Refeeding of infants with acute diarrheal disease Fima Lifshitz, MD, Ulysses F a g u n d e s N e t o , MD, Carlos A l b e r t o G a r c i a Olivo, MD, A n g e l C o r d a n o , MD, a n d Silvia Friedman, PhD From the Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, Manhasset, New York; Hospital Umberto I, Escola Paulista de Medicina, SOo Paulo, Brazil; and the Mead Johnson Research Center, Bristol-Myers United States Nutritional Group, Evansville, Indiana The purpose of this study was to determine which infant formula a m o n g five would be the most efficacious for the refeeding of infants during an a c u t e episode of diarrhea. Fifty male infants less than 42 months of a g e with severe diarrhea and at least 5% dehydration were a d m i t t e d to a m e t a b o l i c unit and studied in a prospective, single-blind protocol. Ten infants randomly received one of five types of formula: two-thirds diluted c o w milk, c o w milk formula (Nanon, Nestle, Inc., Sao Paulo, Brazil), Portagen, Pregestimil, or Prosobee ( M e a d Johnson & Co. Division, Evansville, Ind.). They c o n t i n u e d to receive the same formula for 72 hours unless dehydration occurred. There were no associated infections, and they r e c e i v e d no prior antibiotic treatment. Oral hydration together with intravenous fluid therapy was given to all patients during the initial treatment. During the first 72 hours of refeeding, patients fed Portagen e x c r e t e d the least amount of stool and required r e d u c e d quantities of intravenous fluids or oral hydration. In contrast, patients fed diluted c o w milk or any other formula had more severe diarrhea. Nine of the 40 patients fed Portagen c o m p l e t e d the 72-hour treatment, whereas only 2 of 10 fed diluted c o w milk tolerated it. Similarly, the cumulative proportions for high purging rate, dehydration, c a r b o h y d r a t e intolerance, and vomiting were more f a v o r a b l e for Portagen and least a c c e p t a b l e for diluted c o w milk. No differences were found a m o n g the remaining three formulas tested. These d a t a show that diluted c o w milk is poorly tolerated by infants with severe diarrhea, whereas Portagen is more effective. (J PEDIATR1991;418:$99-408)

There is a general agreement that breast-feeding should continue during acute diarrhea, 1 Additionally, the use of oral rehydration solutions to replace the fluid and electrolyte losses is now considered essential during acute diarrheal episodes. 24, However, the choice of diet to be used for refeeding non-breast-fed infants who have acute diarrhea remains controversial. Lactose intolerance and prolongation of the diarrheal illness have been described in infants

Reprint requests: Fima Lifshitz, MD, Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030. 9/0/2"7126

who were fed cow milk. 57 For these reasons the American Academy of Pediatrics has recommended a lactose-free formula, s However, the World Health Organization (WHO) continues to recommend diluted cow milk or cow milk formula as the first choice for refeeding non-breast-fed infants who have acute diarrhea. 9 This prospective, randomized, single-blind study was designed to determine which of five formulas would be the most efficacious for refeeding infants during an acute episode of severe diarrhea. The response to formula feedings was measured by timing the recovery, evaluating the purging rates, and noting the complications during the refeeding trial. Complications measured included the development of dehydration, the presence of carbohydrate intolerance, and vomiting. $99

S 100

Lifshitz et al.

The Journal of Pediatrics April 1991

Table I. N u t r i e n t composition of five formulas Formulos*

Cow milk'l"

Nanon

Calories Carbohydrate (gm) Type

100 7.7 Lactose

100 11.0 Lactose

Percent of calories Protein (gm) Type

30.8 5.5

44 2.5

Percent of calories Fat (gm) Type

22 5.5 Animal

Percent of calories Linoleate (gin) Linolenic (gm) Percent of calories Vitamin A (I.U.) Vitamin D (I.U.) Vitamin E (I.U.) Vitamin C (rag) Folic acid (#g) Thiamine (mg) Riboflavin (mg) Niacin (mg) Vitamin B6 (mg) Vitamin B12 (~g) Biotin (~g) Pantothenic acid (mg) Vitamin K (#g) Choline (mg) Inositol (rag) Calcium (mg) Phosphorus (mg) Iodine (#g) Ir0n (mg) Magnesium (mg) Copper (mg) Zinc (mg) Manganese (mg) Chloride (mg) Potassium (rag) Sodium (mg) Renal solute load Osmolality (mOsm/kg H20)

47.2 0.13 0.08 49.5 207 1.69 #g 0.06 mg 1.55 8.07 0.06 0.27 20.6 0.06 0.58 5.81 0.52 9.67 32.3 6.61 195 153 5.9 0.08 21 0.02 0.63 0.004 169 250 80.6

52 298 59 1.18 8.04 9.02 0.06 0.14 0.75 0.08 0.22 2.2 0.45 3.06 7.45 4.51 78.4 45.1 5.10 1.18 7.65 0.06 0.75 7.06 76.44 111.72 25.5

300

300

10.0 5.1 80% Milk fat, 20% corn oil 46 0.67

Portagen

Pregestimll

Prosobee

100 11.5 73% Corn syrup solids; 25% sucrose 46 3.5 Sodium caseinate

100 13.5 85% Corn syrup solids, 15% modified tapioca starch 54 2.8 Casein hydrolysate with added L-cysteine, cystein, L-tyrosine, L-tryptophan 11 4.0 40% MCT, 60% corn oil

100 10 100% Corn syrup solids

14 4.8 88% MCT, 12% corn oil, 2% lecithin 40

781 78 3.1 8 16 156 188 2.03 0.20 0.6 8 1.05 15.6 13.3 Trace 94 70 7.2 1.9 20 0.16 0.94 0.12 87 125 48 22 220

35

312 62.5 2.3 8 16 78 94 1.25 0.063 0.3 8 0.47 15.6 13,3 5 94 63 7.2 1.9 11 0.09 0.63 0.03 87 110 48 13 350

40 3.0 Soy isolate plus methionine 12 5.3 55% Coconut oil, 45% corn oil 48

300 63 3.1 8.1 15.66 78 94 1.25 0.063 0.31 7.8 0.47 15.6 7.8 4.7 94 74 10.2 1.88 10.9 0.094 0.78 0.025 83 122 36 200 200

MCT, Medium-chaintriglycerides. *Nanon is a cow milk formula producedby Nestle, Inc., Sao Paulo, Brazil. Portagen,Pregestimil,and Prosobeeare producedby the Mead Johnson & Co. Division of Bristol-Myers,Evansville,Ind. "~Cowmilk formula was diluted to provide67 kcal per 150 ml. All other formulas were fed at full strength and provided 100 kcal per 150 ml.

MATERIAL

AND METHODS

per day in the 24 hours preceding hospitalization and were

Fifty male infants less than 12 months of age who had severe diarrhea for less than 1 week were selected for this

at least 5% dehydrated at the time of admission to the hos-

study. Each had had at least four or more bowel movements

received prior antibiotic treatment. Breast-feeding had been

pital. They had no associated infections and had not

Volume 118 Number 4, Part 2

Refeeding o f infants with acute diarrhea

S 10 1

T a b l e II. Clinical characteristics of infants in five formula groups No. of male infants

Age (mo) 0-2 2-6 6-12 Nutritional status? Normal I

Diluted cow milk*

Cow milk formula

Portagen

Pregestimil

Prosobee

4 4 2

1 7 2

2 4 4

3 3 4

3 3 4

3

3

2

3

3

4

1

3

4

4

5

3

3

4 4 2

4 6 0

4 3 3

II-III 3 6 Pathogens in stools Negative 3 3 E. coli')i 6 6 Othersw 1 1 *Dilutedto provide67 kcal per 150 ml. AII other formulasprovided 100 kcal per 150 ml. tGomez criteria. ~E. coli 0111 (18 patients),0152, 0127, 0167, or 055. w Shigella, Campylobacter, or rotavirus. discontinued in all patients for at least 1 month before hospital admission. The patients were weighed and were placed on metabolic beds. The use of urine bags assured the separate collection of stools and urine. Oral hydration and intravenous therapy were given to all patients. The amount of fluid given was calculated to replace the estimated hydration deficit and the continuing stool losses. The patients were rehydrated between 4 and 12 hours after admission to the hospital. As soon as they were rehydrated, refeeding was initiated and oral hydration or intravenous solutions or both were given in quantities equal to stool losses. Body weight, fluid intake, vomiting, and stool and urine output were carefully measured. Hydration status was monitored, and fluid reqjairements were calculated every 8 hours throughout the study. The refeeding protocol provided maintenance calories during the first day of treatment. Thereafter, oral intake was increased gradually, and patients were fed up to 120 kcal/kg per day during the second or third day of treatment. Feedings were given as desired every 3 hours. Ten infants in each group randomly received one of five types of feedings. Unless dehydration occurred, the patients continued to receive the selected formula for a minimum of 7 2 hours. The nutrient composition of the formulas is listed in Table I. Feedings included diluted (two-thirds strength) cow milk, a standard cow milk formula (Nanon, Nestle, Inc., S~o Paulo, Brazil), and the following proprietary formulas: Portagen, Pregestimil, or Prosobee (Mead Johnson & Co. Division, Evansville, Ind.). Only the cow milk was diluted; each of the formulas was fed at full strength. The first two types of feeding contain lactose as the carbohydrate source, whereas the other three formulas contain corn syrup solids. Portagen contains a small amount of su-

crose. Additionally, the selected formulas varied in content and composition of fat and protein. Portagen contains medium-chain triglycerides and casein; Pregestimil contains casein hydrolysate; and Prosobee contains soy protein isolate. There were also differences in osmolality (Table I). The Pregestimil used in this study was the previously marketed formulation that had a higher amount of carbohydrate, less total fat, a lower amount of medium-chain triglycerides, and a higher osmolality than the formula currently available in the United States. Diluted cow milk had the lowest osmolarity of the feedings used. All the formulas were isocaloric (100 kcal per 150 ml), except for diluted cow milk, which at two-thirds strength provided 67 kcal per 150 ml. Other minor differences in the formula composition concerned microelements, vitamins, and minerals. The formulas fed to the patients were selected by the Hospital Umberto I pharmacy. The dietary department personnel prepared and administered the formulas. The physicians in charge of the patients were unaware of the feeding selection given throughout the study because the formulas were identical in appearance and numbered sequentially according to a randomization chart coded by the pharmacy. The patient's age, nutritional status, and cause of diarrhea are shown in Table II. All five groups of patients who received different formulas had similar nutritional status according to Brazilian anthropometric standards. 1~ The differences in enteropathogens among groups in each feeding category were not significant. During the study, we observed a high frequency of stools infected with Escherichia coli 0111. This organism has been the most frequently isolated enteropathogen in patients with acute diarrhea in S~o

S 10 2

Lifshitz et al.

The Journal of Pediatrics April 1991

150

150

~k

1O0

"~, 100

50

z

50 b-

Q~ 0

40 gm/ kg of body weight per day up to the third day of treatment. If the formula failed, Pregestimil was offered. In patients fed initially with Pregestimil or for those in whom Pregestimil failed as the second formula, 3232A (a Pregestimillike formula without carbohydrate) was given for treatment. Carbohydrate intolerance, not considered a formula failure, was defined by the presence of acid stools or the excretion of carbohydrate in feces or both, and was measured by semiquantitative techniques.5 Recovery was defined as improvement in diarrhea with stools excreted during the third day of refeeding in amounts