Seven-year review of paediatric bacteraemias diagnosed in a Spanish university hospital

This study analysed the clinical and bacteriological patterns of paediatric bacteraemia in a university hospital, by a review of 213 episodes over a period of 7 y. Streptococcus pneumoniae was the most frequent aetiological agent after the neonatal period and Streptococcus agalactiae in neonatal sepsis. Almost half of pneumococci and meningococci were penicillin non-susceptible. Four neonatal deaths attributed to bacteraemia were recorded.

Conclusion: Streptococcus pneumoniae is the leading cause of community-acquired bacteraemia. Mortality due to bacteraemia in children without underlying conditions is rare.     

Changing incidence and outcome of infants with respiratory distress syndrome in the 1990s: a population-based survey

Aim: To evaluate the trends in the incidence, clinical course and outcome of respiratory distress syndrome (RDS) in the newborn in the Oulu University Hospital region in northern Finland. Methods: In the population of 58 990 infants, the incidence rates of RDS specific to gestational age and birthweight in two consecutive periods, 1990-95 and 1996-99, were calculated. Clinical course and other neonatal morbidities were reported. All surviving infants were followed up until 1 y of corrected age. Results: The overall incidence of RDS did not change significantly (8.7/1000 livebirths in 1990-95 vs 7.6 in 1996-99; p = 0.15), but the gestational age-adjusted incidence decreased between the two consecutive periods (p = 0.005). The frequency of infants with gestational age below 28 wk tended to increase towards the late 1990s, while their RDS incidence remained unchanged. RDS-related neonatal mortality decreased in parallel with neonatal mortality, accounting for 15% of all neonatal deaths. The duration of oxygen therapy shortened (8.0 vs 5.5 d) and the incidence of pneumothorax decreased (9.7 vs 4.1%), whereas the rate of chronic lung disease at 36 wk of postconceptional age (16.4 vs 16.7%) and at 1 y of corrected age (9.2 vs 8.2%) remained unchanged, as did also associated neurosensory morbidity (8.8 vs 9.5%).

Conclusion: During the 1990s, the incidence of RDS shifted towards more immature infants and the gestational-age specific incidence decreased. The course of the disease shortened and acute complications decreased. The frequency of chronic pulmonary sequelae (and associated neurosensory morbidity) at the age of 1 y did not change significantly.     

Gram-negative bacilli associated with catheter-associated and non-catheter-associated bloodstream infections and hand carriage by healthcare workers in neonatal intensive care units.

OBJECTIVE: Bloodstream infections caused by Gram-negative bacilli are a substantial cause of morbidity and mortality in infants in neonatal intensive care units. This study describes the species of Gram-negative bacilli causing bloodstream infections in two neonatal intensive care units, compares characteristics of catheter-related and non-catheter-related bloodstream infections, and compares species and antibiotic resistance patterns of these organisms with those isolated from the hands of nurses working in the same neonatal intensive care units. DESIGN: Interventional study. SETTING: Two high-risk neonatal intensive care units. PATIENTS: Neonates hospitalized for >or =24 hrs. INTERVENTIONS: Prospective surveillance for bloodstream infections was performed in two neonatal intensive care units from March 2001 to January 2003. Hand cultures were obtained quarterly from participating nurses immediately after they performed hand hygiene. MEASUREMENTS AND MAIN RESULTS: There were 298 episodes of bloodstream infections among 2,935 admissions (5.75 episodes per 1,000 patient-days); 77 of 298 (26%) episodes were caused by Gram-negative bacilli. Among these, 47 (61.0%) were catheter-related bloodstream infections (2.61 episodes per 1,000 catheter-days). Eleven and 24 Gram-negative bacilli species were isolated from neonates and nurses, respectively. The most common Gram-negative bacilli causing bloodstream infections were Klebsiella pneumoniae (38.7%), Escherichia coli (21.2%), Enterobacter cloacae (11.2%), and Serratia marcescens (11.2%). In contrast, Acinetobacter lwoffi (18.1%), K. pneumoniae (11.7%), E. cloacae (10.6%), K. oxytoca (10.6%), and Pseudomonas spp. (7.4%) were most commonly isolated from hands of nurses. E. coli, P. aeruginosa, E. cloacae, and E. aerogenes were significantly more likely to cause bloodstream infections than to be isolated from nurses' hands (all p < .001). Although 39% of bloodstream infections were non-catheter-related, there were no significant differences in types of organisms or antimicrobial resistance patterns between catheter-related bloodstream infections and non-catheter-related bloodstream infections (all p > or = .35). Resistance patterns were similar between Gram-negative bacilli isolates from neonates and nurses' hands except for a significantly higher proportion of resistance to cefotaxime and gentamicin among neonatal isolates of K. pneumoniae (p < .05). CONCLUSIONS: Gram-negative bacilli species isolated from neonatal bloodstream infections and nurses' hands varied significantly. Clean hands of providers are an unlikely source of endemic Gram-negative bacilli, suggesting that prevention strategies should focus more on control of endogenous neonatal flora or environmental sources.     

The effect of maturation and sedation on amplitude-integrated electroencephalogram of the preterm neonate: results of a prospective study

Background and aim: Amplitude-integrated electroencephalogram (aEEG) is becoming more common in NICUs for monitoring infants after perinatal asphyxia. We used aEEGs for preterm infants, and analysed the influence of sedation and maturation on their aEEG, focusing on continuous activity. Methods: Weekly or biweekly aEEGs were performed in preterm infants and evaluated by visual analysis. Results: We analysed 92 aEEGs of 56 preterm infants (gestational age (GA) 24 + 6 to 34 + 0 wk, median 30 + 0 wk). In their first week of life, children with higher GA had a higher percentage of continuous activity: with a GA ≤ 28 + 0 wk it was 8.1%, 33.5% with a GA from 28 + 1 to 30 + 0 wk (p=0.02), 85.9% with a GA from 30 + 1 to 32 + 0 wk (p=0.005), and 89.1% with a GA from 32 + 1 to 34 + 0 wk. Continuous activity increased with growing postnatal age. With a GA ≤ 28 + 0 wk, it rose from 8.1% (first week) to 55.3% (second week) and reached 96.8% (week 6/7) (p=0.017). With GA from 28 + 1 to 30 + 0 wk, continuous activity was 33.5% (first week) and 86.6% (second week) (p=0.03).

Conclusion: The aEEG of preterm infants appears to be a good tool for monitoring cerebral activity. Continuous activity seems to indicate maturation in the neonatal brain. Further investigations of aEEGs in preterm infants should be performed.     

Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study

Aims: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population-based, complete cohort of young preterms approaching adulthood. Methods. Forty-six preterms with gestational age ≤28 wk or birthweight ≤1000 g, born between 1982 and 1985, were compared to the temporally nearest term-born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. Results: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV ₁ ) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV ₁ . Adjusted for height, gender and age, FEV ₁ was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of preterms had a positive methacholine provocation test compared to 26% of controls.

Conclusion: A substantially decreased FEV ₁ , increased bronchial hyperresponsiveness and a number of established risk factors for steeper age-related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.     

Whole blood interleukin 8 and plasma interleukin 8 levels in newborn infants with suspected bacterial infection

Aim: To evaluate a new micro-method technique for measurement of interleukin 8 in detergent-lysed whole blood (whole blood IL-8) applicable to capillary blood sampling as a test for bacterial infections in neonates. Methods: Whole blood IL-8 was measured at the first suspicion of infection along with IL-8 determined in plasma (plasma IL-8), C-reactive protein and blood cultures in 154 consecutive newborn infants with clinical signs of bacterial infection. Only 20 μl of whole blood were required for the new assay. Results: Blood culture-proven infections were diagnosed in six infants and clinical infection (defined as a combination of clinical and laboratory signs) in 20 infants. 1000 pg/ml was determined as the suitable threshold for whole blood IL-8 by ROC-curve analysis. At that threshold, whole blood IL-8 detected blood culture-proven infections with a sensitivity of 83% and a specificity of 67%. The areas under the ROC curves were similar for whole blood IL-8 and plasma IL-8.

Conclusions: Compared with plasma IL-8, whole blood IL-8 offers the advantages that measurements of whole blood IL-8 require a smaller blood sample volume and are not altered by haemolysis. The diagnostic accuracy of whole blood IL-8 remains to be studied in more detail in the future.     

Better care of immature infants; has it influenced long‐term pulmonary outcome?

Aims: To assess whether lung function in late childhood had improved in subjects born extremely prematurely in the early 1990s compared to the early 1980s, and whether neonatal factors in the respective periods had different impact on long-term pulmonary outcome. Design: Population-based, controlled cohort study. Lung function was determined in 81 of 86 (94%) eligible subjects born with gestational age ≤28 weeks or birthweight ≤1000 g in Western Norway in 1982-85 (n=46) and 1991-92 (n=35), and in 81 matched control subjects born at term. Results: The incidence of bronchopulmonary dysplasia was similar in the two periods. At follow-up, airway obstruction, hyper-responsiveness and pulmonary hyperinflation were similarly increased in both preterm cohorts compared to matched controls. Furthermore, current lung function was similarly related to neonatal respiratory disease in both birth-cohorts: FEV₁ was reduced with respectively 18.6% and 18.7% of predicted in preterms dependent on supplemental oxygen at 36 weeks postmenstrual age. Lack of antenatal treatment with corticosteroids and prolonged neonatal oxygen treatment predicted similar significant airway obstruction in the two birth-cohorts.
Conclusion: Preterms born in different eras of neonatology had similar long-term decreases in lung function. Long periods of oxygen supplementation are still required to salvage immature infants, and airway obstruction may still be a common long-term outcome.     

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

Aim: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at 1 wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. Results: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1.17-3.13, p = 0.006).

Conclusion: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.     

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

Aim: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. Methods: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. Results: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR = 4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan.

Conclusion: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.     

Recovery of metabolic acidosis in term infants with postasphyxial hypoxic-ischemic encephalopathy

Aims: To describe the base deficit (BD) values and the rate of postnatal recovery of the BD of infants with hypoxic ischemic encephalopathy due to intrapartum asphyxia; and to explore the relationships between the rate of recovery of BD, severe adverse outcome and different time patterns (acute total vs prolonged partial) of asphyxia. Methods: Clinical and laboratory data were collected from the neonatal period (n = 244) and outcome data to a minimal age of 1 y (n = 218). Rates of recovery of BD were described in four 60 min blocks of time. The values of rate of recovery were compared between the outcome groups, ignoring correlation structure within subjects and with adjustment by the generalized estimating equations method. Results: The BD normalized within 4 h of birth in all but 9 of 244 infants. The rates of recovery of BD in infants with good and severe adverse outcome respectively were 0.11 [95% confidence interval (95% CI) 0.07, 0.14] and 0.09 (95% CI 0.07, 0.12) mmol l ^-1 min ^-1 over the first 4 h after birth. The rates of recovery were similar with or without buffer therapy, and after acute near-total and prolonged partial asphyxia.

Conclusion: The BD in the great majority of infants with severe intrapartum asphyxia normalizes within 4 h of birth. The BD recovery rate of infants with adverse outcomes was similar to those with relatively good outcome. The different time patterns of asphyxial episode were not associated with differential recovery profiles.     

Immunogenicity and safety in infants of a DTwPHib full liquid vaccine

Aim: Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit, to maintain parents' compliance and to extend vaccine coverage. Different diphtheria, tetanus and whole cell pertussis (DTwP)-containing combination vaccines are licensed and used world-wide. This study assessed the immunogenicity and safety in infants of a combined diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b-CRM₁₉₇ conjugate full liquid vaccine. Methods: The safety and efficacy of a combined ready-to-use liquid vaccine containing diphtheria and tetanus toxoids, cell suspension of Bordetella pertussis and H. influenzae type b-CRM₁₉₇ conjugate vaccine (DTwPHib) were assessed in infants eligible for the local Expanded Programme on Immunization (EPI) in Valencia, Spain. The comparative group received separate injections of reference vaccines DTwP + Hib. Results: Local and systemic reactions and adverse events were generally mild and similar in the two groups. DTwPHib elicited anti-PRP antibody titres ≥0.15 μg ml^-1 in 97% and DTwP + Hib in 94% of infants. Furthermore, 89% of DTwPHib and 78% of DTwP + Hib recipients attained anti-PRP antibody titres ≥1.0 μg ml^-1, signifying long-term protection. The anti-PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group (6.65 vs 3.57 μg ml^-1). In both groups, 99% of infants achieved protective (≥0.01 IU ml^-1) anti-diphtheria antibody levels and all children achieved protective (≥0.1 IU ml^-1) anti-tetanus antibody levels. DTwPHib caused a ≥2-fold increase in anti-pertactin antibody titres in 91% and a ≥4-fold increase in 82% of recipients. The corresponding proportions in the DTwP + Hib group were 95% and 90%. DTwPHib induced a ≥2-fold increase in anti-Aggl2 and 3 antibody levels in 79% and a ≥4-fold increase in 73% of recipients. The corresponding proportions among DTwP + Hib infants were 85 and 82%. Conclusion: Overall, the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants.     

Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

Aim: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. Methods: Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were ≤15 y of age. The diagnosis of sarcoidosis was reconfirmed in 48/81 (59%) patients. In 35/48 (73%) patients, diagnosis was verified by histology, and in 13 it was substantiated by paraclinical/clinical findings. Results: The series comprised 26 boys and 22 girls (male/female ratio 1.18). Median age at diagnosis was 13 y (range 0.7-15). In 1979-1994 the incidence was 0.29 per 100 000 person-years ≤15 y of age. The incidence was 0.06 in children ≤4 y of age and increased gradually with age to 1.02 in children aged 14-15 y. General malaise, fever, weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy and central nervous system symptoms were common; 31% of patients had erythema nodosum, 12.5% sarcoid skin lesions, 25% uveitis/iridocyclitis and 4.2% sarcoid arthritis. Chest X-rays were normal (stage 0) in 10% of patients, and showed pulmonary infiltrates stage I in 71%, stage II in 8.3% and stage III in 8.3%. Lung function tests were examined in 13 patients: 50% had decreased FEV ₁ and vital capacity, 80% decreased D _L CO. Haemoglobin values were normal. Some patients had mild leukopenia, some moderate leukocytosis and a few had moderate eosinophilia. Erythrocyte sedimentation rate was elevated in 40% of the patients. Plasma calcium was elevated in 30% of the patients; 4 patients had severe hypercalcaemia and elevated plasma creatinine, and 1 patient had nephrocalcinosis. Serum angiotensin-converting enzyme was elevated in 55% of the patients. Liver function tests were normal with no sarcoid hepatitis. Urinary examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria.

Conclusion: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults.     

Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units

Aim: There is relatively little published information regarding gastro-oesophageal reflux (GOR) in preterm infants, therefore the aim of this study was to elucidate the incidence of GOR and management regimes employed for this condition in major neonatal intensive care units (NICUs). Methods: A standard questionnaire was sent to consultants in 77 level II (or secondary) and III (or tertiary) NICUs. Results: Seventy-eight percent of consultants responded. Of babies born in these units, 40% were less than 34 wk gestational age and the estimated incidence of GOR in this group was 22%. GOR was diagnosed on a clinical basis alone in 42% of units, 8% used clinical features and/or investigations, and 50% used clinical features plus investigations and/or therapeutic trials. Intra-oesophageal pH monitoring was available in 93% of units but used regularly in only 32% of suspected cases. Common treatment strategies for diagnosed GOR included non-drug options—body positioning (98%) and placement on a slope (96%); and drugs—H ₂ -receptor antagonists (100%), feed thickeners (98%), antacids (96%), prokinetic agents (79%), proton-pump inhibitors (65%) and dopamine-receptor antagonists (53%). However, the frequency with which all of these treatments were used varied widely between units. Surgery was required in only 1% of cases.

Conclusions: GOR is perceived to be a common condition in preterm infants but the lack of published evidence relating to the management of GOR in preterm infants is reflected in the wide variation in diagnostic and treatment strategies used in major NICUs. It is clear that randomized, controlled trials to evaluate appropriate and effective treatments are needed.     

Supraventricular tachycardia: an incidental diagnosis in infants and difficult to prove in children

Aims: To determine (a) the age distribution at first clinical supraventricular tachycardia (SVT) presentation; (b) the time interval between first clinical suspicion and electrocardiographic proof of SVT; c) the most indicative symptoms and signs of SVT; and (d) the SVT mechanism and its age distribution according to surface ECG. Methods: The records of 55 children (32 males and 23 females) with electrocardiographically proven SVT but without congenital heart disease were reviewed. Results: At diagnosis, 27 patients (49%) were younger than 1 y (infants), and 28 (51%) were older than 1 y (children). Only a quarter of infants presented with symptoms. The majority (20/27), however, were detected during routine investigation without having any complaints. Children presented with symptoms (mostly palpitations) in almost 90% of cases. Despite these symptoms, the median time interval between first clinical presentation suggestive of SVT and electrocardiographic proof of SVT was 138 d. Using surface ECG, we were unable to show any age-dependency of the SVT mechanism in our study group.

Conclusion: In infants SVT is a chance finding; SVT can only be proven electrocardiographically with a median delay of 138 d, despite the presence of symptoms; SVT using a (concealed) accessory pathway is the most common mechanism     

Short-term ceftriaxone therapy for treatment of severe non-typhoidal Salmonella enterocolitis

Aim: To evaluate the clinical efficacy of a short-course ceftriaxone therapy in the treatment of paediatric patients with severe non-typhoidal Salmonella enterocolitis. Methods: During a 1 y period, all paediatric patients who were suspected having Salmonella enterocolitis by the presentation of bloody and/or mucoid diarrhoea with or without fever were eligible for the study. Patients with either negative stool cultures or bacteraemia were excluded. Severe enterocolitis was defined as a bloody and/or mucoid diarrhoea associated with high fever persisting for longer than 48 h and signs of moderate or severe dehydration. The patients with severe enterocolitis were assigned to treatment with ceftriaxone (50 mg kg^-1 d^-1) for 3-5 d, while the rest were given supportive treatment only. Before treatment all study patients received blood testing for white blood cell (WBC) count, C-reactive protein (CRP) level and blood culture. The duration of the fevers was recorded. Patients were followed up after clinical recovery for the possibility of relapse. Results: Seventy-three patients with culture-confirmed Salmonella enterocolitis without bacteraemia were analysed. The duration of fever was longer in severe cases who were treated with ceftriaxone than those who were not. However, rapid defervescene was found after short-course ceftriaxone therapy in those patients with severe enterocolitis. CRP was significantly higher in severe cases. There was no significant difference in the WBC count between the two groups of patients. No relapse was found in these patients.

Conclusion: High CRP, prolonged high fever and signs of moderate or severe dehydration appear appropriate to define severe cases of Salmonella enterocolitis. Short-course ceftriaxone therapy is clinically beneficial to these patients. Neither clinical nor microbiological relapse was seen after therapy.     

Diaphragm dimensions of the healthy term infant

Aim: Human neonatal diaphragm development has not been extensively studied. Previous work in children and adults suggests that diaphragm thickness (t[Formula: See Text]) is in scale with body size such that maximal transdiaphragmatic pressure (P[Formula: See Text]) remains relatively constant. Such assessments have not been made in healthy term infants. This study was designed to evaluate the relationships among t[Formula: See Text], body dimensions and P[Formula: See Text] in healthy term infants. Methods: It was hypothesized that in healthy term infants 1) t[Formula: See Text] is positively correlated with body size and 2) calculated P[Formula: See Text] is independent of body weight and length. Fifteen clinically stable term infants (8 males and 7 females) were recruited [birthweight (BW), 3.3 ± 0.7 kg, (mean ± SD); head circumference (HC), 33.7 ± 2 cm; body length (BL) 50 ± 3 cm; gestational age (GA) 39 ± 1 wk; and postnatal age 1.7 ± 0.8 day]. Ultrasound was used to visualize the diaphragm at the level of the zone of apposition and measure t[Formula: See Text]. Standard techniques were used to measure the anthropometric dimensions of the rib cage. P[Formula: See Text] was calculated using the piston-in-cylinder model of diaphragm function. Results: Significant correlations were found among t[Formula: See Text] and BW (R = 0.58), BL (R = 0.58) and HC (R = 0.65) but not between GA (R = 0.20). Larger infants tended to have thicker diaphragms and larger cross-sectional areas of the lower rib cage (A[Formula: See Text]). For the group, calculated P[Formula: See Text] was independent of either body weight or length and was greater than that calculated for adults.

Conclusion: It is concluded that diaphragm mass in healthy term infants is proportional to body size, whereas calcuated P[Formula: See Text] is independent of body size. Since calculated P[Formula: See Text] is greater than that predicted for adults, there may be perinatal diaphragm strengthening. This may assist the infant in generating sufficient pressure to overcome the enormous elastic and resistive loads imposed during perinatal pulmonary transition.     

Plasma nitrite/nitrate and endothelin-1 concentrations in neonatal sepsis

Aim: To determine the changes in plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) concentrations during neonatal sepsis. Methods: In a prospective study, 60 consecutive newborns meeting the criteria for sepsis and without receiving exogenous nitric oxide (25 haemoculture-positive [HC+] and 35 haemoculture-negative [HC-]) were compared with 68 healthy newborns (46 full-term and 22 preterm). NOx and ET-1 concentrations were measured in each newborn within 48 h of diagnosis of sepsis and then every third day up to three determinations. SNAP-II and SNAPPE-II severity scores were performed at the moment of highest clinical severity. Results: At the beginning of the sepsis period, controls and septicaemic newborns had similar NOx and ET-1 levels, with the exception of infants with severe HC+ sepsis. Throughout the sepsis period, NOx increased in moderate HC+ sepsis and decreased in HC- sepsis, reaching a significant difference at the end of the study period (59.9 ± 72.7 vs 33.9 ± 15.3 μmol/L; p = 0.036). Meanwhile, ET-1 in newborns with severe HC+ sepsis remained higher than that in the moderate HC+ sepsis group and HC- group, reaching significant differences in all the periods. The highest ET-1 value was positively correlated with SNAP-II and SNAPPE-II scores.

Conclusion: NOx concentrations increased throughout the neonatal HC+ sepsis period, reaching significant differences after 7-9 d. The highest ET-1 levels in neonatal HC+ sepsis emerged before the NOx peak, at 3-5 d, and later decreased. Only newborns with severe HC+ sepsis presented a significant increase in ET-1 concentrations from the beginning of the septicaemic process.     

Effect of tilting on cerebral haemodynamics in preterm infants with periventricular leucencephalomalacia

Aim: Measurement of cerebral haemodynamics to detect impaired cerebral blood flow and impaired cerebral autoregulation might make prevention of brain lesions and especially periventricular leucencephalomalacia (PVL) achievable. Methods: Changes in cerebral blood volume (CBV) and the cerebral haemoglobin oxygenation index (cHbD) following tilting up and down in 10 preterm infants with PVL and 25 preterm infants without PVL, measured by near infrared spectroscopy (NIRS), were analysed. Tilting manoeuvres were recorded with a polysomnographic system in combination with NIRS. CBV and cHbD of the baseline phase (1 min before tilting) were compared with data from the post-tilting phase (1 min after tilting). Results: Changes in CBV and cHbD after tilting were significantly pronounced in infants with PVL compared with infants without PVL. CBV decreased in infants with PVL, by -0.099 ± 0.081 ml 100 g ^-1 brain (mean ± SD) after tilting up, and increased by 0.106 ± 0.104 ml 100 g ^-1 brain after tilting down. CBV decreased in infants without PVL, by -0.041 ± 0.068 ml 100 g ^-1 brain after tilting up, and increased by 0.020 ± 0.096 ml 100 g ^-1 brain after tilting down. cHbD showed similar changes after tilting.

Conclusion: Changes in CBV and cHbD after tilting were pronounced in preterm infants with PVL and this may indicate reduced cerebral autoregulatory capacity.     

Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation

Aim: To determine cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation during the first three days of life. Low cerebral blood flow has been associated with both intra-ventricular haemorrhage and periventricu-lar leucomalacia. It is well established that cerebral blood flow increases over the first three days of life in extremely preterm infants who are conventionally ventilated with intermittent positive pressure ventilation. However, there is no information about cerebral blood flow in preterm babies undergoing high-frequency oscillatory ventilation. In addition, there are concerns that high-frequency oscillatory ventilation may be associated with an increased incidence of intra-ventricular haemorrhage in premature infants. Methods: Thirteen appropriately grown, preterm infants of less than 28 wk gestation who were admitted to the neonatal unit at University College Hospital, London were studied using near infrared spectroscopy. Left ventricular output and right ventricular output were assessed echocardiographically. Results: Extremely preterm infants undergoing high-frequency oscillatory ventilation have remarkably low cerebral blood flow in the first 12 h of life, median 6.7 (range 4.4-11) mls. 100 g[Formula: See Text] min[Formula: See Text] followed by an increase over the subsequent three days. Left ventricular output also increased over the first three days of life, whereas right ventricular output showed no clear relationship with time. Despite low cerebral blood flow only one infant had evidence of major cerebral injury.

Conclusion: Cerebral blood flow is extremely low in this group of preterm babies. Despite this extremely low cerebral blood flow, the clinical outcome is good. There was an increase in cerebral blood flow and a corresponding increase in left ventricular output over the first few days of life.     

Somatic factors at 8 years of age in children with recurrent use of antibiotics in early infancy

Aim: To examine the influence of recurrent therapy with antibiotics (RTA) in infancy on children's somatic factors at 8 y of age. Methods: Subject selection was based on stratified randomized cluster sampling. Altogether 1287 infants were potential participants in the follow-up study. Children with ≥6 courses of antibiotics (100 children) during their first 18 mo of life and children with no (62%) or ≤2 courses (38%) of antibiotics participated in a clinical examination in a case-control setting (100 matched controls) at the age of 8 y. Results: The children with RTA continued to have more infections and had had more courses of antibiotics compared to controls during the follow-up. There was no clinically significant difference in the somatic and dental status at the age of 8 between the two groups. The parents of the children with RTA reported significantly more often recurrent infections than the parents of the controls.

Conclusions: The children with recurrent therapy with antibiotics in early childhood also continue to be prescribed more antibiotics in later childhood when compared to those who received no or few antibiotics in infancy. However, recurrent infections and medications do not seem to have a marked effect on the somatic and dental status of these children at 8 y of age.