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April 1978 TheJournalofPEDIATRICS

Transient steatorrhea following episodes of mild diarrhea in early infancy Fecal fat excretion was studied after a mild episode of diarrhea in eight infants for whom adequate control data were available. Mean age of onset of diarrhea was 28 days. Duration of the episode, defined as the number of days until the infant was again feeding ad libitum, averaged 5.1 days. Balance studies were carried out 3 to 13 days later. Mean fecal fat excretion rose from a prediarrhea value of 2.9 +_ 1.4 gmCday to 8. 7 ++_3.1 gin~day following diarrhea (P < 0.001). Restudy of five infants one month later showed persistent steatorrhea in one. Mild transient steatorrhea may follow mild diarrhea in infancy and should be considered in infants who are slow to gain weight subsequent to an episode of diarrhea.

William C. MacLean, Jr., M.D.,* Gordon L. Klein, M.D., Guillermo Lopez de Romafia, M.D., Enrique Massa, M.D., and George G. Graham, M . D . ,

Lima, Peru, and Baltimore, Md.

D U R I N G THE COURSE OF CARING for a group of infants on w h o m metabolic balance data were regularly obtained, we have had the opportunity to study eight infants in w h o m a mild, self-limited bout of nonspecific diarrhea occurred. Balance studies subsequent to recovery showed mild-to-moderate steatorrhea in these infants when compared to balance data obtained prior to the diarrheal episode. This paper reports these data as well as fecal fat excretion data for healthy control infants consuming modified cow milk infant formula diets during the first three months of life.

PATIENTS AND METHODS Over the past several years approximately 40 healthy full-term mestizo infants were admitted to the Instituto de From the Instituto de Investigacion Nutricional, and the Gastroenterology and Nutrition Unit, Department of Pediatrics, School of Medicine, and Division of Human Nutrition, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University. Supported by Research Contract Ta/C-1286 with the Agency for International Development, United States Department o f State, Research Grant HD /AM-IOl l lO1 ,from the National Institutes of Health, United States Public Health Service. and a grant from the Mead Johnson Research Center. *Reprint address: 615 N. Wolfe St., Baltimore, MD 21205.

Vol 92, No.4, pp. 562-565

Investigacion Nutricional in Lima. Peru. for custodial care while awaiting adoption.* Virtually all infants consumed one of four modified cow milk infant formulas in which protein pi:ovided approximately 9 to 10% of energy, carbohydrate 40 to 41%. and fat 50%. The source of fat in three diets was soy oil. and in the fourth, a blend of soy and coconut oil. Calcium content ranged from 62.5 to 81 mg/100 kcal, phosphorus from 51.5 to 69 m g / 1 0 0 kcal. Ca:P ratio varied between 1.17 and 1.52. Infants entered the unit at 3 to 5 days of age and were fed ad libitum every 35 to 4 hours, five times per day. Sixday metabolic collections of urine and stool were carried out in 32 infants between the ages of 8 and 12 days. Subsequent collections were obtained in 15 infants at 31 to 36 days of age, 16 infants at 61 to 66 days, and 21 infants at 91 to 96 days of age. All infants were exclusively formula fed during this time. Intakes were fixed and measured during metabolic collections. During the first three months of life. eight of the infants on w h o m adequate control data were available had an episode of diarrhea. Average age at onset of the episode was 28 days. Diarrhea was defined as the acute onset of loose stools of increased number, sufficient to require intake of formula to be severely curtailed or stopped *Admissionof these infants to the I.LN. and the collectionof urine and stool was approved by the agency having guardianship over these infants and the Committee on Human Investigationof the I.I.N.

0022-3476/78/0492-0562500.40/0

9 1978 The C. V. Mosby Co.

Volume 92 Number 4

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Table I. Fecal wet and dry weight and fecal fat excretion in eight term infants before and after an episode of mild diarrhea

Postdiarrhea

Prediarrhea Fecal weight Case No.

Age* (days)

Wet (gin~ day)

445 447 450 451 456 467 468 493 Mean _+ SD

35 11 12 12 10 10 10 34 16.8 +11.0

138 121 63 38 23 110 88 64 80.4 _+40.9

Dry (gm/ day) 10.3 8.9 5.3 7.3 2.4 11.2 9.6 7.2 7.8 _+2.9

Fecal weight

Fecal fat gm/ day 2.6 3.6 119 4.2 0.7 3.5 4.8 1.9 2.9 +1.4

% Intake 11.6 21.6 8.8 15.7 4.0 15.1 27.0 6.9 13.8 _+7.7

% Dry weight

Age* (days)

25.1 59 41.1 30 43.5 32 19.7 32 30.9 31 30.9 29 50.8 31 26.3 83 33.5 40.9 _+10.6 _+19.7

Days+ post diarrhea, 12 12 5 4 13 7 3 6 7.8 _+4.0

Wet (gm/ day)

Dry (gm/ day)

18'1 15.7 230 18.6 192 21.2 93 19.6 134 12.9 154 9.7 i54 15.4 78 15.4 153.6~ 16.3:~ _+47.9 +_3.7

Fecal fat gin~ day 7.4 8.0 12.1 12.7 5.2 5.1 7.2 10.9 8.7~ +3.t

% Intake

% Dry weight

23.8 47.3 30.3 43.1 29.4 57.1 41.0 64.5 19.6 39.7 28.1 50.7 23.0 46.3 27.7 70.8 2 8 . 2 ~ 52.3w _+6.5 _+10.6

*Age at beginning of balance period. ]'Numbers of days between clinical cessation of diarrhea and onset of balance period. Diarrhea was considered to have stopped when stools appeared normal and the infant was agMn consuming full-strength formula ad libitum. :~Differsfrom corresponding prediarrhea value by paired "t" test, P < 0.001. w from corresponding prediarrhea value by paired "t" test, P < 0.05.

altogether. Because of their age and clinical findings, most infants had cultures of blood, stool, and urine. Four infants received antibiotics. Two were treated presumptively for sepsis with parenteral antibiotics. Two received gentamicin orally for possible enteropathogenic Escherichia coli. All cultures were negative for pathogens so antibiotics were discontinued after a m a x i m u m of five days. O f the eight infants, two were treated with diluted formula for several days, three received an oral glucoseelectrolyte solution for one to two days followed by progressive increases of diet. and three were treated initially with rapid intravenous rehydration followed by oral fluids and rapid reintroduction of formula. Diarrhea was defined as being over when stool n u m b e r had again decreased, stools appeared normal to the physician caring for the infant, and the infant was again tolerating ad libitum formula feedings at a level consistent with his prediarrhea intake. Using these criteria, these diarrheal episodes had a mean duration of 5. l days (range 3 to 10 days). Seven of t h e eight infants returned directly to their previous diet following cessation of diarrhea. The eighth was treated with a non-lactose-containing formula of casein, sucrose, and a blend of soy and cottonseed oils. and was consuming this during his postdiarrhea metabolic collections. Metabolic collections of urine and stool were carried out as previously described? Fecal wet weight was measured on daily collections. Fecal dry weight, fecal nitrogen by micro-Kjeidahl, and fecal fat by the method

of Van de K a m e r et aF were determined on aliquots from 3-day pooled specimens. Urinary nitrogen was also estimated by micro-Kjeldahl on 3-day pooled collections. Fecal fat was expressed in grams per day, as a percentage of fat intake, and as a percentage of fecal dry weight. Statistical analysis o f t h e data was Carried out when appropriate by means of Student's t test for paired comparisons or, in some instances, for unpaired data? RESULTS Data from the eigh t infants studied before and after an episode of diarrhea are shown in Table I. The results of the 6-day balance period most closely preceding the episode of diarrhea were use d a s t h e prediarrhea value; in all but two cases this was the initial collection perio d . Stool wet weights ranged from 22.5 to 138 g m / d a y (mean 80.4 gm/day). Fecal fat excretion averaged 2.9 • 1.4 g m / day or 13.8 _+ 7.7% of fat intake. Diarrhea occurred within two weeks of these collections and lasted an average 0 f f i v e days. Data for the postdiarrhea period were obtained an average of 7.8 (range 3 to 13) days after full intake was again tolerated. Fecal wet weight at this time was elevated above control values although stools appeared normal. Fecal dry weight also increased. Fecal fat excretion was significantly greater ( P < 0 . 0 0 1 ) , having increased to 8.7 + 3.1 gm/day, 28.2 _+ 6.5% of fat intake. W h e n fecal fat was expressed as a percentage of fecal dry matter, this was also significantly greater following diarrhea than it had been previously

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MacLean et al.

The Journal of Pediatrics April 1978

Table II. Normal values for fecal wet and dry weight and fecal fat excretion during the first three months of life (mean _+ SD)

Intake Age (days)

N

8-13 31-36 61-66 91-96 Mean

32 15 16 21 84

Energy (kcal/kg/day) 120 • 148 • 152 • 142 + 136 •

21 12 21 19 23

Fecal weight Fat (gm/kg/day) 6.7 8.3 8.5 7.9 7.6

+ 1.1 _+ 0.7 _+ 1.2 _+ 1.1 • 1.3

Fecal fat

Wet (gm / day)

Dry (gin / day)

gm/day

63 86 102 96 83

8.1 • 3.2 11.5 _+ 3.4 13.2 • 4.9 11.4 • 4.0 10.5 + 4.2

3.8 4.4 4.8 3.9 4.0

(52.3 • 10.6% versus 33.5 _+ 10.6%, P < 0.05). The degree of steatorrhea in the three infants treated intravenously (Cases 451,456, and 467) did not differ from that in the remaining five infants. Energy intakes of the eight infants was somewhat higher during the postdiarrhea collections. Rates of weight gain were also slightly higher during the latter period and appeared to be consistent with the greater energy intakes. Apparent nitrogen absorption and retention were not found to differ significantly between the two collection periods. Five children were restudied following the recognition of steatorrhea to determine if the p h e n o m e n o n was transient or longer lived. Within a month, fecal fat excretion in Cases 445, 447, 451, and 467 had returned to normal. Case 468 was restudied 30 days after his postdiarrhea collection. He had had loose stools for two days in the week preceding this collection. His fecal fat excretion continued to be elevated, 6.9 g m / d a y (15.5% of fat intake, 45.9% of fecal dry matter). This child was not subsequently restudied to determine how long steatorrhea persisted. Data on normal fecal wet and dry weight and on fecal fat excretion are shown in Table If. Fecal fat excretion expressed in absolute terms appeared to change little during the first three months of life. Because of increased ad libitum intakes, however, fecal fat expressed as a percentage of intake decreased progressively during this time. Fat as a percentage of fecal dry matter also tended to decrease with time, suggesting that fat absorption was improving. The m e a n values from the 84 six-day balance periods provide a good idea of normal fecal fat excretion in the first three months of infancy. DISCUSSION The diarrhea encountered in these eight children was considered to be of relatively minor clinical importance. Duration, defined as a return to prediarrheal intake associated with a seemingly normal stodl pattern, aver-

+ + • + +

31 33 45 49 42

_+ 2.1 • 2.9 • 1.8 _ 2.5 __ 2.3

I

%

Intake 18.1 _+ 11.2 15.4 • i2.4 12.1 _+ 5.3 10.7 _+ 7.6 14.6 _+ 10.1

%

Dry Weight 44.0 • 37.5 + 34.4 + 32.1 • 38.0 •

11.8 18.1 9.3 10.9 13.3

aged only five days. Although we elected to treat three children initially with fluids intravenously, most of the episodes of diarrhea were of such a nature that the infants would have been easily managed on an outpatient basis had they not already been inpatients. Despite the mild nature of these episodes, however, all eight infants had increased fecal fat losses which were still present 6 to 19 days after diarrhea had ceased, and in one patient persisted for more than a month. The postdiarrhea stool weights, although higher than we usually expectr were not elevated to such a degree that much note would have been taken of them in an otherwise healthy infant. All infants were gaining weight steadily at the time of the second balance studies and apparent nitrogen absorption and retention were unchanged from prediarrhea values (although balance studies carried out at this level of nitrogen intake are admittedly subject to methodologic error)? .~ We suspect that the mild elevations of fecal wet and dry weight and of fecal fat seen in these infants are a frequent and rarely noticed consequence of such diarrheal episodes. Fat absorption in young infants is known to be inefficient in comparison to that in the older child and adult. The detection of unhydrolyzed triglyceride in stools of normal infants suggests that pancreatic lipase activity may be marginal. 7 Studies in infants of bile salt pool size and rate of synthesis have shown that both are decreased on a per M -~ basis relative to the adult. ~ The contracted pool size may be partially responsible for the difficulty of normal infants in achieving an intraluminal concentration of bile salts at or above the critical micellar concentration.,, 9 Transient diarrhea might alter reabsorption of bile salts in the terminal ileum, further reducing pool size and prejudicing fat absorption. Prolonged malabsorption of bile acids to a mild degree could in part explain the slight elevations of stool wet weight seen during the postdiarrhea metabolic collections. Although gastrointestinal transit times were not measured, decreased t r a n s i t time is not an adequate

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explanation for the poor fat absorption noted in our infants. Nitrogen absorption was unaffected, as it would have been if these were the case. Furthermore, lactoseintolerant infants consuming lactose-containing diets have been found to have insignificant changes in fecal fat excretion despite shortened transit time and large stool outputs? ~ Our values for normal fecal fat excretion are generally in accord with tho/se previously reported for infants consuming similar formula diets. 1'-~ The values obtained in these infants point up the real advantage of knowing dietary fat intake when interpreting fecal fat excretion in young infants. Although fecal fat expressed as g m / d a y appeared to differ little between the 32 infants studied at 8 to 13 days and the 21 infants restudied at 91 to 96 days, when fecal fat values were expressed as a percentage of intake, clear difference became apparent. This suggested that fat absorption was improving progressively during the three months of study. Mild transient steatorrhea m a y follow a seemingly insignificant episode of diarrhea. This is probably of minor consequence to most otherwise healthy infants in the United States. It should be considered along with mild lactose intolerance, however, in those infants manifesting slightly abnormal stools or poor weight gain subsequent to an episode of diarrhea. This finding m a y be of special importance in infants subject to repeated mild episodes of diarrhea or in those of low birth weight. In developing countries, where dietary intakes are frequently marginal at best, the increased fecal energy loss from steatorrhea need not be great to jeopardize an infant whose nutritional status is borderline. Any cause of mild malabsorption may be the first step toward the malnutrition-chronic diarrhea cycle in these infants.

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REFERENCES

1. Graham GG, Morales E, Acevedo G, Baertl JM, and Cordano A: Dietary protein quality in infants and children. II. Metabolic studies with cottonseed flour, Am J Clin Nutr 22:577, 1969. 2. Van de Kamer J, Huimink H, and Weyers A: Estimation of fat in feces, food and other biological materials, J Biol Chem 177:347, 1949. 3. Dixon WS, and Massey FJ: Introduction to statistical analysis, ed 3, New York, 1969, McGraw-Hill Book Company, Inc. 4. MacLean WC Jr, and Graham GG: Unpublished observations. 5. Wallace WM: Nitrogen content of the body and its relation to retention and loss of nitrogen, Fed Proc 18:1125, 1959. 6. lsaksson B, and Sj0gren B: A critical evaluation of the mineral and nitrogen balances in man, Proc Nutr Sco 26:106, 1967. 7. Watkins JB, Lester R, Bliss CM, et al: Characterization of newborn fecal lipid, Pediatrics 53:511, 1974. 8. Watkins JB, lngall DI, Szczepanik P, et al: Bile salt metabolism in the newborn, N Engl J Med 288:431, 1973. 9. Lavy V, Silverberg M, and Davidson M: Role of bile acids in fat absorption in low birth weight infants, Pediatr Res 5:387, 1971. 10. Graham GG, and Paige DM: Nutritional implications of low intestinal lactase activity in children, in Borgstrom B, Dahlqvist A, and Hambraeus L, editors: Intestinal Enzyme Deficiencies and Their Nutritional Implications, Symposium of the Swedish Nutrition Foundation XI, Sweden, 1973, Almqvist and Wiksell, p 45. 1I. Fomon SJ, Ziegler EE, Thomas LN, et al: Excretion of fat by normal full term infants fed various milks and formulas, Am J Clin Nutr 23:1299, 1970. 12. Widdowson EM: Absorption and excretion of fat, nitrogen, and minerals from "filled" milks by babies one week old, Lancet 2:1099, 1965. 13. Barness LA, Morrow GIII, Silverio J, et al: Calcium and fat absorption from infant formulas with different fat blends, Pediatrics 54:217, 1974.

Transient steatorrhea following episodes of mild diarrhea in early infancy.

562 April 1978 TheJournalofPEDIATRICS Transient steatorrhea following episodes of mild diarrhea in early infancy Fecal fat excretion was studied aft...
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