technique has been used successfully in preterm infants in our department4 and has been validated against radioisotope measurements in adults.5 The technique is based on serial measurements of the cross sectional area of the gastric antrum (ACSA) as it fills and empties during and after a feed.Using this method we compared the emptying rates of maternal breast milk and a whey based formula milk (Cow and Gate Premium). In addition to other well recognised benefits, breast milk may have additional advantages with respect to more rapid gastric emptying than formula milk. In the only previous study,6 however, a potentially unphysiological marker dilution technique was used and the infants were not studied in a blind, cross over manner. Moreover, most patients studied only received a single milk type. As gastric emptying shows large interindividual variability this makes comparisons between milk type less informative. We have therefore used serial ultrasound measurements of the ACSA as a means of comparing, within individuals, the gastric emptying of expressed breast milk with a whey based formula, and of assessing the reproducibility of the technique.

The effects on gut blood flow velocities of parenteral indomethacin (0-2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent-or in some cases even retrograde-diastolic flow.In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fail in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7-4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantialiy less (22% compared with 47%) and later (median time to maximum fall 37-3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus.These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.Neonatal Unit,

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Caffeine, in the dose usualiy recommended (12-5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controiled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. AU three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophyfline groups showed a significant improvement in apnoea within eight hours.The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response. The methylxanthines-theophylline (and aminophylline) and caffeine-are widely used for the treatment of this condition.3 Theophylline has been the drug most commonly used to treat neonatal apnoea in the UK.4 5 Caffeine, however, has many potential advantages: it has a higher therapeutic ratio, it is absorbed more reliably when administered enterally and has a longer half life, thus enabling the drug to be administered only once daily.6 Caffeine has also been shown to be effective in apnoeic infants who are unresponsive to theophylline. Infants were included in our study if they were less than 31 weeks' gestation at birth and if they had either 10 (or more) apnoeic attacks in eight hours or four apnoeas in one hour. Apnoea was defined as a drop in heart rate of more than 40 beats/minute (bpm) below the resting heart rate in an infant who was not breathing, and who required stimulation to correct the problem. Infants prospectively entering the trial were randomly allocated (by random numbers in sealed envelopes) to one of three treatment groups. Group A ('standard dose caffeine')-a loading dose of 25 mg/kg caffeine citrate (12-5 mg/kg caffeine) and a maintenance dose of 6 mg/kg caffeine citrate (3 mg/kg caffeine) once daily were given to produce a desired plasma concentration of 15 mg/l caffeine (range [13][14][15][16][17][18][19][20] mg/l). Group B ('higher dose caffeine')-a loading dose of 50 mg/kg caffeine citrate (25 mg/kg caffeine) and maintenance dose of 12 mg/kg (6 mg/kg caffeine) once daily were given to produce a desired plasma concentration of 30 mg/l (range 26-40 mg/l). Group C ('theophylline')-a loading dose of 7.5 mg/kg theophylline and a maintenance dose of 3 mg/kg theophylline three times daily were given to produce a desired plasma concentration of 15 mg/l (range 13-20 mg/l). RegionalIn all three treatment groups the maintenance dose of the drug was adjusted if the plasma concentrations were out of the desired range, but in none of these patients were...

SUMMARY Gastro-oesophageal reflux in very low birthweight infants was studied using a new 1 mm monocrystalline antimony oesophageal pH electrode. Gastro-oesophageal reflux was detected in 30 (85%) subjects. The mean (SEM) number of episodes of reflux in 24 hours was 12-1 (2.1), and 3-2 (0.6) lasted over five minutes. The mean reflux index was 4-5 (1.0)%, and the longest episode 17-1 (4 6) 17*1. Reflux was unrelated to postconceptional age or to resting lower oesophageal sphincter pressure. The mean reflux index was low at rest before feeds, being 1-8 (0.6)%, and increased slightly after feeds (3-8 (1-0)%), but was significantly increased after nursing care to 16-4 (3.0)%, and while xanthines were being given (5.9 (1.6)%. A subgroup of seven infants with xanthine resistant apnoea had severe gastro-oesophageal reflux that was not clinically apparent (reflux index 27-4 (3.6)%). Successful treatment of the reflux (reflux index: [3][4][5][6] (1-2)%) was associated with cessation of the apnoea.We conclude that gastro-oesophageal reflux is common, and is usually not clinically apparent, even when severe. It is important to consider gastro-oesophageal reflux in the differential diagnosis of xanthine resistant apnoea in preterm infants.