EAL

H/A: Diarrhea/Malabsorption (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test the hypothesis that exclusive use of a completely elemental diet as primary nutritional therapy would allow faster, more complete recovery in children with persistent diarrhea-malnutrition syndrome, either through reduced intestinal inflammation or through improved absorption of nutrients.

Inclusion Criteria:

Children were recruited to the study if they presented with:

Malnutrition (defined using Wellcome classification)
Persistent diarrhea (defined as duration of 14 days or more)
Consent obtained from parents.

Exclusion Criteria:

Children were not recruited to the study if they had:

Measles
Chicken pox
Neurological disorder (e.g., cerebral palsy)
Still being exclusively breastfed.

Description of Study Protocol:

Recruitment

The study was conducted on the malnutrition ward of the University Teaching Hospital, Lusaka, during the period between 1998 and 2000. Children admitted to the ward are generally severely ill and a high proportion have HIV infection.

Design

Randomized controlled trial. Subjects were randomized to treatment groups by opening consecutive sealed envelopes.

Blinding Used

Single blind.

Intervention

Exclusive diet of amino acid-based elemental feed (amino acids, maltodextrin, safflower oil, refined coconut oil and soya oil, 70kcal per 100ml) compared with standard nutritional rehabilitation (based on skim milk, sugar, vegetable oil and soya) for persistent diarrhea-malnutrition syndrome, for four weeks
Intestinal and systemic infections were treated with routine therapies
All children received oral rehydration therapy.

Statistical Analysis

Primary endpoints in the analysis were weight gain, diarrhea and mortality
Secondary endpoints were developmental milestones achieved, activity and play, and laboratory indicators of severity of illness (hemoglobin, albumin)
Comparison of categorical variables used chi-square or Fisher's exact tests and continuous variables used the Kruskal-Wallis test.

Data Collection Summary:

Timing of Measurements

Measurements made over four-week period.

Dependent Variables

Weight gain
Recovery from diarrhea
Mortality.

Independent Variables

Exclusive diet of amino acid-based elemental feed compared with standard nutritional rehabilitation (based on skim milk and soya) for persistent diarrhea-malnutrition syndrome, for four weeks.

Description of Actual Data Sample:

Initial N: 200 children were randomized (100 in each group), 94 boys and 106 girls, 106 HIV seropositive, 90 HIV seronegative
Attrition (final N): 155 children completed therapy, 39 died, six were lost to follow-up
Age: Median age 17 months in elemental feed group, median age 18 months in control group
Anthropometrics: Groups were well matched. There were no significant differences between groups.
Location: Zambia.

Summary of Results:

Variables	Neocate Group	Control Group	Statistical Significance of Group Difference, P-value
Weight gain (kg) from admission	1.10 (0.55 to 1.55)	0.75 (0.2 to 1.3)	0.006
Weight gain (kg) from nadir	1.7 (1.2 to 2.0)	1.2 (0.6 to 1.7)	0.002
Increase in weight-for-age Z score from admission	0.83 (0.35 to 1.22)	0.43 (0 to 0.9)	0.018
Increase in weight-for-age Z-score from nadir	1.23 (0.89 to 1.57)	0.87 (0.47 to 1.25)	0.002
Increase in weight-for-height Z-score from admission	1.28 (0.52 to 1.88)	0.56 (0 to 1.15)	<0.001
Increase in weight-for-height Z-score from nadir	1.77 (1.30 to 2.26)	1.23 (0.59 to 1.70)	<0.001
Increase in Z-score from nadir in HIV-seropositive children (weight-for-age)	1.2 (0.8 to 1.5)	0.70 (0.4 to 1.2)	0.007
Increase in Z-score from nadir in HIV-seropositive children (weight-for-height)	1.8 (1.1 to 2.3)	0.8 (0.4 to 1.6)	<0.001
Increase in Z-score from nadir in HIV-seronegative children (weight-for-age)	1.29 (0.98 to 1.57)	0.95 (0.5 to 1.45)	0.01
Increase in Z-score from nadir in HIV-seronegative children (weight-for-height)	1.82 (1.47 to 2.38)	1.43 (0.81 to 1.86)	0.009

Other Findings

At randomization, the children were severely malnourished: Median baseline weight-for-age Z-score was -4.0 (interquartile range, IQR -4.4, -3.5). 9% were underweight, 23% had marasmus, 47% had kwashiorkor, and 21% had marasmic-kwashiorkor.

Weight gain was greater in the amino acid-based elemental feed group (median gain in weight-for-age Z-score was 1.23, interquartile range 0.89 to 1.57) compared with the control group (0.87, interquartile range 0.47 to 1.25, P=0.002), although calorie intakes were higher in the control group.

The increase in hemoglobin concentration was also greater in the amino acid-based elemental feed group (0.8g per dL, interquartile range 0 to 1.8) than in the control group (0.3, interquartile range -0.6, 1.6; P=0.04).

Diarrhea frequency and global recovery scores improved equally in both treatment groups and mortality did not differ.

Death was more likely in HIV-seropositive children, in children with marasmus and children with cryptosporidiosis.

Author Conclusion:

Exclusive use of an amino acid-based elemental diet for four weeks was associated with a significantly improved weight gain in Zambian children with severe persistent diarrhea-malnutrition syndrome.

Funding Source:

University/Hospital:

University Teaching Hospital, Lusaka, Zambia

Reviewer Comments:

Authors note that there may have been no effect on diarrhea due to the following:

Children on the ward appeared to experience continuing intestinal infections or new infections with enteropathogens
Period of treatment may have been insufficient to permit complete recovery of small intestinal mucosa
Stool volumes were not measured; recording only frequency may obscure differences between groups
Elemental formulas contain glucose polymers, which may lead to an osmotic purgative effect.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes