Evaluation of body mass index percentiles for assessment of malnutrition in children with cystic fibrosis

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1 (7) 61, & 7 Nture Pulishing Group All rights reserved 954-7/7 $. ORIGINAL ARTICLE Evlution of ody mss index percentiles for ssessment of mlnutrition in children with cystic firosis B Wiedemnn 1, KD Pul 2, M Stern 3, TO Wgner 4 nd TO Hirche 4, on ehlf of the Germn CFQA Group 1 Deprtment of Medicl Informtics nd Biometrics, Technicl University Dresden, Dresden, Germny; 2 Deprtment of Peditrics, Freierg Hospitl, Freierg, Germny; 3 Children s Hospitl, Tueingen University, Tueingen, Germny nd 4 Deprtment of Medicine, University Hospitl Frnkfurt, Frnkfurt, Germny Ojective: To compre the performnce of recently relesed ody mss index percentiles (BMIp) with stndrd nthropometric indexes, including height-for-ge percentile (HAP), weight-for-ge percentile (WAP) nd percent idel ody weight (%IBW), s mesures for nutritionl filure in children with cystic firosis (CF). Design: Cross-sectionl nlysis of growth nd lung function dt from 4577 children with CF reported to the Germn CF qulity ssurnce (CFQA) project from 1995 to 4. Results: Frequency distriution of HAP (men7s.d.:.727.5; fe ) nd WAP ( ; fe ) were skewed, with significnt numers of ptients elow the fifth percentiles of helthy reference popultion. However, ecuse deficits occurred in oth mesures simultneously, men %IBW ( ; fe ) ssumed sujects weight close to the nominl weight-for-height t ll ges. In contrst, men BMIp ws mrkedly reduced ( ; fe ) nd stedily declined with ge. Idel weight-for-ge ws significntly lower when predicted y %IBW compred with BMIp method, prticulrly in sujects with shorter-thn-verge stture. Consequently, less CF children were identified with nutritionl filure ccording to %IBW method (.5%; fe 22.7%) compred with BMIp method (.4%; fe 28.7%). The clinicl relevnce of these findings ws confirmed y stronger correltion of BMIp with impired %forced expirtory volume/s, mrker for disese progression in CF. Conclusion: BMIp predicts nutritionl filure more sensitively nd ccurtely thn conventionl nthropometric indexes, t lest in children with CF. Screening of CF ptients y BMIp could provide n erly wrning sign nd llow for timely therpeutic intervention. (7) 61, ; doi:.38/sj.ejcn.12582; pulished online Jnury 7 Keywords: cystic firosis; ody mss index; percentge idel ody weight; mlnutrition Introduction Nutritionl filure remins common prolem for mny ptients with cystic firosis (CF). It is ssocited with decresed life qulity, excess moridity nd poor prognosis Correspondence: Dr TO Hirche, Deprtment of Medicine, University Hospitl Frnkfurt, Theodor Stern Ki 7, Frnkfurt 59, Germny. E-mil: t.hirche@em.uni-frnkfurt.de Gurntors: B Wiedemnn nd TO Hirche. Contriutors: The uthors hve contriuted to the pper y plnning the study (BW, KDP, TOH), collecting the dt (BW, MS), nlysis of dt (BW, TOH), nd preprtion nd revision of the pper (ll uthors). Received 3 My 6; revised 12 Octoer 6; ccepted 17 Octoer 6; pulished online Jnury 7 (Corey et l., 1988; Steinkmp nd Wiedemnn, 2). Over the lst decde severl studies hve demonstrted improved clinicl outcomes when the cuses of cute nd chronic mlnutrition (i.e., indequte intke, indequte sorption, incresed requirements) re treted ppropritely (Frrell et l., 1997; Zemel et l., ). Therefore, erly detection of mlnutrition is criticl to llow for timely intervention nd rehilittion. The reported prevlence nd degree of nutritionl filure in CF ptients vries sustntilly mong studies, depending on methods nd reference stndrds used (Wright et l., 1994; Li et l., 1998). Accurte ssessment of nutritionl sttus hs een postulted y vrious techniques, including dul energy X-ry sorptiometry (DEXA) (Gorn et l., 1996), mesurements of totl ody potssium (Shepherd et l., 1989) or totl ody electricl conductivity

2 7 Evlution of BMIp in children with CF (Cochrn et l., 1989). These techniques re referred to s ody composition nlyses; tht is, they evlute len nd ft tissue mss insted of ody height nd weight. Yet, the use of these methods is limited to reserch settings ecuse of their complexity/cost nd there is further need for vlidtion studies, prticulrly in children. The most frequently used tools for clinicl screening of mlnutrition remin nthropometric-sed indexes, such s weight-forge, weight-for-height or percentge of idel ody weight (%IBW; mesured weight expressed s percentge of idel weight sed on the sme height percentile) (WHO Working Group, 1995). The ltter hs the dvntge to integrte weight nd height-for-ge in the sme mesure nd correltes with nutritionl filure nd prognosis in CF (Kerem et l., 1992). For the lst decde, %IBW ws recommended y the Cystic Firosis Foundtion (CFF) consensus report on nutrition s preferred mesure of nutritionl sttus in children with CF (Rmsey et l., 1992). However, the sensitivity nd ccurcy of %IBW to detect erly signs of mlnutrition in peditric diseses, including CF, ws questioned y studies tht compred %IBW with other nthropometric-sed indexes (Li et l., 1998) or reference procedures (McNughton et l., ; Stpleton et l., 1). Also, clcultion of %IBW is complex nd requires steps of visul estimtion or pproximte clcultion y polynomil equtions. In this regrd, wide inter- nd intr-exminer vritions hve een reported, mking %IBW vlues unrelile (Poustie et l., ). One of the most commonly used nd recommended prmeters to ssess nutritionl sttus in dults, including CF ptients, is the ody mss index (BMI; weight/height 2 (kg/m 2 )). An dpttion for children hs een limited in the pst, ecuse BMI is not constnt cross the peditric ge rnge (Fung et l., 199). In recent yers, severl countries dded ge- nd sex-specific BMI percentiles (BMIp) to their growth chrts. BMIp now provide wy of compring child s weight, djusted for height, with reference group of the sme ge, ut not necessrily the sme stture. Plotted sequentil BMI vlues cn indicte nutritionl filure erly when the pttern chnges from consistent percentile nd thus the nutritionl sttus cn e trcked continuously from erly childhood through dulthood. BMIp re now widely used to determine the nutritionl sttus of children in helth nd disese, ut there is still no consensus out its use in children with CF, prticulrly s the cutpoints for definition of mlnutrition remin incompletely defined. The revised CFF consensus report on nutrition now recommends to use oth %IBW nd BMIp in comintion, ut not BMIp lone (Borowitz et l., 2); the Europen Nutrition Consensus Report sttes tht no dvntge hs een shown for using BMIp rther thn weight-for-height to ssess mlnutrition in children with CF (Sinsppel et l., 2). A recent study used %IBW nd BMIp methods to ssess the prevlence of mlnutrition in the CFF ptient registry (Zhng nd Li, 4). The uthors report good greement of oth indexes in CF ptients with verge stture, ut n improved ccurcy for BMIp when the weight devited from the reference medin. This study, however, included only ptients from the US nd used popultion-specific reference chrts (from the Centre for Disese Control, CDC). Owing to differences in ethnicity, helth cre (e.g., dietry prctice) nd growth stndrds, results might not e representtive for the Mid-Europen CF popultion. In the present study, we mde use of recently pulished Germn reference growth chrts, including BMIp (Kromeyer- Huschild et l., 1), to screen ll children registered in the Germn CF qulity ssurnce (CFQA) project for presence of mlnutrition. Here, we present convincing evidence tht BMIp etter estimtes the risk of cliniclly relevnt nutritionl filure thn conventionlly used %IBW, t lest in children with CF. Sujects nd methods Study popultion The Germn CFQA project is ptient dtse tht documents the dignosis nd nnul follow-up of CF ptients treted in 111 different CF outptient clinics in Germny. Bsic demogrphic dt, dignostic informtion nd selected clinicl chrcteristics re collected nnully, s descried in detil elsewhere (Wiedemnn et l., 1). For the present study, we otined demogrphic (sex, ge), growth (height, weight) nd clinicl (forced expirtory volume/s, FEV 1 ) dt for ll CF children (n ¼ 4577) tht were mintined in the dtse from 1995 to 4. Sttisticl nlyses were performed seprtely for ech gender ecuse of the well-documented difference in clinicl course etween nd fe CF ptients (Rosenfeld et l., 1997). Computtion of nthropometric indictors Height-for-ge percentiles (HAP), weight-for-ge percentiles (WAP), %IBW nd BMIp for ll CF ptients were clculted in computerized progrm in SPSS (SPSS Inc., Chicgo, IL, USA) y using ge- nd sex-specific reference vlues for Germn children pulished y Kromeyer-Huschild et l. (1). The ltter clculted the ox-cox-power-trnsformtion (L), the medin (M) nd the coefficient of vrition (S) for height, weight nd BMI for oth sexes nd ech month of ge for helthy children etween nd 18 yers. Using the eqution C ðtþ ¼MðtÞð1 þ LðtÞSðtÞz Þ 1=LðtÞ where M(t), L(t) nd S(t) re the corresponding prmeters for given ge (t) one cn clculte ll percentiles C (t) for height, weight nd BMI nd compre them with ptients given mesurement (Cole, 199). Z is defined s z-score referred to stndrd norml distriution (e.g., ¼ 3%, z ¼ 1.881; ¼ %, z ¼ ; ¼ 97%, z ¼ 1.881). The reltive proportion of weight for height ws ssessed y %IBW following modifictions descried y Moore et l.

3 (1985). Briefly, clcultions were performed in computerized progrm in SPSS y the eqution %IBW ¼ðweight mesurementþ=ðidel weightþ; with idel weight eing the weight corresponding to the sme percentile rnking s the child s HAP. Where indicted, BMIp were re-expressed in the percentge unit y dividing the ctul BMI y the ge-djusted medin BMI of the reference popultion, multiplied y. Mixed liner models with repeted mesures (SAS Procedure Mixed; SAS Version 9, SAS Institute Inc., Cry, NC, USA) were pplied to mke sttisticl inferences out the dt. The models included nthropometric indictors s repeted mesure fctors nd ge s covrite. Inner suject effects nd contrsts were tested. Definition of mlnutrition y nthropometric indictors Mnifest nutritionl filure ws ssumed if dt indicted stunting or wsting, tht is if HAP or WAP were elow the fifth percentile (WHO Working Group, 1986; Kuczmrski et l., ). A risk for nutritionl filure ws ssumed t %IBW o9% nd/or BMIp o15th percentile. The greement etween using %IBW o9% nd BMIp o15th percentile for identifying mlnutrition ws ssessed y the Cohen kpp coefficient (k). The hypothesis tht k equls zero ws tested. The %IBW cutoff t 9% corresponds to the stndrds used in the literture nd is recommended y the CFF consensus report (Borowitz et l., 2). The BMIp 15th percentile s cutoff vlue for mlnutrition hs previously een vlidted y DEXA scn nd verge skinfold mesurements (Mei et l., 2). Mthemticlly, the 15th percentile corresponds pproximtely to the 1 s.d. in normlized distriution, which is equivlent to % elow the medin in the %IBW system (Wterlow et l., 1977). In this regrd, recent study reported good greement of the BMI 15th percentile with %IBW 9% for children with CF nd verge stture (Zhng nd Li, 4). Correltion of BMIp nd %IBW with lung function Percentge of predicted FEV 1 (%FEV 1 ) is n ccepted prmeter to ssess lung function nd disese progression in CF ptients. %FEV 1 is routinely mesured t ech clinicl visit nd recorded in the CFQA dtse. In this study, we determined the reltive strength of ssocition etween %IBW or BMIp with %FEV 1 y liner multiple regression nlysis, s descried previously (Zhng nd Li, 4). Briefly, nlysis ws performed using the eqution %FEV 1 ¼ þ 1 ½ð%IBW Þ = or BMIpzŠþ 2 ðge in yersþ: Evlution of BMIp in children with CF BMIpz ws defined s BMIp, re-expressed s Z scores, with 3rd, 15th, th, 85th nd 97th percentile eing mthemticlly equivlent to s.d. 2, 1,, 1 nd 2, respectively. In this model, represents the estimted vlue of %FEV 1 t idel nutritionl sttus (e.g., %IBW ¼ %, BMIp ¼ th percentile) corrected y ge, nd 1 represents the estimted chnge of %FEV 1 for every unit chnge in the nutritionl index. Results Evlution of nutritionl sttus in children with CF y nthropometric indexes For sttisticl comprisons, dt from 4577 CF ptients (ge rnge 18 yers, 51.5%, 48.5% fe), registered in the Germn CFQA dtse, were retrospectively nlyzed. The overll frequency distriution of HAP (men7s.d.:.727.5, fe ) nd WAP ( , fe ) re skewed when compred with the expected norml distriution for the reference popultion, indicting tht CF ptients re shorter nd lighter for their ge nd gender (Figure 1 nd ). A high percentge of ptients rnked elow the fifth percentile (HAP:.1%, 18.2% fe; WAP: 23.%, 21.% fe), which represents the cutoff level for mnifest nutritionl filure for oth indexes. HAP nd WAP show close correltion in oth genders (r ¼.733 over ll ges), ut their mens remin continuously elow the th percentiles of the reference popultion (Figure 1c nd d). A pek in erly childhood is followed y grdul reduction in oth genders, which continues into dulthood. The fct tht deficits in height- nd weight-for-ge occur simultneously in mny CF ptients ers the risk tht indexes relying on comprison of weight nd height lone my e unle to detect nutritionl filure (Stpleton et l., 1). In fct, the men of conventionl %IBW ( ; fe ) indicted tht sujects weights were lwys close to the nominl idel weight-forheight (%), suggesting tht ptients were dequtely nourished t ll ges (Figure 1c nd d). There ws slight decrese in %IBW during dolescence in, ut the men styed well ove the cutoff level (9%), which signls risk for nutritionl filure. The overll correltion of %IBW with oth HAP nd WAP ws low (r ¼.22 nd.41, respectively). Unlike %IBW vlues, the men BMIp ( ; fe ) ws mrkedly elow the th reference percentile for CF children t ll ges (Figure 1c nd d). Men BMIp continuously declined throughout childhood nd dulthood (most prominent in dolescents), nd correlted closely with men WAP (r ¼.796), ut not with HAP (r ¼.25). Prediction of idel ody weight in CF children using %IBW nd BMIp methods If nutritionl sttus ws eqully well predicted y %IBW nd BMIp, clcultion y oth methods should result in identicl 761

4 Evlution of BMIp in children with CF CF ptients [%] fe 5 5 < height-for-ge percentile < weight-for-ge percentile c men 1 9 d 1 9 fe ge [yrs] Figure 1 Frequency distriution of height-for-ge () nd weight-for-ge () percentiles for CF children mintined in the Germn CF dt se (n ¼ 4577). Are under the horizontl line indictes the expected distriution for the reference popultion. (c nd d), Men height-for-ge (solid line), weight-for-ge (dshed line) nd BMI-for-ge (dotted line) (expressed s percentiles) nd men %IBW (dshed-dotted line) (expressed s percentge) for CF children y ge nd gender, reltive to the reference popultion. Medin (th percentile) nd nominl idel weight (%) re mrked y red lines. reference vlues for idel weight over ge. Indeed, when dt from ll CF children were nlyzed, the percentges of idel weights otined y the %IBW method were lrgely similr to those clculted y the BMIp method. This correltion ws holding for oth sexes nd over ll ge groups, with trend towrd higher idel weights otined y the BMIp method (Figure 2 nd ). Idel weights estimted y oth methods were continuously lower thn the corresponding idel weights of the reference popultion, nd differences incresed with ge (Po.1). The idel weight of person depends (in ddition to gender nd ge) lso on his/her stture. As demonstrted ove, CF ptients were significntly shorter for their ge nd sex when compred with the reference popultion (Po.1). We, therefore, compred the performnce of %IBW nd BMIp in sugroup of ptients with short stture (i.e., length o25th percentile). Under these conditions, the idel weights determined y the BMIp method were mrkedly higher thn those otined y the %IBW method for oth sexes, nd the differences incresed with ge (Po.1) (Figure 2c nd d). Predictions of idel weights mde y BMIp method were continuously closer to the corresponding idel reference weight thn predictions mde y %IBW. Next, we compred the reltive percentge of ptients ctul weights with their corresponding idel weights, predicted y either %IBW or BMIp, respectively. As result, ptients ctul weights were closer to their estimted idel weights over ll ges when clcultion ws sed on the %IBW method (men7s.d. 99.%712.24; fe 99.1%712.6) s opposed to the BMIp method ( 95.4%711.9; fe 95.4%712.1) (Figure 3 nd ). The oserved differences ecme more sustined, when sugroup nlysis ws performed for short-sttured ptients (men7s.d. %IBW method:.7%712.5, fe 1.5%712.3; BMIp method: 92.7 %711.4, fe 92.9%711.4) (Figure 3c nd d). Estimtion of mlnutrition in CF children y %IBW or BMIp The risk of nutritionl filure of children with CF ws defined s %IBW o9% nd BMIp o15th percentile, respectively. The cutoff levels were chosen for resons descried in Sujects nd methods. Irrespective of the

5 Evlution of BMIp in children with CF fe 763 All ptients idel weight [kg] c Short sttured ptients idel weight [kg] d ge [yrs] Figure 2 Comprison of men idel weight clculted y %IBW (solid line) nd BMIp (dotted line) for ll CF ptients ( nd ) nd sugroup of children with short stture (c nd d) y ge nd sex. The dshed line represents the idel weight for the reference popultion. Short stture ws defined s height-for-ge o25th percentile. computtion method used, the level of mlnutrition ws high in CF infnts (E %; fee %), ut mrkedly declined t 2 yers of ge in oth genders (E %). This ws followed y de-novo increse t the onset of dolescence, nd levels of mlnutrition peked t yers in (E %) nd yers in fe (E 45%), respectively (Figure 4 nd ). At ll ges, the prevlence of mlnutrition estimted y BMIp o15th percentile (.4%; fe 28.7%) ws significntly higher thn estimted y %IBW o9% method (.5%, fe 22.7%), with the exception of fes in lte dolescence (where similr vlues were recorded). Interestingly, in the sugroup of CF children with short stture, the prevlence of mlnutrition estimted y %IBW ws significntly lower thn estimted for the whole study popultion (Figure 4c nd d). This ws primrily due to decresed prevlence during infncy ( o25%; fe o15%) nd erly childhood (ge 1 yers; verge 6.3%, fe 8.5%), wheres comprle levels were found during dolescence. In contrst, when BMIp ws used to estimte mlnutrition of short-sttured children, similr or incresed prevlence compred with the whole study popultion ws oserved during infncy, erly childhood nd dolescence. The overll prevlence of mlnutrition in the sugroup of ptients with short stture ws higher when estimted y BMIp o15th percentile ( 39.1%; fe 35.6%) thn y the %IBW o9% method ( 16.7%; fe 15.4%) nd the gp etween oth grphs sustntilly incresed compred with the dt collected for the whole study popultion. As shown ove, estimtion of nutritionl sttus y %IBW o9% nd BMIp o15th percentile depends on sex, ge nd stture. Therefore, to nlyze the distriution of mlnutrition predicted y either %IBW o9%, BMIp o15th percentile or oth methods, we compred ptients stture y sex nd ge (Figure 5 nd ). The vst mjority of ptients ws consistently clssified y oth criteri s either norml weight or underweight, nd k-sttistics indicted good greement ( k ¼.635; fe k ¼.766). However, significnt discrepncy etween using %IBW o9% nd BMIp o15th percentile for identifying mlnutrition occurred when the stture devited from the medin. CF children who were identified s eing mlnourished y BMIp o15th percentile only (i.e., with %IBW X9%) were locted in the lower rnge of the length distriution. In contrst, children estimted mlnourished y %IBW o9% only (i.e., with BMIp X15%) were locted in the upper rnge of length distriution. Of note, s stture itself is n importnt predictor of nutritionl sttus in children with CF, estimtion of mlnutrition elow the

6 764 All ptients c Short sttured ptients ctul weight / idel weight [%] ctul weight/idel weight [%] d ge [yrs] fe Figure 3 Comprison of the reltive percentge of ctul weight to the idel weight predicted y %IBW (solid line) nd BMIp (dotted line) for ll CF ptients ( nd ) nd sugroup of short sttured children (c nd d) y ge nd sex. BMIp ws re-expressed into percentge unit to fcilitte numericl comprison with %IBW. The horizontl line highlights optiml weight rtio (%) for oth indexes. Short stture ws defined s height-for-ge o25th percentile. Evlution of BMIp in children with CF fe All ptients nutritionl filure [%] c d Short sttured ptients nutritionl filure [%] ge [yrs] Figure 4 Prevlence of mlnutrition y ge nd sex in ll CF children ( nd ) nd in sugroup of ptients with short stture (c nd d). Nutritionl filure ws defined y %IBW o9% (solid line) nd/or BMIp o15th percentile (dotted line). Short stture ws defined s height-forge o25th percentile.

7 Evlution of BMIp in children with CF fe height [cm] ge [yrs] Figure 5 ( nd ) distriution of nutritionl sttus in children with CF y stture, ge nd sex. Nutritionl filure ws defined y %IBW o9% nd/or BMIp o15th percentile. Blck tringles indicte ptients unnimously identified s mlnourished y oth criteri (i.e., with BMIp o15th percentile nd %IBW o9%). Grey squres indicte ptients with norml nutritionl sttus ccording to oth indexes (i.e., with BMIp X15th percentile nd %IBW X9%). Note tht the mjority of ptients tht were predicted mlnourished y %IBW only (i.e., with BMIp X15th percentile; red tringles) were locted in the upper rnge of length distriution, wheres ptients predicted mlnourished y BMIp only (i.e., with %IBW X9%; lue crosses) were locted in the lower rnge of length distriution. These differences were most prominent during dolescence irrespective of gender. 1 1 fe All ptients FEV 1 [% predicted] 1 %IBW BMIp β β 1 R 2 96,8 6,3,19 97,8 8,4,24 1 %IBW BMIp β β 1 R 2 94,1 6,8,17 96,1 9,2,22 %IBW BMIp 3rd 15th th 75th 97th 3rd 15th th 75th 97th c 1 d 1 Short sttured ptients FEV 1 [% predicted] 1 %IBW BMIp β β 1 R 2 94,7 8,,26 99,6 9,4,27 %IBW BMIp 3dr 15th th 75th 97th 3rd 15th th 75th 97th 1 %IBW BMIp β β 1 R 2 91,4 9,2,23 98,7 11,,26 Figure 6 Associtions of %IBW (solid line) nd BMIp (dotted line) with %FEV 1 y multiple regression nlysis. Gender specific nlysis ws performed for ll CF ptients ( nd ) nd sugroup of children with short stture (c nd d). Higher 1 nd R 2 vlues in ll pnels indicte tht BMIp is more sensitive to/etter correltes with %FEV 1 thn %IBW. The verticl line indictes the idel nutritionl sttus for oth indexes. Short stture ws defined s height-for-ge o25th percentile. medin of length (i.e., y BMIp o15th percentile) is more likely to e of clinicl relevnce thn prediction of mlnutrition ove the medin of length (i.e., y %IBW X9%). Correltion of %IBW nd BMIp with lung function in children with CF To further ssess the clinicl relevnce of nutritionl sttus estimted y %IBW nd BMIp, we nlyzed the ssocition

8 766 of ech method with %FEV 1, vlidted prmeter of lung function nd disese severity for CF ptients s descried in Sujects nd methods. The 1 ws significntly lrger in the BMIp model thn the %IBW model in oth sexes, indicting tht BMIp is more sensitive to chnges in %FEV 1 thn in %IBW (Figure 6 nd ). Consistently, R 2 ws lrger in the BMIp model thn in the %IBW model, indicting etter correltion of BMIp with %FEV 1. The sme finding, stronger ssocition of %FEV 1 with BMIp thn with %IBW, ws mde for the sugroup of ptients with short stture (Figure 6 nd c), further suggesting tht BMIp is more vlule thn %IBW method s screening tool for cliniclly relevnt mlnutrition in CF children. Discussion Evlution of BMIp in children with CF The ojective of this study ws to compre the performnce of stndrd nthropometric indexes, including HAP, WAP nd %IBW to the performnce of recently relesed BMI percentiles to screen children with CF for risk of mlnutrition. Our results demonstrte tht despite dvnces in medicl tretment nd dietry dvice, mny CF children in Germny continue to grow poorly, s reflected y low men HAP nd/ or WAP compred with the reference popultion. Approximtely % of ll CF ptients were elow the 5 percentile for HAP nd/or WAP, thus presenting with mnifest stunting nd/or wsting. The rtes of growth retrdtion in this study re comprle to those reported for CF children from the United Sttes nd Cnd (Li et l., 1999). We found strong correltion etween decresed HAP nd WAP, indicting tht deficits in oth mesurements occurred simultneously in mny CF ptients. This is most importnt, s it ers the risk tht indexes relying on weight for height proportion, such s %IBW nd BMIp, my fil to detect mlnutrition (Stpleton et l., 1). Indeed, when ssessed y %IBW, our study popultion ws thought to e resonly nourished, with men vlues within the norml rnge over ll ges. In contrst, men BMIp for CF ptients were more informtive, s they rnked mrkedly elow the reference medin, decresed with ge nd correlted strongly with WAP. When used to clculte idel weights, oth %IBW nd BMIp predicted significntly lower vlues for CF ptients compred with the reference popultion over ll ges. This prediction seems duious, s lower weight in CF ptients is not likely to e cused y the inherent genetic defect ut rther y chronic mlnutrition nd clinicl progress of the disese, which should not impct defined idel weight (Fried et l., 1991). In this respect, it hs een shown tht ptients with CF who receive optiml dietry support nd tretment cn ttin levels of growth similr to the reference popultion (Collins et l., 1999; Li et l., 1999). Idel weight clculted y %IBW dropped nd devited further from the reference medin, when sugroups of shorter-thn-verge or older individuls were nlyzed. Despite the fct tht shorter nd older CF ptients crry n incresed risk for nutritionl filure (Beker et l., 1), the reduced idel weight predicted y %IBW resulted in fewer ptients identified with mlnutrition. In contrst, idel weight clculted y BMIp ws less ffected y ltertions of stture nd ge, styed closer to the reference idel weight t ll times nd, s result, identified significntly more ptients with nutritionl filure thn the %IBW method. The finding tht the extent of mlnutrition cn e significntly underestimted y weight-for-height indexes, including %IBW, is supported y the literture. In children with mlignncies, mesurement of skinfold thickness nd midrm circumference s reference stndrd reveled high prevlence of nutritionl filure (Oguz et l., 1999). Yet, %IBW vlues of most ptients remined within the norml rnge. This oservtion ws confirmed in study tht nlyzed nutritionl sttus in children with CF (Stpleton et l., 1). Deficits in skinfold thickness nd lim circumference identified 48.4% of sujects s mlnourished, ut %IBW method predicted only 9.7% with nutritionl filure. Likewise, study tht used levels of totl ody mss potssium s reference stndrd identified mlnutrition in 29.9% of nd 22% of fe CF ptients, wheres weight-for-height indexes predicted only 7.5% of the ptients s mlnourished (McNughton et l., ). Our finding tht BMIp is more sensitive nd ccurte in screening for mlnutrition in CF ptients confirms nd extends dt from recent study tht nlyzed the nutritionl sttus of CF ptients mintined in the CFF registry (Zhng nd Li, 4). When compred with BMIp, %IBW underestimted the severity of mlnutrition, nd this discrepncy incresed with ge nd lso when the children s stture devited from the medin. In children with short stture, the prevlence of mlnutrition predicted y %IBW ws significntly lower (7.3%) thn y BMIp (25.7%) method. The oserved discrepncies etween %IBW nd BMIp in the prediction of mlnutrition re primrily due to their differences in defining the idel weight for given ge. According to the %IBW method, the idel weight is the weight corresponding to the sme percentile rnking s the person s height-for-ge (Rmsey et l., 1992). Thus, idel weight is ssumed if HAP nd WAP re exctly t the sme rnking. However, this ssumption is only vlid if the person s HAP is close to the th percentile. When the stture devites from the medin, the mount of weight gin per increment of height gin is not constnt. For this reson, tll person tends to e slimmer nd short person more oese compred with n verge-length person. The %IBW method disregrds this phenomenon nd therefore underestimtes the idel weight for short person (Zhng nd Li, 4). In contrst, the BMIp ssumes the idel weight for given ge nd stture s the medin BMI t tht ge derived

9 from corresponding reference popultion. In other words, the BMIp method descries child s weight reltive to other similr children, nd therefore is less ffected y chnges in stture nd ge. In the BMI, the exponent to which height hs een rised ws derived y regressing height on weight (fter conversion of the vriles to nturl logrithms) nd llows to reduce the influence of height on weight (Fung et l., 199). Also, the %IBW method expresses the devition from the ctul to the idel weight in the percentge system, which does not correspond to the sme s.d. score cross ge (Wterlow et l., 1977). BMIp expresses the devition in the percentile system (which is mthemticlly interchngele with the s.d. system) nd is therefore to e preferred to clculte devition of ctul to idel weight rther thn the %IBW method. In ddition, BMIp is le to cpture the chnge in the weight height reltion y growth velocity chrts nd provides longitudinl mesure tht cn e used continuously into dulthood (Rollnd-Ccher et l., 1991). From prcticl stndpoint, BMIp cn e esily determined in routine clinicl settings nd is less prone to errors thn %IBW (Poustie et l., 5). The clinicl relevnce nd ccurcy of our findings were confirmed y compring the ssocition of %IBW or BMIp with %FEV 1, commonly used mesure of lung disese in CF ptients. Irrespective of sex, ge nd stture, estimtion of nutritionl filure y BMIp ws more sensitive to chnges in %FEV 1 nd hd stronger ssocition with impired lung function thn %IBW. Overll, our dt provide dditionl support for the use of BMIp rther thn %IBW to screen for nutritionl filure in children with CF. On the sis of our results nd previous reports y Zhng nd Li (4), we propose the 15th BMI centile s useful cutpoint to define mlnutrition, t lest in children with CF. Results from recent study tht investigtes mlnourishment in children with severe cries indicte tht the use of the 15th BMI centile s vlid cutpoint for nutritionl filure could e extended to other peditric diseses (Clrke et l., 6). BMIp remins n expression of weight nd correltes with ody composition (i.e., muscle, ft nd len tissue mss) only to the extent tht weight does (Flegl et l., 2). Just s with height- nd weight-percentile chrts, n individul BMIp vlue reflects genetic (e.g., prentl stture), s well s helth fctors. Consequently, not ll ptients in the t-risk ctegory will in fct hve nutritionl insufficiency, nd prudence nd expertise will need to e used to determine who requires closer evlution nd follow-up (Borowitz et l., 2). It hs een suggested to cross-vlidte BMIp y other more direct mesures of ody composition, such s skinfold thickness, mid-rm circumferences nd/or impednce mesurements, which require reltively little resources nd could e performed during outptient visits (Wrner, ). Recently, n expert pnel of the Europen CF society (ECFS) clled for implementtion of DEXA scns s prt of the nnul nutritionl ssessment in CF children over yers of ge (Kerem et l., 5). However, in terms of vlidity, ody Evlution of BMIp in children with CF composition mesurements continue to show significnt vritions depending on the type/genertion of equipment used nd the trining/skills of the investigtor (Plnk, 5). There is continuing need for normtive dt out the ody composition, prticulrly in children. Trnsltion equtions hve to e developed to cross-clirte nd vlidte the results from different nutritionl indexes. Improved reliility of detecting nutritionl filure in CF children could provide n erly wrning sign to clinicins nd llow timely therpeutic interventions to hve the gretest positive impct. Acknowledgements We re grteful to the Scientific Advisory Bord of the CFQA project for permission to nlyze the Germn CF dtse, nd cknowledge the lrge mount of work y stff from the 111 CF centers who reported ptient dt to the project. 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