Harish Amin

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis

OBJECTIVE To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

Consent for clinical research in the neonatal intensive care unit: a retrospective survey and a prospective study

Background: Recruitment into research studies in the neonatal intensive care unit has been problematic. Therefore suggestions have been made to take decision making about enrolment out of the hands of the parents. Objective: To understand parental perceptions of the process of recruitment and enrolment for research in the neonatal intensive care unit. Method: A questionnaire was developed and used in both a retrospective survey and a prospective study of parents whose newborns were enrolled in trials in a neonatal intensive care unit. Closed ended and open ended questions were included, as well as demographic questions. Results: The retrospective survey had a 79% response rate (29 of 38). Overall, 90% of parents felt that they had made informed decisions, and 93% were against the option that a doctor decide if the newborn should be enrolled into a study, rather than the parent. Although some parents (38%) found that recruitment did add “stress to an already stressful situation”, 90% felt that they had made informed decisions and understood the elements of the study. Most parents had been requested to enrol their newborn into more than one trial, and, on average, they thought that they would be comfortable with enrolment into two studies (range 0–6). When asked how the process could be improved, parents suggested that information be made available before delivery. The responses of parents in the prospective study were mostly consistent with those from the retrospective survey. Conclusions: Overall the parents did not support the suggestion that decision making about enrolment be taken away from parents and put into the hands of doctors. The healthcare team should support parents in their role of decision maker, enhance availability of the research staff, and provide more information about the research.

Does necrotising enterocolitis impact the neurodevelopmental and growth outcomes in preterm infants with birthweight ≤1250 g?

Aim:  To compare the long‐term growth and neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birthweight (BW) ≤ 1250 g) with necrotising enterocolitis (NEC) with BW‐matched controls.

Plasma L-arginine concentration, oxygenation index, and systemic blood pressure in premature infants

OBJECTIVE To determine the relationships between plasma L-arginine concentrations and the severity of respiratory distress syndrome (RDS) or systemic blood pressure in premature infants. DESIGN Prospective, observational study. SETTING Neonatal intensive care, tertiary referral hospital. SUBJECTS Fifty-three premature infants. INTERVENTIONS We measured arginine and nutritional intake, plasma arginine concentration, total amino acid concentrations, and blood pressure on days 3, 7, 14, and 21 of life. In 33 infants who received assisted ventilation, oxygenation index could be calculated to reflect the severity of RDS. The relationships between plasma arginine and oxygenation index or blood pressure were analyzed using multiple linear regression. MEASUREMENTS AND MAIN RESULTS On day 3, plasma arginine concentrations were decreased compared with normal published values. Arginine concentrations increased with the day of life of measurement (p < .001) and with arginine intake (p < .001). After adjusting for arginine intake and day of life, an inverse relationship was found between oxygenation index and plasma arginine concentrations: (p = .025). No similar relationship was found between oxygenation index and the concentration of total amino acids. A weak positive relationship was found between plasma arginine concentration and systemic blood pressure. CONCLUSIONS Increments in the oxygenation index, reflective of an increased severity of RDS, are associated with a decrease in plasma arginine concentration. This finding may reflect arginine consumption by the nitric oxide synthase pathway in the lungs of premature infants with RDS, or may be explained by increased arginine catabolism. The lack of a similar relationship between total plasma amino acids and oxygenation index supports the first interpretation.

Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants.

Aim:  To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV).

Renal consequences of preterm birth

BackgroundThe developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond.ObjectivesThe purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty.ResultsKidney size and nephron number are known to be reduced in surviving premature infants due to disruption of organogenesis at a crucial developmental time point. Inflammation, hyperoxia, and antiangiogenic factors play a role in epigenetic conditioning with potential life-long consequences. Additional kidney injury from hypoperfusion and nephrotoxicity results in structural and functional changes over time which are often unnoticed. Nephropathy of prematurity and acute kidney injury confound glomerular and tubular maturation of preterm kidneys. Kidney protective strategies may ameliorate growth failure and suboptimal neurodevelopmental outcomes in the short term. In later life, subclinical chronic renal disease may progress, even in asymptomatic survivors.ConclusionAwareness of renal implications of therapeutic interventions and renal conservation efforts may lead to a variety of short and long-term benefits. Adequate monitoring and supplementation of microelement losses, gathering improved data on renal handling, and exploration of new avenues such as reliable markers of injury and new therapeutic strategies in contemporary populations, as well as long-term follow-up of renal function, is warranted.

Neonatal Ventricular Tachyarrhythmias in Medium Chain Acyl-CoA Dehydrogenase Deficiency

We describe an unusually severe case of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in a term female neonate, who presented at 12 h of age with lethargy, poor feeding, hypoglycemia and ventricular tachyarrhythmias. While arrhythmias are common in other disorders of fatty acid beta-oxidation, ventricular tachyarrhythmias have rarely been reported with MCAD deficiency in childhood. Since the results of newborn metabolic screening are usually not available within the first 3 days of life, our case highlights the need for health care professionals to be made aware of this early and uncommon but potentially fatal presentation of MCAD deficiency.

Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis

Aim:  This study aimed to compare the long‐term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight ≤ 1250 gm) who received supplementation with l‐arginine during the first 28 days of life with controls.

Validating objectives and training in Canadian paediatrics residency training programmes

Background: Changing health care systems and learning environments with reduction in resident work hours raises the question: “Are we adequately training our paediatricians?” Aims: (1) Identify clinical competencies to be acquired during paediatric residency training to enable graduates to practise as consultant paediatricians; (2) Identify gaps in preparedness during training and; (3) Review and validate competencies contained in the Royal College of Physicians and Surgeons of Canada (RCPSC) objectives of training (OTR) for paediatrics. Methods: A questionnaire with 19 classification domains containing 92 clinical competencies was administered to RCPSC certified paediatricians who completed residency training in Canada from June 2004 to June 2008. For each competency, paediatricians were asked to indicate the importance and their degree of preparedness upon entering practice. Gap scores (GSs) between importance and preparedness were calculated. Results: Response rate was 43% (187/435); 91.3% (84/92) of competencies in the RCPSC OTR were identified as important. Paediatricians felt less than adequately prepared for 25% (23/92) of competencies; 40 competencies had GSs >10%. Conclusions: The unique approach used in this study is useful in validating OTR as well as the preparation of residents in relation to OTR. The results indicate a potential need for additional training in specific competencies.

Maternal haemolysis, elevated liver enzymes and low platelets syndrome: Perinatal and neurodevelopmental neonatal outcomes for infants weighing less than 1250 g

Objectives:  To study mortality and short‐term morbidity of infants born to women with HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome and to compare the long‐term neurodevelopmental morbidity of a subgroup with birth weight (BWT) less than 1250 g (study group) with weight matched controls.