Effect of intermittent versus continuous enteral feeding on energy expenditure in premature infants

Judi th Gran t , MB, MRCP(UK), a n d Scot t C. Denne, MD

From the Section of Neonatal-Perinatal Medicine, Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis

The purpose of this study was to examine whether premature infants have higher rates of energy expenditure and diet-induced thermogenesis during intermittent feeding compared with continuous feeding. Using open-circuit respiratory cal- orimetry, we measured energy expenditure in 11 premature newborn infants on 2 successive days for 5 to 7 hours during and after either intermittent or contin- uous feeding. Infants were fed the same quantity of formula each day, either for 5 minutes or by continuous drip for 2 to 3 hours. The order of feeding type was randomized. No response of diet- induced thermogenesis to continuous feeding was found, whereas a peak increase of 15% over baseline was observed after intermittent feeding. Overall energy expenditure during the study period was significantly greater after intermittent compared with continuous feeding (2.18 _ 0.07 kcal /kg per hour vs 2.09 _+ 0.05 kcal /kg per hour; p <0.05). Thus there was a mean 4% difference (range up to 17%) in energy expenditure between the two feeding modes. These results are similar to those obtained with adults and support the concept of the increased energy efficiency of continuous feeding. Further study will be necessary to document whether the increased energy efficiency provided by continuous feeding may be clinically significant. (J PEDIATR 1991;118:928-32)

Energy expenditure in the newborn infant is influenced by many factors, including postnatal age, activity level, ther- mal stresses, positioning, and sleep state. 15 The adminis- tration of feedings also increases energy expenditure; diet- induced thermogenesis is thought to represent the energy required for the absorption and storage of nutrients. 6 Studies examining DIT in term and preterm infants have demonstrated increases in metabolic rate of 11% to 18% in response to feeding. 79

In adults the mode of feeding has been shown to affect DIT10, 11; energy expenditure was significantly greater dur- ing intermittent feeding than during continuous dietary

Supported in part by National Institutes of Health Diabetes Research Training Center grant PHS P60DK20542-13, and by the James Whitcomb Riley Memorial Association. Submitted for publication Oct. 22, 1990; accepted Jan. 7, 1991. Reprint requests: Scott C. Denne, MD, Department of Pediatrics, Indiana University School of Medicine, 702 Barnhill Dr., RR208, Indianapolis, IN 46202-5210. 9/23/27757

formula infusion. No study of energy metabolism in new- born infants comparing continuous with intermittent gav- age feedings, both of which are commonly used feeding techniques in low birth weight preterm infants, has been reported. Improved weight gain has been shown for contin- uous versus intermittent feeding in some cross-sectional studies12, 13 but not in others. TM

DIT Diet-induced thermogenesis [

The purpose of this study was to examine whether low birth weight premature infants have higher rates of energy expenditure and DIT during intermittent gavage feeding than during continuous gavage feeding.

M E T H O D S

The subjects were 11 premature infants weighing <2 kg who were already receiving orogastric feedings and who were receiving a total intake of at least 115 ml/kg per day. Usual feedings were given every 3 hours (n = 7) or every 2

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Volume 118 Comparison of enteral feedings on energy expenditure 9 2 9 Number 6

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Fig. t. Time course of 02 consumption after initiation (time zero) of test feeding.

hours (n = 4). None of the infants had been continuously fed before entry into the study. All infants were of appro- priate weight for gestational age. The infants studied weighed 1.48 + 0.07 kg (range 1.13 to 1.84 kg)and were 30 _+ 0.5 weeks of gestational age (range 28 to 33 weeks) at birth. The infants were studied at 18.5 + 2.0 days of age (range 8 to 28 days), and weighed 1.54 _+ 0.08 kg at the time of study (range 1.05 to 1.98 kg). For the 7 days before the study the rate of weight gain was 14.9 _+ 3.3 gm/kg per day (range -3.4 to 29.5). Excluded from study were babies with congenital anomalies and those receiving supplemen- tal oxygen therapy or antibiotics; The protocol was ap- proved by the Indiana University Institutional Review Board, and informed written consent was obtained from the parents of all babies enrolled in the study.

Each infant was studied twice on consecutive days and received either a 5-minute or a continuous feeding on each day. The order of feedings was randomized; six infants re- ceived the intermittent feeding first, and five infants re- ceived the continuous feeding first. Orogastric tubes were in place before the start of the study. The intermittent feeding was administered through the orogastric tube by syringe pump for 5 minutes, and the continuous feeding by syringe pump for 3 hours to infants usually fed every 3 hours, or for 2 hours to infants usually fed every 2 hours.

To minimize the thermic effect of previous feedings, in- fants were fasted on each study day for twice the normal feeding interval (i.e., for 4 to 6 hours) before the initiation of the study feeding. The study feeding was identical in vol- ume and content to the feeding administered immediately before the commencement of the study. For those infants receiving expressed human milk (n = 3), separate aliquots from the same expression were thawed, brought to approx-

imately room temperature, and administered for the study feeding on each of the 2 days of the study. The temperature of the human milk was not directly measured; however, if variation in temperature occurred, it most likely did not in- fluence the results, as evidenced by the fact that if infants receiving human milk are excluded from analysis, all com- parisons made with the data remain the same. Formula-fed infants received Enfamil Premature Formula (24 cal/ounce [0.8 cal/ml]) (n = 8), administered at room temperature. The feeding amount given in the study was 15.1 +_ 1.0 ml/kg (range 10.5 to 20.0 ml/kg).

Infants were studied while they were prone and placed under a servomechanism-controlled radiant warmer set to a skin temperature of 36.5 ~ C. Axillary temperatures obtained every 2 hours throughout the study were stable at 36.8 ~ C (SEM + 0.02) and were the same on both study days. The activity of the infants during the study was assessed every 2 minutes according to a 6-point scale designed by Rubecz and Mestyan+ 2 in which 0 indicates that the infant is asleep and totally quiet and 5 indicates vigor- ous activity with crying.

Oxygen consumption and carbon dioxide production were measured with an open-circuit indirect respiratory calorimetry system. 15 A plastic hood was placed over the baby's head, and a suction pump was used to draw air through the hood. The air exiting from the hood was mixed in a baffled chamber, and the 02 and CO2 concentrations were measured with a model MGA-100 medical gas analyzer (Perkin-Elmer Corp., Pomona, Calif.). The ana- lyzer was calibrated by using gravimetrically prepared standard gas mixtures. The flow of air was measured and maintained by a servomechanism-controlled flow regulator (Brooks Instruments, Hatfield, Pa.) The 02 and CO2 con-

9 3 0 Grant and Denne The Journal o f Pediatrics June 1991

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centrations were continuously recorded on a model 2600 chart recorder (Gould Inc., Cleveland Ohio). Combustion of absolute ethyl alcohol in the system gave results within 4% of expected values for all measurements, and within 2% for O2 consumption.

Respiratory calorimetry was performed beginning 1 hour before the test feeding and continued through twice the normal feeding interval (a total of 5 hours for infants fed every 2 hours, and 7 hours for infants fed every 3 hours). Oxygen consumption and CO2 production were calculated at 20-second intervals throughout the study. Values were averaged in 10-minute intervals to facilitate subsequent analysis and presentation of the data. Energy expenditure was calculated from the mean values for 02 consumption and respiratory quotient measurements. 16 All calculations were based on the infants' measured weight at the time of study.

For analysis, the 1-hour period before the study feeding and that before the next normal feeding were designated the "prefeeding" periods, and baseline energy expenditure was considered to occur during those periods. Measurements obtained during these periods were combined for one mean prefeeding value. The remaining time after the initiation of the test feeding was designated as the "feeding" period, and energy expenditure was calculated during this time. This period was 3 hours for infants fed every 2 hours (n = 4) and 5 hours for infants fed every 3 hours (n = 7). This period of analysis is longer than the time of continuous feeding, so that any delayed change in energy expenditure as a result of the feeding would be reflected.

Continuous recordings of heart rate were not made dur- ing our studies. Heart rate has been correlated with energy

expenditure; however the R value for an individual newborn infant is only in the range of 0.7.17 In addition, the corre- lation is particularly poor at the lower range of heart rates (resting or basal) in both neonates and adults. 17, 18 There- fore, although continuous heart rate tracings may have provided an additional measure of the DIT response, it is also possible that heart rate recordings may not sufficiently reflect DIT in newborn infants.

All data are reported as mean _ SEM. Statistical com- parisons were made by paired t test.

R E S U L T S

The time course of 02 consumption after the test feeding (time 0) is illustrated in Fig. 1. After the intermittent feed- ing, Oz consumption rose, reaching a Peak at 80 minutes and returning to baseline values between 120 and 160 minutes. The mean peak O2 consumption (mean of all 80-minute values) was 8.4 ml/kg per minute and represented an increase of 15% above baseline values. During the contin- uous feeding, 02 consumption remained relatively constant. The mean O2 consumption during the entire feeding period was significantly greater during intermittent than during continuous administration (7.23 • 0.2l vs 6.94 + 0.17 ml/kg per minute; p = 0.03).

Activity, as assessed by the activity scoring system, was similar during the intermittent and continuous feeding pe- riods (1.65 _+ 0.09 vs 1.53 _+ 0.08; not significant). Most of the time the infants were sleeping or quiet during both studies.

Energy expenditure in the prefeeding period was similar for both continuous and intermittent feedings (2.08 _+ 0.07 vs 2.12 + 0.06 kcal/kg per hour; not significant). In

Volume 118 Comparison of enteral feedings on energy expenditure 9 3 1 Number 6

contrast, energy expenditure in the feeding period was sig- nificantly greater during intermittent administration (2.18 _+ 0.07 vs 2.09 + 0.05 kcal/kg per hour;p <0.05), a mean 4% difference (range up to 17%) in energy expendi- ture between the two feeding modes (Fig. 2).

No DIT response could be demonstrated for continuous feeding, as reflected by the similar prefeeding and feeding energy expenditure values. During intermittent adminis- tration, however, a significant increase in energy expendi- ture over prefeeding values was observed (Fig. 2).

There were no statistical differences between the DIT re- sponses of infants fed every 2 hours versus every 3 hours. However, the small number of infants fed every 3 hours (n = 4) may have precluded finding a difference if it existed.

D I S C U S S I O N

Our findings demonstrate an increase in energy expendi-

ture after intermittent but not after continuous feeding in premature newborn infants. This difference in the DIT re- sponse between the two modes of feeding resulted in an en- ergy expenditure during the study period that was 4% greater after intermittent than after continuous feeding. These results are similar to those obtained with adults.

The DIT response of premature newborn infants to intermittent feeding has been measured by several investi- gators. Stothers and Warner 7 found a 13% increase in 02 consumption in infants 32 to 36 weeks of gestational age during the first hour after feeding. Studying preterm infants 28 to 32 weeks of gestational age, Brooke and Alvear 8 dem-

onstrated an increased metabolic rate of 11% after feeding in those who were small for gestational age and of 18% in those who were of appropriate size for gestational age. Rubecz and Mestyan 9 demonstrated a 15% increase in metabolic rate in very low birth weight (1000 to 1500 gm) premature infants fed human milk; the peak increase occurred between 50 and 80 minutes after feeding. Similar measurements were obtained in our study; energy expendi- ture increased 15% over baseline values and peaked at 80 minutes after the intermittent feeding.

In adults the DIT response is also greater during inter- mittent than during continuous feeding. 1~ 11 Nacht et al. 1~

measured energy expenditure in 10 normal adults after an overnight fast and after continuous or intermittent feeding. Diet-induced thermogenesis represented 10% of the energy ingested during intermittent feeding but only 8% during continuous administration; total energy expenditure for the 6-hour period of study was less during continuous feedings but did not reach statistical significance. In another study of healthy adults, Heymsfield et al. 11 demonstrated a re- duction in both the DIT response and total energy expen- diture during continuous feeding. The four subjects each received formula continuously for 2 weeks and intermit-

tently for 2 weeks. As in our study, no increase in energy expenditure over baseline values was measured during con- tinuous feeding. In addition, total 24-hour energy expendi- ture was significantly lower (~8%) during continuous administration. Thus available data in both adults and pre- mature infants support the concept of the increased energy efficiency of continuous feeding.

The mechanism of such an increase in efficiency, how- ever, remains a matter of speculation. Because stimulation

of sympathetic activity may be an important component of the DIT response, 19 it is possible that the mode of feeding may affect catecholamine release differently. We did not measure catecholamine concentrations, but no differences in plasma levels of norepinephrine or epinephrine were found between continuous and intermittent administration in the study by Nacht et al. I~

Differences in nutrient storage may also provide a possi- ble explanation for the energy efficiency of continuous feeding. The metabolism of absorbed substrate into storage fuels requires significant energy; nutrients may be quickly absorbed and converted to storage during intermittent ad- ministration for later use as energy substrate between feed- ings. In contrast, substrates supplied by continuous admin- istration may be utilized for energy as they are absorbed, thus reducing at least some of the energy cost of storage.

We conclude that the mode of nutrient administration affects energy expenditure and the DIT response in prema- ture infants as it does in adults; lower values are obtained during continuous feeding. However, the magnitude of dif- ference is relatively small (approximately 4%) and obtained under experimental conditions. Nevertheless, for individual babies the difference in energy expenditure may be consid- erable (up to 17%). Further investigation for longer periods will be necessary to document whether the increase in en- ergy efficiency provided by continuous feeding may result in clinically significant improvements in energy balance.

We thank Cheryl A. Karn, RN, for expert assistance in performing these studies.

R E F E R E N C E S

1. Sauer P J J, Dane H J, Visser HKA. Longitudinal studies on metabolic rate, heat loss, and energy cost of growth in low birth weight infants. Pediatr Res 1984;18:254-9.

2. Rubecz I, Mestyan J. Activity, energy metabolism and post- natal relationship in low birth weight infants. Acta Paediatr Sci Hung 1975;16:351-62.

3. Mestyan J, Jarai I, Kekete M, Soltesz GY. Specific dynamic action in premature infants kept at and below the neutral tem- perature. Pediatr Res 1969;3:41-50.

4. Materson J, Zucker C, Schulze K. Prone and supine position- ing effects on energy expenditure and behavior of low birth weight neonates. Pediatrics 1987;80:689-92.

5. Stothers JK, Warner RM. Oxygen consumption and neonatal sleep states. J Physiol 1978;278:435-40.

9 3 2 Grant and Denne The Journal of Pediatrics June 1991

6. Danforth E. Diet and obesity. Am J Clin Nutr 1985;41: 1132-45.

7. Stothers JK, Warner RM. Effect of feeding on neonatal oxy- gen consumption. Arch Dis Child 1979;54:415-22.

8. Brooke OG, Alvear J. Post-prandial metabolism in infants of low birth weight. Hum Nutr Clin Nutr 1982;36C:167-75.

9. Rubecz I, Mestyan J. Post-prandial thermogenesis in human milk-fed very low birth weight infants. Biol Neonate 1986; 49:301-6.

10. Nacht CA, Schutz Y, Vernet O, Christin L, Jequier E. Con- tinuous versus single bolus enteral nutrition: comparison of energy metabolism in humans. Am J Physiol 1986;251:E524- E529.

11. Heymsfield S, Casper K, Grossman G. Bioenergetic and met- abolic response to continuous v intermittent nasenteric feeding. Metabolism 1987;36:570-5.

12. Krishnan V, Satish M. Continuous vs intermittent nasogastric (NG) feeding in very low birth weight infants. [Abstract]. Pe- diatr Res 1981;15:537.

13. Urrutia JG, Poole E. Continuous nasogastric versus intermit-

tent gavage feedings in very low birth weight infants [Ab- stract]. Pediatr Res 1983;17:203.

14. Toce ST, Keenan WJ, Homan SM. Enteral feeding in very-low-birth-weight infants. Am J Dis Child 1987;141: 439-44.

15. Denne SC, Kalhan SC. Glucose carbon recycling and oxida- tion in human newborns. Am J Physiol 1986;251:E71-E77.

16. Lusk G. Animal calorimetry: analysis of the oxidation of mix- tures of carbohydrate and fat. J Biol Chem 1924;49:41-7.

17. Chessex P, Reiehman B, Veretlen G, Putet G. Relation between heart rate and energy expenditure in the newborn. Pediatr Res 1981;15:1077-82.

18. Christensen C, Frey H, Foenstelien E, Eng E. A critical eval- uation of energy expenditure estimates based on individual 02 consumption/heart rate curves and average daily heart rate. Am J Clin Nutr 1983;37:468-72.

19. Landsberg L, Saville M, Young J. The sympathoadrenal sys- tem and regulation of thermogenesis. Am J Physiol 1984;247: E181-9.

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