Continuous intra-arterial blood-gas monitoring in infants and children with cyanotic heart disease

We have evaluated the accuracy and reliability of the Paratrend 7 continuous blood-gas analyser in infants and small children under conditions of severe hypoxaemia admitted to the paediatric intensive care unit in the perioperative period with cyanotic congenital heart disease. PO2, PCO2 and pH (hydrogen ion concentration) were measured continuously via a femoral arterial sensor and compared with 100 simultaneous paired arterial blood-gas measurements. Data were analysed by Bland-Altman analysis for bias and precision. Sensors were placed in 10 children of median age 5.43 (range 0.03-45) months, median weight 3.74 (2.79-15.4) kg and remained in place for up to 27 h after operation. PO2 values were 2.5-8.2 kPa (median 5.3 kPa). Co-oximeter saturation ranged from 37.1% to 90.6% (median 75.8%). Bias and precision values were 0.04/0.87 kPa for PO2, -0.44/0.74 kPa for PCO2 and -2.61/6.98 nmol litre-1 for hydrogen ion concentration (i.e. 0.02/0.06 for pH). We conclude that perioperative continuous arterial gas monitoring is clinically accurate under conditions of severe hypoxaemia in small infants and children with cyanotic congenital heart disease.     

Status and after-care of young adults with congenital heart defects

INTRODUCTION: We studied patients with congenital heart defects born in 1975 and followed by our institution. We were interested in the outcome of these patients at the age of 20 years with regard to professional status, physical activity and psychosocial aspects. Furthermore, we investigated the handover from the paediatric to the adult cardiologist as well as the information level concerning antibiotic prophylaxis against bacterial endocarditis. METHODS: From a previous follow-up study to the age of 16 years, we knew 224 patients with congenital heart disease born in 1975, 119 were considered to need further cardiological follow-up. In 112 (94%) we have a complete follow-up to the age of 20 years with a structured interview by phone. RESULTS: Mortality and medical care during the period between 16 and 20 years of age were at a lower level than in the previous periods. Except in patients suffering from complex or surgically treated cyanotic heart disease, the results, compared to the standard population at the age of 20 years, are better with regard to professional status, and equal for physical activity and psychosocial integration. Only 60% of the patients were followed by an adult cardiologist and only 45% of the patients needing antibiotic prophylaxis against bacterial endocarditis are aware of this. CONCLUSION: Except in patients with complex congenital or surgically treated cyanotic heart diseases, the outcome at the age of 20 years with regard to professional status, physical activity and psychosocial integration is very good compared with the standard population at the age of 20 years. The handover to the adult cardiologist is inadequate and knowledge and awareness of antibiotic prophylaxis against bacterial endocarditis is also insufficient-both aspects need improvement.     

The haematological management of patients with cyanotic congenital heart disease. A time for consensus?

AIMS: Recurrent venesection of patients with cyanotic congenital heart disease may be detrimental, with an increased risk of cerebrovascular events and symptomatic iron-deficiency. The aim of this study was to determine the venesection policies as practised in hospitals within a U.K. region and to determine if these policies followed current recommendations. METHODS AND RESULTS: Fifty-eight consultants (56% response rate) in cardiac specialties completed self-assessment questionnaires regarding the indications for and practice of venesection. Sixty-one percent of those responding were involved directly in the care of patients with cyanotic congenital heart disease and of these clinicians 97% used venesection. Indications for venesection varied, with 51% of those responding using an elevated haemoglobin per se (6.5-21.0 g. dl-1); 78% an elevated haematocrit (0.55-0.75) and 83% symptoms. Desired maintenance haemoglobin and haematocrit levels also varied greatly. Fifty percent of the consultants responding routinely screened their patients for iron deficiency and 23% felt there was no indication for investigating a low mean corpuscular volume. Only 18% of the policies described followed any evidence based principles. CONCLUSIONS: The practice of venesecting patients with congenital cyanotic heart disease varies greatly. Policies in many hospitals do not reflect the minimal benefits and considerable risks associated with recurrent venesection.     

Safety and efficacy of chloral hydrate sedation in children undergoing echocardiography

The purpose of this prospective study was to determine the safety and efficacy of chloral hydrate sedation in children with known or suspected congenital heart disease. The study population included 405 children with a median age of 13 months (3 weeks to 14 years). Cyanotic heart disease was present in 64 of the children. The median dosage of chloral hydrate given was 77 mg/kg, with a range of 25 to 125 mg/kg. Sedation was achieved in 397 (98%) of the children. The complete study time averaged 2.2 hours (range, 1.6 to 5.2 hours). The time to achieve sedation was 30 minutes or less in 82%, more than 30 but less than 60 minutes in 12%, and more than 60 minutes in 4%; 2% failed to achieve sedation. Children aged 3 years or younger were more likely to be successfully sedated with chloral hydrate (p = 0.003). The type of heart disease did not affect the success of sedation. No child had a clinically significant change in heart rate or blood pressure during sedation; however, oxygen saturation decreased in 24 (6%) of 397 children successfully sedated. Decreases in oxygen saturation occurred more commonly in children with trisomy 21 (7/13) than in children without genetic syndromes (17/384). Vomiting occurred in 23 (6%) of the 405 study subjects, usually immediately after drug administration. Chloral hydrate is a safe and effective agent for sedation of children with known or suspected congenital heart disease who are undergoing echocardiography in the outpatient cardiology clinic.     

Evaluation of small caliber vascular prostheses implanted in small children: activated angiogenesis and accelerated calcification

Healing characteristics of small-caliber vascular prostheses used in small children have rarely been observed because removing specimens are troublesome. Modified Blalock Taussig shunt procedures were performed using small caliber expanded polytetrafluoroethylene (ePTFE) vascular grafts and fabric grafts in 13 patients with congenital heart disease. At the time of total corrective procedures, a piece of 10 ePTFE grafts in 10 patients and six fabric grafts in four patients were removed from the distal pulmonary anastomosis, and evaluated. The implantation duration was from 11 months to 5 years and 7 months (mean, 2 years and 6 months). At removal, average patient age was 4 years and all grafts were patent. Microscopically, the wall of three ePTFE grafts were calcified, and macrophages were immunohistologically observed in the graft wall. Thrombus formation, intimal hyperplasia, and pannus detachment was common. In the fabric grafts, many capillaries infiltrated the interstices and often reached the lumen from the perigraft side. These results suggested that in cyanotic small children, angiogenesis in and around fabric grafts was active and calcification was accelerated in ePTFE grafts. Complete endothelialization throughout the length, caused by angiogenesis, might be possible in small children when highly porous fabric vascular prostheses are used.     

Depression as a risk factor for ischaemic heart disease in men: population based case-control study

OBJECTIVE: To determine the relation between depression, anxiety, and use of antidepressants and the onset of ischaemic heart disease. DESIGN: Population based case-control study. SETTING: All 5623 patients registered with one general practice. SUBJECTS: 188 male cases with ischaemic heart disease matched by age to 485 male controls without ischaemic heart disease; 139 female cases with ischaemic heart disease matched by age to 412 female controls. MAIN OUTCOME MEASURE: Adjusted odds ratios calculated by conditional logistic regression. RESULTS: The risk of ischaemic heart disease was three times higher among men with a recorded diagnosis of depression than among controls of the same age (odds ratio 3.09; 95% confidence interval 1.33 to 7.21; P=0.009). This association persisted when smoking status, diabetes, hypertension, and underprivileged area (UPA(8)) score were included in a multivariate model (adjusted 2.75; 1.13 to 6.69; P=0.03). Men with depression within the preceding 10 years were three times more likely to develop ischaemic heart disease than were the controls (3.13; 1.27 to 7.70; P=0.01). Men with ischaemic heart disease had a higher risk of subsequent depression [corrected] than men without ischaemic heart disease (adjusted 2.34; 1.34 to 4.10; P=0.003). Depression was not a risk factor for ischaemic heart disease in women on multivariate analysis (adjusted 1.34; 0.70 to 2.56; P=0.38). Anxiety and subsequent ischaemic heart disease were not significantly associated in men or women. CONCLUSION: Depression may be an independent risk factor for ischaemic heart disease in men, but not in women.     

Hydroxyurea use during pregnancy: a case report in sickle cell disease and review of the literature

A patient being treated for sickle cell disease with hydroxyurea (1 g/d) conceived, and drug treatment was discontinued at nine weeks gestational age. The pregnancy and delivery were complicated by vaso-occlusive crises. A healthy male infant was born at 39 weeks with no evidence of congenital malformations. A literature review, including this case, suggests that the risk of hydroxyurea exposure during in pregnancy may have been overestimated. Further studies are required to determine its safety in pregnancy.     

Diaphragmatic dysfunction after heart or lung transplantation

The research presented here investigated platelet activation in cyanotic and acyanotic congenital heart diseases (CHD). Children with cyanotic CHD are prone to both thrombosis and hemorrhage. However, patients with acyanotic CHD may also have a mild bleeding disorder. The platelet activation in CHD was investigated in support of a hypothesis that platelet activation may play a role in the hemostatic abnormalities reported in these patients. Platelet activation was determined by using flow cytometry with anti-CD62 monoclonal antibody (mAb), which has been shown to be a specific marker of platelet activation. Thirteen children with cyanotic CHD, 33 children with acyanotic CHD and 17 healthy children serving as controls were studied. Platelet activation was significantly higher in the cyanotic group and also in the acyanotic group compared with the healthy children (P = 0.0000 and P = 0.019, respectively). In the cyanotic group, platelet activation showed a direct correlation with arterial O2 saturation (SaO2) (P = 0.014). There was no correlation between platelet activation and erythrocyte related parameters in either group. Platelet activation occurs in CHD, particularly in patients with cyanotic CHD (even in patients with no evidence of clinical thrombosis) and it may play a role in the pathogenesis of thrombotic disorders seen in these patients.     

Role of tumor necrosis factor and nitric oxide in the cytotoxic effects of Clostridium difficile toxin A and toxin B on macrophages

Clostridium difficile, the bacterium involved in antibiotic-associated colitis, produces two exotoxins, toxin A (TxA) and toxin B (TxB). Although these toxins are well recognized as being cytotoxic to several mammalian cell types, the mechanisms involved are not fully understood. The aim of the present investigation was to examine the cytotoxicity of TxA and TxB to peritoneal macrophages in culture and to investigate whether tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) are involved in the process. As a control, the effect of E. coli LPS was also investigated. TxA, TxB and LPS were dose-dependently cytotoxic to macrophage monolayers, with TxB being the most potent. All of the toxins stimulated the release of TNF-alpha from macrophages. TxB was again the most active in inducing this response. The TNF-alpha released appears to be involved in the action of LPS and TxA, but not of TxB, since a mAb against TNF-alpha inhibited the cytotoxicity of the former two but had no effect on the latter. NO is not involved in the effects of TxA and TxB since these toxins did not induce the production of this mediator in macrophages, even in the presence of IFN-gamma. In addition, L-imino-ethyl-L-ornithine (L-NIO), a NO synthase inhibitor, did not modify the macrophage death caused by TxA or TxB. Although LPS was able to induce the production of high amounts of NO, NO did not mediate the LPS cytotoxicity since L-NIO did not influence the degree of macrophage death caused by LPS. TxA and TxB therefore appear to exert cytotoxic effects on cultured macrophages by different mechanisms. TNF-alpha is involved in TxA and LPS-mediated cytotoxicity but not in the toxicity caused by TxB. NO is not involved in the killing action of any of these toxins.     

Cerebral emboli during cardiac surgery in children

BACKGROUND: Microemboli occur commonly during cardiac surgery in adults, and, when present, increase the risk of neuropsychological deficits. Their incidence and significance during correction of congenital heart disease is unknown. The authors hypothesized that microemboli would occur before bypass with right-to-left cardiac shunts and would also occur in large numbers when the aortic crossclamp was released in children during repair of congenital heart defects. METHODS: In 25 children studied with carotid artery Doppler, embolic signals were counted and timed in relation to 13 intraoperative events. Patients were classified as either at high risk (obligate right-to-left shunt or uncorrected transposition of the great arteries) or at low risk (net left-to-right shunt or simple obstructive lesions) for paradoxical (venous to arterial) emboli. RESULTS: The median number of emboli detected was 122 (range, 2-2,664). Forty-two percent of all emboli were detected within 3 min of release of the aortic crossclamp. The high-risk group had significantly more emboli (median, 66; range, 0-116) during the time interval before cardiopulmonary bypass than did the low-risk group (median, 8; range, 0-73), with P < 0.01. There was no significant difference between the high- and low-risk groups in the total number of emboli detected. There was no apparent association between number of emboli and gross neurologic deficits. CONCLUSIONS: Microemboli can be detected in the carotid arteries of children undergoing repair of congenital heart disease and are especially prevalent immediately after release of the aortic crossclamp. The role of emboli in causing neurologic injury in children undergoing repair of congenital heart disease remains to be determined.     

The operability of patient with pulmonary hypertension judged from hemodynamic changes before and after surgery

1) In congenital heart disease with pulmonary hypertension, the place for surgical correction still remains even with almost systemic PA pressure if R to L shunt ratio on lung scintigram is lower than 25%. 2) The patient with pulmonary hypertension in congenital heart disease younger than 3 years of age has wider acceptability for surgery compared to older patient. 3) In patients with mitral valvular disease, surgical correction seems to be indicated irrespective of PA pressure, if their preoperative U/L are lower than 2.4.     

The young platelet population in children with cyanotic congenital heart disease

Some morphological, biochemical and functional parameters of platelet population in children with cyanotic congenital heart disease (CCHD) were studied by making comparisons of the normal platelet population in both CCHD patients and controls. The mean volume of the platelets from cyanotic patients was greater than from normals. The platelet size distribution curves demonstrated a shift towards larger than normal size in the case of CCHD. The mean protein content, as well as the mean PF3 content of platelets was increased in CCHD. Following addition of kaolin, PF3 release was more rapid and of shorter duration with platelets from CCHD patients as compared to normal platelets. They also released more PF3 than did normal platelets. After addition of ADP, collagen, or adrenalin, platelets of CCHD patients were more responsive than similarly treated platelets from normals. Platelets from CCHD showed an increased initial rate of aggregation and greater maximum aggregation. These data suggested that the platelet population of CCHD patients consists of larger, younger and functionally more active platelets than does the platelet population of normals.     

Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects?

Down syndrome is commonly associated with significant congenital heart disease with the potential for early development of pulmonary hypertension. As such, children with Down syndrome may be at increased risk for both perioperative and long-term mortality. The purpose of this study, using data collected from a population-based outcomes study, is to analyze the potential role that Down syndrome plays in the outcome of surgically "corrected" congenital heart disease. Data were collected from a registry of all Oregon residents who, in the period 1958 to the present, had a reparative operation for one of 14 congenital cardiac malformations when younger than 18 years (N = 3965 patients). Down syndrome was present in 289 (7%) of the total registry patients. In evaluating the cardiac mortality associated with Down syndrome for each of the repaired cardiac malformations, only complete atrioventricular septal defect was associated with significantly higher perioperative (13% vs 5%) as well as higher overall late cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The survival outcomes for each of the other cardiac malformations were similar for children with and without Down syndrome.     

A comparison of epidemiologic, histologic, and virologic studies on Hodgkin''s disease in western Kenya and Nagasaki, Japan

AIMS: The aim of the present study was to determine which medical variables were predictors of long-term behavioural/emotional outcome after surgical correction for congenital heart disease in infancy and childhood. METHODS: The Child Behavior Checklist (CBCL) was used to predict parent-reported behavioural/emotional problems in 125 10-15 year-old congenital heart disease children from: (1) biographical status (2) medical history (3) heart surgery (4) short-term post-operative course and (5) number of heart operations and (6) extra cardiac concomitant anomalies. RESULTS: Higher CBCL total problem scores at follow-up were associated with a greater number of heart operations and deep hypothermic circulatory arrest (< 22 degrees). 'Internalizing problems' were associated with a greater number of heart operations, deep hypothermic circulatory arrest, a short gestational age, low systemic oxygen saturation, and older age at surgical repair. 'Externalizing problems' were associated with a greater number of heart operations only. CONCLUSION: Several medical variables were significant predictors and can be used to identify those congenital heart disease children who are at risk of long-term behavioural/emotional maladjustment.     

Inflammatory mediator and organ dysfunction syndrome

PURPOSE: To assess the role of serum folate in the risk for coronary heart disease in a national cohort of US adults. METHODS: Data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (N = 1921) were used to determine whether a low serum folate concentration was associated with an increased risk for incident coronary heart disease (N = 284). The Cox proportional hazards model adjusted for age, sex, race, education, serum cholesterol, systolic blood pressure, body mass index, cigarette smoking, and alcohol consumption. RESULTS: The association between folate and risk for coronary heart disease differed by age group (p = 0.03). Among persons aged 35-55 years, the relative risk for heart disease was 2.4 (95% confidence interval (CI), 1.1-5.2) for persons in the lowest quartile (< or = 9.9 nmol/L) when compared with those in the highest quartile (> or = 21.8 nmol/L). However, among persons > or = 55 years the relative risk was 0.5 (95% CI, 0.3-0.8) for comparisons of the lowest versus highest quartiles. CONCLUSIONS: If the age differences in the risk for heart disease are confirmed, randomized clinical trials assessing the role of folic acid for the prevention of heart disease may need to include young adults in order to demonstrate benefits related to folate supplementation.     

Linear growth velocity in children with cerebral palsy

Retrospective analysis of an anthropometric database collected prospectively in children with cerebral palsy (CP) was carried out to evaluate linear growth velocity and identify risk factors for poor linear growth. Growth velocity measures were compared with published norms for prepubertal growth velocity and z scores were calculated. Mean growth velocity z score (Gvz) was -0.97+/-1.9. Boys grew more slowly than girls (mean Gvz = -1.5+/-1.9 versus -0.3+/-1.7 P = 0.003). Gvz did not correlate with type of CP or presence/absence of microcephaly. Young age was a risk factor for poor linear growth (mean Gvz = -2.40+/-2.6 for children under 2 years of age versus -0.76+/-1.9 ages 2 to 6 and -0.77+/-1.6 ages 6 to 10, P = 0.04). Children at nutritional risk (triceps skinfold thickness < or =55%) grew poorly (mean Gvz = -1.46+/-1.5 versus -0.30+/-1.8, P = 0.01). For children over 2 years, those with cognitive impairments grew more slowly than those with normal cognition (mean Gvz = -1.25+/-1.9 versus -0.12+/-1.8, P = 0.02) and non-ambulatory children grew more slowly than ambulatory children (mean Gvz = -1.20+/-1.5 versus -0.35+/-1.9, P = 0.03). Prepubertal children with CP grow more slowly than expected compared with age- and sex-based standards. Sex, age, cognitive impairment, ambulatory status, and nutritional state are factors which may contribute to slow growth. These results add to the growing data that children with CP have unique growth patterns. Further study is needed to clarify the factors which contribute to poor linear growth in this population.     

Distribution of myocardial beta-adrenoceptor subtypes and coupling to the adenylate cyclase in children with congenital heart disease and implications for treatment

In congestive heart failure, down-regulation of myocardial beta-adrenoceptors (beta-AR) due to an elevated sympathetic tone is well known. In infancy and childhood, heart failure is usually related to congenital heart disease (CHD). Therefore, 71 samples of right atrial tissue of infants and children with CHD undergoing cardiac surgery were studied for beta-adrenoceptor density and distribution of the beta 1-/beta 2-AR subtypes. In 49 cases, the coupling of the beta-AR to the adenylate cyclase (AC) was examined. In a further study of 19 myocardial samples, AC was selectively stimulated with beta 1- or beta 2-AR whereas the other subtype was blocked by an antagonist. The following results were obtained: (1) Infants and children with severe acyanotic or cyanotic CHD had severely reduced beta-AR densities. (2) In most of the cases, the beta-AR down regulation is beta 1-subtype selective, but in critically ill newborns with congenital aortic valve stenosis or transposition of the great arteries, there is additional significant beta 2-AR down-regulation. In Fallot patients treated with the beta-antagonist propranolol, a significant increased beta-AR number compared with untreated Fallot patients was found. (3) beta-Adrenoceptor reduction in CHD is correlated with elevated noradrenaline plasma levels, thus proving a sympathetic dysregulation. (4) In CHD with moderate hemodynamic load, beta 2-AR coupling to AC was markedly more efficient than beta 1-AR coupling. The small number of myocardial beta 2-AR produced most of the cyclic adenosine monophosphate. (5) In severe acyanotic and cyanotic CHD, a partial decoupling of the beta 2-AR to the AC occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mapping of the human thromboxane synthase gene (TBXAS1) to chromosome 7q34-q35 by two-color fluorescence in situ hybridization

Thromboxane synthase (TS) catalyzes the conversion of the prostaglandin endoperoxide into thromboxane A2 (TxA2), a potent vasoconstrictor and inducer of platelet aggregation. In concert with prostacyclin TxA2 plays a pivotal role in the maintenance of hemostasis. Deficiency of platelet TS activity has been shown to result in bleeding disorders. The potent effect of TxA2 on platelet function and vascular activity suggests a possible involvement of TS in normal and pathophysiological conditions such as cardiovascular disease. To aid in establishing the correlation of TS to disease states, we localized the human TS gene (TBXAS1) to chromosome 7q34-q35 using dual-color fluorescence in situ hybridization.     

Perioperative risk factors affecting hospital stay and hospital costs in open heart surgery for patients > or = 65 years old

OBJECTIVE: Demographic changes, associated with increased demands for open heart surgery in the elderly, place increased burden on financial resources. To evaluate perioperative risk factors affecting incidence of hospital events and estimation of hospital charges, 2577 patients > or = 65 years (range 65-91), operated on from January 1991 to December 1994, were compared with a concurrent cohort of 2642 younger patients. METHODS: Statistical analysis, by surgical procedure, focused on hospital mortality, key postoperative complications affecting length of hospital stay and hospital charges. RESULTS: Overall hospital mortality was 4.7%, 3.5% in younger patients versus 6.1% in the older group (P < 0.01). Mortality was significantly lower in patients less than 65 years undergoing coronary artery bypass grafting (3% versus 5%, P < 0.01) and valve replacement (4% versus 9%, P = 0.01). Significant risk factors for hospital death in the elderly: diabetes (P < 0.01), hypertension (P < 0.01), myocardial infarction (P < 0.01) and congestive heart failure (P < 0.01). Significant postoperative events, more common in older patients, included prolonged ventilation (P < 0.01), congestive heart failure (P < 0.01), infection (P < 0.01), cerebrovascular accident (P < 0.01), and intra aortic balloon pump (P < 0.01). Incremental risk factors for morbidity in the elderly were: higher New York Heart Association class, congestive heart failure, emergent operation, and female gender. Mean length of hospital stay for the < 65 group was 15.3 versus > 19.5 days for the > 65 group (P < 0.01). Length of stay over 18 days positively correlated with increased morbidity in both age groups. For patients > or = 65 years of age, the average hospital charge for open heart surgery was 172% higher for patients with a length of stay greater than 18 days compared with 165% for patients less than 65 years of age. CONCLUSIONS: Higher operative mortality and longer length of stay in elderly patients, resulting in increased health care costs, was associated with more co-morbidities. These results suggest interventions designed to reduce congestive heart failure and other co-morbidities may improve patient's recovery and reduce costs.     

Echocardiographic evidence of aortopulmonary collaterals in premature infants after closure of ductus arteriosus

Aortopulmonary collaterals occur in a variety of congenital heart diseases, in chronic pulmonary infection and abscesses, in association with lung tumors, and after multiple pulmonary emboli. In patients with congenital cyanotic heart disease aortopulmonary collaterals mainly occur in conditions with reduced pulmonary blood flow. We investigated 12 preterm low-birth-weight infants, gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from moderate to severe chronic lung disease after a period of mechanical ventilation. All patients developed aortopulmonary collaterals after closure of a patent ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color Doppler echocardiography and originated mainly from the descending aorta or the aortic arch. Hypoxic and hypercapnic episodes favored the development of aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and respiratory function had improved. In only one patient coiling of a large col lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels potentially aggravate chronic lung disease by increasing collateral pulmonary blood flow and reducing lung compliance. We conclude that aortopulmonary collaterals occur in bronchopulmonary dysplasia and can cause major problems in ventilated premature infants. Echocardiographic evaluation is important to prevent aggravation of chronic lung disease of infants at risk.