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Background: Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants., Objectives: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants., Search Strategy: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), conference proceedings, and previous reviews., Selection Criteria: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital., Data Collection and Analysis: The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two authors. Data were synthesised using a fixed effects model and reported using typical relative risk, typical risk difference and weighted mean difference., Main Results: 2365 preterm infants have participated in seven randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation and four trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality with adequate allocation concealment, blinding of caregivers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. Glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical risk difference 0.00 (95% confidence interval -0.03 to 0.02). The only trial that assessed long-term outcomes did not find any statistically significant differences in various assessments of neurodevelopment at 18 months corrected age. Glutamine supplementation does not have a statistically significant effect on other neonatal morbidities including invasive infection, necrotising enterocolitis, time to achieve full enteral nutrition, or duration of hospital stay., Authors' Conclusions: The available data from good quality randomised controlled trials indicate that glutamine supplementation does not confer benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.

Background: Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants., Objectives: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants., Search Strategy: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE (1966 - August 2004), EMBASE (1980 - August 2004), conference proceedings, and previous reviews., Selection Criteria: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm babies at any time from birth to discharge from hospital., Data Collection and Analysis: We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference., Main Results: More than 2300 infants have participated in six randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation, and three trials assessed parenteral glutamine supplementation. These trials were generally of good methodological quality with adequate allocation concealment, blinding of care-givers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. We found that glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.21); typical risk difference 0.00 (95% confidence interval -0.03 to 0.03). One of the trials assessed longer term neurodevelopmental outcomes (Poindexter 2004). The investigators reported that they did not find any statistically significant differences in various assessments of neurodevelopment (including Bayley scales) on follow up at 18 months corrected age. We found that glutamine supplementation does not have a statistically significant effect on the incidence of systemic infection (typical relative risk 1.02 (95% confidence interval 0.92 to 1.13); typical risk difference 0.01 (95% confidence interval -0.03 to 0.05)), necrotising enterocolitis (typical relative risk 1.02 (95% confidence interval 0.79 to 1.33); typical risk difference 0.00 (95% confidence interval -0.02 to 0.03)), days to full enteral nutrition (weighted mean difference -1.1 days (95% confidence interval -3.4 to 1.2)), or duration of hospital stay (weighted mean difference 0.65 days (95% confidence interval -2.9 to 4.2))., Authors' Conclusions: The available data from good quality randomised controlled trials suggest that glutamine supplementation does not confer clinically significant benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.

Background: Two carotenoids, lutein and zeaxanthin are found in the retinal pigment epithelium of the eye where they are believed to protect it against oxidative and light damage. The amounts of these carotenoids consumed by premature infants are not known., Objective: The objective of the investigation was to measure these carotenoids in human and formulae milks., Design: In all, 28 human milk samples were obtained at various times between days 1 and 41 of lactation from 13 mothers. Six formula milks commonly used in hospitals were also analysed., Setting: Mothers who provided the milk samples had infants in the neonatal ward at the Royal Maternity Hospital, Belfast., Results: Median lutein and zeaxanthin concentrations in human milk were 4.79 (range 0.42-9.98) nmol/g fat and 0.55 (0.00-1.70) nmol/g fat, respectively. Five of the six formula milks also contained lutein and zeaxanthin with concentrations that varied over a wide range (0.7-9.7 and 0.1-1.2 nmol/g fat, respectively)., Conclusions: Carotenoid concentrations usually decreased with the duration of lactation. Some formula milks that were specially formulated for premature infants contained high concentrations of the lutein and zeaxanthin and the source may be egg yolk., Sponsorship: These studies were supported by the University of Ulster and the Northern Ireland Mother and Baby Appeal.

Objective: The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates., Design: Randomized controlled trial., Methods: Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18)., Results: There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups., Conclusions: Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN.

We assessed the clinical outcome of pregnancies with non-Rh-D antibody in Northern Ireland using retrospective case note review. During the study period (April 1999- March 2000) 186 women with clinically significant antibodies were identified from the records of the antenatal laboratory of the Northern Ireland Blood Transfusion Service. Eighty-five women were included in the study using the criteria mentioned above. None of the fetuses required intrauterine transfusion during this period. One baby required exchange transfusion, three were given top-up transfusions and 17 had phototherapy. Nine babies with a positive direct antiglobulin test (DAT) received no treatment. The incidence of anti-Kell could be reduced by transfusing Kell negative red cells to premenopausal women. It is important that all pregnant women are tested at least twice in their pregnancy to detect the antibodies formed late in the pregnancy. It is useful to formulate a standard protocol for antenatal interventions. Non Rh-D antibodies can cause significant anaemia for up to six weeks in the neonatal period, hence early detection of maternal antibodies is important so that the neonates are followed up for an appropriate length of time.

Background: Monitoring oesophageal pH conventionally detects "acid reflux" (pH less than 4). The pH of the gastric contents determines whether or not reflux can be detected., Aim: To monitor gastric and oesophageal pH simultaneously in order to determine the effect of milk feeds on gastric pH and how this would influence interpretation of the oesophageal pH record., Methods: Milk fed infants for whom oesophageal pH monitoring was requested underwent simultaneous gastric and oesophageal pH monitoring using a dual channel pH probe., Results: Twenty of 24 records were technically satisfactory. Mean reflux index was 1.0%, range 0.0-4.0%. Gastric pH was less than 4 for 24.5% (range 0.6-69.1%) of the total time. The average time the gastric pH was greater than 4 after feeds was 130 minutes (range 29-212 minutes). The corrected reflux index (limited to the time the gastric pH was less than 4) was 2.6% (range 0.0-11.0%)., Conclusion: The pH of the gastric contents may be greater than 4 for prolonged intervals, during which oesophageal pH monitoring using current criteria cannot detect reflux nor correlate it with clinical events. A low reflux index may reflect prolonged buffering of gastric acidity rather than the absence of reflux.

Aims: To determine effects of maternal iron depletion and smoking on iron status of term babies using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood., Methods: Iron, ferritin, STfR, and haemoglobin (Hb) concentration were measured and TfR-F index calculated in 67 cord /maternal blood pairs. Twenty six mothers were iron depleted (ferritin <10 microg/l) and 28 were smokers., Results: Maternal iron depletion was associated with decreased cord ferritin (113 v 171 microg/l) and Hb (156 v 168 g/l) but no change in STfR or TfR-F index. Smoking was associated with increased cord Hb (168 v 157 g/l) and TfR-F index (4.1 v 3.4), and decreased ferritin (123 v 190 microg/l). Cord TfR-F index and Hb were positively correlated (r = 0.48)., Conclusions: Maternal iron depletion is associated with reduced fetal iron stores but no change in free iron availability. Smoking is associated with increased fetal iron requirements for erythropoiesis.

Aim: To determine what percentage of therapeutic interventions for very low birth weight infants undergoing neonatal intensive care is evidence based., Methods: The management of 80 very low birth weight infants admitted to our neonatal unit during 1998 was retrospectively reviewed. For each clinical diagnosis e.g. respiratory distress syndrome, patent ductus arteriosus or chronic lung disease all interventions were recorder. Each intervention was then categorised according to the level of supporting evidence. Level I was supported by evidence from randomised controlled trials or meta-analysis of multiple trials. Level II included interventions backed by convincing non-experimental evidence where randomised controlled trials would be unnecessary or unethical. Level III were treatments in common use without substantial supporting evidence. These categorizations were made after extensive researching of Medline, The Cochrane Database and the Randomised Controlled Trial Register, detailed hand-searching of the literature as well as using local expertise and knowledge., Results: 943 separate interventions were recorded in the charts of the 80 babies. Overall 91.3% were shown to be evidence-based of which 58.7% were level I, 32.6% were level II and only 8.7% were level III., Conclusions: 91.3% of interventions for very low birth weight infants in our neonatal intensive care unit were evidence-based and only 8.7% had no substantial supporting evidence. Care of the very low birthweight infants is largely evidence-based.

Seventy six babies of less than 1500 g birth weight who had surfactant replacement therapy for severe respiratory distress syndrome were studied to assess the presence and stage of subsequent retinopathy of prematurity (ROP). A control group of 90 babies, matched for birth weight and gestational age, who did not have surfactant therapy were also studied. Threshold ROP or greater was found in 1.7% of the surfactant group and 7.8% of the controls. For the babies of less than 1000 g birth weight 4.0% of the surfactant babies and 16.3% of the controls reached threshold disease or greater. It is concluded that surfactant therapy is not associated with an increased incidence or severity of severe ROP in this preterm population.

Plasma manganese levels were determined at birth and then serially to 3 months of age in 40 very low birth weight (VLBW) infants (mean birth weight 1,027 g). Mean plasma manganese concentration was 3.6 micrograms/l at birth and 3.0 micrograms/l at 3 months of age. These levels were approximately 3-fold greater than those of a group of 9 adults analysed using the same methods (mean 1.1 micrograms/l). Manganese was also measured in parenteral nutrition fluids, breast milk and 3 preterm formulas. There was no relationship between manganese intake and plasma manganese concentration.

To determine if surfactant replacement treatment is associated with an increase in the prevalence of retinopathy of prematurity (ROP) we studied 76 preterm babies who were treated with porcine surfactant (Curosurf) for severe respiratory distress syndrome from 1985 to 1990. Babies were first examined by indirect ophthalmoscopy at the equivalent of 32 weeks post-menstrual age and subsequently at 2-week intervals until discharge from hospital. Findings were documented according to the International Classification of ROP. Sixty-two (82%) babies survived to discharge, 7 survivors were not examined due to transfer elsewhere. Acute ROP developed in 14 (29%) of the 49 babies examined (7 stage I, 4 stage II, 2 stage III, and 1 stage IV); one baby required cryotherapy. No baby of birthweight greater than 1,500 g developed ROP. The prevalence of ROP was similar to that reported for non-surfactant-treated very-low-birthweight babies. We conclude that Curosurf treatment does not increase the risk of acute ROP in surviving very-low-birthweight babies.

Plasma hypoxanthine concentration was measured in twelve preterm babies with respiratory distress syndrome (RDS) treated with 200 mg/kg of a porcine surfactant (Curosurf). Five of the babies died within one week and seven survived the neonatal period. Surviving babies had no significant changes in plasma hypoxanthine concentration throughout a one hour study period following the administration of surfactant. By contrast, in nonsurvivors the mean plasma hypoxanthine concentrations increased from 6.8 mumol/l before surfactant administration to 14.2 mumol/l 15 minutes after surfactant treatment. Survivors had a mean maximal increase in plasma hypoxanthine of 1.9 mumol/l 15-30 min factor surfactant treatment compared with 9.4 mumol/l in nonsurvivors (p < 0.05). The babies who developed intracranial hemorrhage had significantly higher maximal plasma hypoxanthine increase (mean 9.6 mumol/l) compared with babies who did not develop intracranial hemorrhage (mean 1.1 mumol/l) (p < 0.01). The combination of high PaO2 and high hypoxanthine concentration could lead to an increased production of oxygen radicals which might be harmful. We conclude that plasma hypoxanthine concentration may serve as an indicator of the prognosis in preterm babies treated with natural surfactant. Further, it seems important to reduce oxygen supplementation as soon as surfactant is given to possibly limit oxygen radical production.

Objective: To determine the effectiveness of clinical examination, chest radiography, and electrocardiography compared with echocardiography in detecting congenital heart disease early in the life of children with Down's syndrome., Design: Prospective two year screening survey., Setting: Regional paediatric cardiology service, Northern Ireland., Patients: 81 newborn infants with Down's syndrome born in Northern Ireland between November 1987 and November 1989., Interventions: Clinical examination, chest radiography, and electrocardiography soon after birth followed by cross sectional Doppler echocardiography., Main Outcome Measures: Diagnostic ability of clinical examination, radiography, and electrocardiography compared with echocardiographic findings., Results: 34 babies had congenital heart disease detected by echocardiography (13 had atrioventricular septal defects, seven secundum atrial septal defects, six a solitary patent ductus arteriosus, five isolated ventricular septal defects, and three combinations of heart defects). Individual examination methods were insensitive (the sensitivity of clinical examination was 0.53, of radiography 0.44, and of electrocardiography 0.41) but highly specific (the specificity of clinical examination was 0.94, of radiography 0.98, and of electrocardiography 1.0), although sensitivity improved when the three techniques were combined (the sensitivity was 0.71, the specificity 0.91)., Conclusion: Echocardiography performed early in life can detect congenital heart disease that might otherwise be missed. Early detection may help prevent complications such as pulmonary vascular disease that may adversely affect the outcome of cardiac surgery.

Very low birth weight infants often receive multiple blood transfusions. We measured the plasma levels of the trace elements selenium, manganese, and glutathione peroxidase in 20 very low birth weight infants prior to blood transfusion and then at 24, 48 and 72 h after transfusion. There was no detectable change in mean selenium or glutathione peroxidase concentrations after transfusion, but the mean (SD) plasma manganese increased from 3.8 (1.5) to 6.0 (2.3) micrograms/l at 72 h.

There is controversy over the effect of hypertension in pregnancy on the incidence of neonatal respiratory distress syndrome. We investigated the association between maternal hypertension and the incidence of respiratory distress syndrome in 268 very low birthweight babies of less than 34 weeks' gestation. A lower incidence of respiratory distress syndrome was associated with growth retardation and membrane rupture greater than 24 hours. Maternal hypertension was associated with an increased incidence of respiratory distress syndrome. We used the multiple logistic regression model to control for confounding variables, as the maternal and neonatal factors associated with respiratory distress syndrome were not evenly distributed between the two groups. After adjustment for birth weight, gestational age, growth retardation, and membrane rupture greater than 24 hours, the risk of developing respiratory distress syndrome was significantly greater in babies of hypertensive mothers. Significance was lost when labour before delivery and mode of delivery were taken into account. The increased incidence of respiratory distress syndrome in babies of hypertensive mothers may be due to the absence of labour before delivery because of the greater likelihood of caesarean section.

Objective: To estimate the cost of treating babies with severe respiratory distress syndrome with natural porcine surfactant., Design: Retrospective controlled survey., Setting: Regional neonatal intensive care unit, Belfast., Patients: 33 Preterm babies with severe respiratory distress syndrome who were enrolled in a European multicentre trial during 1985-7. 19 Babies were treated with surfactant and 14 served as controls., Interventions: Treatment with natural porcine surfactant., Main Outcome Measure: Cost associated with surfactant replacement treatment per extra survivor in the treatment group and cost per quality adjusted life year for each extra survivor., Results: Fifteen (79%) of the 19 treated babies and five (36%) of the 14 control babies survived. On average, the control babies required 20 days in hospital compared with 61 days for the treated babies (or 95 [corrected] days per extra survivor in the treatment group). The cost per extra survivor in the treatment group was pounds 13,720, with the cost per quality adjusted life year estimated at pounds 710., Conclusion: These costs compare favourably with those of established forms of treatment in adults. Thus surfactant replacement treatment for severe respiratory distress syndrome is fairly inexpensive and cost effective.

Surfactant replacement for respiratory distress syndrome (RDS) following very prolonged rupture of the membranes (PROM) is of uncertain value. Seven preterm babies born after PROM (median 48 days, range 22-61 days) were compared with 14 babies without PROM. All had clinical and radiological evidence of severe RDS, requiring mechanical ventilation with inspired oxygen concentrations greater than or equal to 60%. Indices of oxygenation and "compliance" were compared before and serially up to 4 h after surfactant treatment. Before treatment the PROM babies had more severe lung disease, based upon higher inspired oxygen concentration and mean airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the PROM group than the comparison group at all times after treatment. The poor response of the PROM group, perhaps because of pulmonary hypoplasia, suggests that surfactant replacement may not be beneficial for RDS in these babies.

We describe a case of ventricular tachycardia in association with acute Coxsackie B4 virus infection occurring in an otherwise normal infant. The dysrhythmia responded to flecainide acetate.

Glutathione peroxidase (GPX) and selenium are important in the prevention of cellular oxidant damage. Whole-blood GPX and plasma selenium were measured at birth and sequentially afterwards in 75 preterm babies. GPX activity at birth was 2.74 +/- 0.08 (mean +/- SEM) U/ml. Mean GPX activity remained relatively unchanged for up to 70 days postnatal age. Plasma selenium at birth was 0.43 +/- 0.02 (mean +/- SEM) mumol/l), decreasing to low levels by 10 weeks postnatal age. Neither GPX activity nor plasma selenium was related to birth weight, gestational age or infant sex.