ABSORPTION
OF
FAT
AND
VITAMIN
A
IN
PREMATURE
INFANTS
III.
Effect
of
Surface
Active
Agents
on
the
Absorption
of
These
Substances
By SELMA E. SNYDERMAN, M.D., SOLEDAD MORALES, M.D., ARTHUR W. CHUNG, M.D.,
J.
M. LEWIS, M.D.,* ANGELINA MESSINA, A.B., AND L. EMMETT HOLT, JR., M.D.New York City
P
REVIOUS studies by some of the authors reported that particle size was an importantvariable in the absorption of lipids by premature infants. A comparison between an
unemulsified preparation and a homogenized preparation containing particles no larger
than two microns in diameter showed that the latter gave better absorption of both fat and
vitamin A.
Since this work was undertaken considerable interest has developed in a group of sur-face-active agents, the ‘‘tweens,’ ‘ as adjuvants to fat absorption. These sorbitan polyoxy. ethylene esters have hydrophilic and hydrophobic groups and act as emulsifying agents, a
property that should be conducive to improved lipid absorption. Data reported by Jones et
al.2 in adult steatorrheas indicated that a significant improvement of absorption could be
obtained with ‘‘tween 80.’ ‘ However, Johnson and his collaborators3 failed to find improved
fat absorption in premature infants supplemented with this agent. Because of the relatively
small number of infants studied by them it seemed desirable to extend these observations.
It was also possible that the unpalatability of “tween 80” might have exercised an
un-favorable effect or have masked a favorable one. Observations were therefore also made
with a more palatable preparation, “tween G1205.”f The present report deals with 32
controlled observations on premature infants and two observations on older children with
steatorrhea.
ExPERIMENTAL PROCEDURES
‘
Healthy premature infants between 4 and 38 days of age were employed. Complete fecal collec-tions were obtained by use of metabolism frames or by means of plastic diapers. The metabolism periods consisted of 4 days each, stools being marked with carmine at the beginning and end of each period. In general the first period was a control period without tween ; this was followed by atween period and, finally, by a second control period without tween. In the first experiments no interval elapsed between periods. Subsequently a 48 hr. interval was introduced between each. The presence of this interval seemed in no way to affect the results.
The control feeding consisted of a standard milk formula prepared from dried cow’s milk and
cane sugar providing approximately the following percentage distribution of calories : protein 15%
fat 35% and carbohydrate 50%. In some instances a special milk formula in which corn oil was
From the Department of Pediatrics, New York University College of Medicine, The Children’s Medical Service, Bellevue Hospital, and the Pediatric Department of Beth Israel Hospital, New York
City.
Aided by grants from the Atlas Powder Co., Mead Johnson & Co. and from The Loyal League
for Philanthropies.
(Received for publication Dec. 13, 1952.)
* Deceased.
f Supplied by the Atlas Powder Company, Wilmington, Del.
TABLE 1
EFFECT OF TWEEN 80 ON FAT AND VITAMIN AABsomIoN
Patient
Initial Weight
(gm.)
Fat Absorption (%) Vitamin A Absorption (%)
Pre-
Post-Control Tween Control
Period Period Period
Pre-
Post-Control Tween Control
Period Period Period
Panico Gilmore Henderson Jones Gibson Caramata Santos Jones Brewster 1300 1440 1899 1970 1490 1200 879 1580 1450
74.2 82.4 810
80.0 89.5 66.1
72.5 82.6 84.6
49.0 57.9 51.9
77.7 83.5 81.5
82.3 93.4 84.1
71.6 87.2 79.6
70.1 75.6 84.0
68.6 77.4 88.4
63.75 84. 70.
66.5 85. 65.
45. 85. 72.
50. 50. 49.
60.75 62. 49.
76.5 84. 69.
57.5 77. 70.
58. 66. 70.
65. 72. 57.
Average 71.8 81.1 77.9 60.3 73.0 63.4
TABLE 2
EFFECT OF TWEEN G1205 ON FAT AND VITn A ABsoapTioN
Patient
Initial Weight
(gm.)
Fat Absorption (%) Vitamin A Absorption (%)
Pre-
Post-Control Tween Control
Period Period Period
Pre-
Post-Control Tween Control
Period Period Period
Jones Santos Brewster Wong Scalfoni Bartelio I Brodus I Strict Bartelioll Brodus II Ortega 1580 879 1450 1550 1580 1080 920 1920 1420 1200 1650
71.5 92.6 79.4
70.0 77.3 84.0
68.4 85.0 88.4
54.5 53.9 41.8
74.0 87.5 68.0
77 .6 80.0
-37.7 57 .8 43.,9
57.5 75.0 69.2
38.4 66.5 62.5
45.3 67.6 60.5
74.,5 81.7 77.1
57.5 76.0 65.0
58.! 73.1 70.0
65.0 58.2 57.1
42.0 78.0 56.0
69.0 86.0 66.0
Average 60.9 74.9 67.5 58.5 74.0 63.0
* Specimen partially lost.
substituted for butter fat was used. This was fed at levels providing approximately 1 30 cal./kg. Feedings in the tween periods were identical with those on control periods except for addition of tween. Quantity of tween given was proportional to fat intake. Preliminary observations had shown that a
dose of tween 40 mg/gm. fat was well tolerated; this dose was therefore adhered to. In the early experiments tween was given by medicine dropper between feedings ; in later experiments it was
homogenized in feedings.*
* Experimental food in which corn oil was used was prepared for the authors at the laboratories of
* Milk feedings with supplement of melted 1)utter were employed in these 2 studies. TABLE 3
EFFECT OF TWEEN G1205 ON FAT ABSORPTION
Patient Initial Weight (gm.) Control I (%) With Tween (%) Control II (%)
Romero 1690 40.8
40.6
56.4
64.5
Rosadol 1985 55.0
61.5
53.0
74.5
Rosadoll 1515 45.8
86.0
76.0 92.2
Dugan 1590 83.3 87.2 91.0
Isalde 1510 61.0 73.0 72.2
Average 59.2 72.1
TABLE 4
EFFE2T OF TWEEN G1205 ON FAT ABSORPTION IN PREMATURE INFANTS RECEIVING CORN OIL
. Patient Romero Rosadol Rosado II Dugan . . . Initial Weight (gm.) 1690 1985 1515 1590
Fat Absorption (%)
Corn Oil Control Corn Oil+Tween
65.9 72.3 62.8 68.8 88.2 85.5 95.5 96.2 Butter Fat 40.6 61.5 86.0 83.3
Average 78.1 80.7 67.9
TABLE 5
EFFECT OF TWEEN G-1205 ON FAT ABSORPTION IN PATIENTS WITH CYSTIC FIBROSIS
OF PANCREAS AND CONGENITAL BILI.itY ATRESIA
Patient
Period I-lControl) Period Il-Tween Added
Fat Intake (gm.) Fat Absorbed Fat Intake (gm.) Fat Absorbed
Gm. % Gm. %
Gross* 8yr.old
Congenital bili-ary atresia
168.8 78.8 (46.6%) 168.8 91.7 (54.3%)
Pavlmti*
llyr.old
Cystic fibro3is of pancreas
CHART 1
Aliquots of stool from each experimental period were assayed for vitamin A by a modification of the Carr-Price procedure.4 The remainder of stool was dried and assayed for fat by the procedure of Tidwell and Holt.’ Fat and vitamin A intake were similarly assayed. Vitamin A intake was derived in part from milk and in part from a supplement of oleum percomorphum given once daily. Intake
varied slightly depending on size of feeding, range being between 20,000 and 22,000 units/day.
REsu LTS
These are given in tables 1 to 5. In table 1 are shown observations on nine infants who received a supplement of tween 80. It is apparent that there is approximately a 10% im-provement in fat absorption and a slightly greater increase in vitamin A absorption. The values decrease after the discontinuance of the tween but do not return to the precontrol
level, as might be expected in view of the slightly more mature state of the infant.
Averag-ing the pre- and the post-control periods indicates a fat absorption of 74.9% in the controls
and 81.1% for the tween periods. The vitamin A absorption in the pre- and post-control
periods when averaged is 61 .0% as compared to 73.0% for the tween 80 periods.
Ef’’ect
or
Tween
on
Fat
Abo2ption
a)
Cl
0
CIIsitr 2
a)
Cl
0
ci
ci
I
Lffect
of
Tween
on Vitamin
A Ab5orption
Table 2 shows similar findings in the case of 1 1 infants studied on tween G1205. An average of the pre- and post-control periods gives a figure of 64.2% for fat absorption
as compared with 74.9% when tween was added. In the case of vitamin A the average absorption for the pre-and post-control periods was 60.8% as compared to 74.0% with tween.
The improved absorption on tween is not seen in every instance. In some cases the
infant showed better absorption in the post-control period than in the tween period. It may
also be observed that the correlation between improved fat absorption and improved
vita-mm
A absorption is not a close one.Table 3 shows a smaller group of infants studied subsequently who received a
supple-ment of tween G1205. With one exception only a single pre-control period was carried out. It is apparent, however, that the findings are closely comparable to those of table 2.
assimilation when a more readily assimilable fat than butter fat was employed. A few observations were therefore made with corn oil, with and without tween. These are shown in table 4. Here it may be seen that with the higher percentage absorptions found with corn
oil relatively less benefit results from the addition of tween.
A summary of all the data on premature infants receiving either tween 80 or tween
G1205 indicates that fat absorption was increased from an average control value of 69.1% to 76.6% (chart 1
)
and that vitamin A absorption was increased from an average controlfigure of 61.4% to 74% (chart 2).
Two observations were made on older children suffering from marked steatorrhea, one,
a case of congenital biliary atresia and the other, a case of cystic fibrosis of the pancreas.
Both patients were on high fat diets and were gaining weight. Some measure of
improve-ment was noted in the case of biliary atresia whose percentage absorption of fat rose from
46.6% to 54.3%. Improvement was not observed in the patient with cystic fibrosis of the
pancreas.
DISCuSSION
The results reported confirm the findings of Jones and Culver2 in adults in regard to the
improvement of fat absorption brought about by tweens in states of steatorrhea. Contrary
to the observations of Johnson et al.,3 they indicate that premature infants are no exception to the rule.
The improvement in absorption though significant is not a striking one and one
may well question whether as a practical measure such a procedure is worth while in view of the fact that increased fat absorption of considerably greater degree can be brought about by other means. It can be brought about by the substitution of more readily assimila-ble fats for butter fat,6 among which corn oil may now be included. It may also be effected by increasing the fat intake as the authors have shown elsewhere.7
SUMMARY
Observations on premature infants have shown that fat assimilation and vitamin A
assimilation can be increased by the use of either tween 80 or tween G1205. The increase is a relatively small one and of questionable practical importance.
REFERENCES
1. Morales, Soledad, Chung, A. W., Lewis, J. M., Messina, Angelina, and Holt, L. E., Jr., Absorption of fat and vitamin A in premature infants. II. Effect of particle size on absorption of these
substances, PEDIATRICS 6:644, 1950.
2. Jones, C. M., Culver, P. J., Drummey, G. D., and Ryan, A. E., Modification of fat absorption in digestion tract by use of emulsifying agent, Ann. Int. Med. 29: 1, 1948.
3. Johnson, A. L., Scott, R. B., and Newman, L. H., “Tween 20” and fecal fat in premature infants,
Am. J. Dis. Child. 80:545, 1950.
4. Lewis. J. M., Bodansky, 0., and Haig, C., Level of vitamin A in blood as index of vitamin A
absorption in infants and children, Am. J. Dis. Child. 62:1129, 1941.
5. Tidwell, H. C., and Holt, L. E., Jr., Estimation of total lipids and lipid partition in feces, J. Biol. Chem. 112:605, 1936.
6. Tidwell, H. C., Holt, L. E., Jr., Farrow, H. L., and Neale, S., Fat absorption in premature infants
and twins, J. Pediat. 6:481, 1935.
7. Morales, Soledad, Chung, A. W., Lewis, J. M., Messina, Angelina, and Holt, L. E., Jr., Absorption
of fat and vitamin A in premature infants, I.Effect of different levels of fat intake, PEDIATRICS
SPANISH ABSTRACT
Absorcidn de las Grasas y Vitamina A en Ti#{241}osPrematuros
III.
Efectode
Agentes Detergentes Sobre Ia Absorci6n de Estas SubstanciasEn un estudio previo, los autores observaron que el tamaflo de las partIculas de los Ilpidos es un
factor importante para su absorci#{243}nen los ni#{241}osprematuros; las grasas y la vitamina A de una
mezcla homogeneizada, con partIculas no mayores de 2 micrones de di#{225}metro, fueron absorbidas m#{225}s f#{225}cilmente que las de otra mezcla sin emulsionar. Dc este trabajo naci#{243}el inter#{233}s de ver el efecto
en Ia absorci#{243}nde las grasas, de substancias detergentes, las liamadas “Tweens,” #{233}sterescon grupos hidr#{243}fllose hidr#{243}fobos que act#{252}ancomo agentes emulsionantes, propiedad que facilitarIa Ia absorci#{243}n lipoldica. En efecto, esto se ha observado en adultos con esteatorrea, usando el “Tween 80 ‘; pero
no asI en prematuros con este mismo agente (Johnson y colaboradores) por lo que los autores del presente artIculo trataron de ampliar el n#{252}mero de casos estudiados. El ‘‘Tween 80” es de sabor muy
desagradable que pudo haber ejercido efectos desfavorables, o bien ocultado mejores respuestas ; por lo tanto, en esta experiencia se empled adem#{225}s,una preparaci#{243}n de mejor sabor, el “Tween G 1205.”
Las observaciones en este grupo de prematuros mostraron que realmente hay mejor absorci#{243}n de
grasas y de vitamina A con el uso del “Tween 80’ 0 del “Tween G 1205,” pero en forma tan
discreta que su importancia prflctica es dudosa si se consideran los mejores resultados de otros medios,
por ejemplo, el uso de grasas de por sI m#{225}sf#{225}cilmente absorbibles, como el aceite de maIz. o
aumentando Ia ingestion de grasas.