Background
There are many prediction equations currently in use to calculate energy requirements in healthy infants [
1‐
4]. These are popular among many health care practitioners due to their ease of use. For many of these equations only length and weight of the infants need to be measured prior to calculations. Some of the most commonly utilized equations for infants include those from the World Health Organization [
1], Schofield [
2] and Oxford [
3]. However, some of these prediction equations [
1,
2] were based on limited data obtained over 80 years ago utilizing non-standardized techniques [
3,
5]. Derivation of all of these prediction equations [
1‐
4] were based on short-term metabolic measurements. For example, only 30-45 minute measurements of resting metabolic rates in individuals were utilized for the derivation of the World Health Organization [
1], Schofield [
2] and Oxford equations [
3]. In an attempt to improve the accuracy of calculating energy requirements for infants, new prediction equations derived and published from our laboratory [
4] were based on 50 four-hour morning metabolic measurements in the Enhanced Metabolic Testing Activity Chamber (EMTAC).
The EMTAC was applied in the first ever direct 24-hour measurement of energy expenditure, resting and sleeping metabolic rates in both healthy [
6] and in those infants recovering from malnutrition [
7]. The aim of this analysis was to use data from previously published direct 24-hour metabolic measurements in healthy infants [
6] as a reference to evaluate 11 prediction equations for calculating 24-hour energy expenditure, resting and sleeping metabolic rates [
1‐
4].
Results
Energy expenditure (EE), resting (RMR) and sleeping metabolic rates (SMR) of the 10 healthy reference infants used for this evaluation, as directly measured for 24-hours in the EMTAC, are shown in Table
1. Calculated results from the EMTACEE-WT, EMTACRMR-WT, EMTACSMR-WT and EMTACSMR-LWT prediction equations were in agreement (p = NS) with that obtained for the reference infants (Table
3). The percentage difference from the 10 healthy reference infants that had direct 24-hour metabolic rate measurements was less than 5% when utilizing these prediction equations for calculating 24-hour EE, RMR and SMR (Table
3). This was further verified by the fact that the mean differences calculated utilizing the Bland and Altman limit analysis method had a close proximity to zero or were close to the mean value (Table
3).
Table 3
Statistical analysis for prediction equations that are in agreement with direct 24-hour metabolic measurements
EMTACEE-WT | 81.3 ± 1.8 | 4.5 ± 12.0 | 0.42 | 2.6 ± 19.6 |
EMTACRMR-WT | 65.0 ± 3.9 | 4.0 ± 7.9 | 0.16 | 2.4 ± 9.8 |
EMTACSMR-WT | 63.3 ± 1.1 | -2.2 ± 7.4 | 0.23 | -1.7 ± 9.6 |
EMTACSMR-LWT | 66.7 ± 2.4 | 3.0 ± 8.2 | 0.29 | 1.8 ± 10.0 |
Calculated results from the EMTACEE-LWT, EMTACRMR-LWT, WHO, SCH-LWT, SCH-WT, OXFORD-LWT, OXFORD-WT prediction equations were not in agreement (p < 0.05) with that obtained for the reference infants (Table
4). The percentage difference from the 10 healthy reference infants that had direct 24-hour metabolic rate measurements was greater than 11% when utilizing these prediction equations for calculating 24-hour EE and RMR (Table
4). This was further verified by the fact that average differences calculated utilizing the Bland and Altman limit analysis method were close to, or over two standard deviations from the mean (Table
4).
Table 4
Statistical analysis for prediction equations that are not in agreement with direct 24-hour metabolic measurements
EMTACEE-LWT | 86.6 ± 3.3 | 11.2 ± 12.7 | <0.01 | 7.9 ± 19.2 |
EMTACRMR-LWT | 73.3 ± 3.2 | 11.4 ± 9.3 | <0.01 | 7.3 ± 11.2 |
WHO | 53.6 ± 0.8 | -18.6 ± 5.5 | <0.01 | -12.4 ± 8.2 |
SCH-WT | 54.9 ± 0.8 | -16.6 ± 5.1 | <0.01 | -11.1 ± 7.6 |
SCH-LWT | 57.9 ± 5.6 | -12.2 ± 9.0 | <0.01 | -8.1 ± 11.8 |
OXFORD-WT | 56.2 ± 0.6 | -14.7 ± 5.2 | <0.01 | -9.9 ± 7.6 |
OXFORD-LWT | 58.1 ± 3.1 | -11.9 ± 6.2 | <0.01 | -8.0 ± 8.6 |
Discussion
This is the first time were direct 24-hour energy expenditure measurements in healthy infants with a standardized methodology [
6], was used as a reference to test the accuracy of several previously published prediction equations [
1‐
4] for calculating 24-hour energy expenditure, resting and sleeping metabolic rates. In this comparison the weight based prediction equations for calculating 24-hour energy expenditure, resting and sleeping metabolic rates, derived from the short-duration metabolic measurements in the EMTAC, agreed with their respective reference values. Moreover, the length-weight based prediction equation for sleeping metabolic rate, derived from similar metabolic measurements in the EMTAC, also agreed with its respective reference value. However, neither of the length-weight based prediction equations for calculating resting and sleeping metabolic rate, as derived from short-duration metabolic measurements in the EMTAC, were in agreement with their respective reference values. Finally, the World Health Organization, Schofield or Oxford prediction equations for calculating resting metabolic rate were not in agreement with the respective reference values. Some of the problems encountered in the derivation of these early equations included data obtained from measurements utilizing closed circuit indirect calorimetry [
3]. There were many problems associated with the closed circuit technique including the absorption of carbon dioxide not allowing for the calculation of the respiratory quotient [
14], hyperventilation due to the subject knowledge of air being re-circulated and no direct measurement of oxygen. Furthermore, most of the laboratory technicians did not record whether the subject was post absorptive and/or in a relaxed state prior to resting metabolic rate measurements. Moreover, many of the early measurements of resting metabolic rate were not conducted in a thermo-neutral environment where the room temperature was kept between 22-27 degrees C [
15]. Finally, a lot of the data were obtained in a limited number of ethnic groups. For example, much of the data utilized to derive the Schofield equations included a disproportionately large number Italians who have been found to have a higher resting metabolic rate per kg body weight [
16]. As a result, the Schofield equations tended to over-estimate resting metabolic rate in many tropical ethnic groups by as much as 25% [
5]. The minor ethnic group differences in body composition might also contribute to the World Health Organization [
1] and Schofield [
2] equations over estimating resting metabolic rate in many ethnic groups today [
17].
In a previous study in our laboratory [
4] we derived new prediction equations for calculating 24-hour energy expenditure, resting and sleeping metabolic rates in healthy infants utilizing the EMTAC instrument. Moreover, all metabolic measurements were conducted under standard conditions [
4] at the same time in the morning between 9:00 AM and 1:00 PM. It is possible that variations in energy expenditure over the course of 24-hours, as shown by the presence of the metabolic circadian rhythm [
6], might contribute to inherent inaccuracies when utilizing the World Health Organization [
1], the Schofield [
2] and the Oxford [
3] prediction equations. Moreover, the metabolic measurement period of less than one hour might have also contributed to the inherent inaccuracies in these equations [
1‐
3]. Despite using only the first four hours of metabolic data, the fact that measurements were conducted at the same time of day and were run at least three additional hours, as compared to the length of measurement when the World Health Organization [
1], Schofield [
2] and Oxford [
3] prediction equations were derived, might have improved the consistency and accuracy of the metabolic data in the derivation of our new weight-based equations [
4]. This is most likely due to the inclusion of some periods of increased physical activity and sleep in the infants [
4]. This is further substantiated by the fact the infants have a two to four hour sleep-wake cycle between birth and six months of age [
18].
These preliminary results suggest that the World Health Organization [
1], the Schofield [
2] and the Oxford [
3] prediction equations may not be suitable for calculating caloric requirements in infants. Furthermore, both of the length-weight equations derived with the EMTAC instrument [
4] for calculating energy expenditure and resting metabolic rate, respectively, were also not suitable for use in healthy infants. Moreover, these results suggest that additional 24-hour metabolic measurements need to be conducted in a greater number of infants from various ethnic groups. This will allow derivation of new equations that will be accurate for calculating energy requirements in healthy infants, accounting for all the metabolic variations that occur over a 24-hour period. Moreover, infants with various clinical disorders also need to be included such as those from our prior study in infants suffering from primary and secondary malnutrition [
7].
In general both the length-weight prediction equations derived with the EMTAC instrument tended to over-estimate their respective metabolic parameters. This might be due to the fact that metabolic measures were performed in the morning [
10,
12], possibly representing the infants most active part of the day. This is further verified by the direct 24-hour metabolic measurements that showed a lower energy expenditure and physical activity during the evening and early morning hours [
6]. However, the World Health Organization [
1], the Schofield [
2] and the Oxford [
3] prediction equations greatly underestimated resting metabolic rate. The lack of standardized methods, limited number of subjects less than six-months old and some of the data being obtained over 80 years ago probably contributed to errors in their derivation and consistent under estimates in resting metabolic rate when utilized in today's infants.
Conclusions
This is the first time actual 24-hour metabolic measurements in the Enhanced Metabolic Testing Activity Chamber (EMTAC) were used as a reference to evaluate several previously published prediction equations. We found those prediction equations by the World Health Organization, Schofield and Oxford, as well as the two length-weight based prediction equations from the EMTAC instrument, were inaccurate. However, the weight based prediction equations derived from our previous short-term metabolic measurements of four-hours in the EMTAC were accurate for calculating energy requirements in healthy infants up to six months of age.
Competing interests
The author declares that they have no competing interests.
Authors' contributions
The author has contributed to the design and performance of the statistical analysis. Furthermore, the author participated in some of the previous studies that provided the data for this analysis. Moreover, the author also generated some of the grant proposals necessary for the financial support of this analysis and prepared the final version of this manuscript.