Liliane Sacre

Milk-Thickening Agents as a Treatment for Gastroesophageal Reflux

Milk thickening agents are believed to reduce episodes of gastroesophageal reflux, but their use has not been evaluated thoroughly. We studied the effect of these agents in 30 bottle-fed babies, 6-8 weeks old, with clinical gastroesophageal reflux pathology. Continuous 24-hour esophageal pH monitoring revealed gastroesophageal reflux pathology for all parameters studied: reflux index (18.4%), duration of the longest reflux episode (23.3 min), number of reflux episodes in 24 h (34.5), number of reflux episodes > 5 min (6.8). All investigations were performed in prone-anti-Trendelenburg position. The infants were treated with milk thickening agents (1 g to 115 ml, as recommended by Carre). Most (n = 25) showed clinical improvement of their symptoms. A second pH monitoring was performed under treatment conditions after 7-14 days, and showed in 24 infants a decrease of the number of reflux episodes (15.1 in 24 h) (p < 0.001), but a comparable reflux index (17.8%) (NS) and number of long lasting (>5 min) reflux episodes (7.8) (NS). The duration of the longest reflux episode, however, increased significantly (56.6 min) (p < 0.001). In six infants all parameters were within normal ranges at follow-up. Milk thickening agents seem clinically effective as a treatment for gastroesophageal reflux in individual cases, but can lead to occult gastroesophageal reflux episodes of long duration, possibly increasing the risk for esophagitis or respiratory dysfunction.

Preliminary data on a field study with a new hypo-allergic formula.

The incidence of atopic manifestations due to cows milk proteins was analysed in five groups of 15 newborns considered to be at risk for atopy because of a positive family history. All infants were studied over a 4-month period. The infants received either an adapted formula (AdFo), breast milk or a new hypo-allergic formula (HAF). Atopic manifestations appeared in 1 out of 15 breast-fed infants compared with 18 out of 45 infants fed with an AdFo. None of the infants receiving the HAF (exclusively from birth for 2–4 months) developed symptoms of atopy. Symptoms in each infant receiving an AdFo (n=18) disappeared with the HAF. Although the results of this study are promising, data on a larger population and double-blind investigations are needed before firm conclusions can be drawn.

Incidence of gastroesophageal reflux in sleep, awake, fasted, and postcibal periods in asymptomatic and symptomatic infants.

The incidence of gastroesophageal reflux (GER) in infants has been shown to be dependent on different factors, e.g., position, feeding, age. Using continuous esophageal pH monitoring, we examined 30 asymptomatic (15 were 1.5-2.5 months old; 15 were 2.5-4.5 months old) and 20 symptomatic infants (1.5-4.5 months old) for GER. The occurrence of GER was analyzed in different periods of interest: awake, asleep, fasted, and postcibal periods. The increasing incidence of GER we reported previously in asymptomatic infants according to their age appeared to be due to an increased occurrence in the awake (and postcibal) periods. In symptomatic infants, however, the increase was noticed mostly during the sleep (fasted) periods as far as the reflux index, the duration of the longest reflux episode, and the number of reflux episodes of greater than 5 min are concerned.

Effects of formula feeding on gastric acidity time and oesophageal pH monitoring data.

Gastro-oesophageal reflux (GOR) occurs mainly during postcibal (PC) periods. The duration of PC gastric acidity and the incidence of GOR were analysed in 11 asymptomatic premature infants. GOR was studied during PC periods of 120 min and also during the following 120 min defined as fasting (FT) periods. These infants were subjected to simultaneous continuous gastric and oesophageal pH monitoring using a double-blind crossover technique. Two formulae with different fat contents (2.6 vs 3.6 g/100 ml) and different carbohydrate concentrations (8.1 vs 7.3 g/100 ml; malto-dextrin 2.8 vs 1.9 g/100 ml) were given. Gastric acidity (pH<4) in the PC periods lasted significantly (P<0.001) longer (68 min±10) with the low fat/high malto-dextrin formula versus 43 min±11 with the high fat/low malto-dextrin formula. Oesophageal pH monitoring data were within normal limits for the total investigation time in all infants. During PC periods acid GOR was detected more frequently in the group with a low fat formula. More PC GOR was recorded when the gastric acidity time was longer.

74 RESPIRATORY ABNORMALITIES DURING SLEEP ASSOCIATED WITH GASTROESOPHAGEAL REFLUX IN INFANCY

To determine whether gastroesophageal reflux (GER) might be a factor in the pathogenesis of (awake) apnea in some infants, we analysed the frequency of prolonged apnea (> 15s) and of irregulary frequently repeated short apneas (5-15s) (“respiratory dysfunction) in control infants (n:584), infants with a GER-pathology (n:60), and in infants presenting with an ALTE (Acute Life-Threatening Event) (n:62). In infants with a resp dysf (n:76), the incidence of GER (assessed by pH monitoring) was looked after. Resp function during sleep was assessed by Oxy-Cardio-Respirography (n:197) or by polysomnography (n:585). Results failed to show any causal relationship between prolonged apnea and GER. Resp dysf, although NOT indicating an increased SIDS-risk, appeared to be related to GER (p<0.01). pH Data were abnormal in 8%, and resp dysf present in 5% of the control infants. In controls with a resp dysf, GER was present in 76%. According to different parts of the study GER-path was detected in 43-100%; a resp dysf was observed in 50-100%. Resp dysf was associated with abnormal pH data in 40-71%. If the GER was treated efficiently (significant decrease or normalisation of pH data), resp dysf disappeared in 95%. If GER was resistant to therapy, resp dysf was still present in 79% (15/19 infants) (p< 0.001). If resp dysf persisted, GER was still present in 76% (16/21 infants) (p<0.01). Analysis of pH data and sleep investigations were performed double blind. A majority of ALTE-infants have significant GER, especially if ALTE occured awake. We conclude that GER in infants is often associated to a typical breathing pattern during sleep.

Cimetidine Influence on Gastric Emptying Time in Neonates

(open circles), and four controls (closed circles), with similar basal aldosterone levels. Hospital Regional Universitario Reina Sofia University of Cordoba A vda Menendez Pidal 1 14004 Cordoba, Spain P. BENITO, M.D. P. ALJAMA, M.D. M. CASTRO, M.D. J.A. JIMENEZ, M.D. of metoclopramide on the secretion and metabolism of aldosterone in man. J Clin Endocrinol Metab 1981;52:1014-8. 4. PRATT JH, GANGULY A, PARKINSON CA,WEINBERGER MH. Stimulation of aldosterone secretion by metoclopramide in humans. Apparent independence of renal and pituitary medication. Metabolism 1981;30:129-34. 5. NOTH RH, MCCALLUM RW, CONTINO C, HAVELICK J. Tonic dopaminergic supression of plasma aldosterone. J Clin Endocrinol Metab 1980;51 :64-8. 6. SOWERS JR, TUCK ML, GOLUB MS, SOLLARS EG. Dopaminergic modulation of aldosterone secretion is independent of alteration in renin secretion. Endocrinology 1980;107:397-41. 7. BENITO P, ALJAMA P, JIMENEZ JA, PEREZ JIMENEZ F. Bromocriptine does not modify aldosterone secretion. Drug Intell Clin Pharm 1984;18:80-1. 8. MCKENNA TJ, ISLAND DP, NICHOLSON WE,LIDDLE GW. Dopamine inhibits angiotensin stimulated aldosterone biosynthesis in bovine adrenal cells. J Clin Invest 1979;64:287-91.

90 PLASMA FATTY ACIDS IN PARENTERALLY FED PREMATURE AND TERM BORN INFRANTS: CHANGES INDUCED BY INTRALIPID AND SUNFLOWER-SEED OIL

Premature infants receiving PN free of fat soon develop essential fatty acid (EFA) deficiency, whereas they often have less than 1% of their body weight as fatdeposit. Experience has shown that Intralipid (IL) is a good source of calories and EFA. However, infants who are hypoxic, acidotic or septic present intolerance for IV administered fat-solutions, even at rates of infusion that have been tolerated before (Pediatr58:787, 1976). Because these conditions, are frequently encountered in premature babies and neonates, articles on cutaneous application of sunflower-oil (SO) appeared very attractive (Pediatr58:650,1976). 19 premature and term born babies on PN were studied during 14 days. IL 20% was administerd to 10; SO was rubbed 6times daily on the skin of 9. Plasma fatty acids were determined at birth, day 7 and 14. Levels of C16:0, C18:1, C18:2 and C20:4 did not change in the IL-group. In the SO-group a deficiency in C18:2 developed, that could be corrected by the administration of IL. We conclude that despites IL administration, is often controversal in prematures (displacement of albumin-bound bilirubin, altered synthesis of prostaglandins, cholestasis, impairment of pulmonary function and vasculitis, fat-overloading syndrome,...), the latter is necessary to prevent EFA deficiency. A deficiency in C18:2 can not be prevented by topical application of SO, even not in very-low-birth-weight infants.

Effect of a new gastrokinetic agent (Cisapride) on GER in infants

Gastroesophageal reflux (GER), due to a dysfunction of the distal part of the esophagus, is common in infants. The 24 hour continuous esophageal pH monitoring has been shown to be one of the most reliable investigation techniques for GER in infants. 20 symptomatic infants with an initially abnormal pH monitoring for all parameters studied (refluxindex (32%), duration of the longest reflux episode(95 min), number of reflux episodes(45), number of reflux episodes > 5 min (14)) were treated with Cisapride, a new non-dopamine blocking gastrokinetic drug which showed in animal models an increased gastric, dudenal and jejunal motility and contractility. The administered dose was 5 dr/kg bodyweight, 4 times daily. No side-effects were observed. pH Monitoring was repeated after 2 weeks of treatment, in the same conditions. All infants became asymptomatic, and all parameters ( refluxindex (7 %), duration of the longest reflux episode (14 min), number of reflux episodes (21), number of reflux episodes > 5 min (3) in 24 hours ) showed a significant (P < 0.001 for all parameters, except for number of refuxes P < 0.01) improvement.Cisapride seems to be a save new drug, very effective in infants with an overt GER pathology.

CONTINUOUS 24 H ESOPHAGEAL pH MONITORING IN 200 ASYMPTOMATIC INFANTS (FROM 0 TO 15 MONTHS OLD)

A continuous 24 h esophageal pH monitoring, a non-agressive investigation technique in physiological circumstances, was performed in 200 asymptomatic infants between 5 days and 15 months old with a Memolog 600 system. During 24 h, 1 pH value every 7.5 s was stored in memory. Several parameters (refluxindex (RI), average duration of the longest reflux episode, number of all reflux episodes and those > 5 min) were studied in different groups of infants according to their age : 5–15 days old, 1, 2, 4, 6, 8, 15 months.For all parameters we obtained significantly different results in infants younger and older than 4 months The RI e.g. in newborns is 1.16%. This index increases to 1.78% at 1 month, to 2.53% at 2 months. At 4 months differences are significant (P<0.01 to RI at 2 months; P<0.001 to RI at 1 month or neonatal) as the RI reaches 4.21%. At 6 months RI is 3.22%, at 8 months 3.85%. At 15 months finally RI decreases to 2.55% (P<0.01 to RI at 4 or 8 months). Our data stress the importance to establish age-related ranges for physiologic GER incidence in asymptomatic infants.