terminal processing of Aq-NF-κB in human cells, and processing requires C-terminal serines in Aq-NF-κB. Unlike NF-κB p100, C-terminal sequences of Aq-NF-κB do not inhibit its DNA-binding activity. Tissue of a black encrusting demosponge contains NF-κB site DNA-binding activity, as well as nuclear and processed NF-κB. Treatment of sponge tissue with LPS increases both DNA-binding activity and processing of NF-κB. A. queenslandica transcriptomes contain homologs to upstream NF-κB pathway components. This is first functional characterization of NF-κB in sponge, the most basal multicellular animal.

Management preferences in ECMO mode for congenital diaphragmatic hernia.

PURPOSE: The purpose of this study was to identify management preferences that may exist in the care of infants with CDH receiving ECMO with emphasis on VV-ECMO. METHODS: A survey was created to measure treatment preferences regarding ECMO use in CDH. The survey was distributed to all APSA and ELSO/Euro-ELSO members via e-mail. Survey results were summarized using descriptive statistics. RESULTS: The survey had 230 respondents. The survey participants were surgeons (75%), neonatologists/intensivists (23%), and "other" (2%). The mean annual center volume was 11.6(±9.6) CDH cases, and the average number treated with ECMO was 4.5 (±6.4) cases/yr. The most agreed upon criteria for ECMO initiation were preductal O2 saturation <80% refractory to ventilator manipulation and medical therapy (89%), oxygenation index >40 (80%), severe air-leak (79%), and mixed acidosis (75%). Over 60% of respondents agreed the VV-ECMO would be optimum for average risk neonates. However, this preference diminished as the pre-ECMO level of cardiac support increased. When asked about why each respondent would choose VA-ECMO over VV-ECMO, the responses varied significantly between surgeons and non-surgeons. CONCLUSION: While there seem to be areas of consensus among practitioners, such as criteria for initiation of ECMO, this survey revealed substantial variation in individual practice patterns regarding the use of ECMO for CDH. TYPE OF STUDY: Qualitative, Survey. LEVEL OF EVIDENCE: IV.

Trends in Mortality and Risk Characteristics of Congenital Diaphragmatic Hernia Treated With Extracorporeal Membrane Oxygenation.

Although the mortality of infants with congenital diaphragmatic hernia (CDH) has been improving since the late 1990s, this observation has not been paralleled among the CDH cohort receiving extracorporeal membrane oxygenation (ECMO). We sought to elucidate why the mortality rate in the CDH-ECMO population has remained at approximately 50% despite consistent progress in the field by examining the baseline risk profile/characteristics of neonates with CDH before ECMO (pre-ECMO). Neonates with a diagnosis of CDH were identified in the Extracorporeal Life Support Organization (ELSO) Registry from 1992 to 2015. Individual pre-ECMO risk score (RS) for mortality was categorized to pre-ECMO risk-stratified cohorts. Temporal trends based on individual-level mortality by risk cohorts were assessed by logistic regression. We identified 6,696 neonates with CDH. The mortality rates during this time period were approximately 50%. The average baseline pre-ECMO RS increased during this period: mean increase of 0.35 (95% confidence interval [CI]: 0.324-0.380). In the low-risk cohort, the likelihood of mortality increased over time: each 5 year change was associated with a 7.3% increased likelihood of mortality (odds ratio [OR]: 1.0726; 95% CI: 1.0060-1.1437). For the moderate-risk cohort, the likelihood of mortality decreased by 7.05% (OR: 0.9295; 95% CI: 0.8822-0.9793). There was no change in the odds of mortality for the high-risk cohort (OR: 0.9650; 95% CI: 0.8915-1.0446). Although the overall mortality rate remained approximately constant over time, the individual likelihood of death has declined over time in the moderate-risk cohort, increased in the low-risk cohort, and remained unchanged in the high-risk cohort.

Outcomes of infants with congenital diaphragmatic hernia treated with venovenous versus venoarterial extracorporeal membrane oxygenation: A propensity score approach.

PURPOSE: Previous studies comparing extracorporeal membrane oxygenation (ECMO) modality for congenital diaphragmatic hernia (CDH) have not accounted for confounding by indication. We therefore hypothesized that using a propensity score (PS) approach to account for selection bias may identify outcome differences based on ECMO modality for infants with CDH. METHODS: We utilized ELSO Registry data (2000-2016). Patients with CDH were divided to either venoarterial (VA) or venovenous (VV) ECMO. Patients were matched by PS to control for nonrandom treatment assignment. Subgroup analyses were conducted based on timing of CDH repair relative to ECMO. Primary analysis was the "intent-to-treat" cohort based on the initial ECMO mode. Mortality was the primary outcome, and severe neurologic injury (SNI) was a secondary outcome. RESULTS: PS matching (3:1) identified 3304 infants (VA = 2470, VV = 834). In the main group, mortality was not different between VA and VV ECMO (OR = 1.01, 95% CI: 0.86-1.18) and there was no difference in SNI between VA and VV (OR = 0.80; 95% CI: 0.63-1.01). For the pre-ECMO CDH repair subgroup, 175 VA cases were matched to 70 VV. In these neonates, mortality was higher for VV compared to VA (OR = 2.10, 95% CI: 1.19-3.69), without any difference in SNI (OR = 1.48; 95% CI: 0.59-3.71). For the subgroup that did not have pre-ECMO CDH repair, 2030 VA cases were matched to 683 VV cases. In this subgroup, VV was associated with 27% lower risk of SNI relative to VA (OR = 0.73, 95% CI: 0.56-0.95) without any difference in mortality (OR = 0.94, 95% CI: 0.79-1.11). CONCLUSION: This study revalidates that ECMO mode does not significantly affect mortality or SNI in infants with CDH. In the subset of infants who require pre-ECMO CDH repair, VA favors survival, whereas, in the subgroup of infants that did not have pre-ECMO CDH repair, VV favors lower rates of SNI. We conclude that neither mode appears consistently superior across all situations, and clinical judgment should remain a multifactorial decision. LEVEL OF EVIDENCE: Level III.

Development and Validation of Extracorporeal Membrane Oxygenation Mortality-Risk Models for Congenital Diaphragmatic Hernia.

The purpose of our study was to develop and validate extracorporeal membrane oxygenation (ECMO)-specific mortality risk models for congenital diaphragmatic hernia (CDH). We utilized the data from the Extracorporeal Life Support Organization Registry (2000-2015). Prediction models were developed using multivariable logistic regression. We identified 4,374 neonates with CDH with an overall mortality of 52%. Predictive discrimination (C statistic) for pre-ECMO mortality model was C = 0.65 (95% confidence interval, 0.62-0.68). Within the highest risk group, based on the pre-ECMO risk score, mortality was 87% and 75% in the training and validation data sets, respectively. The pre-ECMO risk score included pre-ECMO ventilator settings, pH, prior diaphragmatic hernia repair, critical congenital heart disease, perinatal infection, and demographics. For the on-ECMO model, mortality prediction improved substantially: C = 0.73 (95% confidence interval, 0.71-0.76) with the addition of on-ECMO-associated complications. Within the highest risk group, defined by the on-ECMO risk score, mortality was 90% and 86% in the training and validation data sets, respectively. Mortality among neonates with CDH needing ECMO can be reliably predicted with validated clinical variables identified in this study. ECMO-specific mortality prediction tools can allow risk stratification to be used in research and quality improvement efforts, as well as with caution for individual case management.

Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias.

There is a striking and unexplained male predominance across many cancer types. A subset of X-chromosome genes can escape X-inactivation, which would protect females from complete functional loss by a single mutation. To identify putative 'escape from X-inactivation tumor-suppressor' (EXITS) genes, we examined somatic alterations from >4,100 cancers across 21 tumor types for sex bias. Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (based on a false discovery rate < 0.1), in comparison to zero of 18,055 autosomal and PAR genes (Fisher's exact P < 0.0001). Male-biased mutations in genes that escape X-inactivation were observed in combined analysis across many cancers and in several individual tumor types, suggesting a generalized phenomenon. We conclude that biallelic expression of EXITS genes in females explains a portion of the reduced cancer incidence in females as compared to males across a variety of tumor types.

Birth Tourism and Neonatal Intensive Care: A Children's Hospital Experience.

Objective The aim of this article is to examine characteristics of birth tourism (BT) neonates admitted to a neonatal intensive care unit (NICU). Methods This was a retrospective review over 3 years; BT cases were identified, and relevant perinatal, medical, social, and financial data were collected and compared with 100 randomly selected non-birth tourism neonates. Results A total of 46 BT neonates were identified. They were more likely to be born to older women (34 vs. 29 years; p < 0.001), via cesarean delivery (72 vs. 48%; p = 0.007), and at a referral facility (80 vs. 32%; p < 0.001). BT group had longer hospital stay (15 vs. 7 days; p = 0.02), more surgical intervention (50 vs. 21%; p < 0.001), and higher hospital charges (median $287,501 vs. $103,105; p = 0.003). One-third of BT neonates were enrolled in public health insurance program and four BT neonates (10%) were placed for adoption. Conclusion Families of BT neonates admitted to the NICU face significant challenges. Larger studies are needed to better define impacts on families, health care system, and society.

Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early Diagnosis of Intubation-related Subglottic Injury.

RATIONALE: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury. OBJECTIVES: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness. METHODS: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1-104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome. MEASUREMENTS AND MAIN RESULTS: Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P < 0.001; multiple r(2) = 0.44) and subglottic (P < 0.001; multiple r(2) = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure. CONCLUSIONS: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates. Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).

Non-contact heart rate monitoring utilizing camera photoplethysmography in the neonatal intensive care unit - a pilot study.

BACKGROUND: Presently the heart rate is monitored in the Neonatal Intensive Care Unit with contact sensors: electrocardiogram or pulse oximetry. These techniques can cause injuries and infections, particularly in very premature infants with fragile skin. Camera based plethysmography was recently demonstrated in adults as a contactless method to determine heart rate. AIM: To investigate the feasibility of this technique for NICU patients and identify challenging conditions. STUDY DESIGN AND PARTICIPANTS: Video recordings using only ambient light were made of 19 infants at two NICUs in California and The Netherlands. Heart rate can be derived from these recordings because each cardiovascular pulse wave induces minute pulsatile skin color changes, invisible to the eye but measurable with a camera. RESULTS: In all infants the heart beat induced photoplethysmographic signal was strong enough to be measured. Low ambient light level and infant motion prevented successful measurement from time to time. CONCLUSIONS: Contactless heart rate monitoring by means of a camera using ambient light was demonstrated for the first time in the NICU population and appears feasible. Better hardware and improved algorithms are required to increase robustness.

Functional analysis of microRNAs in human hepatocellular cancer stem cells.

MicroRNAs are endogenous small non-coding RNAs that regulate gene expression and cancer development. A rare population of hepatocellular cancer stem cells (HSCs) holds the extensive proliferative and self-renewal potential necessary to form a liver tumour. We postulated that specific transcriptional factors might regulate the expression of microRNAs and subsequently modulate the expression of gene products involved in phenotypic characteristics of HSCs. We evaluated the expression of microRNA in human HSCs by microarray profiling, and defined the target genes and functional effects of two groups of microRNA regulated by IL-6 and transcriptional factor Twist. A subset of highly chemoresistant and invasive HSCs was screened with aberrant expressions of cytokine IL-6 and Twist. We demonstrated that conserved let-7 and miR-181 family members were up-regulated in HSCs by global microarray-based microRNA profiling followed by validation with real-time polymerase chain reaction. Importantly, inhibition of let-7 increases the chemosensitivity of HSCs to sorafenib and doxorubicin whereas silencing of miR-181 led to a reduction in HSCs motility and invasion. Knocking down IL-6 and Twist in HSCs significantly reduced let-7 and miR-181 expression and subsequently inhibited chemoresistance and cell invasion. We showed that let-7 directly targets SOCS-1 and caspase-3, whereas miR-181 directly targets RASSF1A, TIMP3 as well as nemo-like kinase (NLK). In conclusion, alterations of IL-6- and Twist-regulated microRNA expression in HSCs play a part in tumour spreading and responsiveness to chemotherapy. Our results define a novel regulatory mechanism of let-7/miR-181s suggesting that let-7 and miR-181 may be molecular targets for eradication of hepatocellular malignancies.

Mesentric oxygen saturations in premature twins with and without necrotizing enterocolitis.

OBJECTIVE: To report the use of near-infrared spectroscopic monitoring to recognize mesenteric oxygen desaturations in a preterm neonate with necrotizing enterocolitis as well as the demonstration of reassuring mesenteric tissue perfusion in a twin sibling with an uncomplicated course. DESIGN: Case report. SETTING: Neonatal intensive care unit in a tertiary care children's hospital. PATIENTS: A 12-day-old growth-restricted preterm female twin with necrotizing enterocolitis and her twin who did not develop disease. INTERVENTIONS: In the twin with symptoms of necrotizing enterocolitis, reduction in the mesenteric saturations was recorded in the injured bowel tissue as later confirmed during surgery. After resection of the ischemic bowel, mesenteric saturations returned to values comparable to those measured in the healthy twin. Reduced saturations were not observed in the asymptomatic twin. CONCLUSIONS: The use of optical oximetry to monitor mesenteric tissue saturation may provide a measure of bowel perfusion that could enhance clinical management in at-risk preterm neonates.

Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: a prospective, randomized, open-label, placebo-controlled pilot study.

OBJECTIVE: This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates. METHODS: This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality. RESULTS: Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality. CONCLUSIONS: L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.

Advances in diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease.

BACKGROUND: This article aims to review recent advances in the diagnosis and treatment of pulmonary arterial hypertension in neonates and children with congenital heart disease. DATA SOURCES: Articles on pulmonary arterial hypertension in congenital heart disease were retrieved from PubMed and MEDLINE published after 1958. RESULTS: A diagnosis of primary (or idiopathic) pulmonary arterial hypertension is made when no known risk factor is identified. Pulmonary arterial hypertension associated with congenital heart disease constitutes a heterogenous group of conditions and has been characterized by congenital systemic-to-pulmonary shunts. Despite the similarities in histologic appearance of pulmonary vascular disease, there are differences between pulmonary arterial hypertension secondary to congenital systemic-to-pulmonary shunts and those with other conditions with respect to pathophysiology, therapeutic strategies, and prognosis. Revision and subclassification within the category of secondary pulmonary arterial hypertension based on pathophysiology were conducted to improve specific treatments. The timing of surgical repair is crucial to prevent and minimize risk of postoperative pulmonary arterial hypertension. Drug therapies including prostacyclin, endothelin-receptor antagonist, phosphodiesterase inhibitor, and nitric oxide have been evolved with promising results in neonates and children. CONCLUSIONS: Among the different forms of congenital heart diseases, an early correction generally prevents subsequent development of pulmonary arterial hypertension. Emerging therapies for treatment of patients with idiopathic pulmonary arterial hypertension also improve quality of life and survival in neonates and children with congenital heart disease associated with pulmonary arterial hypertension. Heart and lung transplantation or lung transplantation in combination with repair of the underlying cardiac defect is a therapeutic option in a minority of patients. Partial repair options are also beneficial in some selected cases. Randomized controlled trials are needed to evaluate the safety and efficacy of these therapies including survival and long-term outcome.

Angiotensin Converting Enzyme Inhibitor (ACEI)-Induced Acute Renal Failure in Premature Newborns with Congenital Heart Disease.

We report three cases of angiotensin converting enzyme inhibitor (ACEI) induced nephrotoxicity in preterm infants with congenital heart disease. Patients developed acute renal failure after starting captopril or enalapril at doses commonly prescribed for term neonates. There was no underlying renal disease found in these infants and the acute renal failure was reversible upon discontinuation of the ACEI. Conservative starting doses of ACEI should be used in patients with multiple risk factors for nephrotoxicity. A summary of previously reported ACEI induced renal failure in premature infants and congenital heart disease is included.