Randomised controlled study of clinical outcome following trophic feeding

AIMS: To determine the effect of trophic feeding on clinical outcome in ill preterm infants. METHODS: A randomised, controlled, prospective study of 100 preterm infants, weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition, was performed. Group TF (48 infants) received trophic feeding from day 3 (0.5-1 ml/h) along with parenteral nutrition until ventilatory support finished. Group C (52 infants) received parenteral nutrition alone. "Nutritive" milk feeding was then introduced to both groups. Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks, sepsis incidence, liver function, milk tolerance, duration of respiratory support, duration of hospital stay and complication incidence. RESULTS: Groups were well matched for birthweight, gestation and CRIB scores. Infants in group TF had significantly greater energy intake, mean difference 41.4 (95% confidence interval 9, 73.7) kcal/kg p=0.02; weight gain, 130 (CI 1, 250) g p = 0.02; head circumference gain, mean difference 0.7 (CI 0.1, 1.3) cm, p = 0.04; fewer episodes of culture confirmed sepsis, mean difference -0.7 (-1.3, -0.2) episodes, p = 0.04; less parenteral nutrition, mean difference -11.5 (CI -20, -3) days, p = 0. 03; tolerated full milk feeds (165 ml/kg/day) earlier, mean difference -11.2 (CI -19, -3) days, p = 0.03; reduced requirement for supplemental oxygen, mean difference -22.4 (CI-41.5, -3.3) days, p = 0.02; and were discharged home earlier, mean difference -22.1 (CI -42.1, -2.2) days, p = 0.04. There was no significant difference in the relative risk of any complication. CONCLUSIONS: Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition.     

Randomised controlled trial assessing the effectiveness of a booklet on the duration of breast feeding

OBJECTIVE: To test the efficacy of an information booklet to increase the duration of breast feeding. RESEARCH DESIGN: Randomised design, stratifying by maternal residence and working activity. Two hundred women were recruited, 103 received the booklet and verbal counselling and 97 verbal counselling only. POPULATION: Infants observed from 15 September 1993 to 15 June 1994 in the well baby outpatient clinic of the Paediatric Institute of the Catholic University of Rome, Italy. MAIN RESULTS: No statistically significant difference was found between the two groups in the prevalence of exclusive or complementary breast feeding at 6 months of age: 48.5% and 59.2% in the intervention group, 43.7% and 51.5% in the control group. The median duration of exclusive or complementary breast feeding was 24 and 27 weeks in the treated group, 22 and 25 in the control group. CONCLUSIONS: The information booklet alone does not seem to increase the duration and the prevalence of breast feeding at 6 months of age. The use of written material with a more individualised support and more extensive use of randomised clinical trials in the evaluation of health promoting programmes is recommended.     

Randomised controlled trial of intravenous maintenance fluids

Aim:   Traditional paediatric intravenous maintenance fluids are prescribed using hypotonic fluids and the weight-based 4:2:1 formula for administration rate. However, this may cause hyponatraemia in sick and post-operative children. We studied the effect of two types of intravenous maintenance fluid and two administration rates on plasma sodium concentration in intensive care patients.
Methods:   A Factorial-design, double-blind, randomised controlled trial was used. We randomised 50 children with normal electrolytes without hypoglycaemia who needed intravenous maintenance fluids for >12 h to 0.9% saline (normal saline) or 4% dextrose and 0.18% saline (dextrose saline), at either the traditional maintenance fluid rate or 2/3 of that rate. The main outcome measure was change in plasma sodium from admission to 12–24 h later.
Results:   Fifty patients (37 surgical) were enrolled. Plasma sodium fell in all groups: mean fall 2.3 (standard deviation 4.0) mmol/L. Fluid type ( P  = 0.0063) but not rate ( P  = 0.12) was significantly associated with fall in plasma sodium. Dextrose saline produced a greater fall in plasma sodium than normal saline: difference 3.0, 95% confidence interval 0.8–5.1 mmol/L. Full maintenance rate produced a greater fall in plasma sodium than restricted rate, but the difference was small and non-significant: 1.6 (−0.7, 3.9) mmol/L. Fluid type, but not rate, remained significant after adjustment for surgical status. One patient, receiving normal saline at restricted rate, developed asymptomatic hypoglycaemia.
Conclusion:   Sick and post-operative children given dextrose saline at traditional maintenance rates are at risk of hyponatraemia.     

Randomised controlled trial of combined paracetamol and ibuprofen for fever.

A randomised open label study of the combined use of paracetamol and ibuprofen to rapidly reduce fever is reported. The advantage of using both medications is less than half a degree centigrade in the first hour, and insufficient to warrant routine use.     

Randomised controlled trial of aminophylline for severe acute asthma.

OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment.     

Randomised trial of different rates of feeding in acute diarrhoea.

OBJECTIVE: To compare the effect of different feeding frequencies on the speed of recovery from diarrhoea. METHODS: A randomised, non-blinded trial provided 0.452 MJ/kg/day as either 6 or 12 feeds of cows' milk each day to 262 hospitalised male infants aged 3-12 months with acute diarrhoea. Stool frequency, stool weight, body weight, and diarrhoea complications were monitored until recovery or for 14 days. RESULTS: A proportional hazards regression model controlling for age, diarrhoea aetiology, and severity of dehydration on admission revealed that the frequently fed group had a significantly shorter duration of diarrhoea (hazards ratio, 1.29; 95% confidence interval, 1.002 to 1.653). Frequently fed infants had a significantly greater weight gain and significantly lower faecal frequency and faecal weight. CONCLUSIONS: Breast feeding remains the preferred method of feeding infants with acute diarrhoea, but feeding cows' milk to adequately nourished infants with acute diarrhoea is safe and is more rapidly effective if provided in frequent feeds with low energy loads.     

Randomised controlled trial of allopurinol prophylaxis in very preterm infants.

Allopurinol, an inhibitor of xanthine oxidase (an enzyme capable of generating superoxide radicals following hypoxiaischaemia), was investigated in preterm infants to determine its ability to prevent the complications of neonatal intensive care which may be associated with oxidative injury. Four hundred infants of between 24 and 32 weeks'' gestation were randomly allocated to receive enteral allopurinol (20 mg/ml) or an equivalent dose of placebo for seven daily doses. At admission, plasma hypoxanthine concentrations were significantly higher in infants who subsequently developed periventricular leucomalacia (PVL), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP), but there was no difference in the primary endpoint (PVL) between the treated and control groups. The failure of allopurinol prophylaxis in this group of infants is probably related to the complex nature of the pathological processes and to the timing of treatment. If oxidant injury is an important mechanism of cellular injury in these preterm infants, an alternative biochemical modulator would be required, or a combination of agents might be effective.     

Randomised controlled trial of cisapride in preterm infants

AIM: To determine the effect of cisapride on gastrointestinal motility in preterm infants. METHODS: Cisapride (0.2 mg/kg, 8 hourly ) or placebo was given first for seven days in a double blind randomised crossover study of 10 preterm infants. Gastrointestinal motility was assessed on day 3 of each treatment. The half gastric emptying time (GET1/2) was determined by using ultrasonography to measure the decrease in the gastric antral cross sectional area after a feed. The whole gastrointestinal transit time (WGTT) was assessed by timing the transit of carmine red through the gut. Treatments were compared using the Wilcoxon matched pairs signed ranks test. RESULTS: Median (range) birthweight was 1200 (620, 1450) g and postconceptional age 33 (29, 34) weeks at recruitment. GET1/2 was significantly longer during cisapride treatment than during placebo; the median of the differences (95% confidence interval) was 19.2 (11, 30 minutes, p=0.008). WGTT was also longer during cisapride treatment, but the difference was not significant; the median of the differences was 11(-18, 52 hours, p=0.1). CONCLUSIONS: Cisapride delays gastric emptying and may delay WGTT in preterm infants. Its use to promote gastrointestinal motility in this group cannot be recommended.     

Randomised controlled trial assessing the effectiveness of a booklet on the duration of breast feeding

Accepted 14 February 1997
OBJECTIVE—To test the efficacy of an information booklet to increase the duration of breast feeding.
RESEARCH DESIGN—Randomised design, stratifying by maternal residence and working activity. Two hundred women were recruited, 103 received the booklet and verbal counselling and 97 verbal counselling only.
POPULATION—Infants observed from 15 September 1993 to 15 June 1994 in the well baby outpatient clinic of the Paediatric Institute of the Catholic University of Rome, Italy.
MAIN RESULTS—No statistically significant difference was found between the two groups in the prevalence of exclusive or complementary breast feeding at 6 months of age: 48.5% and 59.2% in the intervention group, 43.7% and 51.5% in the control group. The median duration of exclusive or complementary breast feeding was 24 and 27 weeks in the treated group, 22 and 25 in the control group.
CONCLUSIONS—The information booklet alone does not seem to increase the duration and the prevalence of breast feeding at 6 months of age. The use of written material with a more individualised support and more extensive use of randomised clinical trials in the evaluation of health promoting programmes is recommended.

     

Randomised controlled trial adapting US school obesity prevention to England.

OBJECTIVES: To determine whether a school obesity prevention project developed in the United States can be adapted for use in England. METHODS: A pilot cluster randomised controlled trial and interviews with teachers were carried out in 19 primary schools in South West England. Participants included 679 children in year 5 (age 9-10). Baseline and follow-up assessments were completed for 323 children (screen viewing) and 472 children (body mass index). Sixteen lessons on healthy eating, physical activity and reducing TV viewing were taught over 5 months by teachers. Main outcome measures were hours of screen activities, body mass index, mode of transport to school and teachers' views of the intervention. RESULTS: Children from intervention schools spent less time on screen-viewing activities after the intervention but these differences were imprecisely estimated: mean difference in minutes spent on screen viewing at the end of the intervention (intervention schools minus control schools) adjusted for baseline levels and clustering within schools was -11.6 (95% CI -42.7 to 19.4) for a week day and was -15.4 (95% CI -57.5 to 26.8) for a Saturday. There was no difference in mean body mass index or the odds of obesity. CONCLUSIONS: It is feasible to transfer this US school-based intervention to UK schools, and it may be effective in reducing the time children spend on screen-based activities. The study has provided information for a full-scale trial, which would require 50 schools ( approximately 1250 pupils) to detect effects on screen viewing and body mass index over 2 years of follow-up.     

Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing.

BACKGROUND: Previous studies suggest that recurrent episodes of coughing and wheezing occur in up to 75% of infants after acute viral bronchiolitis. AIM: To assess the efficacy of budesonide given by means of a metered dose inhaler, spacer, and face mask in reducing the incidence of coughing and wheezing episodes up to 12 months after acute viral bronchiolitis. METHODS: Children under the age of 12 months admitted to hospital with acute viral bronchiolitis were randomised to receive either budesonide or placebo (200 microg or one puff twice daily) for the next eight weeks. Parents kept a diary card record of all episodes of coughing and wheezing over the next 12 months. RESULTS: Full follow up data were collected for 49 infants. There were no significant differences between the two study groups for the number of infants with symptom episodes up to six months after hospital discharge. At 12 months, 21 infants in the budesonide group had symptom episodes compared with 12 of 24 in the placebo group. The median number of symptom episodes was 2 (range, 0-13) in those who received budesonide and 1 (range, 0-11) in those who received placebo. Because there is no pharmacological explanation for these results, they are likely to be caused by a type 1 error, possibly exacerbated by there being more boys in the treatment group. CONCLUSION: Routine administration of budesonide by means of a metered dose inhaler, spacer, and face mask system immediately after acute viral bronchiolitis cannot be recommended.     

Randomised controlled trial of infantile colic treated with chiropractic spinal manipulation.

AIMS: To investigate the efficacy of chiropractic spinal manipulation in the management of infantile colic. METHODS: One hundred infants with typical colicky pain were recruited to a randomised, blinded, placebo controlled clinical trial. RESULTS: Nine infants were excluded because inclusion criteria were not met, and five dropped out, leaving 86 who completed the study. There was no significant effect of chiropractic spinal manipulation. Thirty two of 46 infants in the treatment group (69.9%), and 24 of 40 in the control group (60.0%), showed some degree of improvement. CONCLUSION: Chiropractic spinal manipulation is no more effective than placebo in the treatment of infantile colic. This study emphasises the need for placebo controlled and blinded studies when investigating alternative methods to treat unpredictable conditions such as infantile colic.     

Randomised controlled trial of site specific advice on school travel patterns.

AIMS: To evaluate the effect of site specific advice from a school travel coordinator on school travel patterns. METHODS: Cluster randomised controlled trial of children attending 21 primary schools in the London boroughs of Camden and Islington. A post-intervention survey measured the proportion of children walking, cycling, or using public transport for travel to school, and the proportion of parents/carers very or quite worried about traffic and abduction. The proportion of schools that developed and implemented travel plans was assessed. RESULTS: One year post-intervention, nine of 11 intervention schools and none of 10 control schools had travel plans. Proportions of children walking, cycling, or using public transport on the school journey were similar in intervention and control schools. The proportion of parents who were very or quite worried about traffic danger was similar in the intervention (85%) and control groups (87%). However, after adjusting for baseline and other potential confounding factors we could not exclude the possibility of a modest reduction in parental concern about traffic danger as a result of the intervention. CONCLUSIONS: Having a school travel coordinator increased the production of school travel plans but there was no evidence that this changed travel patterns or reduced parental fears. Given the uncertainty about effectiveness, the policy of providing school travel coordinators should only be implemented within the context of a randomised controlled trial.     

Randomised controlled trial of combined paracetamol and ibuprofen for fever

A randomised open label study of the combined use of paracetamol and ibuprofen to rapidly reduce fever is reported. The advantage of using both medications is less than half a degree centigrade in the first hour, and insufficient to warrant routine use.     

Randomised trial of different rates of feeding in acute diarrhoea

OBJECTIVE—To compare the effect of different feeding frequencies on the speed of recovery from diarrhoea.
METHODS—A randomised, non-blinded trial provided 0.452 MJ/kg/day as either 6 or 12 feeds of cows'' milk each day to 262 hospitalised male infants aged 3-12 months with acute diarrhoea. Stool frequency, stool weight, body weight, and diarrhoea complications were monitored until recovery or for 14days.
RESULTS—A proportional hazards regression model controlling for age, diarrhoea aetiology, and severity of dehydration on admission revealed that the frequently fed group had a significantly shorter duration of diarrhoea (hazards ratio, 1.29; 95% confidence interval, 1.002 to 1.653). Frequently fed infants had a significantly greater weight gain and significantly lower faecal frequency and faecal weight.
CONCLUSIONS—Breast feeding remains the preferred method of feeding infants with acute diarrhoea, but feeding cows'' milk to adequately nourished infants with acute diarrhoea is safe and is more rapidly effective if provided in frequent feeds with low energy loads.
     

Randomised controlled trial of thiopental for intubation in neonates

AIMS: To determine the effects of premedication with thiopental on heart rate, blood pressure, and oxygen saturation during semi-elective nasotracheal intubation in neonates. METHODS: A randomised, placebo controlled, non-blinded study design was used to study 30 neonates (mean birthweight 3.27 kg) requiring semi-elective nasotracheal intubation. The babies were randomly allocated to receive either 6 mg/kg of thiopental (study group) or an equivalent volume of physiological saline (control group) one minute before the start of the procedure. Six infants were intubated primarily and 24 were changed from orotracheal to a nasotracheal tube. The electrocardiogram, arterial pressure wave, and transcutaneous oxygen saturation were recorded continuously 10 minutes before, during, and 20 minutes after intubation. Minute by minute measurements of heart rate, heart rate variability, mean blood pressure (MBP) and transcutaneous oxygen saturation (SpO(2)) were computed. The differences for all of these between the baseline measurements and those made during and after intubation were determined. Differences in the measurements made in the study and the control groups were compared using Student's t test. RESULTS: During intubation, heart rate increased to a greater degree (12.0 vs -0.5 beats per minute, p < 0.03) and MBP increased to a lesser degree (-2.9 vs 4.4 mm Hg; p < 0.002) in the infants who were premedicated with thiopental. After intubation only the changes in MBP differed significantly between the two groups (-3.8 vs 4.6 mm Hg; p < 0.001). There were no significant changes in the oxygen saturation between the two groups during or after intubation. The time taken for intubation was significantly shorter in the study group (p < 0.04). CONCLUSIONS: The heart rate and blood pressure of infants who are premedicated with thiopental are maintained nearer to baseline values than those of similar infants who receive no premedication. Whether this lessening of the acute drop in the heart rate and increase in blood pressure typically seen during intubation of unmedicated infants is associated with long term advantages to the infants remains to be determined.     

Randomized controlled study of digestive enzyme activity following trophic feeding

A randomized, controlled, prospective study of 80 preterm infants of birthweight less than 1750 g requiring ventilatory support was performed. While ventilatory support was required group TF (39 infants) received trophic feeding (0.5-1 ml h -1 ) along with parenteral nutrition, whereas group C (41 infants) received parenteral nutrition alone. When ventilatory support was no longer required milk feeds were started in group C and then increased in both groups until full milk feeds were established. The ratio of lactase to sucrase activity (L:S ratio) was measured in aspirated proximal intestinal fluid on 3 occasions: immediately after ventilatory support was withdrawn (T0), 7 days later (T7) and 14 days later (T14). On the same 3 occasions faecal chymotrypsin activity was measured. The mean difference (95% confidence interval) L:S ratio was significantly higher in group TF at both T0 and T14, 1.8 (0.03, 3.57) and 0.78 (0.2, 1.35) U l -1 , respectively. There was no significant difference in faecal chymotrypsin concentration.

Conclusion : Trophic feeding alters relative intestinal disaccharidase activity, probably by inducing lactase production, but has no effect on pancreatic chymotrypsin activity.     

早期微量喂养改善极低出生体重儿宫外生长与预后的半随机对照试验

目的观察早期微量喂养对极低出生体重儿(VLBWI)生后6周宫外生长与预后的影响。方法选择2007年1月至2009年1月无锡市儿童医院与南京医科大学附属南京儿童医院NICU收治的出生体重(1500g且需要辅助通气和静脉营养的VLBWI为研究对象,根据单双病床号分为早期微量喂养组和对照组。早期微量喂养组:在静脉营养的同时从生后第3天开始经鼻饲管给予早产儿配方乳0.5～1mL.h-1,直至辅助通气结束;对照组:仅予静脉营养直至辅助通气结束。监测生后6周内的能量摄入、生长状况、脓毒症(血培养阳性)发生率、肝功能、喂养耐受情况、辅助通气时间、住院时间和喂养相关并发症的发生率。结果早期微量喂养组18例,对照组22例进入分析。早期微量喂养组入组时胎龄、出生体重和新生儿临床危险指数评分与对照组差异均无统计学意义。①早期微量喂养组生后6周内总能量摄入显著高于对照组,平均差异为261.1kJ.kg-1,P=0.03。②早期微量喂养组生后6周时点体重增长值显著高于对照组,两组差异为120g,P=0.02;头围增长值显著高于对照组,平均差异为0.6cm,P=0.04;中臂围两组差异为0.30cm,P=0.48;三头肌皮肤皱褶厚度两组差异为0.22mm,P=0.51。③两组生后6周内肝功能指标与黄疸持续时间差异无统计学意义;早期微量喂养组生后6周内脓毒症发生率显著低于对照组,P=0.03。④早期微量喂养组需要静脉营养的时间显著少于对照组,P=0.03;过渡到完全肠内营养的时间显著少于对照组,P=0.03。⑤早期微量喂养组需氧时间显著少于对照组,P=0.02;平均住院时间显著少于对照组,P=0.03。⑥两组生后6周内各种喂养相关并发症(腹胀、呕吐、坏死性小肠结肠炎和吸入性肺炎)的发生率差异无统计学意义。结论早期微量喂养可改善VLBWI生后6周宫外生长状况。