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Abstract Objectives--To determine the effect of phototherapy on the oxygen consumption and resting energy expenditure of term and preterm newborn infants. Methods--A total of 202 infants (gestation 30-42 weeks; body [...]

Abstract Aim--To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants. Methods--A prospective, double blind, [...]

AIM: To investigate the inter-relation between leptin and other metabolic hormones in preterm and term infants and to explore whether a functional "adipoinsular axis" might exist in preterm newborns. METHODS: A total of 140 preterm and term newborns were prospectively recruited and categorised according to gestation length. Blood samples were taken at 24 hours (day 1), and on day 4-5 of life. RESULTS: Serum leptin, cortisol, free thyroxine, and plasma ACTH on day 1 were significantly higher in term than in preterm infants. The relation between serum leptin and gestation followed a non-linear pattern; the slope of the curve began to increase steeply between 33 and 35 weeks gestation. Serum leptin on day 1 was significantly associated with serum insulin, insulin:glucose ratio, and plasma ACTH in infants less than 34 weeks gestation; serum leptin on day 1 and day 4-5 were significantly correlated with insulin:glucose ratio in infants 34 or more weeks gestation. Significant changes in the pattern of metabolic hormones were observed in the first week of life. Serum insulin and plasma glucose were significantly increased between day 1 and day 4-5; serum leptin was significantly decreased. CONCLUSIONS: The circulating leptin concentration increases markedly after 34 weeks gestation and bears a close temporal relation with the exponential accumulation of body fat mass during that period. The inter-relation between serum leptin and insulin or insulin:glucose ratio before and after 34 weeks gestation indicates that the "adipoinsular axis" is likely to be functional in early (<34 weeks gestation) intrauterine life. The rapid decline in the circulating concentrations of leptin after birth may be of physiological advantage to preterm and term newborns by limiting their body energy expenditure and conserving nutritional reverses for subsequent growth and development.

To compare the efficacy of a colloid (5% albumin) and a crystalloid (isotonic saline) solution for treating hypotension in mechanically ventilated preterm infants.

AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined. RESULTS: Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p = 0.001). Group A2 showed a small improvement in blood gases. CONCLUSIONS: Even the highest deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.

To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated.

AIMS: To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development. METHODS: A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I). RESULTS: No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D. CONCLUSIONS: There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.

AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.

AIM: To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome. METHODS: Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications. RESULTS: More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects. CONCLUSION: These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.

AIMS: To evaluate the effectiveness of oral vancomycin in the prophylaxis of necrotising enterocolitis in preterm, very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 140 very low birthweight infants consecutively admitted to the neonatal unit. The babies were randomly allocated to receive oral vancomycin (15 mg/kg every 8 hours for 7 days) or an equivalent volume of placebo solution. Prophylaxis was started 24 hours before the start of oral feeds. All suspected cases of necrotising enterocolitis were investigated with a full sepsis screen and serial abdominal radiographs. Necrotising enterocolitis was diagnosed and staged according to modified Bell's criteria. RESULTS: Nine of 71 infants receiving oral vancomycin and 19 of 69 infants receiving the placebo solution developed necrotising enterocolitis (p = 0.035). Infants with necrotising enterocolitis were associated with a significant increase in mortality (p = 0.026) and longer duration of hospital stay (p = 0.002). CONCLUSIONS: Prophylactic oral vancomycin conferred protection against necrotising enterocolitis in preterm, very low birthweight infants and was associated with a 50% reduction in the incidence. However, widespread implementation of this preventive measure is not recommended, as it would only be effective in necrotising enterocolitis caused by Gram positive organisms and could increase the danger of the emergence of vancomycin resistant or dependent organisms. Its use should be restricted to a high prevalence nursery for a short and well defined period in a selected group of high risk patients.

AIMS: To compare the efficacy of salbutamol delivered by metered dose inhaler (MDI), jet nebuliser, and ultrasonic nebuliser in ventilated infants with chronic lung disease. METHODS: Twenty preterm ventilated infants with chronic lung disease were enrolled in two studies. In study 1 (n = 10), each infant was given 200 micrograms of salbutamol at 4 hour intervals and in random sequence from a metered dose inhaler-spacer device, a jet nebuliser, and an ultrasonic nebuliser with a small medication cup. The infants were monitored for heart rate, transcutaneous pO2, pCO2, and oxygen saturation, respiratory system resistance and compliance before and after each treatment. Infants in study 2 (n = 10) were similarly studied except for the use of a different jet nebuliser. RESULTS: The mean (SEM) maximum percentage decreases in respiratory system resistance, observed at 30 minutes after aerosol delivery were study 1: MDI: 44.3 (4.3)%; jet: 32.3 (3.4)%; ultrasonic: 56.1 (3.2)%; study 2: MDI: 28.6 (1.0)%; jet: 16.9 (1.4)%; ultrasonic: 42.1 (1.6)%. During the first hour after treatment, a significantly faster heart rate and higher transcutaneous pO2 were associated with the use of the ultrasonic nebuliser or MDI than with the jet nebulisers in both studies. The use of the ultrasonic nebuliser but not the other devices also resulted in a lower transcutaneous pCO2 and improved respiratory system compliance in study 2. CONCLUSIONS: These findings suggest that among the devices tested, the delivery of salbutamol aerosol to the lower respiratory tract was greatest using the ultrasonic nebuliser, and least with the jet nebulisers.

AIMS: To evaluate the commonly used markers--namely IL-6, TNF alpha, IL-1 beta, C-reactive protein and E-selection for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment. METHODS: Very low birthweight infants in whom clinical sepsis was suspected when they were > 72 hours of age were eligible for study. A full sepsis screen was performed in each episode. Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7. The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1. The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined. RESULTS: One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants. Forty five episodes were proved to be infections. The optimal cutoff values were IL-6 31 pg/ml, TNF alpha 17 pg/ml, IL-1 beta 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml. IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0. However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively. The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests. Performing IL-6 and C-reactive protein on day 0, together with either TNF alpha on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection. CONCLUSIONS: Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined. Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNF alpha should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.

AIM: To compare the efficacy of using isotonic saline (crystalloid) or 5% albumin (colloid) as replacement fluid in partial exchange transfusion (PET) for the treatment of neonatal polycythaemia. METHODS: One hundred and two polycythaemic full term infants were randomly allocated to receive PET with either isotonic saline or 5% albumin. The criteria for PET were: (a) venous haematocrit > or = 0.7; or (b) venous haematocrit 0.65-0.69 with symptoms or signs attributable to polycythaemia. RESULTS: PET with either saline (n = 53) or 5% albumin (n = 50) resulted in a significant and sustained decline in haematocrit up to 24 hours after PET. Although the immediate haemodilution effect of isotonic saline was statistically smaller than that of 5% albumin (decline in haematocrit 19.3% vs 22.8% of pre-PET value), the difference was too small to be of any clinical significance, and the haematocrit at 4 or 24 hours after PET did not differ significantly between the two groups. PET with either replacement fluid was not associated with any complication. The serum sodium and potassium concentrations were not significantly affected by the PET in either group. CONCLUSIONS: Both isotonic saline and 5% albumin are effective when used as replacement fluid in PET for the treatment of neonatal polycythaemia. Isotonic saline, which is cheaper and free of infection, should be the replacement fluid of choice.