Abstract:
A method for predicting fat free mass (FFM) and total body water (TBW) of a prepubertal child infected with human immunodeficiency virus (HIV) comprises the steps of measuring a child&#39;s height, measuring the child&#39;s total body resistance, and predicting fat free mass (FFM) and total body weight (TBW) of said child using the measured height and total body resistance.

Description:
BACKGROUND OF THE INVENTION 
     Growth failure and wasting are common complications of Human Immunodeficiency Virus (HIV) infection in children, contributing to the morbidity and mortality. The ability to measure body composition gain or loss in these children associated with infection is crucial to clinical study in ways to alleviate these problems. Developing precise methods for measuring body composition in order to monitor nutritional status in these children is an important area of research. Traditional methods for determining body composition have limited availability and can be difficult to perform, especially with young children. 
     Bioimpedance analysis (BIA), on the other hand, is inexpensive, rapid and non-invasive. To perform body composition analysis, the bioimpedance analyzer is affixed to a patient&#39;s wrist and ankle with electrodes. A current of approximately 800 microamps at 50 kHz is then delivered. Resistance (the voltage drop of the applied current) and reactance (opposition to electric current caused by capitance) are then measured in a matter of minutes. These values, along with other variables, are used to predict different body composition variables. 
     Due to its ease of use and portability, BIA has been demonstrated to be an attractive alternative to traditional methods for estimating total body water (TBW) and fat free mass (FFM) in children. For instance, the following predictive equations have been developed for estimating TBW using BIA where H=height, R=resistance, W=weight and Z=impedance. 
     Fjeld et al. developed equations for predicting TBW in well and malnourished children as: 
     TBW=0.48+0.68(H 2  /R), and TBW=0.76+0.18(H 2  /R)+0.39(W). Fjeld et al., Total Body Water Measured by 0 Dilution and Bioelectric Impedance in Well and Malnourished Children, 27 Pediatric Research 98-02 (1990). 
     Danford et al. determined a predictive equation for TBW, using the tetrapolar method of BIA as: 
     TBW=1.84+0.45(H 2  /R)+0.11(W). Danford et al., Comparison of Two Bioelectrical Impedance Analysis Models for Total Body Water Measurement in Children, 19 Annals of Human Biology 603-607 (1992). 
     Davies et al. found that TBW results using the following equation were highly predictive: 
     TBW=-0.5+0.60(H 2  /R). Davies et al., The Prediction of Total Body Water Using Bioelectric Impedance in Children and Adolescents, 15 Annals of Human Biology, 237-240 (1987). 
     Gregory et al. used the following equation to predict TBW in children with growth disorders: 
     TBW=0.79+0.55(H 2  /Z). Gregory et al., Body Water Measurement in Growth Disorders: A Comparison of Bioelectrical Impedance and Skinfold Thickness Techniques With Isotope Dilution, 66 Archives of Disease in Children 220-222 (1991). 
     Davies and Gregory went on to find that combining their equations into one equation resulted in a more accurate predictor of TBW: 
     TBW=0.13+0.58(H 2  /Z). Davies and Gregory, Body Water Measurements in Growth Disorders, 66 Archives of Diseases in Childhood 1467 (1991). 
     The following predictive equations have been developed for estimating FFM. Deurenberg et al. found that several predictive equations were required to estimate FFM and that choice of the most accurate equation was dependent on the age of the children. Two of the equations are: 
     FFM=0.640(10 4 )(H 2  /R)+4.83, (Ages 7-9 for boys &amp; girls) FFM=0.488(10 4 )(H 2  /R)+0.221(W)+12.77(H)-14.7, (Ages 10-12 for girls and 10-15 for boys). Deurenberg et al., Assessment of Body Composition by Bioelectric Impedance in Children and Young Adults is Strongly Age-Dependent, 44 European Journal of Clinical Nutrition 261-268 (1989). 
     Cordain et al. evaluated BIA with children using the following equation to predict FFM: 
     FFM=6.86+0.81(H 2  /R). Cordain et al., Body Composition Determination in Children Using Bioelectrical Impedance, 52 Growth, Development &amp; Aging 37-40 (1988). 
     Houtkooper et al. studied several predictive equations and recommended the following for predicting FFM: 
     FFM=-0.61(H 2  /R)+0.25(W)+1.31. Houtkooper et al., Bioelectrical Impedance Estimation of Fat-Free Body Mass in Children and Youth: A Cross-Validation Study, 72 J. Anal. Physiol. 366-73 (1992). 
     No studies, however, have assessed the accuracy of BIA, using standard equations, in predicting TBW and FFM in children infected with HIV. 
     An object of the present invention is to provide an improved method for predicting FFM and TBW in children infected with HIV which is more accurate than other known methods. 
     A further object of the invention is to provide a method for estimating FFM and TBW in these subjects which is clinically practical and more accommodating than other methods. 
     Further objects of the invention will readily appear to those skilled in the art from a review of the invention as disclosed and claimed. 
     SUMMARY OF THE INVENTION 
     In accordance with the present invention, a method for predicting fat free mass (FFM) and total body water (TBW) of a prepubertal child infected with human immunodeficiency virus (HIV) is disclosed whereby total body resistance and height are measured to predict the body composition values. 
     Preferably, the total body resistance is determined by performing bioimpedance analysis (BIA) on a subject using the results to calculate resistance according to previously derived formulae known in the art. A tetrapolar bioimpedance analyzer is preferred. 
    
    
     DETAILED DESCRIPTION 
     A study using 20 subjects was performed to assess the performance of bioimpedance analysis (BIA) in the prediction of total body water (TBW) and fat free mass (FFM) using standard equations in children infected with human immunodeficiency virus (HIV). The study suggests that TBW and FFM can be estimated in children with HIV using BIA with special equations specifically developed in this group of children. 
     Methods and Subjects 
     The subjects were twenty prepubertal children ages 4-11 years with HIV infection as defined by the Centers for Disease Control and Prevention (CDC) criteria. They were recruited for the study from the St. Lukes-Roosevelt Hospital Center Pediatric HIV/AIDS Program. 
     The characteristics of the study subjects are presented in Table 1 below. Nineteen of the subjects acquired HIV as a result of perinatal transmission and one was infected as a result of a blood transfusion while a neonate. Most of them had moderate to severe symptoms of HIV infection including moderate to severe immunodeficiency. None had known or suspected active secondary or opportunistic infections or clinically apparent cardiac or renal disease. 
     After an overnight fast, measurements were taken. The subjects were weighed to the nearest 0.01 kg using a beam balance. Their height was measured to the nearest 0.1 cm using a fixed wall-mounted stadiometer. Total body resistance (R) and reactance were measured with a tetra polar bioelectrical impedance analyzer manufactured by RJL Systems (RJL model 101 A, Detroit, Mich.) using bioimpedance analysis (BIA) techniques as disclosed in allowed U.S. patent application Ser. No. 08/353,933 to Kotler, now pending, filed on Dec. 12, 1994, which is incorporated herein by reference. 
     To assess the accuracy of the BIA, TBW was independently measured by a dilution technique with an oral dose of 0.1 gm/lb of body weight of deuterium oxide with concentration of tracer measured in saliva ( 2  H 2  O dilution). FFM was also assessed by dual energy x-ray absorptiometry (DXA) using Lunar DPX and pediatric software, v. 8e. Growth and results of lymphocyte phenotype analyses performed within 3 months of the study were obtained from each subject&#39;s medical records. 
     Eight published prediction equations, as disclosed above, for TBW and FFM in children, based on BIA, including two developed for children with growth disorders, which used simple, easily obtained measurements, were selected for the study. The values predicted by these prior art equations were compared to the measured values in the subjects of the present invention using the paired t test. 
     According to the present invention, new equations have been derived for TBW and FFM using regression techniques. The Box-Cox family of transformations was used to determine if it was necessary to transform the dependent variables and to identify the transformations. The set of independent variables considered for inclusion in the model included (height 2  /resistance), (height 2  /reactance), weight and age. Residual analyses were performed on the final equations. The Epinfo (USD, Inc. Stone Mountain Ga.) software package was used for calculation of the height, weight and weight for height-age-percentiles. All statistical calculations were performed using the STATA (Computing Resource Center, Santa Monica, Calif.) and SAS (SAS Institute, Inc., Cary, N.C.) software packages for personal computers. The level of significance for all statistical tests was 0.05. 
     Results 
     Table 2 presents results of the comparison of TBW and FFM predicted from the published equations referenced above with TBW measured by  2  H 2  O dilution and FFM measured by DXA. The values predicted by each equation were significantly different from those measured (correlation coefficient (p) values ranging from 0.02 to 0.001). 
     Since none of the tested published equations adequately predicted TBW or FFM in the sample group of the present invention, two regression equations according to the present invention were developed for this sample as follows: 
     
         Log(TBW)=1.65+0.05 (H.sup.2 /R) (r.sup.2 =0.95, SEE=0.068) 
    
     and 
     
         FFM=1.34+0.70(A)+0.68(H.sup.2 /R) (r.sup.2 =0.95, SEE=1.23); 
    
     where: 
     TBW=total body water (1) 
     FFM=fat free mass (kg) 
     H=height (cm); 
     A=age (yrs); 
     R=resistance (ohms); 
     r 2  =correlation coefficient; and 
     SEE=standard error estimate. 
     The addition of sex, weight and (height 2  /reactance) did not significantly improve the prediction of either TBW or FFM in the study. 
     Discussion 
     These results indicate that the published standard equations established for generally predicting body composition from BIA-derived measurements in children are not valid for application to children with HIV infection. This study also indicates that highly predictive equations specific for this population using simple, standard variables can be devised. Indeed, predictive equations based on BIA-derived resistance which provide estimates of TBW and FFM comparable to those of traditional, more complex methods of body composition measurements were derived in the present invention. As a result, the new equations of the present invention provide a means for using BIA to predict body compartments (TBW or FFM) in children with moderate to severe symptoms of HIV, moderate to severe immunodeficiency, and with abnormal growth, such as those included in the study. 
     While the foregoing indicates the preferred embodiments of the invention claimed below, those skilled in the art will appreciate that there are variations of this disclosure which do not depart from the scope of the invention claimed herein. For example, different methods of BIA may be used in conjunction with the claimed equations such as those providing different amperages and frequencies. 
     
                       TABLE 1______________________________________Characteristics of 20 HIV-infected children undergoing study.Variable______________________________________              Mean ± SD (range)Age (yrs)           6.5 ± 2.3 (4-11)Height (cm)        117.4 ± 13.8 (97.9-147.5)Height-for-age-percentile (%)               35.2 ± 29.8 (0.1-93.1)Weight (kg)         23.3 ± 7.9 (14.1-44.5)Weight-for-age-percentile (%)               43.4. ± 36.6 (2.5-96.5)Weight-for-height percentile               56.2 ± 36.4 (2.8-99.9)(%)Total body water (L).sup.a               13.7 ± 4.6 (8.0-25.7)Fat free mass (kg).sup.b               18.4 ± 5.5 (11.6-31.0)Resistance (ohms)  785 ± 116 (543-1012)Height.sup.2 /Resistance               18.38 ± 5.94CD4 count (no/dl)  319 ± 330 (4-1099)CD4 percent (%)     16.8 ± 13.8 (0.6-40.4)              No. (%)Race/ethnicityBlack               6 (30)Hispanic            14 (70)CDC classificationN3                  1 (5)A2                  3 (15)B2                  3 (15)B3                  5 (25)C1                  2 (10)C2                  3 (15)C3                  3 (15)Growth patternAIDS Wasting Syndrome.sup.c               2 (10)Progressive stunting.sup.d               9 (45)Normal              9 (45)Sexmales               9 (45)females             11 (55)______________________________________ .sup.a Total Body water determnined by deuterium oxide dilution. .sup.b Fat free mass determined by dual energy absorptiometry. .sup.c Weight loss of ≧10% within 3 months of study. .sup.d Decline in heightfor-age-percentile of 2 or more SD (e.g. 95th, 75th, 50th, 25th, 5th percentile for age) within 2 years before, or 6 months after the time of study and without weight loss. 
    
     
                                           TABLE 2__________________________________________________________________________Evaluation of BIA-based predictive equations for TBW andFFM with TBW measured by deuterium oxide dilution and FFM by dualX-ray absorptiometry in children infected with HIV.                       Predicted                Body   Weight                             Predicted -Study N  Age (yrs)         Variables                Compartment                       (+SD) (kg).sup.1                             Measured.sup.2                                   p__________________________________________________________________________Fjeld et 30 0.4-3         H.sup.2 /R,W                TBW    12.95 .75   .02al.                         (4.1)Danford et 37 5-9  H.sup.2 /R,W                TBW    12.81 .88   .009al.                         (3.94)Davies et 26  5-18         H.sup.2 /R                TBW    10.61 3.03  .001al.                         (3.64)Gregory et 34  7-15         H.sup.2 /R                TBW    11.03 -2.67 .001al.                         (3.3)Davies and 60  5-18         H.sup.2 /R                TBW    10.93 -2.77 .001Gregory                     (3.5)Deurenberg 827     7-25         H.sup.2 /R,G,A,W,H                FFM    16.08 -2.28 .001et al.                      (4.88)Cordain et 30  9-14         H.sup.2 /R                FFM    21.75 3.39  .001al.                         (4.82)Houtkooper 94 10-14         H.sup.2 /R,W,X.sub.c                FFM    19.69 1.33  .001et al.                      (4.93)__________________________________________________________________________ .sup.1 Values expressed as mean ± SD. .sup.2 TBW measured by deuterium oxide dilution (mean = 13.7 L) and FFM measured by dual Xray absorptiometry (mean = 18.4 kg), as presented in Table 1. TBW = total body water FFM = fat free mass H = height W = weight R = resistance A = age G = gender X.sub.c = Reactance N = number subjects studied p = correlation coefficient