Plasma lipid and apolipoprotein concentrations in full term infants fed formula supplemented with long-chain polyunsaturated fatty acids and cholesterol

Recent data indicate that supplementation of infant formula with ω-3 and ω-6 long-chain polyunsaturated fatty acids might offer developmental benefits for full term infants. We investigated biochemical consequences of feeding formula supplemented with egg lipids to provide long-chain polyunsaturated fatty acids and compared triglyceride, cholesterol, lipoprotein cholesterol (HDL₂-cholesterol, HDL₃-cholesterol, non-HDL-cholesterol) and apolipoprotein A-I, A-II and B concentrations in full term infants fed either conventional formula (n = 10) or a formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol in amounts similar to those found in mature human milk (n = 12). At the age of 5 days, cholesterol, non-HDL-cholesterol and triglyceride concentrations were significantly higher in infants fed supplemented than in those receiving conventional formula. At the age of 30 days, triglyceride concentrations were significantly higher with supplemented than with conventional formula. Thereafter throughout the study, no significant differences were seen between the two groups. Conclusion Full term infants fed formula supplemented with ω-3 and ω-6 long-chain polyunsaturated fatty acids and cholesterol showed significantly higher plasma cholesterol and triglyceride concentrations than infants receiving conventional formula on day 5 and on days 5 and 30, respectively. Thereafter no appreciable effect of diet on plasma phospholipid, triglyceride, cholesterol, lipoprotein cholesterol and apolipoprotein concentrations were seen. Received: 13 March 1996 / Accepted: 21 October 1996     

Inhibition of enteropathogenic Escherichia coli adhesion to HEp-2 cells by colostrum and milk from mothers delivering low-birth-weight neonates

Breast milk samples from three groups of Brazilian women were evaluated for their inhibitory effect on enteropathogenic Escherichia coli (EPEC) adhesion to HEp-2 cells: G1, mothers delivering preterm babies of appropriate birth weight (n = 12); G2, mothers delivering term babies of low birth weight (n = 11); G3, the control group, mothers delivering term babies of appropriate birth weight (n = 39). Colostrum samples were obtained at 48–72 h and milk samples on the 7th, 30th and 60th days after delivery. All samples showed strong inhibitory activity (66%–100%), without significant differences among the three groups and four periods. Total IgA and anti-EPEC IgA concentrations were significantly higher in colostrum than in milk samples in the three groups studied. The levels of colostral IgA and anti-EPEC IgA observed in G1 and G2 were significantly higher compared to the control group. Western blotting assays showed that individual samples as well as pools of colostrum or milk samples contain IgA antibodies to many EPEC outer membrane proteins. A 94 kDa band with molecular weight consistent with the EPEC adhesin named intimin, was recognized by all samples analysed. Bands of different molecular weight were also recognized by some samples of colostrum and milk, such as a band of ∼ 18.4 kDa, with molecular weight equivalent to bundle-forming pilus subunits. Conclusion Our results suggest that colostrum and milk from mothers of premature and small-for-date term neonates are as effective in protecting the newborn against EPEC infections as those from mothers of term babies of appropriate birth weight. Received: 14 July 1996 / Accepted: 12 October 1996     

Serum concentration of granulocyte colony stimulating factor in term and preterm infants

We measured serum granulocyte colony stimulating factor (GCSF) concentration and absolute neutrophil count in four groups of infants: (1) 15 healthy term newborn infants; (2) 21 healthy preterm newborn infants, with mean (SD) birth weight 1583 (533) g, and gestational age 32.0 (3.8) weeks; (3) 5 infected newborn infants; (4) 22 6-month-old control infants. Median (range) serum GCSF concentration was 132.2 (41.5–176.0) pg/ml in term infants, 51.5 (1.8–175.7) pg/ml in preterm infants and 138.9 (54.1–449.8) pg/ml in 6-month-old control infants, with a significant reduction in preterm infants, as compared to term and control infants. GCSF levels were significantly higher in the infected infants, as compared to healthy neonates. Conclusion A significant positive relationship was found in term and preterm infants between serum GCSF concentration and gestational age or birth weight. No relationship was found between serum GCSF concen tration and neutrophil count. The low GCSF baseline levels may contribute to the increased incidence and severity of infection in preterm infants. Received: 17 May 1996 and in revised form: 20 July 1996 / Accepted: 29 July 1996     

Total energy expenditure in infants with bronchopulmonary dysplasia is associated with respiratory status

Growth failure is a well-known problem in infants with bronchopulmonary dysplasia (BPD). We studied BPD infants' total daily energy expenditure (Ee), nutritional balance, and growth in relation to their past and current clinical status. Applying the doubly labelled water technique, Ee was measured in nine preterm infants with BPD receiving supplemental oxygen (postnatal age 61 ± 13 days) and nine matched controls (36 ± 21 days) during a 6-day period. Energy and protein balance, past and present respiratory status, and growth were assessed as well. The results show that Ee was higher in the BPD infants compared to controls (73 ± 9 vs 63 ± 8 kcal/kg/day, P < 0.05), but their faecal energy loss was lower (P < 0.01). Weight gain, energy intake, energy cost of growth, protein retention, and physical activity were not different. The respiratory frequency (RR) in the BPD infants was elevated in comparison with controls (P < 0.01). Within the BPD group, RR was positively correlated with energy expenditure (regression equation: Ee [kcal/kg/day] = 26.3 + 0.71*RR [min⁻¹]; r ² = 0.82, P < 0.001), and was the single most significant determinant of Ee. Conclusion Total energy expenditure in BPD infants is elevated and is strongly associated with their respiratory status. These findings could be of practical value for the nutritional management in infants with severe BPD. Received: 17 January 1996 / Accepted: 23 July 1996     

Effect of blood transfusion on apnoea, bradycardia and hypoxaemia in preterm infants

We studied the effect of blood transfusion on the frequency of apnoea, bradycardia and hypoxaemia in 21 spontaneously breathing preterm infants with a median gestational age at birth of 28 (range 23–31) weeks. Age at time of study was 22 days (3–84), weight 925 g (640–2120). The patients exhibited frequent episodes of bradycardia and/or hypoxaemia and were anaemic (median haemoglobin level 109 (82–120) g/l). One infant received two transfusions and was thus studied twice. Four-hour recordings of pulse oximeter saturation (SpO₂), pulse waveforms, transcutaneous oxygen pressure, electrocardiogram, breathing movements and nasal airflow were performed immediately before and after transfusion, and again after a further interval of 12 h. Recordings were analysed for isolated and periodic apnoeas (> 4 s), bradycardias (heart rate < 2/3 of baseline), and episodic desaturation (SpO₂≤ 80%). There were no significant changes in the frequency, severity and/or duration of apnoea, bradycardia or desaturation following transfusion. The average SpO₂ nadir reached during each desaturation, however, increased by 3% following transfusion (P < 0.05), and there was a trend towards shorter desaturations. Conclusion The occurrence of frequent episodes of apnoea, bradycardia and/or hypoxaemia does not, on its own, justify a blood transfusion in moderately anaemic preterm infants. Received: 25 July 1996 / Accepted: 24 September 1996     

The effect of blood transfusion on oxygenation in premature ventilated neonates

The effect of blood transfusion to maintain a preset packed cell volume (PCV) level in preterm ventilated infants has been investigated. Fifty infants, median gestational age 26 (range 23–33) weeks and postnatal age 4 (1–29) days, transfused a median of 15 ml/kg of blood in response to a PCV ≤ 40% were retrospectively identified and their medical records reviewed to determine the change in PCV and haemoglobin resulting from the transfusions. In addition, their mean airway pressure (MAP) was noted and, as an index of oxygenation, their oxygenation index (OI), alveolar/arterial oxygen gradient (AaDO₂) and arterial/alveolar (a/A) ratio calculated 12 h, 6 h and immediately prior to the transfusion and immediately post, 12, 18 and 24 h after the transfusion. The transfusion improved the PCV and haemoglobin (P < 0.0001). No significant changes in MAP or level of oxygenation were experienced in the 12 h prior to the transfusion. Post transfusion, despite no significant change in MAP, the AaDO₂ OI and a/A ratios compared to immediately prior to the transfusion were significantly better at 12, 18 and 24 h. Conclusion It is useful to transfuse ventilated preterm infants to maintain their PCV above a preset level. Received: 8 March 1996 / Accepted: 1 July 1996     

[18F]-Fluorodeoxyglucose-positron emission tomography findings in preterm infants with severe periventricular leukomalacia and hypsarrhythmia

Two preterm infants with extensive periventricular leukomalacia (PVL) were examined by [¹⁸F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) at the corrected ages of 18 and 34 days. They showed similar clinical courses including oculoclonic seizure, hypsarrhythmia and severe mental retardation, in addition to spastic quadriplegia. FDG-PET study of these two infants with severe PVL disclosed poorly developed metabolic activity in the primary sensorimotor cortex, while the MRI images displayed only periventricular white matter lesions. Conclusion Positron emission tomography may dis‐close cortical involvement in infants with severe periventricular leukomalacia. Received: 23 March 1996 / Accepted: 10 August 1996     

A critical appraisal of current management practices for infant regurgitation – recommendations of a working party

Regurgitation is a common manifestation in infants below the age of 1 year and a frequent reason of counselling of general practitioners and paediatricians. Current management starts with postural and dietary measures, followed by antacids and prokinetics. Recent issues such as an increased risk of sudden infant death in the prone sleeping position and persistent occult gastro-oesophageal reflux in a subset of infants receiving milk thickeners or thickened “anti-regurgitation formula” challenge the established approach. Therefore, the clinical practices for management of infant regurgitation have been critically evaluated with respect to their efficacy, safety and practical implications. The updated recommendations reached by the working party on the management of infant regurgitation contain five phases: (1A) parental reassurance; (1B) milk-thick ening agents; (2) prokinetics; (3) positional therapy as an adjuvant therapy; (4A) H2-blockers; (4B) proton pump inhibitors; (5) surgery. Received: 26 July 1996 / Accepted: 22 November 1996     

Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants

Nasal continuous positive airway pressure (CPAP) applied shortly after birth is said to be an effective treatment of respiratory distress in very low birth weight infants (VLBW). We tested the hypothesis that the use of early nasal CPAP (applied as soon as signs of respiratory distress occurred, usually within 15 min after birth) reduces the need for intubation, the duration of intermittent mandatory ventilation and the incidence of bronchopulmonary dysplasia. All liveborn VLBW infants (birth weight < 1500 g) admitted to our tertiary neonatal intensive care unit in 1990 (historical controls) and in 1993 (early nasal CPAP group) entered the study. The intubation rate was significantly lower after introduction of nasal CPAP (30% vs 53%, P = 0.016). Median duration of intubation was 4.5 days (interquartile range 3–7 days) before versus 6.0 days (2.8–9 days) after nasal CPAP was introduced (P = 0.73). The incidence of bronchopulmonary dysplasia was not reduced significantly (32% vs 30%, P = 0.94). Survival until discharge was 89.5% before versus 92.9% after introduction of nasal CPAP (P = 0.54). Conclusion Early nasal CPAP is an effective treatment of respiratory distress in VLBW infants, significantly reducing the need for intubation and intermittent mandatory ventilation, without worsening other stan dard measures of neonatal outcome. We found no significant decrease in the incidence of bronchopulmo nary dysplasia. Received: 5 February 1996 and in revised form: 12 September 1996 / Accepted: 23 October 1996     

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant

 Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. Conclusion Surfactant therapy normalizes the sur factant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients. Received: 23 October 1995 / Accepted: 20 May 1996     

Fatty acid balance studies in preterm infants fed formula milk containing long-chain polyunsaturated fatty acids (LCP) II

A milk formula (Prematil-LCP) containing long-chain polyunsaturated fatty acids (LCP) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants. A double-blind randomized controlled trial was performed comparing fatty acid absorption from Prematil-LCP (n = 10) and standard Prematil (n = 10). Formula-fed preterm infants underwent 3 d fat balances (once full enteral feeds were established) along with a parallel human milk fed group (n = 11). Plasma samples were taken on the last day. Median total fat excretion (absorption, %) was 2.34 g kg (82.0), 2.64 g kg (82.9) and 1.65 g kg (87.8) with Prematil, Prematil-LCP and human milk feeding, respectively. This reflected differences in the excretion and absorption of long-chain saturated fatty acids. All groups excreted detectable LCP. LCP disappearance was higher in infants fed human milk than in those fed Prematil-LCP, particularly for n -6 LCP (p <0:01). Nevertheless, excreted LCP equated to <30% dietary intake, with Prematil-LCP feeding. Plasma lipid fatty acid composition reflected differences in dietary LCP intake.     

The effect of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in newborn infants investigated by near infrared spectrophotometry

The objective of this study was to investigate the influence of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables in newborn infants. Thirteen preterm infants with anaemia (haematocrit < 0.33) and ten infants with polycythaemia (haematocrit > 0.65) were studied during blood transfusion and haemodilution respectively using adult red blood cells and partial plasma exchange transfusion. Changes in cerebral concentrations of oxyhaemoglobin (cO₂Hb), deoxyhaemoglobin (cHHb), total haemoglobin (ctHb), (oxidized - reduced) cytochrome aa₃ (cCyt.- aa₃) were continuously measured using near infrared spectrophotometry throughout the whole procedure. Simultaneously, changes of mean CBFV in the internal carotid artery were continuously measured using pulsed Doppler ultrasound. Heart rate, transcutaneous partial pressure of oxygen and carbon dioxide, and arterial O₂ saturation were continuously and simultaneously measured. Blood transfusion resulted in increase of cO₂Hb, cHHb, ctHb and red cell transport (product of CBFV and haematocrit), whereas CBFV decreased. The increase of cO₂Hb exceeded that of cHHb, reflecting improvement of cerebral O₂ supply. Haemodilution resulted in a decrease of cO₂Hb, cHHb and ctHb, whereas CBFV increased. Red cell transport was unchanged. The decrease of cO₂Hb exceeded that of cHHb, reflecting decreased cerebral O₂ supply. cCyt.aa₃ decreased after blood transfusion and remained unchanged after haemodilution, but the reliability of these results is uncertain. With the exception of a small, but significant increase in transcutaneous partial pressure of oxygen after blood transfusion, the other variables showed no changes. Each blood withdrawal during exchange transfusion resulted in only a significant increase in heart rate without changes in the other variables measured, suggesting unchanged cerebral perfusion. Conclusion In newborn infants blood transfusion in anaemia results in improvement of cerebral oxygenation, but haemodilution in polycythaemia does not improve cerebral oxygenation despite possible improvement of cerebral perfusion. Received: 21 December 1995 and in revised form: 29 August 1996 / Accepted: 4 September 1996     

Final height and puberty in 40 patients after antileukaemic treatment during childhood

Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal patients treated for 2–3 years with intensive maintenance therapy blunted growth resulted in a significant loss of −1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM protocol) final height equalled projected adult height, despite 18 Gy CI. Conclusions (1) multiagent chemotherapy is of major impact for growth and puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on age when antileukaemic therapy is applied. Received: 22 April 1996 / Accepted: 24 September 1996     

The effect of obesity, age, puberty and gender on resting metabolic rate in children and adolescents

During puberty fat-free mass (FFM) and fat mass (FM) change quickly and these changes are influenced by sex and obesity. Since it is not completely known how these changes affect resting metabolic rate (RMR), the aim of the present study was to investigate the effect of body composition, age, sex and pubertal development of postabsorptive RMR in 9.5- to 16.5-year-old obese and non-obese children. Postabsorptive RMR was measured in a sample of 371 pre- and postpubertal children comprising 193 males (116 non-obese and 77 obese) and 178 females (119 non-obese and 59 obese). RMR was assessed by indirect calorimetry using a ventilated hood system for 45 min after an overnight fast. Body composition (FFM and FM) was estimated from skinfold measurements. The mean (± SD) RMR was significantly (P < 0.001) lower in non-obese (males: 5600 ± 972 kJ/24h; females: 5112 ± 632 kJ/24h) than in obese (males: 7223 ± 1220 kJ/24h; females: 6665 ± 1106 kJ/24h) children. This difference became non-significant when RMR was adjusted for body composition (FFM + FM). However, the difference between the genders still remained significant (control male: 6118 ± 507, control female: 5652 ± 507, P < 0.001; obese male: 6256 ± 507, obese female: 5818 ± 507 kJ/24h, P < 0.001). The main determinant of RMR was FFM. In the whole cohort, FFM explained 79.8% of the variation in RMR, followed by age, gender and FM adding further 3.8%, 1.1% and 0.8% to the predictability of RMR, respectively. No significant contribution for study group (obese, non-obese), pubertal stage, or fat distribution was found in the regression for RMR. The adjusted value of RMR (for FFM and FM) slightly, but significantly (P < 0.01) decreased between the age of 10–16 years, demonstrating the important effect of age on RMR. Conclusions The resting metabolic rate of obese and control children is not different when adjusted for body composition. The main determinant of RMR is the fat-free mass, however, age, gender and fat mass are also significant factors. Pubertal development and fat distribution do not influence RMR independently from the changes in body composition. Received: 4 March 1996 / Accepted: 21 August 1996     

Blood transfusion

To study the relationship between blood transfusion, iron load and retinopathy of prematurity (ROP), we performed a prospective observational cohort study in a level III neonatal intensive care unit. During a 24-month period, data on the volume of blood transfused during the first 6 weeks of life and on the incidence of ROP were collected in all surviving very low birth weight infants (n = 114 median birth weight␣1130␣g, range 520–1500 g). Associations between these data and values for serum iron, transferrin and ferritin measured at weekly intervals were analysed in a nested case-control design by logistic regression. There was a significant association between the volume of blood transfused and the incidence of ROP. After adjustment for gestational age at birth, duration of oxygen therapy FiO₂> 0.3) and duration of mechanical ventilation, the relative risk of developing ROP was 6.4 (95% CI 1.2–33.4) for infants who had received 16–45 ml/kg, and 12.3 (1.6–92.5) for those who had received more than 45 ml/kg of blood (reference, 0–15 ml/kg). In contrast, there was no independent relationship between ROP and any of the parameters on iron metabolism analysed. Conclusion This study confirms the role of blood transfusions as an independent risk factor for ROP. This relationship, however, does not appear to be mediated via an increased iron load. Received: 5 September 1996 and in revised form: 17 October 1996 / Accepted: 26 October 1996     

Long-chain polyunsaturated fatty acid status and early growth of low birth weight infants

We correlated arachidonic acid (AA) and docosahexaenoic acid (DHA) status with anthropometric measures and growth rates in a group of low birth weight infants (≤2500 g; gestational ages 30–41 weeks; n = 143). AA and DHA status were measured in erythrocytes (RBC) and plasma cholesterol esters (CE) during days 10 to 42. Infants received preterm formula without long-chain polyunsaturated fatty acids (LCP; n = 81), with LCP (n = 29) or maternal milk (n = 33). RBC AA contents on day 10 were correlated (P < 0.05) with birth weight in breast-fed infants and all formula-fed infants, with on day 10 a standard deviation score (SDS) for weight, length and occipito-frontal circumference in all formula-fed infants, and with on day 10 an SDS for length in breast-fed infants. Brain weight was related to RBC DHA and CE DHA contents on both day 10 and day 42 in formula-fed infants. Of the variances of brain growth parameters on day 42, 21–34% were explained by DHA status on day 42 and protein intake from days 10–42. Conclusion We conclude that parameters of early neonatal AA status are related to intra-uterine rather than to post-natal growth. Parameters of post-natal brain growth are related to RBC DHA and CE DHA contents on day 42, and to dietary protein intake. These results point to the importance of dietary DHA for brain growth in the first 6 post-natal weeks. Received: 23 July 1996 / Received in revised form and accepted: 18 June 1997     

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

 Administration of human growth hormone (GH) has yielded conflicting results concerning its role on thyroid function in patients with Ullrich-Turner syndrome. Therefore, we investigated the course of thyroid hormone parameters and thyroxin binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox) or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During the 1st year the patients received only GH. There was no change in T4, fT4, and TSH levels, T3 increased significantly (P <  0.01) after 6 and 12 months, resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased after 6 months and remained elevated at 12 months. A significant positive correlation was found between the change of T4 and TBG after 6 months (r = 0.47, P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were further investigated after addition of an anabolic compound; 7 received Ox (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological age was comparable in these groups (10.7 ±  2.7 vs 10.7  ± 3.6 years). After 6 months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3 showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after 6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05). There was no correlation between the changes in T4 and IGF-I, TSH and TBG, respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same extent as in the Ox-treated patients, whereas the thyroid parameters did not change. Conclusion The observed changes in thyroid hormone and TBG levels in the Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be linked to altered pancreatic functions regulating carbo-hydrate metabolism. Received: 22 April 1996 / Accepted: 1 August 1996     

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk,standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids

The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n=18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with -linolenic acid and linoleic acid (n=11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n=12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from -linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding.Conclusion Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.     

Technical considerations for inhaled nitric oxide therapy: time response to nitric oxide dosing changes and formation of nitrogen dioxide

The aim of the present study was to analyse the time response to nitric oxide (NO) dosing changes as well as the formation of nitrogen dioxide (NO₂) with different ventilation systems, respirator settings and application sites during NO inhalation. The inspired NO and NO₂ concentrations were continuously measured using chemiluminiscence within a dummy ventilatory system equipped with two different respirator systems (Siemens Servo 900c and Bear BP 2001). NO was either introduced into the afferent limb of the ventilatory circuit close to the endotracheal tube (site A) or into the so-called low pressure port of the Servo 900c respirator, far away from the endotracheal tube (site B). In addition, the decay of the inspired NO concentration after cessation of the NO gas flow was studied. This decay was considerably prolonged when NO was introduced at site B (time constants: τ = 7.19 min versus τ = 0.29 min). Within the concentration range studied (0–25 ppm NO) a linear correlation between the NO and NO₂ concentration was found. At site A and an inspired oxygen concentration of > 0.95 NO₂ formation amounts to 1.14% ± 0.11% of the NO concentration. Using this value one can calculate the NO₂ formation for a given NO dose. For example, when 40 ppm NO are applied, a concentration of 0.45 ppm NO₂ can be expected, which is well below the relevant toxic concentrations. However, when NO was introduced at site B, NO₂ formation was significantly increased to 1.61% ± 0.16%. Passage of the ventilated gas through soda lime led only to a slight and insignificant reduction in NO₂ concentration. The continuous flow respirator BP 2001 showed a significantly lower NO₂ concentration when compared to the non-continuous flow respirator Servo 900c (0.64 ± 0.11% vs.1.14 ± 0.11%). Conclusion The application of NO close to the endotracheal tube is associated with a much faster response of the actual inspired NO concentration to dosing changes and shows the lowest NO₂ formation. In order to avoid toxic NO₂ concentrations, an upper limit of 40 ppm NO is recommended for continuous NO inhalation. Received: 21 May 1996 / Accepted: 16 September 1996     

Corticosteroid treatment of erythema multiforme major (Stevens-Johnson syndrome) in children

 The effectiveness of systemic corticosteroids in erythema multiforme major (EMM) is controversial. We therefore evaluated the efficacy of corticosteroids in the treatment of EMM in a prospective study of 16 children with EMM admitted to our department within 3 days from the onset of rash. Ten patients (group A) received bolus infusions of methylprednisolone (4 mg/kg/day) while six had only supportive treatment (group B). The early use of corticosteroids compared to supportive treatment resulted in: (1) significant reduction of the period of fever (4.0 ± 1.9 vs 9.5 ± 4.2 days P = 0.01); (2) reduction of the period of acute eruption (7.0 ± 3.3 versus 9.8 ± 3.0 days P = 0.08); and (3) milder signs of prostration. Complications were minimal in both groups. Conclusion The early and short course of corticosteroids favourably influences the course of erythema multiforme major in children. Received: 29 March 1996 / Accepted: 30 July 1996