# Insulin Growth Factor-I in Protein-Energy  Malnutrition  during Rehabilitation in Two Nutritional Rehabilitation Centres in Burkina Faso

Authors: S. Kouanda; B. Doulougou; V. De Coninck; L. Habimana; B. Sondo; R. Tonglet; J. M. Ketelslegers; A. Robert
Journal: Journal of Tropical Medicine
 (2009)

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## Abstract

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)
μg/L on admission, 8.6 (1.8) μg/L at day 7 and 13.6 (2.0) μg/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.


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## Body

## 1. Introduction

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 [1]. 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 [2].The usual signs of children
malnutrition are clinical signs and anthropometric measures. 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 [3–5].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
[8–10], but the highest concentrations of IGF-I are observed in blood [11, 12].
IGF-I is also synthesized by several tissues [13, 14].Many factors intervene in the regulation of the
IGF-I but the most important are growth hormone (GH), insulin, and nutritional
status [15].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 [18].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 [19–21]. 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 [22–24].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.


## 2. Patients and Methods

The study of protocol was reviewed and approved by the Ethics
Committee for Research in Health of Burkina Faso.


### 2.1. Subjects

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). Then, a capillary blood
sample was taken from the child finger. 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.The children admitted for malnutrition were well-cared for. 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.
Table1 shows the sociodemographic characteristics of the 59 children. 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. The average
maternal breast-feeding duration was 9±3 months.Table 1
Social and demographic
characteristics of the household and the children admitted in two the
nutritional rehabilitation centres in Burkina Faso.
Social and demographic
characteristicsNMean± SD or %Gender of the childrenBoys3762.7Girls2237.3Mean age of children (months)5914± 6Age categories of children
(months)0–546.86–11610.212–234576.324–3546.8Age of  the mothers5627.3± 6.1Age categories (years)≤19610.720–241323.225–291526.830–341425.035–39814.3Scholarship of the
motherYes23.4No5796.6Scholarship of the
fatherYes711.9No5288.1Employment of the motherHousewife5593.2Independents/employees46.8Employment of the fatherFarmer5288.1Independent/employees711.9


### 2.2. Evaluation of Nutritional Status

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 [25]
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
[25].


### 2.3. Blood Sampling

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 5–10 minutes at
ambient temperature (30–35°C) and were
kept at 4°C for 1–2 weeks before
processing.All filter paper samples were transferred for analyses to the Unit
of Diabetes and Nutrition, Belgium. Samples were collected between October 2005
and May 2006.


### 2.4. Sample Processing and IGF-I Assay

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 [25].The extraction recovery of IGF-I was
of84.4±3.4%. IGF-I was determined by RIA, using the antiserum at a 1/15000
dilution, and I125- 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
[25].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 [25].


### 2.5. Statistical Methods

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. Statistical analyses were performed using SPSS 15.0 software.


### 3. Results

### 3.1. Evaluation of the Nutritional Status and IGF-I Values of Children upon Admission and during Rehabilitation

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. Three children presented
oedemas at admission and their WHZ was lower than −2.0.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. The proportion of IGF-I Z-score of <−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.Figure 1
Increase in IGF-I during
nutritional rehabilitation in 59 children admitted for malnutrition in Burkina
Faso.During nutritional rehabilitation, IGF-I increased from 6.36 (1.40)μg/L (geometric mean and SD) upon admission, to 8.59
(1.81) μg/L after one week, and to 13.65 (2.0) μg/L after two weeks of
nutritional rehabilitation (Figure 1).Table2 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.Table 2
Weight for height and IGF-I
increase during nutritional rehabilitation, in 59 malnourished children in
Burkina Faso.
Absolute
measurementsWeight (kg)IGF-I ratio to admissionnMean
± SDn[95% confidence interval]Admission595.520±1.003591After 7 days595.943±1.022591.59 [1.29; 1.89]After 14 days596.362±1.143592.52 [2.10; 2.94]Age- and sex-adjusted* weight for
height Z-scorenMean± SDAdmission59−3.56±0.85After 7 days59−3.05±0.79After 14 days59−2.44±1.06Age- and sex-adjusted** weight
for height Z-scoreIGF-I Z-scorenMean
± SDnMean
± SDAdmission59−1.87±0.8959−2.55±0.80After 7 days59−1.45±0.9059−2.03±1.22After 14 days59−1.07±1.0259−1.16±1.39Reference  values from Burkina Faso.International**  reference values.After 7 days of nutritional rehabilitation, IGF-I was multiplied by
1.587, as a significant increase of 58.7% on average. After 14 days, IGF-I
increase was about 151.8% on average.There was a significant increase  in log-scaled IGF-I, as well as in
IGF-I Z-scores  one week after admission (pairedt-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 Figure2, upon admission  (a)  and after 14 days (b).Relationship between age- and sex-adjusted IGF-I Z-score and weight
for height Z-score with Burkina Faso data as references, at admission and after
14 days of nutritional rehabilitation in 59-malnourished children from Burkina
Faso.
(a)(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.).Relationship between the
change in IGF-I expressed as an increase in Z-score (a) or as a ratio
in absolute measurements (b) and the change in age- and sex-adjusted
weight for height Z-score using Burkina Faso data as references, after 14 days
of nutritional rehabilitation.
(a)(b)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, withr=0.38 (P<.003)
for differences in IGF-I Z scores, and r=0.39 (P<.003) for IGF-I
absolute value ratios.


## 2.1. Subjects

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). Then, a capillary blood
sample was taken from the child finger. 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.The children admitted for malnutrition were well-cared for. 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.
Table1 shows the sociodemographic characteristics of the 59 children. 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. The average
maternal breast-feeding duration was 9±3 months.Table 1
Social and demographic
characteristics of the household and the children admitted in two the
nutritional rehabilitation centres in Burkina Faso.
Social and demographic
characteristicsNMean± SD or %Gender of the childrenBoys3762.7Girls2237.3Mean age of children (months)5914± 6Age categories of children
(months)0–546.86–11610.212–234576.324–3546.8Age of  the mothers5627.3± 6.1Age categories (years)≤19610.720–241323.225–291526.830–341425.035–39814.3Scholarship of the
motherYes23.4No5796.6Scholarship of the
fatherYes711.9No5288.1Employment of the motherHousewife5593.2Independents/employees46.8Employment of the fatherFarmer5288.1Independent/employees711.9


## 2.2. Evaluation of Nutritional Status

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 [25]
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
[25].


## 2.3. Blood Sampling

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 5–10 minutes at
ambient temperature (30–35°C) and were
kept at 4°C for 1–2 weeks before
processing.All filter paper samples were transferred for analyses to the Unit
of Diabetes and Nutrition, Belgium. Samples were collected between October 2005
and May 2006.


## 2.4. Sample Processing and IGF-I Assay

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 [25].The extraction recovery of IGF-I was
of84.4±3.4%. IGF-I was determined by RIA, using the antiserum at a 1/15000
dilution, and I125- 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
[25].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 [25].


## 2.5. Statistical Methods

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. Statistical analyses were performed using SPSS 15.0 software.


## 3. Results

## 3.1. Evaluation of the Nutritional Status and IGF-I Values of Children upon Admission and during Rehabilitation

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. Three children presented
oedemas at admission and their WHZ was lower than −2.0.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. The proportion of IGF-I Z-score of <−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.Figure 1
Increase in IGF-I during
nutritional rehabilitation in 59 children admitted for malnutrition in Burkina
Faso.During nutritional rehabilitation, IGF-I increased from 6.36 (1.40)μg/L (geometric mean and SD) upon admission, to 8.59
(1.81) μg/L after one week, and to 13.65 (2.0) μg/L after two weeks of
nutritional rehabilitation (Figure 1).Table2 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.Table 2
Weight for height and IGF-I
increase during nutritional rehabilitation, in 59 malnourished children in
Burkina Faso.
Absolute
measurementsWeight (kg)IGF-I ratio to admissionnMean
± SDn[95% confidence interval]Admission595.520±1.003591After 7 days595.943±1.022591.59 [1.29; 1.89]After 14 days596.362±1.143592.52 [2.10; 2.94]Age- and sex-adjusted* weight for
height Z-scorenMean± SDAdmission59−3.56±0.85After 7 days59−3.05±0.79After 14 days59−2.44±1.06Age- and sex-adjusted** weight
for height Z-scoreIGF-I Z-scorenMean
± SDnMean
± SDAdmission59−1.87±0.8959−2.55±0.80After 7 days59−1.45±0.9059−2.03±1.22After 14 days59−1.07±1.0259−1.16±1.39Reference  values from Burkina Faso.International**  reference values.After 7 days of nutritional rehabilitation, IGF-I was multiplied by
1.587, as a significant increase of 58.7% on average. After 14 days, IGF-I
increase was about 151.8% on average.There was a significant increase  in log-scaled IGF-I, as well as in
IGF-I Z-scores  one week after admission (pairedt-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 Figure2, upon admission  (a)  and after 14 days (b).Relationship between age- and sex-adjusted IGF-I Z-score and weight
for height Z-score with Burkina Faso data as references, at admission and after
14 days of nutritional rehabilitation in 59-malnourished children from Burkina
Faso.
(a)(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.).Relationship between the
change in IGF-I expressed as an increase in Z-score (a) or as a ratio
in absolute measurements (b) and the change in age- and sex-adjusted
weight for height Z-score using Burkina Faso data as references, after 14 days
of nutritional rehabilitation.
(a)(b)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, withr=0.38 (P<.003)
for differences in IGF-I Z scores, and r=0.39 (P<.003) for IGF-I
absolute value ratios.


## 4. Discussion

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 [20]. During the sepsis, Yumet et al. observed an
increase of GH with a reduction of 40–50% of plasma IGF-I in rat at 12 hours
and 24 hours after GH administration [28].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.We observed variations of IGF-I with respect to the nutritional
rehabilitation. 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 [22]. 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. [22] 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 4–8 weeks of
nutritional rehabilitation. In children with marasmus (n = 13), the values of
IGF-I were 1.6±0.4 nmol/L on admission and 5.2±1.1 nmol/L after complete
nutritional rehabilitation [22].Palacio et al. [24]  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 [22].Bhutta et al. [23]  and Palacio et al. [24] 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].Smith et al. [29] 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.



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*Source: 832589-2009-03-17.xml*