 
 protein - energy malnutrition ( pem ) 
 remains a major public health problem in the world , particularly in developing 
 countries . according to the world health organization ( who )
, pem affects   one - third of children around the world , and 43% of   children in developing 
 countries ( 230 million ) , presenting a delay in staturoponderal growth . in burkina faso ,
the prevalence of children    with acute malnutrition is 
 19% , while 39% present a delay of statural growth , and 38% have weight 
 insufficiency .
however , 
 biological   markers such as albumin , transthyretin , transferrin , and retinol binding 
 protein are also used for nutritional diagnosis   and rehabilitation aftercare . 

several surveys have shown the relationship between clinical , anthropometric , or biological indicators and 
 mortality of children suffering from pem in hospitals [ 35 ] .
more recently 
 used markers like insulin - growth factor - i ( igf - i ) used to measure the deficit 
 in growth hormone ( gh ) , and the insulin growth factors binding proteins 
 ( igfbps ) also draw attention .
insulin - like growth factor - i ( igf - i ) is single - chain 
 peptides of   7.5 kilodaltons ( kdas ) .  
her structure is similar to the igf - ii and proinsulin [ 6 , 7 ] .  
the liver is believed 
 to be the main source of production of igf - i 
 [ 810 ] , but the highest concentrations of igf - i are observed in blood [ 11 , 12 ] . 

many factors intervene in the regulation of the 
 igf - i but the most important are growth hormone ( gh ) , insulin , and nutritional 
 status .
nutritional status plays an important role in 
 the regulation of the igf - i .
adequate food intake is essential for maintaining 
 normal igf - i and igfbp-3 circulating rates in the serum[16 , 17 ] .
indeed , 
 energy and protein restrictions 
 in children lead to 
 a decrease of circulating igf - i and igfbp-3 rates .
the variations of serum igf - i rates observed in 
 response to different nutritional states suggest that igf - i may serve as a 
 marker for children nutritional state [ 1921 ] .
the igf - i 
 appears indeed as a marker potentially more sensitive than the serum albumin or 
 the transferrin , even if the effect of infection on circulating concentration 
 must be taken into account [ 2224 ] .
only two surveys have been conducted on igf - i and the nutritional rehabilitation among children under 5 years old but both were inconclusive because of low sample sizes    [ 22 , 24 ] , but both were inconclusive because of low - sample 
 sizes .
these two studies did not    also analyse the 
 change of igf - i and the changes of nutritional status .
so , the purpose of our 
 study is to analyse the relationship between the igf - i values and the 
 nutritional status of children hospitalised for nutritional rehabilitation in 
 the context of a west - african country .
the study of protocol was reviewed and approved by the ethics 
 committee for research in health of burkina faso .
this study was conducted in two nutritional rehabilitation 
 centres : ( cren ) of the regional hospital ( chr ) and the persis medical centre 
 ( cm ) of the city of ouahigouya , located in the northern part of burkina faso .
all consecutively admitted patients with pem should be included in 
 the study . among these patients ,
the criteria for selection were the age < 60 months and the absence of known pathology like hiv , diabetes , congenital 
 diseases , and tumours . upon admission , social and demographic characteristics ( age , 
 sex , and vaccination past records )  
were collected ; weight and height were 
 measured , and different clinical data were checked ( presence of oedema , 
 coloration of hair , splenomegaly , and hepatomegaly ) .
the children were followed up and the 
 anthropometric data and the capillary blood samples were again taken again on 
 the 7th and the 14th days 
 after admission .
they 
 benefited from a free standard feeding which consisted of milk f75 for 7 days 
 at 135  kcal / kg weight per day and milk f100 after the week at 100  kcal / kg 
 weight per day .
this posology was increased by 20  kcal every 3 days until 200  kcal / kg per day , as necessary . in addition , the children received enriched pulp 
 five times a day . a treatment for bacterial infections and malaria was 
 available at any time if required .
a total of 68 children were recruited for the 
 study but only 59 were included because the ages of 9 children were unknown . 

the sex 
 ratio was 1.68 for boys ; 76.3% of the children were aged between 1 and 2 years . 

most of the mothers ( 96.6% ) and the fathers ( 88.1% ) had no scholarship 
 education .
mothers were mainly housewives and fathers were mainly farmers . with 
 regard to vaccine status , two thirds of the children
were fully vaccinated , 
 30.9% not fully vaccinated , and 3.6% were not vaccinated at all .
weight and height were determined on a salter balance and the height 
 was rounded to the nearest centimetre . for children younger than 2 years , 
 height ( length )
was measured on a supine table as follows : an assistant held 
 the head against the headboard and another straightened the legs . for children 
 older than 2 years , a stadiometer was used .
nutritional status , expressed as weight for height ( whz ) and height for 
 age ( haz ) , was standardised for age and sex using either the reference tables 
 from the burkina faso reference tables 
 or the united states national center for health statistics ( nchs ) [ 26 , 27 ] .
the reference tables of 
 burkinabe children were constructed from anthropometric measures collected 
 during the survey on the reference values of igf - i in burkina faso 
  .
blood was obtained by vein 
 puncture and 2 drops per circle were immediately collected on ( free falling ) 
 the filter paper ; 2 circles per paper were systematically filled ; the samples 
 were dried after 510 minutes at 
 ambient temperature ( 3035c ) and were 
 kept at 4c for 12 weeks before 
 processing .
all filter paper samples were transferred for analyses to the unit 
 of diabetes and nutrition , belgium .
we validated the methods of 
 determining the igf - i levels from dried blood spots on filter paper on igf - i 
 ria , after separating the igf - i from its binding proteins using sep - pack 
 chromatography .
igf - i was determined by ria , using the antiserum at a 1/15000 
 dilution , and i- igf - i was labeled by the iodogene method and 
 purified by rp - hplc .
the concentration of the standard curve spans over a range 
 of 0.05 to 2 ng / ml . intra - assay and total imprecision of the ria were of 5% 
 and 16% at a level of 0,25  ng / ml and of 5% and 22% at a level of 1.01  ng / ml 
 .
igf - i absolute measurements were also standardised for age and sex , 
 and reported as igf - i z scores , using the reference values of igf - i in children 
 from birth to the age of 5 in burkina faso .
results are expressed as proportions for 
 discrete variables , as means and standard deviations ( sds ) for continuous 
 variables with a normal distribution , and as geometric means with geometric 
 standard deviations for continuous variables with a log - normal distribution , 
 like igf - i . standardised values 
 are expressed as z - scores and are reported as 
 mean  sd and proportion under 2.00 or under 3.00 .
igf - i was considered 
 either as an absolute measurement and analysed on a log scale , or as an age- 
 and sex - adjusted normal z - score and analysed on a linear scale .
relationships 
 between igf - i and whz at baseline and after 14 days of nutritional 
 rehabilitation were assessed using r , the pearson cross - product correlation 
 coefficient .
changes in igf - i after 14 days of nutritional rehabilitation were 
 expressed as ratio for absolute measurements and as differences for 
 standardised values , and changes were tested using student 's paired t - test . 

relationships between changes in igf - i and increases in whz were assessed using 
 also r. no p - value was corrected for multiple comparisons and a p value < .05 was considered as statistically 
 significant .
two children ( 3.4% ) were admitted to the nutritional rehabilitation 
 centre because of kwashiorkor , 55 children ( 93.2% ) were admitted for marasmus , 
 and two presented with both kwashiorkor and marasmus .
one child died during the 
 follow - up . at the time of admission , 
 using international reference values as standards , 57 children ( 96.6% ) had an 
 age- and sex - adjusted weight for height z - score lower than 
 2.0 , including 43 children with a whz   < 3.0 .
out of the 57 children with a whz < 2.0 , 51 ( 89.5% ) had also an 
 age- and sex- adjusted igf - i z - score of < 2.0 .
an igf - i z score of < 2.0 was also observed in 90.7 % ( 39/43 ) of children presenting with a whz   < 3.0 . when using burkina 
  faso 
  age and sex reference values for 
 standardising , 44% ( 26/59 ) of children had a whz < 2.0 , and 8% ( 5/59 ) had a 
 whz < 3.0 .
2.0    was 89% ( 23/26 ) in 
 children with whz < 2.0 and 80% ( 4/5 ) in children with whz < 3.0 .
after 14 days of nutritional rehabilitation , 22 children ( 37% ) 
 reached a whz 2.0 according to international references , and 91% of these 
 children ( 20/22 ) also attained an igf - i z - score 2.0 . using burkina faso data 
 as standards ,
the whz was 2.0 
  in 80% ( n = 47 ) of children after 14 days of nutritional 
 rehabilitation , and 81% of these children ( n = 38 ) also reached an igf - i z - score 
 2.0 , suggesting a quick recovery of igf - i , as illustrated in figure 1 . during nutritional rehabilitation , igf - i increased from 6.36 ( 1.40 )  g / l ( geometric mean and sd ) upon admission , to 8.59 
 ( 1.81 ) 
g / l after two weeks of 
 nutritional rehabilitation ( figure 1 ) . 

table 2 shows the parallel increase in weight and in igf - i , from 
 admission to 7 and 14 days after nutritional rehabilitation .
data are presented 
 as absolute measurements , as standardised measurements using international 
 references for age and sex adjustments , and as standardised measurements using 
 burkina faso data as standards .
after 7 days of nutritional rehabilitation , igf - i was multiplied by 
 1.587 , as a significant increase of 58.7% on average .
. there was a significant increase   in log - scaled igf - i , as well as in 
 igf - i z - scores   one week after admission ( paired t - test , p = .003 , and p = .007 ) , and two weeks after 
 admission ( paired t - test , p < .001 , and p = .001 ) .
a significant increase was also observed for weight for height 
 z - scores , with both standardisations .
the relationship between age- and 
 sex - adjusted igf - i score and weight for height z - score using the burkina faso 
 reference for standardisation is illustrated in figure 2 , upon admission   ( a )   and after 14 days ( b ) . upon admission , the proportion of 
 children who had both whz of < 2.0   and igf - i z score < 2.0 was 39% 
 ( 23/59 ) , but 47% ( 28/59)a high proportion of children  had an igf - i z score of < 2.0 and whz of 2.0 , leading to a low correlation ( p = .69 ) .
after 14 days of nutritional 
 rehabilitation , the proportion of children who both had whz 2.0 and igf - i z 
 score of 2.0 increased 64% ( 38/59 ) , with highly significant correlation , as 
 reflected in figure 2(b ) . expressing the change in igf - i as 
 a difference in igf - i z scores or expressing the change in igf - i as a ratio 
 between igf - i value after 14 days and igf - i value upon admission
, there was 
 significant correlation with the increase in weight for height z - scores ( p < .01 
 on figure 3(a ) , and p < .01 on figure 3(b ) , resp . ) .
when using the international nchs 
 references for standardisation , there was an even higher correlation between 
 changes in igf - i and increases in weight for height z - scores , with r = 0.38 ( p < .003 ) 
 for differences in igf - i z scores , and r = 0.39 ( p < .003 ) for igf - i 
 absolute value ratios .
the objective of this study was to assess the relationship between 
 the igf - i values and the nutritional status of children hospitalised for 
 nutritional rehabilitation .
the study also sought to determine igf - i values as 
 forecast markers of mortality .
however , this last objective has not been 
 achieved because the care given to children admitted in rehabilitation helped 
 maintain a low mortality rate ( 1 
  in 68 children enrolled in the present study ) .
one of the limitations of our study is that the influence of factors 
 like infection was not taken in consideration .
the acute or chronic inflammatory 
 status could interfere on the rate of igf - i production .
it was shown that in 
 the experimental model , the stimulation of an inflammatory status by injection 
 of endotoxin leads 
 to a reduction of igf - i rates due to a resistance of the gh . during the sepsis , yumet et al . observed an 
 increase of gh with a reduction of 4050% of plasma igf - i in rat at 12 hours 
 and 24 hours after gh administration .
as far as the 
 evaluation of nutritional status is concerned , most of our patients suffered 
 from protein and energy malnutrition , with a few cases of kwashiorkor . using 
 nchs references , only two children had a whz 2.0 at admission , and 73 % 
 presented severe malnutrition ( whz < 3 ) .
when using local references , 56% of 
 children had a whz 2.0   at admission , and only 8% presented severe 
 malnutrition .
of course , malnutrition is better defined using nchs references 
 than local ones in a developing country such as burkina faso . but both references 
 were used to standardise nutritional status in our study because age and sex 
 reference values for igf - i were available at the local level only .
low igf - i values were observed in hospital children suffering 
 from protein and energy malnutrition [ 22 , 23 ] . but values 
 were lower in children suffering from marasmus than in children suffering from 
 kwashiorkor ; this suggests that the secretion of igf - i is closely related to 
 energy consumption than to protein consumption .
after the nutritional 
 rehabilitation of children admitted for protein and energy malnutrition , the 
 igf - i increased significantly in children that had kwashiorkor or marasmus .
but 
 the igf - i values after 14 days of nutritional rehabilitation were still lower 
 than in healthy children [ 22 , 23 ] .
there was no good agreement between the 
 igf - i values and the weight for height z - scores upon admission , owing to the 
 fact that a severe malnutrition was present in 73% of children and igf - i values 
 were too low to allow for correlation .
but after 14 days , we observed good 
 agreement between igf - i values and whz values ; the increase in igf - i also 
 paralleled the increase in weight for age z - scores .
these results suggest that 
 igf - i can be a dynamic indicator of nutritional recovery .
the study conducted in gabon   by zamboni et al .   reported igf - i values of 2.7  0.7
nmol / l upon admission of 9 children ( mean age : 
 17.2  5.4 months ) with kwashiorkor and the igf - i increased to 7.6  1.7 
nmol / l 
 after 48 weeks of 
 nutritional rehabilitation . in children with marasmus ( n = 13 ) ,
l on admission and 5.2  1.1  nmol / l after complete 
 nutritional rehabilitation .
.    found that igf - i 
 concentrations increased significantly after 10% weight recovery in 
 malnourished children ( n = 15 ) . on admission ,
the igf - i values were 3.5  1.0  ng / ml 
 and reached 5.9  2.0  ng / ml after 10% body weight gain .
palacio et al .   reported 
 that an increase in igf - i rates in malnourished children and its relation with 
 weight gain was observed during the rehabilitation .
this was   not observed for 
 markers such as prealbumin or serum albumin [ 23 , 24 ] .
observed that the caloric restriction induced a reduction in igf - i and igfbp-3 in adults and children . 

after nutritional rehabilitation , an increase was achieved , but without 
 reaching the initial rates . a reduction in igf - i rates
was also reported in 
 other types of malnutrition such as mental anorexia , coeliac , acquired immune deficiency syndrome ( aids ) , or crohn 's 
 disease [ 30 , 31 ] .
the ability of igf - i to follow variations of nutritional 
 status shows that it is potentially a good clinical marker to follow 
 nutritional rehabilitation in children with protein and energy malnutrition .
the 
 prognostic interest of igf - i remains to be demonstrated by the implementation 
 of studies which will measure the impact of igf - i on the mortality of children with 
 malnutrition in comparison with other markers of nutrition like albumin , 
 prealbumin , and rbp . if the prognostic interest of igf - i were proved , the use 
 of igf - i will be recommended .
the experience shows that the cost of technology 
 could be reduced 
 quickly with the development of the research .
 
 objective . to investigate the relationship between igf - i and the nutritional status of west - african children hospitalised for nutritional rehabilitation . 
 
 patients and methods . 
 a cohort study was performed in two centres for nutritional rehabilitation and education ( cren ) in burkina faso . 
 children were followed and the anthropometric data as well as the capillary blood samples were taken on the 7th and on the 14th days after their admission . 
 igf - i levels were determined from dried blood spots on filter paper on igf - i ria , after separation of the igf - i from its binding proteins , using sep - pak chromatography . 
 results . 
 a total of 59 children was included in the cohort . 
 the igf - i mean geometric values ( sd ) were 6.3 ( 1.4 ) 
 g / l on admission , 8.6 ( 1.8 ) g / l at day 7 and 13.6 ( 2.0 ) g / l at day 14 . 
 the differences between these values were statistically significant ( p < .001 ) . 
 there is a significant correlation between the changes of igf - i with the change of weight for height z - score ( p = .01 ) . 
 
 conclusion . 
 these results suggest that igf - i can be considered as a potential marker to follow the nutritional status of children admitted in hospital for protein and energy malnutrition . 
1. Introduction
2. Patients and Methods
3. Results
4. Discussion