Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda

RESEARCH Open Access T ansi ion om F-75 o eady- o-use he apeu ic ood in child en wi h se e e acu e malnu i ion, an obse a ional s udy in Uganda Be y Lanye o 1,2* , Hani a Namusoke 1 , Nicole e Nabukee a-Ba ungi 2,3 , Benedik e G eno 2 , Ezekiel Mupe e 3 , Kim Fleische Michaelsen 2 , Ch is ian Mølgaa d 2 , Vibeke B ix Ch is ensen 4 , Hen ik F iis 2 and And é B iend 2,5 Abs ac Backg ound: Wo ld Heal h O ganiza ion now ecommends he ansi ion om F-75 o eady- o-use he apeu ic oods (RUTF) in he managemen o se e e acu e malnu i ion (SAM). We desc ibed he ansi ion om F-75 o RUTF and iden i ied co ela es o ailed ansi ion. Me hods: We conduc ed an obse a ional s udy among child en aged 6–59 mon hs ea ed o SAM a Mulago hospi al, Kampala, Uganda. The apeu ic eeding du ing ansi ion phase was p o ided by i s o e ing hal o he ene gy equi emen s om RUTF and he o he hal om F-75 and hen inc easing g adually o RUTF as only ene gy sou ce. The child was conside ed o ha e success ully ansi ioned o RUTF i child was able o g adually consume up o 135 kcal/kg/day o RUTF in he ansi ion phase on i s a emp . Failed ansi ion o RUTF included child en who ailed he accep ance es o hose who had p og essi ely educed RUTF in ake du ing he subsequen days. Failu e also included hose who de eloped p o use dia hoea o omi ing when RUTF was inges ed. Resul s: Among 341 o 400 child en ha eached he ansi ion pe iod, 65% success ully ansi ioned om F-75 o RUTF on i s a emp while 35% ailed. The median (IQR) du a ion o he ansi ion pe iod was 4 (3–8) days. The age o he child, mid-uppe a m ci cum e ence, weigh - o -heigh z-sco e and weigh a ansi ion nega i ely p edic ed ailu e. Each mon h inc ease in age e lec ed a 4% lowe likelihood o ailu e (OR 0.96 (95% CI 0.93; 0.99). Child en wi h HIV (OR 2.73, 95% CI 1.27; 5.85) and hose a ed as se e ely ill by ca egi e (OR 1.16, 95% CI: 1.02; 1.32) we e mo e likely o ail. A he beginning o he ehabili a ion phase, he majo i y (95%) o he child en e en ually accep ed RUTF while only 5% comple ed ehabili a ion in hospi al on F-100. Conclusion: T ansi ion om F-75 o RUTF o hospi alized child en wi h SAM by g adual inc ease o RUTF was possible on i s a emp in 65% o cases. Younge child en, se e ely was ed, HIV in ec ed and hose wi h se e e illness as a ed by he ca egi e we e mo e likely o ail o ansi om F-75 o RUTF on i s a emp . Keywo ds: Se e e acu e malnu i ion, T ansi ion, RUTF, Child en, Uganda * Co espondence: [email p o ec ed] 1 Mwanamugimu Nu i ion Uni , Depa men o Paedia ics, Mulago Na ional Re e al Hospi al, P.O. Box 7051, Kampala, Uganda 2 Depa men o Nu i ion, Exe cise and Spo s, Uni e si y o Copenhagen, -1958 F ede iksbe g C, DK, Denma k Full lis o au ho in o ma ion is a ailable a he end o he a icle © The Au ho (s). 2017 Open Access This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion 4.0 In e na ional License (h p://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. The C ea i e Commons Public Domain Dedica ion wai e (h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed. Lanye o e al. Nu i ion Jou nal (2017) 16:52 DOI 10.1186/s12937-017-0276-z Backg ound Acu e malnu i ion a ec s mo e han 52 million child en wo ldwide [1]. O hese, an es ima ed 16 million ha e he se e e o m o acu e malnu i ion. Pa ien s wi h se e e acu e malnu i ion (SAM) a e classi ied in o hose wi h and wi hou medical complica ions depending on he p esence o medical illness and/o in eg a ed managemen o childhood illness (IMCI) dange signs. The ea men o complica ed SAM is di ided in o s abiliza ion and e- habili a ion phases, wi h a pe iod o ansi ion in be ween. In-pa ien he apeu ic eeding used o in ol e he use o wo milk-based o mulae: F-75 (low p o ein, low ene gy) in s abiliza ion and F-100 (high p o ein and high ene gy) in ehabili a ion [2]. Only pa ien s wi h SAM and medical complica ions equi e hospi aliza ion o s abilize while hose wi hou medical complica ions can be managed in he ou pa ien he apeu ic ca e (OTC) on eady- o-use he apeu ic ood (RUTF). WHO ecommends he use o eady- o-use he apeu ic ood (RUTF) du ing he ehabili- a ion phase [3]. RUTF is a lipid-based he apeu ic ood whose nu i ional composi ion is simila o F-100. T ansi- ion phase eeding e e s o he eeding egimen o e ed o child en du ing he ansi ion phase [4]. Du ing his phase, he he apeu ic eed is g adually changed om F-75 o F-100 o RUTF. Howe e , he e is no clea guideline on how a g adual ansi ion om s abiliza ion o ehabili a- ion in he he apeu ic eeding can be done [3]. A sys em- a ic e iew done in 2012 on ansi ion app oach ound no s udies ha demons a ed he app op ia e amoun s o composi ion o eed o be o e ed a e s abiliza ion [5]. WHO sugges s a slow and g adual ansi ion phase eed- ing in which F-100 o eady- o-use he apeu ic ood (RUTF) is in oduced in an equal olume as F-75 o 2– 3 days be o e o e ing la ge olumes in ended o ca ch- up g ow h in he ehabili a ion phase [3]. In 2013, WHO ecommended he di ec ansi ion om F-75 o RUTF in in-pa ien se ings using RUTF as al e na i e o p e iously used F-100 [3]. This would en- able he ehabili a ion phase o child en wi h SAM o be comple ed a home while hey ecei e he nu ien -dense RUTF. The success o he communi y-based manage- men o acu e malnu i ion (CMAM) app oach has been in pa due o a ailabili y o RUTF ha is used o ou - pa ien managemen o uncomplica ed SAM [6]. Based on expe opinion, WHO sugges s wo app oaches o ansi ion om F-75 o RUTF; he i s app oach in- ol es gi ing a child RUTF in amoun s as p esc ibed o he ansi ion phase, i he child does no ake he p e- sc ibed amoun o RUTF, hen a op-up wi h F-75 is gi en. The amoun o RUTF is g adually inc eased o e 2–3 days un il he child akes he ull equi emen o RUTF. The sec- ond app oach in ol es gi ing he child he p esc ibed amoun o RUTF o he ansi ion phase. I he child does no akea leas hal hep esc ibedamoun o RUTFin he i s 12 h, he RUTF is s opped and he child is gi en F-75 again. The same app oach is e- ied a e ano he 2 days un il he child akes he app op ia e amoun o RUTF o mee he ene gy needs [3]. In addi ion o he limi ed e idence o he mos app o- p ia e app oach, limi ed guidance exis s on he es ima- ion o he co ec amoun o he op-up wi h F-75 eed wi hou exceeding he ene gy equi emen o his phase o managemen (100–135 kcal/kg/day). We also do no know he p opo ion o he child en a e mos ly likely o ail o ansi om F-75 o RUTF on i s a emp . We desc ibe he esul s om a clinical s udy whe e we an- si ioned hospi alized child en aged 6–59 mon hs wi h SAM om F-75 o RUTF, using he i s app oach by i s p o iding hal o he ene gy equi emen s om RUTF and he o he hal om F-75 and hen inc easing g adually o RUTF as only ene gy sou ce. We hen e al- ua ed he co ela es o ailed ansi ion o RUTF. Me hods S udy design This was a p ospec i e obse a ional s udy nes ed wi hin a andomized clinical ial (www.is c n.com, ISRCTN16454889) in es iga ing he e ec o p obio- ics on dia hoea in child en wi h SAM. S udy popula ion Using he eligibili y c i e ia o he andomized clinical ial, a o al o 400 child en aged 6–59 mon hs wi h SAM ((weigh - o -heigh /weigh - o -leng h z-sco e (WHZ/ WLZ) < −3 o mid-uppe a m ci cum e ence (MUAC) <11.5 cm o bipedal pi ing oedema)) [3] we e en olled be ween Ma ch 2014 and July 2015. Child en whose ca e- gi e was willing o consen and come back o ollow-up we e included. Child en in shock, se e e espi a o y dis- ess, admission weigh less han 4.0 kg and ob ious con- geni al anomalies we e excluded om he s udy. S udy se ing The s udy was conduc ed in Mwanamugimu Nu i ion Uni (MNU) Mulago Hospi al, Kampala, Uganda. Mulago hospi al se es as he na ional e e al hospi al ecei ing pa ien s om a ious egions o he coun y and p o ides basic heal h ca e o he su ounding popula ion. Wi h an 80 bed capaci y, MNU admi s app oxima ely 100 child en mon hly, p o iding bo h in-pa ien (ITC) and ou pa ien he apeu ic ca e (OTC) se ices o pa ien s wi h SAM. Pa ien managemen All pa ien s in he s udy ecei ed s anda d ea men in addi ion o he wo p obio ic s ains o placebo. The s anda d pa ien managemen a MNU ollowed he in e- g a ed managemen o acu e malnu i ion guidelines o Uganda adap ed om he WHO guidelines [3]. Wi hin Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 2 o 10 he na ional e e al hospi al, en olled pa ien s we e sc eened a acu e ca e uni , hen ans e ed o MNU. A ained nu i ionis pe o med a de ailed nu i ion assess- men while a paedia ician on he s udy pe o med e alu- a ion o medical complica ions. F om hese wo, hospi aliza ion was conside ed. In he s abiliza ion phase, pa ien s ecei ed F-75 (Nu ise , Malaunay, F ance) a 100–135 kcal/kg/day and we e moni o ed o imp o ing appe i e, esol ing medical complica ions and/o educing bila e al pedal oedema. When appe i e had imp o ed wi h he child comple ing mo e han 80% o he apeu ic eeds p e- sc ibed o a 24 h pe iod, oedema subsided o g ade one o wo and medical complica ions esol ing, he pa ien was conside ed eady o ansi ion phase. Du ing ansi ion phase, he he apeu ic eed was g ad- ually changed om F-75 o RUTF, Plumpy’nu ®, o F-100 bo h om Nu ise , Malaunay, F ance. An accep ance es ha e alua ed whe he a child could ake RUTF was pe o med a he s a o ansi ion. The accep ance es was conduc ed in a sepa a e and quie co ne o he wa d a 12:00 pm e e y day, jus be o e eeding ime, wi h he help o he ca egi e . The ca egi e was in- o med abou he p ocess, asked o wash his/he hands and ins uc ed o gi e he child small quan i ies o RUTF di ec ly om he sache o app oxima ely 30 min while o e ing sa e d inking wa e . By obse a ion, he s udy nu i ionis conside ed he es passed i he child com- ple ed a leas app oxima ely a hi d o he 92 g sache . Taking in o conside a ion he ecommended ene gy in- ake o he ansi ion phase, 100–135 kcal/kg/day, he o al in ake o he day was calcula ed and subdi ided such ha on he i s day o ansi ion, 50 kcal/kg was ob ained om RUTF and he o he 50 kcal/kg om F- 75. Fo he subsequen days, mo e RUTF han F-75 was p esc ibed while main aining he 100–135 kcal/kg/day in ake un il he child ecei ed RUTF alone. A child was conside ed success ully ansi ioned on he i s a emp om F-75 o RUTF i he/she ook 135 kcal/kg/day. The ood in ake, quan i ies and ole ance o RUTF we e closely moni o ed by he s udy nu i ionis who also made adjus men s in he eeding plan daily. Failed ansi ion In his s udy, ailed ansi ion o RUTF on i s a emp was de ined as a child who ailed he accep ance es despi e he imp o ed appe i e wi h F-75 and clinical well s a e o one who had p og essi ely educed RUTF in ake du ing he subsequen days o one who de eloped p o- use dia hoea o omi ing when RUTF was inges ed. Those who ailed ansi ion o RUTF bu we e clinically well, ecei ed F-100. Du ing he ansi ion pe iod, he s udy eam moni- o ed he child o appe i e, omi ing eeds, p o use dia hoea and dehyd a ion, e-accumula ion o oedema, clinical de e io a ion in he espi a o y a e, pulse a e and empe a u e o de elopmen o nega i e eac ions o he RUTF. In he p esence o any o hese symp oms and signs, he clinician ans e ed he child back o F- 75 in s abiliza ion phase. Fo hose ha success ully ansi ed o RUTF on he i s a emp , hey we e ans e ed o comple e he e- habili a ion phase in he ou -pa ien he apeu ic ca e (OTC). A discha ge om hospi al, RUTF was p esc ibed a 200 kcal/kg/day and a ollow-up appoin men was gi en. Fo child en who simply ejec ed RUTF wi h no nega i e eac ions, ano he a emp o gi e RUTF was done a e 2–3 days in ehabili a ion phase while o hose ha de eloped p o use wa e y dia hoea and omi ing, no u he a emp s o RUTF we e made. These child en comple ed he ehabili a ion phase in hospi al on F-100. Da a collec ion p ocedu es A case epo o m was used o documen all da a ob- ained om he ca egi e and pa ien examina ion ind- ings. A admission, da a was collec ed on age, sex, da e o bi h, ma e nal age and educa ion le el, p e ious medical and ea men his o y o he child and he p e- sen ing symp oms. The ca egi e s we e asked o g ade he se e i y o he child’s illness a admission on a isual analogue scale (VAS) anging om 0 o 10. A ull phys- ical examina ion o include g ade o oedema, dehyd a- ion s a us, skin changes and i al signs ( espi a o y a e, pulse a e and empe a u e) was pe o med by a s udy medical doc o . Body weigh was measu ed using a digi al scale (Seca 813, Hambu g, Ge many) o he nea es 100 g. Leng h/ heigh was measu ed using an in an leng h boa d (In- an /Child Sho -Boa d®, Ma yland, USA) and mid-uppe a m ci cum e ence (MUAC) using colou coded apes (Child 11.5 ed/pac-50, UNICEF), bo h o he nea es 1 mm. T iple measu emen o weigh , leng h/heigh and MUAC we e aken and an a e age ob ained. An- h opome ic z-sco es o weigh - o -heigh (WHZ) and heigh - o -age (HAZ) we e compu ed using WHO An h o e sion 3.2.2. The s udy paedia ician oge he wi h he nu i ionis s conduc ed a daily clinical assess- men o he s udy pa ien s including moni o ing o i al signs, g ade o oedema, appe i e, ype and amoun o eeding egimens gi en h ough s abiliza ion, ansi ion and ehabili a ion phases. Labo a o y es s Blood sampling was pe o med a admission, discha ge and 8 weeks a e discha ge. A admission, 4 ml o en- ous blood was collec ed in o hepa inized e acua ed ubes (Bec on Dickinson, USA) o un es s o HIV, blood cell coun s, haemoglobin and C- eac i e p o ein Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 3 o 10 (CRP). HIV se ological es ing was done using apid es s (De e mine HIV-1/2, Abbo Labo a o ies, USA) and posi i e es esul s we e u he con i med using HIV 1/2 S a -Pak Dips ick Assay ki . Fo child en less han 18 mon hs, HIV s a us was con i med by an HIV DNA PCR es a Baylo HIV clinic. Samples we e analyzed o cell blood coun s and haemoglobin a he Uganda cance ins i u e labo a o y. A copy o he esul s was p o ided o doc o s on he wa d o suppo pa ien managemen . A sample o he blood was cen i uged a 1300–2200 g o 10 min, s o ed a −80 °C and shipped on d y ice o he la- bo a o y a Depa men o Nu i ion Exe cise and Spo s, Uni e si y o Copenhagen, whe e C- eac i e p o ein was analyzed using Pen a 400, (Ho iba ABX, F ance). Da a analysis All da a was en e ed in o Epida a e sion 3.1 and ana- lyzed using S a a e sion 12. Desc ip i e s a is ics using means, medians and p opo ions was used o p esen he socio-demog aphic cha ac e is ics, ma e nal cha ac- e is ics and labo a o y da a. To de e mine he s eng h o associa ion o he p edic o s o ailed ansi ion om F-75 o RUTF, a se ies o logis ic eg ession models we e i ed. Du a ion o s abiliza ion phase, HIV in ec ion, se- e i y o illness o he child a admission in addi ion o age and sex we e e alua ed as po en ial con ounde s. Each o hese ac o s did no change he unadjus ed odds a io by mo e han 10% hence no included in he inal eg ession model. The independen a iables we e adjus ed o age and sex. P- alues below 0.05 we e s a is- ically signi ican . Resul s Socio-demog aphic cha ac e is ics The mean (±SD) age o he child en ha eached ansi ion phase was 17.1 (±8.7) mon hs and 42% we e emales (Tabl 1). Thei mean WHZ and HAZ we e −2.5 (±1.5) and −3.1 (±1.4), espec i ely. A admission, 66% o child en p e- sen ed wi h oedema. The mean ma e nal age was 25 (±5.8) yea s, wi h 185 (58%) o he mo he s ha ing a ained p i- ma y le el educa ion o lowe (da a no p esen ed). T ansi ion om F-75 o RUTF O 400 child en en olled, 341 (85%) eached ansi ion phase (Fig. 1). O hese, 223 (65%) succeeded in ansi- ion om F-75 o RUTF on he i s a emp while 118 (35%) ailed (Fig. 1). I ook on a e age 1.4 (±1.4) days o g adually change he eed om RUTF wi h op up o F- 75 o RUTF alone du ing he ansi ion pe iod. Twel e pe cen (27/223) o child en ansi ioned di ec ly om F-75 o RUTF wi hou he need o op-up wi h F-75. O e all, he median (IQR) du a ion o he en i e ansi- ion pe iod was 4 (3–8) days, which included ime o an- si om F-75 o RUTF o F-100 and esolu ion o medical complica ions. Howe e , his du a ion was longe o hose ha ailed ansi ion o RUTF on he i s a emp , [4 (3–6) days s 7.5 (4 .0–11) days, p< 0.01]. The e was no di e ence in numbe o days in s abiliza ion phase among hose succeeding compa ed o hose ailing o ansi ion o RUTF (10.5 s. 9.6 days, p=0.15). Table 1 Cha ac e is ics o 341 se e e acu e malnu i ion child en eaching ansi ion a Child cha ac e is ics Age a , mon hs 341 17.1 ± 8.7 Female sex, n (%) 341 143 (42%) How sick a admission, VAS b 340 6.0 ± 1.8 Weigh - o -heigh z 339 −2.5 ± 1.5 Weigh o heigh z sco e ≥−2 125 (37%) <−2 and > −3 65 (19%) <−3 and > −4 90 (27%) <−4 and > −5 44 (13%) ≤−5 14 (4%) Heigh - o -age z 339 −3.1 ± 1.4 Mid-uppe a m ci cum e ence, cm 341 11.6 ± 1.5 HIV s a us, n (%) 323 Nega i e 229 (70.9%) Posi i e 32 (10%) Exposed, nega i e 62 (19%) Symp oms on admission, n (%) Cough 340 225 (66%) Dia hea 340 194 (57%) Fe e 340 180 (53%) Clinical da a on admission, n (%) Oedema 341 G ade 1 22 (7%) G ade 2 64 (19%) G ade 3 139 (41%) Flaky pain de ma osis 341 22 (6%) Labo a o y da a on admission Se um C- eac i e p o ein, mg/dl > 10 303 183 (60%) Hemoglobin 259 8.8 ± 2.1 Clinical da a a ansi ion Oedema, n (%) 341 G ade 1 58 (17%) G ade 2 5 (2%) Weigh , kg 294 6.7 ± 1.6 No. o days wi h dia hoea in s abiliza ion 339 4.1 ± 3.9 a Da a a e numbe o child en wi h da a, and mean ± s anda d de ia ion o numbe (%) b isual analogue scale Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 4 o 10 The child en ha we e success ully ansi ioned o RUTF a he i s a emp we e hen ans e ed o comple e ehabili a ion in OTC. On he second a emp o accep ance o RUTF du ing ehabili a ion phase, 101 (86%) o he 118 ha ecei ed F-100 now accep ed he p esc ibed RUTF and we e ans e ed o OTC o comple e ehabili a ion. The emaining 14% (17/118) child en did no accep RUTF a all. The child en ha did no accep RUTF a all con inued wi h he ehabili a- ion phase o a ain ca ch-up g ow h in hospi al while ecei ing F-100 and allowed home a e ull eco e y on locally a ailable oods (Fig. 1). Co ela es o ailed ansi ion The age o a child was nega i ely associa ed wi h ailed ansi ion om F-75 o RUTF on he i s a emp . An odds a io o 0.96 (95% con idence in e al (CI) 0.93; 0.99) o age e lec s a 4% lowe likelihood o ailu e o ansi ion om F-75 o RUTF o each mon h inc ease in age (Table 2). A WHZ lowe han −3 was associa ed wi h highe odds o ailu e (Table 2). Inc easing MUAC (OR 0.79, 95% CI 0.68; 0.94) and weigh a ime o an- si ion (OR 0.68, 95% CI: 0.53; 0.86) we e associa ed wi h a lowe isk o ailu e. We ound a 32% educ ion in he isk o ailu e o e e y kilog am inc ease in he weigh a he ime o ansi ion. The HIV posi i e child en we e mo e likely o ail ansi ion o RUTF (OR 2.73, 95% CI: 1.27; 5.85). The se e i y o illness o he child as a ed by he ca egi e a admission using isual analogue scale was ound o be associa ed wi h ailu e (OR 1.16, 95% CI: 1.02; 1.32). Nei he symp oms o cough, dia hoea, e e no p esence o oedema whe he a admission o a he ime o ansi ion we e associa ed wi h ailu e (Table 2). T ans e back o s abiliza ion O he 341 child en ha eached ansi ion phase, 51 (15%) we e ans e ed back o s abiliza ion phase. The clinical cha ac e is ics o he child en on he day o ans- e back o s abiliza ion a e p esen ed in Table 3. Nea ly hal (47%) o hose ans e ed back o s abiliza ion had an inc eased espi a o y a e and 18% we e diagnosed o ha e se e e pneumonia (Table 3). Age, lowe WHZ sco e, MUAC and weigh a ansi ion we e nega i e p edic o s o ans e back o s abiliza ion (Table 4). Discussion WHO ecommends a g adual p ocess o ansi ion om F-75 o RUTF o F-100 [3]. Howe e , he app oach o ansi ion p ocess especially o RUTF is lacking in e i- dence. This s udy desc ibes a me hod o g adual ansi- ion om F-75 o RUTF wi h a s uc u ed s ep up o Failed ansi ion om F- 75 o RUTF/ gi en F-100 (n = 118) Success ul ansi ion om F-75 o RUTF (n= 223) esahpnoi a ilibaheR Child en en olled (N=400) RUTF RUTF F-100 RUTF (n=101) Child en eaching ansi ion phase (N= 341) F-100 F-100 (n=10) F-100 o he s (n=7) noi isna T Died (n=39) Sel -discha ge (n=15) Excluded (n=5) esahpnoi aziliba S T ans e back o s abiliza ion (n=51) (n=223) Fig. 1 P opo ion o child en wi h se e e acu e malnu i ion ha ailed o succeeded ansi ion om F-75 o RUTF on i s a emp . 118 child en ailed ansi ion o RUTF. Those who ailed we e child en who ailed he accep ance es o who had p og essi ely educed RUTF in ake du ing he subsequen days o de eloped nega i e eac ions such as p o use dia hoea o omi ing when RUTF was inges ed. Those who ailed we e gi en F-100. A beginning o ehabili a ion phase, ano he a emp o RUTF was done o hose who had ailed ansi ion o RUTF. O he 118 child en, 101 changed eed om F-100 o RUTF, while 10 child en emained on F-100 and 7 ecei ed o he eeds such as po idge. Among he 341 child en ha we e ansi ion, 51 de eloped signs and symp oms o clinical de e io a ion while in ei he ansi ion o ehabili a ion phase and we e ans e ed back s abilisa ion Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 5 o 10 amoun o RUTF o be gi en du ing he ansi ion phase. We ound ha 65% o child en wi h SAM ansi- ioned om F-75 o RUTF on i s a emp a e he s abiliza ion phase while 35% ailed. This p o ides good e idence o suppo he ecommenda ion by WHO. A ecen s udy conduc ed in Malawi [7] has u he showed ha he in oduc ion o RUTF du ing ansi ion phase has no e ec on he s ool pH o du a ion o hos- pi al s ay compa ed o F-100. Fu he mo e, we no e ha he majo i y (95%) o he child en in his s udy la e accep ed RUTF in he ehabili a ion phase wi h only 5% no aking RUTF a all. Tha he majo i y o he child en e en ually accep RUTF as hey begun he ehabili a ion phase is ele an in o ma ion because i implies ha many mo e child en can hen be managed on an ou pa ien basis ollowing s abiliza ion o hei medical complica- ions. Since endo semen o he CMAM app oach by he UN agencies [8], he use o RUTF in he managemen o uncomplica ed SAM has sa ed millions o li es o child en h ough imp o ed co e age o nu i ion p og ammes, Table 2 Co ela es o ailed ansi ion om F-75 o RUTF among 341 child en ea ed o se e e acu e malnu i ion a Unadjus ed Age and sex adjus ed OR 95% CI pOR 95% CI P Child cha ac e is ics Age, mon hs 0.96 0.93;0.99 0.02 0.96 0.93;0.99 0.01 Female sex, n (%) 0.83 0.53;1.31 0.42 0.80 0.51;1.28 0.37 How sick, VAS b 1.14 1.01;1.29 0.03 1.16 1.02;1.32 0.02 HIV s a us, n (%) Exposed 1.03 0.56;1.86 0.91 0.96 0.52;1.79 0.92 Posi i e 2.58 1.22;5.48 0.01 2.73 1.27;5.85 0.02 Weigh - o -heigh z 0.77 0.68;0.91 0.001 0.82 0.69; 0.95 0.01 Weigh - o -heigh z ≥−2 e <−2 and > −3 1.37 0.71; 2.68 0.34 1.31 0.67; 2.57 0.42 <−3 and > −4 2.42 1.35; 4.34 0.003 2.13 1.17; 3.88 0.01 <−4 and > −5 2.10 1.01; 4.33 0.04 1.81 0.86; 3.81 0.12 ≤−5 3.03 0.98; 9.32 0.05 2.52 0.81; 7.94 0.11 Heigh - o -age z 0.91 0.78;1.06 0.24 0.86 0.72;1.02 0.07 MUAC, cm 0.77 0.66;0.89 0.001 0.79 0.68;0.94 0.01 Symp oms on admission (%) Cough 1.05 0.65;1.69 0.83 1.04 0.64;1.67 0.89 Dia hea 1.03 0.66;1.62 0.87 1.00 0.62;1.59 0.99 Fe e 1.27 0.81;1.98 0.30 1.27 0.80;2.01 0.31 Clinical signs on admission (%) Oedema G ade 1 1.41 0.56;3.54 0.46 1.55 0.61;3.93 0.35 G ade 2 1.08 0.58;2.03 0.79 1.20 0.63;2.28 0.57 G ade 3 0.68 0.41;1.16 0.16 0.80 0.46;1.38 0.42 Flaky pain de ma osis 1.08 0.44;2.66 0.86 1.12 0.45;2.78 0.80 Labo a o y da a on admission C- eac i e p o ein, mg/l > 10 0.97 0.60;1.57 0.92 0.98 0.61;1.60 0.96 Hemoglobin, g/dl 0.96 0.85;1.08 0.52 0.96 0.84;1.08 0.52 Weigh a ansi ion, kg 0.73 0.61;0.86 <0.001 0.68 0.53;0.86 0.002 No. o days wi h dia hoea du ing s abiliza ion 1.01 0.95;1.07 0.80 0.99 0.94;1.06 0.97 No. o days o s abiliza ion phase 1.02 0.98;1.07 0.31 1.02 0.97;1.06 0.36 a Da a a e odds a io (OR), 95% con idence in e al (CI) and p- alues b isual analogue scale Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 6 o 10 educed mo ali y a es, imely ea men o SAM and e- duced cos s o hospi al ca e [6, 9–11]. This s udy p o ides e idence ha suppo s he di ec ansi ion om F-75 o RUTF and subsequen ly hese child en a e managed in he ou -pa ien he apeu ic p og ammes. I is also impo - an o no e ha no all child en we e able o ansi ion success ully om F-75 o RUTF a he same speed. We ound ha he child en ha ansi ioned success- ully om F-75 o RUTF on he i s a emp , he g adual inc ease in RUTF ill hey we e on RUTF alone ook be- ween 1 and 2.8 days. This is consis en wi h he cu en ecommenda ion o 2–3 days [3] hence u he s eng hens he cu en ecommenda ion. In his s udy, he en i e ansi ion pe iod las ed 3–8 days among all chil- d en ha eached ansi ion. This inding is in line wi h he WHO 1999 guidelines [2] showing ansi ion pe iod o las o 3–7 days. Howe e his ansi ion pe iod was longe o hose ha ailed o ansi smoo hly o RUTF. P edic o s o ailed ansi ion Inc easing age was associa ed wi h a lowe isk o ailu e. Younge child en pe haps could ha e some di icul y wi h he consis ency o RUTF in i s cu en semi-solid s a e. Coupled wi h he physiological changes o educed muscle mass o include he muscles o mas ica ion, in- ake o RUTF may be somewha a ec ed compa ed o F- 75 o F-100 ha is in liquid o m, easie o d ink and swallow. I is also p obable ha hese child en wi h mal- nu i ion also ha e delayed in oduc ion o complemen- a y eeds and commonly he i s complemen a y eeds a e luid in consis ency. S udies in an u ban dis ic o Nai obi [12] and a u al dis ic in Uganda [13] showed highe p obabili y o ecei ing liquid o a semisolid o solid complemen a y ood among child en in he de el- oping coun ies. Ano he s udy conduc ed in he wes - e n u al dis ic in Uganda [14] ound 19% o child en in he communi y aged 6–8 mon hs we e s ill exclusi ely b eas eed ins ead o ecei ing complemen a y eeds. A e iew on he global pe spec i e o complemen a y eed- ing [15] e ealed ha a ce eal based po idge o en wi h plen y o wa e was he main complemen a y ood gi en in many de eloping coun ies. A s udy conduc ed in Bangladesh [16], 78% o malnou ished p egnan and lac- a ing women ound he RUTF unaccep able. They u - he sugges ed making changes o as e, smell and consis ency o make i mo e liquid [16]. Fu he mo e, we ound ha was ing as measu ed by dec easing WHZ and MUAC we e associa ed wi h a highe isk o ailu e. The odds o ailu e we e highe wi h dec easing ini ial WHZ. Child en wi h WHZ less han −5 SD we e 3 imes mo e likely o ail o ansi o RUTF on he i s a emp . P obably he mos was ed child en ha ing been h ough longe pe iods o s a a- ion in addi ion o unc ional and s uc u al changes in he body o gans due o educ i e adap a ion will simi- la ly equi e longe pe iod o e-adap when he apeu ic eeding is ini ia ed. HIV in ec ion and se e i y o illness as epo ed by he ca egi e we e posi i ely associa ed wi h highe isk o ailu e o ansi o RUTF. Con a y o his inding, s ud- ies conduc ed in Tanzania [17] and Malawi [18], RUTF Table 3 Clinical cha ac e is ics a he ime o ans e back o s abiliza ion 1 Clinical cha ac e is ics * N=51 Weigh , kg 6.15 ± 1.32 Tempe a u e, °C 36.9 ± 0.83 Pulse a e 2 , b/min 128 ± 15 Oxygen sa u a ion 3 , (%) 92.3 ± 5.8 Visual analogue scale, VAS 3.0 ± 3.1 Respi a o y a e No mal 27 (53%) Inc eased 24 (47%) Ches in-d awing No 41 (80%) Yes 10 (20%) B ea h sounds on auscul a ion No mal 41 (80%) C epi a ions 6 (12%) Diminished 1 (2%) Pneumonia None 37 (72%) Pneumonia 5 (10%) Se e e pneumonia 9 (18%) Oedema None 45 (88%) G ade 1 3 (6%) G ade 2 2 (4%) G ade 3 1 (2%) ReSoMal p esc ibed 4 None 33 (65%) Plan A 10 (20%) Plan B 8 (15%) Appe i e None 5 (10%) Poo 15 (29%) Good 31 (61%) 1 Da a p esen ed a e mean (SD) o n (%) 2 N=13 3 N=7 4 ReSoMal Plan A; 30-50mls o ReSoMal pe loose s ool o child en wi h no dehyd a ion, ReSoMal plan B; 5mls/kg o i s 30 min ollowed by 5-10mls/kg o ReSoMal o 6–8 h gi en o some o se e e dehyd a ion * A child could ha e one o mo e o hese cha ac e is ics Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 7 o 10 has been used success ully among he HIV in ec ed chil- d en wi hou medical complica ions du ing he home- based he apy o SAM wi h good esul s in weigh gain. Howe e he s udy in Malawi [18] showed only 56% s 84% o child en wi h ull eco e y in WHZ among he HIV-in ec ed child en compa ed o he HIV-nega i e child en espec i ely. This was a ibu ed o de elop- men o cough, e e and dia hoea. A s udy by Zei z e al. [19] documen ed lac ase de iciency in nea ly 50% in HIV pa ien s hence inc easing he isk o malabso p ion and dia hoea. This poin s o p obable di e ences in he me abolic al e a ions in HIV-in ec ed compa ed o he HIV-nega i e child en ha could equally in luence an- si ion o RUTF. Use o RUTF in HIV-in ec ed child en me i s u he e alua ions o imp o e nu i ion ou comes. We ound 15% o he child en in his s udy we e ans e ed back o s abiliza ion phase a e success ul ansi ion due o clinical de e io a ion wi h symp oms and signs o inc eased espi a o y a e, pneumonia and dia hoea wi h dehyd a ion. Sys ema ic e iews [5, 20] indica e ha clinical mani es a ions o espi a o y dis- ess, ca diac ailu e o le ha gy while in ansi ion phase may o en be misin e p e ed o sepsis o pneumonia ye Table 4 Co ela es o ans e back o s abiliza ion among 341 child en ea ed wi h se e e acu e malnu i ion a Unadjus ed Age and sex adjus ed OR 95% CI pOR 95% CI p Child cha ac e is ics Age, mon hs 0.97 0.93; 0.99 0.04 0.96 0.93; 0.99 0.04 Female sex, n (%) 0.78 0.47; 1.29 0.33 0.76 0.45; 1.26 0.29 Se e i y o illness, VAS b 0.83 0.72; 0.94 0.01 0.83 0.73; 0.95 0.01 HIV s a us, n (%) Exposed 0.74 0.37; 1.49 0.40 0.72 0.36; 1.47 0.37 Posi i e 1.62 0.73; 3.56 0.23 1.68 0.75; 3.72 0.20 Weigh - o -heigh z 0.72 0.61; 0.86 <0.001 0.75 0.62; 0.89 0.002 Heigh - o -age z 0.95 0.80; 1.13 0.59 0.91 0.76; 1.09 0.33 MUAC, cm 0.77 0.64; 0.91 0.003 0.79 0.66; 0.95 0.01 Symp oms on admission (%) Cough 1.16 0.68; 1.97 0.58 1.14 0.67; 1.95 0.62 Dia hea 0.92 0.56; 1.51 0.73 0.87 0.53; 1.45 0.61 Fe e 0.94 0.57; 1.54 0.81 0.94 0.57; 1.55 0.81 Clinical signs on admission (%) Oedema G ade 1 1.12 0.42; 3.00 0.81 1.22 0.45; 3.28 0.69 G ade 2 0.80 0.40; 1.61 0.54 0.86 0.43; 1.75 0.68 G ade 3 0.55 0.31; 0.99 0.05 0.63 0.34; 1.15 0.13 Flaky pain de ma osis 0.91 0.32; 2.54 0.855 0.94 0.33; 2.66 0.91 Labo a o y da a on admission C- eac i e p o ein, mg/l > 10 0.87 0.51; 1.47 0.61 0.88 0.52; 1.49 0.64 Hemoglobin, g/dl 1.12 0.98; 1.29 0.09 1.13 0.99; 1.29 0.06 Clinical da a a ansi ion Edema a ime o ansi ion G ade 1 0.53 0.24; 1.12 0.10 0.53 0.23; 1.16 0.11 G ade 2 1.91 0.31; 11.6 0.48 3.28 0.47; 22.45 0.23 Weigh a ansi ion, kg 0.72 0.58; 0.87 0.001 0.64 0.48; 0.84 0.001 Dia hoea du ing s abiliza ion 1.02 0.96; 1.09 0.39 1.02 0.96; 1.08 0.54 Du a ion o s abiliza ion phase 0.97 0.92; 1.02 0.27 0.96 0.92; 1..02 0.24 a Da a a e odds a io (OR), 95% con idence in e al (CI) and p- alues b isual analogue scale Lanye o e al. Nu i ion Jou nal (2017) 16:52 Page 8 o 10 hey a e he mani es a ions o e eeding synd ome. A e- iew o e eeding synd ome [21] highligh ed ha he se- e ely was ed indi iduals wi h p olonged as ing o low ene gy die in ake we e a a highe isk o e eeding syn- d ome. Re eeding synd ome commonly p esen s wi h symp oms and signs o hypophospha emia and hypo- magnesaemia such as espi a o y dis ess, weakness, ca - diac ailu e, nausea and dia hoea [21]. Howe e ecen s udies conduc ed in Uganda [22, 23] showed inc easing le els o plasma phospha e in he ansi ion phase and a discha ge among child en managed o SAM. This ol- lows he WHO ecommenda ions ha imp o ed phos- pha e con en in he he apeu ic eeds hence e eeding synd ome is unlikely. We did no ind any co ela ion be ween ailed ansi- ion and oedema ei he a admission o a he ime o ansi ion. This suppo s he ecommenda ion o he use o RUTF when oedema is g ade II o I as is done in he ou pa ien he apeu ic p og ammes [3]. O he ac o s we would ha e liked o measu e as po- en ial e ec modi ie s a e he iming o in oduc ion o complemen a y eeds, he ype o complemen a y eeds in oduced and p e ious exposu e o RUTF. The p e i- ous exposu e o RUTF in he child en would p obably ease he in ake o RUTF since his is a as e and consis ency he child has been exposed o o i he child did no like i p e iously, he would ejec i when i is gi en his ime. Du ing he selec ion o s udy pa ici- pan s, we excluded he child en wi h ce eb al palsy who a e known o ha e eeding di icul ies. This g oup o child en would ha e modi ied he e ec on he es ima e as hey a e mo e likely o ail. S eng hs and limi a ions This is among he i s s udies ha desc ibes he ansi- ion eeding o hospi alized child en wi h SAM ollowing he ecen WHO ecommenda ions. The s udy was con- duc ed in a con olled en i onmen du ing a clinical ial. This acili a ed close moni o ing o he eeding in child en bo h du ing day and nigh . Amongs he s udy limi a ions, i s ly, he s udy selec- ion c i e ia did no include he se e ely ill child en and hose wi h disabili ies hence may a ec he ex e nal al- idi y o he indings. Secondly, he p ocess o de e min- ing whe he a child was eady o ansi ion phase as his p ocess is ela i ely subjec i e and dependen on he e u n o appe i e. The e is no li e a u e ha demon- s a es sensi i i y o speci ici y o he e u n o appe i e in co ec ly iden i ying hose eady o ansi ion. I is also no ce ain whe he he e usal o RUTF was be- cause o he new as e o he child a he han a di e en consis ency om he F-75 p e iously aken du ing s abiliza ion. Howe e he p ocess and moni o ing o ansi ion phase was conduc ed by well ained and expe ienced nu i ionis s. Las ly, we we e no able o ca y ou blood es s o se um elec oly es such as phospha e, magnesium, and po assium du ing ansi ion phase. Re- eeding synd ome is associa ed wi h hypophospha emia, hypomagnesemia and hype kalemia. The e o e we canno say o su e ha signs o espi a o y dis ess, dia hoea ob- se ed in he child en who we e ans e ed back o s abiliza ion we e a esul o e eeding synd ome. Conclusion T ansi ion om F-75 o RUTF du ing he ansi ion phase o hospi alized child en wi h SAM was possible on i s a - emp in he majo i y o child en wi h SAM. The me hod o i s p o iding hal he ene gy equi emen s using RUTF and he emaining hal by F-75 hen g adually inc easing o RUTF as he only sou ce o ene gy du ing ansi ion p o- ides guidance o p ac i ione s managing hospi alized chil- d en wi h SAM.Younge child en, se e ely was ed, HIV in ec ed and hose epo ed o be se e ely ill by he ca e- gi e we e mo e likely o ail ansi ion o RUTF on i s a - emp . The ansi ion p ocess om F-75 o RUTF wa an s u he esea ch o e alua e he mos app op ia e me hod o ansi ion wi h minimal ailu es and o ad ance in mo e objec i e and ield app op ia e me hods o de e mine eadi- ness o ansi o s abiliza ion o me abolic al e a ions in child en wi h SAM. Abb e ia ions CMAM: Communi y Managemen o Acu e Malnu i ion; HIV: Human Immunode iciency Vi us; ITC: In-pa ien he apeu ic ca e; MNU: Mwanamugimu Nu i ion Uni ; MUAC: Mid-uppe a m ci cum e ence; OTC: Ou -pa ien he apeu ic ca e; RUTF: Ready- o-use he apeu ic ood; SAM: Se e e acu e malnu i ion; VAS: Visual Analogue scale; WHO: Wo ld Heal h O ganiza ion Acknowledgemen s We hank all he child en and ca egi e s who pa icipa ed in he s udy and he s udy s a in ol ed in da a collec ion and ca e o he pa ien s. E hical app o al and consen o pa icipa e Ins i u ional e iew boa d app o al was gi en om he Make e e Uni e si y School o Medicine Resea ch and E hics Commi ee (SOMREC) and a consul a i e app o al om he Na ional Commi ee o Heal h Resea ch E hics in Denma k and inal clea ance was gi en by Uganda Na ional Council o Science and Technology. The e e ence numbe o he P obiSAM s udy is # REF REC 2013–132. A w i en in o med consen was ob ained om all he ca egi e s o pa en s o he pa icipa ing pa ien s be o e ec ui men in o he s udy. Funding Funding was ecei ed om Ch . Hansen A/S, Uni e si y o Copenhagen and Inno a ion Fund Denma k. A ailabili y o da a and ma e ials The da ase s used and/o analyzed in his s udy a e a ailable om he co esponding au ho on easonable eques . Au ho s’con ibu ions BL, HN, NNB, BG, HF designed he s udy, HN, BG, NNB, BL we e esponsible o da a collec ion, BL analyzed he da a, d a ed he manusc ip and all au ho s c i ically e iewed and app o ed he manusc ip . Lanye o e al. 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