Method and apparatus for determining the energy requirements of premature newborns

A method and apparatus is disclosed for determining the energy requirements of premature newborns. The method includes identifying a series of groups of newborns in which the age and weight of each newborn within each group are within defined ranges. A characteristic mathematical relationship is generated for each group and relates the mean heart rate to the mean energy expenditure over the group. The mean heart rate of a subject newborn, the energy expenditure which is to be determined is measured and applied to the mathematical relationship appropriate to the group into which the subject falls, so as to determine the mean energy expenditure appropriate to that mean heart rate, said expenditure indicating the energy requirement of the subject.

This invention relates to a method and apparatus for determining the energy 
requirements of premature human infants (newborns). 
In the care and treatment of premature newborns, careful control of calorie 
intake is necessary in order to ensure proper growth and development, 
particularly where the infant is significantly premature and/or has 
medical problems. This control is usually exercised by closely supervising 
the weight of the infant and, if the infant does not gain weight normally, 
increasing its daily calorie intake as determined by the professional 
skill and experience of the supervising medical personnel. At best, 
control of calorie intake is imprecise even under the most favourable 
circumstances, not only because questions of judgement are involved, but 
also because changes in the weight of the infant will normally be very 
small and may not immediately be detected. 
An object of the present invention is to provide an improved method and 
apparatus for determining the energy requirements of premature newborns. 
BRIEF SUMMARY OF THE INVENTION 
According to the invention, there is provided a method of determining the 
energy requirements of premature newborns. The method involves 
establishing a data base and then comparing against that data base, a 
subject premature newborn, the energy requirements of which are to be 
determined. The data base is established by: 
(1) identifying a series of groups of newborns in which the age and weight 
of each newborn within each group are within defined ranges; 
(2) measuring the oxygen uptake, the respiratory quotient and the 
cumulative heart rate of each newborn within each group over a 
predetermined period; 
(3) calculating from said oxygen uptake and said respiratory quotient, the 
energy expended by each newborn over said predetermined period; 
(4) determining the mean energy expended and mean heart rate of each 
newborn over said predetermined period; and, 
(5) generating in respect of each group a characteristic mathematical 
relationship between the mean heart rate and the mean energy expended for 
each member of said group and calculating the mean of the relationships 
over the group. 
A subject premature newborn is then compared against the data base by: 
(1) measuring the cumulative heart rate of the subject over a predetermined 
period; 
(2) determining the mean heart rate of the subject over that period; 
(3) determining the said group appropriate to the subject; 
(4) applying the mean heart rate of the subject to the mathematical 
relationship appropriate to that group so as to determine the mean energy 
expenditure appropriate to that mean heart rate, said expenditure 
indicating the energy requirement of the subject. 
The invention also provides an apparatus for determining the energy 
requirements of a subject premature newborn from a measurement of the 
cumulative heart rate of the subject over a predetermined period. 
The invention will now be more particularly described with reference to the 
accompanying drawings, in which:

DETAILED DESCRIPTION 
FIG. 1 shows an example of an actual graph which was generated during a 
study of a particular individual newborn. The graph illustrates a definite 
correlation between heart rate and energy expenditure for that particular 
individual. FIGS. 2 and 3 are graphs which were generated from studies of 
groups of infants of which the age and weights were within defined ranges, 
and show a similar correlation. FIG. 2 represents a typical graph which 
could actually be used in practice to determine the energy requirements of 
a particular subject newborn falling into the group in question. Similar 
graphs would be provided for other groups of newborns having different age 
and weight characteristics. The manner in which these graphs are generated 
will be more particularly described later in the sequence in which they 
were prepared in actual practice. The following description will also 
indicate how a subject newborn, the energy expenditure of which is to be 
determined will be compared with the graph appropriate to its age and 
weight ranges and how the graph will be used to determine its energy 
requirements. 
Actual tests which were conducted in formulating the invention will now be 
described with particular reference to FIGS. 1, 2 and 3. In all cases, 
data was acquired by known computerized, open-circuit indirect calorimetry 
techniques, for example as previously described in Swyer, P. R., Putet, 
G., Smith, J. M. and Heim, T.: Energy metabolism and substrate utilisation 
during total parenteral nutrition in the newborn. In: Intensive Care of 
the Newborn II. Stern, L., Friis-Hansen, B. Eds. Masson Publishing U.S.A. 
Inc., New York, N.Y., 1978, p 307. 
These techniques were used to record oxygen uptake (V02), carbon dioxide 
production (VC02) and respiratory quotient (R) in a thermoneutral 
incubator environment. Respiratory quotient is defined as a ratio 
indicating the relation of the volume of carbon dioxide given off in 
respiration to the volume of oxygen consumed. Cumulative heart beats were 
measured by on/line ECG monitoring equipment. 
Oxygen uptake and cumulative heart rate were initially recorded over short 
periods of time (15 to 30 minutes) for individual infants displaying 
variable activities and heart rates. The recorded values were then plotted 
on a graph of mean heart rate against oxygen uptake and a typical one of 
such graphs appears as FIG. 1. The plotted co-ordinates for the various 
periods during which heart rate and oxygen uptake were recorded for that 
particular individual are shown as circular markings on the graph. A 
linear regression curve was then generated through the plotted 
co-ordinates and it will be seen that the graph clearly shows a linear 
heart rate-energy expenditure correlation within experimental limits 
(correlation significant to P&lt;0.001 level of significance). 
FIG. 2 illustrates a characteristic graph which was obtained by plotting 
mean heart rate against mean metabolic rate (energy expenditure) in 
respect of a group of newborns, the ages and weights of which were within 
defined ranges. 
Thirty five studies were performed in 16 newborn infants of birthweight 
(mean .+-.SD) 1.55.+-.0.65 kg (range: 0.75 to 3.1 kg) and gestational age 
32.+-.5 weeks (range: 26 to 42 weeks). The mean age at the time of study 
was 26.5.+-.15.7 days (range: 5 to 61 days) and the mean weight at the 
time of study was 1.78.+-.0.5 kg (range: 0.96 to 2.75 kg). The infants 
studied fell into 2 groups: 10 orally fed, very low birthweight, premature 
infants (birthweight 1.18.+-.0.2 kg; weight at study 1.46.+-.0.2 kg) and 6 
larger babies, receiving total parenteral nutrition following abdominal 
surgery (birthweight 2.12.+-.0.7 kg; weight at study 2.11.+-.0.5 kg). 
Analysis shows similar results in both groups and they were therefore 
combined. From these 35 studies relationships between heart rate and 
metabolic rate (energy expenditure) were defined. 
Metabolic rate (energy expenditure) was calculated from the caloric value 
of O.sub.2 for the specific measured respiratory quotient (R). Infants 
were studied for periods of 1 to 24 hrs (mean 4.5 hrs) and a total of 8269 
minute by minute simultaneous measurements of VO.sub.2, VCO.sub.2, R, 
metabolic rate and heart rate were recorded during periods of quiet and 
active sleep as well as awake states and periods of crying. In the case of 
a newborn having a respiratory quotient of 1, one liter of oxygen 
represents 5 calories. 
The data were evaluated as follows: 
(a) Minute by Minute Measurements: 
From the minute by minute measurements of heart rate (beats/min) and 
metabolic rate (cal/kg. min) for all 35 studies combined (8269 
measurements), regression analyses were performed to define the 
relationship between these variables. The data were analysed in 24 defined 
heart rate categories at intervals of 5 beats per min (111-115, 116-120, . 
. . , 226-230 beats per min) and a regression constructed of the mean 
metabolic rate (MR) with the corresponding mean heart rate (HR). 
(b) Cumulative Heart Rate Measurements: 
From the cumulative heart rate and the mean VO.sub.2 or mean metabolic rate 
(MR) recorded over the whole period of the study, the following factors 
were calculated for each study: 
OXYGEN UPTAKE PER HEART BEAT (.mu.l/kg. beat)=mean VO.sub.2 .times. 
duration of study (min)/cumulated heart beats 
ENERGY EXPENDITURE PER BEAT (cal/kg. beat)=mean MR.times. duration of study 
(min)/cumulated heart beats. 
The curve relating mean heart rate and mean metabolic rate .+-.1 SD is 
represented in FIG. 2. The line of best fit for all points between 110 to 
230 beats/minute is a polynominal distribution to the third degree which 
is represented by the equation: 
EQU y=-0.0000291x.sup.3 +0.01685x.sup.2 -2.93x+197. 
This correlation is highly significant (r=0.99; p&lt;0.001). From the mean 
.+-.SD metabolic rate measured for each heart rate group, a coefficient of 
variation of 11.5% (range: 4 to 16%) was determined for this curve. Above 
a heart rate of 140/min (representing 85% of all measurements) there is a 
highly significant linear relationship between metabolic rate and heart 
rate: 
EQU y=0.29x-6.1 (r=0.0997 p&lt;0.001). 
The flattening of the curve below 140 beats per min suggests that a resting 
metabolic rate is reached, and can be estimated at 53 kcal/kg. d (222 
kJ/kg. d) for this group of infants. 
From the cumulative heart rate measurements and mean metabolic rate over 
the whole study, oxygen uptake per heart beat and metabolic rate per heart 
beat factors were calculated for individual studies. From these individual 
results the mean .+-.SD metabolic rate per heart beat calculated for the 
whole group: 
OXYGEN UPTAKE PER HEART BEAT =51.8.+-.6.8 .mu.l O.sub.2 /kg 
ENERGY EXPENDITURE PER BEAT =0.258.+-.0.03 cal/kg (1.1 J/kg) 
The relationship between heart rate and metabolic rate in this specific 
group of infants is constant with a coefficient of variation of 11.5%. 
In order to assess the ability to predict individual energy expenditure by 
measurement of heart rate, 10 additional studies were performed in a 
similar population of newborns for periods of 5.5.+-.1.5 hrs (range: 3 to 
7.5 hrs) with continuous monitoring of heart rate during the metabolic 
study. Using both the polynomial relationship and the constant energy 
expenditure per heart beat factor determined from the 35 studies, and 
estimative error of predicting individual metabolic rate was obtained for 
these 10 additional studies. FIG. 3 shows the previously defined 
polynomial distribution on which the additional measured metabolic rates 
and mean heart rates of these 10 studies are plotted. All measurements are 
within .+-.1 SD of the original curve and the mean error of estimate is 
5.6.+-.4% (range: -5% to +14%). Using the factor of 0.258 cal/kg per heart 
beat, the mean error of estimate was 5.7.+-.4% (range: -4% to +11.5%), and 
the predictive error was less than 10% in 8 of the 10 studies. Further 
corroboration of the consistency of the HR-MR relationship was derived 
from a study in a newborn with congenital hyperthyroidism. His mean heart 
rate of 199 beats/min and measured metabolic rate of 53 cal/kg. min fell 
on the upper end of the defined curve as shown in FIG. 3 and is 
represented as a triangle in that view. 
The equation identified above or the graphical representation of FIG. 2 may 
be used in practice to determine the mean energy expenditure appropriate 
to the mean heart rate of a subject premature newborn whose age and weight 
are within the ranges of the group. 
A similar characteristic graph may be obtained for each of several groups 
of premature newborns in which the age and weight of each newborn in each 
group are within defined ranges. In order to determine the energy 
requirements of a subject premature newborn, the cumulative heart rate of 
the subject is measured over a predetermined period, and a mean heart rate 
calculated for that period. A determination is then made as to the group 
(in terms of age and weight ranges) into which the subject falls. The 
characteristic graph or equation for that group is then used to determine 
the metabolic rate (mean energy expenditure) appropriate to the mean heart 
rate calculated for the subject. This expenditure indicates the energy 
requirement of the subject (in calories per kilogram of subject weight per 
minute). 
Of course, the vertical (y) axis of the FIG. 2 graph can easily be 
recalibrated to indicate the daily energy expenditure of the subject 
infant (as k. cal/kg/day). The daily energy requirements of a particular 
newborn can then be read directly from this scale. 
A characteristic mathematical relationship for a particular group of 
newborns can of course be mathematically calculated instead of being 
derived from a graphical representation, for example, wholly or partially 
using automatic equipment such as computers. For example, a series of 
graphs of the form shown in FIG. 2 could be generated, one for each group 
of newborns, by manually plotting results on graph paper or by means of a 
computer fed with data collected from test groups of newborns. 
Alternatively, a mathematical calibration factor could be generated either 
manually or by computer. Having generated this "data base" all that is 
necessary is to measure the heart rate of a subject newborn and mean the 
heart rate, determine the group into which the subject falls, and apply 
the characteristic mathematical relationship for that group to the mean 
heart rate. Again, this can be done manually by measuring the heart rate, 
say, using a conventional ECG machine and manually applying the 
appropriate mathematical relationship. Alternatively, automated equipment 
could be used. For example, an ECG machine could be modified to 
automatically mean the heart rate of a subject and apply the appropriate 
mathematical relationship to give a direct readout of energy requirements. 
The machine would be provided with an appropriate selector (such as a 
rotary dial) for indicating the particular group into which the subject 
falls. The supervisory medical personnel would adjust the selector to 
indicate the particular group and the machine would then automatically 
apply the appropriate mathematical relationship to the mean heart rate of 
the subject to provide a direct indication of the daily calorific 
requirements of the subject. 
By way of example, FIGS. 4 and 5 are block diagrams illustrating 
alternative forms of apparatus which may be provided for determining the 
energy requirements of premature newborns in accordance with the 
invention. Suitable electronic equipment for performing the various 
functions indicated by the block diagrams will be readily apparent to a 
person skilled in the art. 
The apparatus shown in FIG. 4 includes a heart rate measuring unit which 
may be represented by a conventional ECG machine. A heart rate averaging 
unit receives measurement of the cumulative heart rate of a subject 
premature newborn over a predetermined period and determines the mean 
heart rate of the subject over that period. The apparatus further 
comprises comparator means which compares this mean heart rate to a 
predetermined linear relationship established for the appropriate group of 
newborns, equivalent to a graphic representation as in FIG. 3. The 
comparator means will include a selector by which the appropriate linear 
relationship can be selected from a series of such relationships for 
various groups of newborns. The energy requirement of the subject 
premature newborn is then directly indicated by the comparator means, e.g. 
by a digital display. 
FIG. 5 illustrates an alternate form of the apparatus in which the 
comparator means of FIG. 4 is replaced by signal processing means for 
determining the the mean energy expenditure appropriate to the mean heart 
rate received from the heart rate averaging unit. The signal processing 
means calculates the energy requirement in accordance with the 
mathematical relationship established for the appropriate group of 
newborns and directly indicates the energy requirement of the subject. 
Again, appropriate selector means will be provided so that the appropriate 
mathematical relationship can be chosen from a series of such 
relationships. 
Alternative means of implementation would use an electronic computing 
device to calculate metabolic rate from the value of mean heart rate using 
the equations relating these variables. This would permit the calculation 
of metabolic rates over short time intervals (e.g. 1 minute) which would 
in turn be summed to provide a more accurate estimate of energy 
expenditure over long time periods (e.g. several hours). 
Apparatus of the form generally shown in FIGS. 4 and 5 can of course be 
directly incorporated into a conventional ECG machine or can be designed 
as a separate unit to receive a heart rate input from an ECG machine. 
It will of course be understood that the particular units referred to above 
are not to be considered as limitive. Appropriate scale factors can of 
course be applied, e.g. to express cal/kg/min as cal/kg/day.