Nahed O. ElHassan

Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes

Background: Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality. Methods: This study aimed to identify the mutation present in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy. Results: In all four, a novel mitochondrial m.8528T→C mutation was identified. This results in a change of the initiation codon in ATPase 6 to threonine and a concurrent change from a highly conserved hydrophobic amino acid, tryptophan, at position 55 of ATPase 8 to a highly basic arginine. To our knowledge, this is the first report of a mutation affecting both mitochondrial genome-encoded complex V subunit proteins. Testing of the relatives of one patient indicated that the mutation is heteroplasmic and correlated with disease. Conclusion: Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.

Prolonged extracorporeal membrane oxygenator support among neonates with acute respiratory failure: a review of the Extracorporeal Life Support Organization registry.

The objective of this study was to identify types of neonatal diseases associated with prolonged (≥21 days) extracorporeal membrane oxygenation (ECMO), characteristics of survivors and nonsurvivors among those requiring prolonged ECMO, and factors associated with mortality. Data were obtained from the Extracorporeal Life Support Organization registry over the period from January 1, 1998, through December 31, 2011, for all neonates (age <31 days), with respiratory failure as the indication for ECMO. The primary outcome was survival to hospital discharge. Survivors and nonsurvivors were compared for 1) patient demographics, 2) primary diagnosis, 3) pre-ECMO clinical course and therapies, and 4) ECMO course and associated complications. The most common diagnosis associated with prolonged ECMO support in neonates is congenital diaphragmatic hernia (CDH; 69%). Infants with meconium aspiration syndrome had the highest survival rate (71%) compared with other diagnoses analyzed (26.3%; p < 0.001). Nonsurvivors were more likely to experience complications on ECMO, and multivariate analysis showed that the need for inotropes while on ECMO support (odds ratio, 2.2 [95% confidence interval, 1.3–3.7]; p = 0.003) was independently associated with mortality. Neonates requiring prolonged ECMO support have a 24% survival to discharge. Many of these cases involve CDH. Complications are common with prolonged ECMO, but only receipt of inotropes was shown to be independently associated with mortality. This report may help guide clinical decision making and family counseling for neonates requiring prolonged ECMO support.

Vancomycin usage in central venous catheters in a neonatal intensive care unit.

Background. We previously reported that vancomycin in hyperalimentation solution reduces catheter-related infections in the neonatal intensive care unit. Since June 1993 vancomycin (25 &mgr;g/ml) was routinely added to central venous catheter solutions, primarily hyperalimentation solution. Because the prophylactic use of vancomycin could lead to the emergence of resistant organisms, the decision to discontinue this practice was made in April of 1999. The use of vancomycin was reserved for documented infections with vancomycin-susceptible organisms. Objective. To compare catheter longevity, rate of laboratory-confirmed blood stream infections and total vancomycin exposure between two 18-month periods before and after the cessation of prophylactic vancomycin use. Methods. Data were evaluated for every neonate in whom a percutaneous central venous catheter was placed. Results. There were 394 neonates enrolled. No statistically significant difference was identified between the two periods regarding the mean catheter days or number of catheters per patient. There was a higher rate of Gram-negative laboratory-confirmed blood stream infections during Period I in patients with percutaneous central venous catheters in place. There were more isolates of coagulase-negative staphylococci in Period II, resulting in more frequent vancomycin therapy institution and thus an overall increase in the amount of vancomycin used in that period Conclusion. Discontinuing the use of prophylactic vancomycin resulted in exposure of fewer neonates to vancomycin but a higher total amount of vancomycin used. The impact of low dose widespread exposure to vancomycin vs. high dose limited exposure on the microbiologic flora in the neonatal intensive care unit should be further examined.

A neonate with left pulmonary artery thrombosis and left lung hypoplasia: a case report

IntroductionSpontaneous intrauterine arterial thrombosis and congenital pulmonary hypoplasia are rare conditions and have not been reported to occur together. The literature rather includes two reports of babies with neonatal pulmonary artery occlusion and post-infarction cysts of the lungs.Case presentationWe report a case of a live Caucasian male newborn with left lung hypoplasia that occurred in association with left pulmonary artery thrombosis. Despite a critical neonatal course, including extracorporeal membrane oxygenation, this infant is alive and well at 18 months of age without any neurodevelopmental sequelae or reactive airway disease.ConclusionThis association suggests the possibility of an intrauterine vascular event between the fifth and eighth weeks of gestation during early pulmonary artery and lung development.

STAR syndrome is part of the differential diagnosis of females with anorectal malformations

STAR Syndrome is Part of the Differential Diagnosis of Females with Anorectal Malformations Yuri A. Zarate,* Jessica M. Farrell, Maria P. Alfaro, and Nahed O. Elhassan Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas Division of Neonatology, University of Arkansas for Medical Sciences, Little Rock Molecular Genetic Pathology, Arkansas Children’s Hospital, Little Rock, Arkansas

The Effect of Early Feeding on Initial Glucose Concentrations in Term Newborns

Objective To evaluate the influence of early feeding on initial glucose concentrations in healthy term newborns who were not at risk for hypoglycemia. Study design This retrospective observational study was conducted at the University of Arkansas for Medical Sciences where universal early glucose screening was standard of care for newborn infants. Plasma glucose concentrations were compared in term infants born in 2008 who were not at risk for neonatal hypoglycemia and who were fed before (early feeders) and after (late feeders) their initial glucose screens. Multiple linear regression models were built to determine whether glucose concentrations differed significantly between early vs late feeders. Results In the 315 early and 572 late feeders, the mean (SD) age of first feeding was 0.9 (0.6) and 3.8 (2.0) hours, respectively. The age at initial glucose specimen collection was 2.2 (1.1) and 1.8 (0.8) hours, respectively. The initial glucose concentration was not higher in early vs late feeders (51.8 ± 11.9 vs 55.5 ± 13.3 mg/dL; P < .001). In linear regression analyses of all infants, the mean initial glucose concentration was 3.61 (95% CI 1.75‐5.48) mg/dL lower in early vs late feeders. Conclusions Early feeding in otherwise healthy term newborns did not increase initial glucose concentrations compared with newborns who fed later (ie, fasted). Before direct evidence is available, these observations may be instructive for managing early asymptomatic hypoglycemia in at‐risk newborns.

Variation and comparative effectiveness of patent ductus arteriosus pharmacotherapy in extremely low birth weight infants

BACKGROUND Patent ductus arteriosus (PDA) occurs in 70% of extremely low birth weight (ELBW, birth weight <1000 g) infants. Approximately 34% of ELBW infants with a PDA have spontaneous closure. Failure of the ductus arteriosus to close has been associated with multiple morbidities. OBJECTIVE To examine variability over time and across hospitals in early therapeutic (2-7 day) use of indomethacin (INDO) vs ibuprofen (IBU) for PDA treatment in outborn ELBW infants and examine the outcomes and side effects of both pharmacological agents in this population. METHODS Data were extracted from the Pediatric Health Information System. ELBW infants born between January 1, 2007 and December 31, 2010 and admitted on day of life 0 were eligible for inclusion. 732 infants had a PDA diagnosis and met inclusion criteria. We explored the variability in PDA pharmacotherapy over time and across hospitals. We compared outcomes of both agents for in-hospital mortality, need for surgical ligation, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. Statistical methods included chi square and multivariable regression analysis. Instrumental variable analysis was used to control for selection bias and omitted variables. RESULTS There was large variability in PDA pharmacotherapy over time and across hospitals. INDO use declined as IBU use grew from 12.8 to 38.9%. There was no difference in hospital or NICU characteristics between high and low IBU using NICUs. Renal failure was more common in infants receiving INDO compared to IBU. CONCLUSION We noted large variability in PDA pharmacotherapy. Renal failure was more common with INDO use. Until further studies to compare the long-term effects of both drugs, our data support IBU as the preferred medication for PDA pharmacotherapy in ELBW infants.

Chromosomal Abnormalities Affect the Surgical Outcome in Infants with Hypoplastic Left Heart Syndrome: A Large Cohort Analysis

Patients with hypoplastic left heart syndrome (HLHS) can have associated genetic abnormalities. This study evaluated the incidence of genetic abnormalities among infants with HLHS and the short-term outcomes of this population during the first hospitalization. This is a retrospective analysis of the multi-center Pediatric Heath Information System database of infants with HLHS who underwent Stage I Norwood, Hybrid, or heart transplant during their first hospitalization from 2004 through 2013. We compared clinical data between infants with and without genetic abnormality, among the three most common chromosomal abnormalities, and between survivors and non-survivors. Multivariable analysis was completed to evaluate predictors of mortality among patients with genetic abnormalities. A total of 5721 infants with HLHS were identified; 282 (5%) had associated genetic abnormalities. The three most common chromosomal abnormalities were Turner (25%), DiGeorge (22%), and Downs (12.7%) syndromes. Over the study period, the number of patients with genetic abnormalities undergoing cardiac operations increased without any significant increases in mortality. Infants with genetic abnormalities compared to those without abnormalities had longer hospital length of stay and higher morbidity and mortality. Variables associated with mortality were lower gestational age, longer duration of vasopressor therapy, need for dialysis, and cardiopulmonary resuscitation; and complicated clinical course as suggested by necrotizing enterocolitis, septicemia. Presence of any genetic abnormality in infants with HLHS undergoing cardiac surgery is associated with increased mortality and morbidity. Timely genetic testing, appropriate family counseling, and thorough preoperative case selection are suggested for these patients for any operative intervention.

The impact of prematurity and maternal socioeconomic status and education level on achievement-test scores up to 8th grade

Background The relative influence of prematurity vs. maternal social factors (socioeconomic status and education level) on academic performance has rarely been examined. Objective To examine the impact of prematurity and maternal social factors on academic performance from 3rd through 8th grade. Methods We conducted a retrospective cohort study of infants born in 1998 at the University of Arkansas for Medical Sciences. The study sample included 58 extremely low gestational age newborns (ELGANs, 23‒<28 weeks), 171 preterm (≥28‒<34 weeks), 228 late preterm (≥34‒<37 weeks), and 967 term ((≥37‒<42 weeks) infants. Neonatal and maternal variables were collected including maternal insurance status (proxy measure for socioeconomic status) and education level. The primary outcomes were literacy and mathematics achievement-test scores from 3rd through 8th grade. Linear mixed models were used to identify significant predictors of academic performance. All two-way interactions between grade level, gestational-age (GA) groups, and social factors were tested for statistical significance. Results Prematurity, social factors, gender, race, gravidity, and Apgar score at one minute were critical determinants of academic performance. Favorable social factors were associated with a significant increase in both literacy and mathematic scores, while prematurity was associated with a significant decrease in mathematic scores. Examination of GA categories and social factors interaction suggested that the impact of social factors on test scores was similar for all GA groups. Furthermore, the impact of social factors varied from grade to grade for literacy, while the influence of either GA groups or social factors was constant across grades for mathematics. For example, an ELGAN with favorable social factors had a predicted literacy score 104.1 (P <.001), 98.2 (P <.001), and 76.4 (P <.01) points higher than an otherwise similar disadvantaged term infant at grades 3, 5, and 8, respectively. The difference in their predicted mathematic scores was 33.4 points for all grades (P <.05). Conclusion While there were significant deficits in academic performance for ELGANs compared to PT, LPT, and term infants, the deficit could be offset by higher SES and better-educated mothers. These favorable social factors were critical to a child’s academic achievement. The role of socioeconomic factors should be incorporated in discussions on outcome with families of preterm infants.

Gastrostomy tube placement among infants with hypoplastic left heart syndrome undergoing stage 1 palliation

OBJECTIVE Different feeding strategies have been suggested to improve growth and survival of infants with hypoplastic left heart syndrome following stage 1 palliation. The study objective was to assess hospital mortality following stage 1 palliation among infants with hypoplastic left heart syndrome who had two feeding modalities, gastrostomy tube vs no gastrostomy tube. DESIGN Retrospective study design. SETTING Multicenter pediatric heath information system database. PATIENT About 4287 patients with hypoplastic left heart syndrome who underwent stage 1 Norwood procedure from 2004 through 2013. Infants who had gastrostomy tube with or without fundoplication procedure were identified and their clinical characteristics were compared. INTERVENTION None. OUTCOMES MEASURES The primary outcome was discharge hospital mortality following stage 1 palliation. RESULTS About 1214 patients who underwent stage 1 palliation had gastrostomy tube placement prior to hospital discharge. About 881 only had this procedure, while 333 patients also underwent fundoplication. Infants who had a gastrostomy tube placement vs no gastrostomy procedure had longer hospital stay, but significantly lower hospital mortality (5% vs 19%, P < .001). Hospital mortality was lower in infants who had only gastrostomy vs gastrostomy with fundoplication procedure (4% vs 8%, P = .004). In the multivariable analysis, gastrostomy procedure was associated with a higher likelihood of survival to hospital discharge (HR: 0.06, CI [0.04, 0.1]), whereas additional fundoplication procedure increased the risk of mortality (HR: 2.77, CI [1.52, 5.04]). CONCLUSIONS The gastrostomy procedure did not place infants with hypoplastic left heart syndrome at higher risk of mortality. These infants should be considered for gastrostomy tube placement if they had persistent difficulty in oral feeding following stage 1 palliation.