EAL

H/A: Diarrhea/Malabsorption (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To conduct a longitudinal investigation of infant gut function using the lactulose/mannitol dual sugar permeability test.

Inclusion Criteria:

None specifically mentioned.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

The last 238 of 632 mothers in a RCT were recruited for a study regarding their infant's health. HIV-infected women between 28 and 32 weeks gestation were recruited from the antenatal clinic at McCords Hospital, Durban, South Africa.

Design

A longitudinal analysis of a cohort of infants from a subset of mothers participating in a RCT.

Intervention

Mothers received 1.5mg retinyl palmitate and 30mg beta-carotene daily plus 60mg retinyl palmitate at delivery
Placebo group received identical placebo capsules at the same times
No women received antiretroviral therapy
When infants were one, six and 14 weeks of age, lactulose/mannitol dual sugar intestinal permeability tests were performed.

Statistical Analysis

Lactulose/mannitol ratios and mannitol concentrations were log-transformed to normalize distributions; therefore, geometric means are presented
Treatment groups at each individual time point were compared by ANOVA with and without particular covariates
Covariates offered into analyses were maternal plasma retinol and blood CD4 and CD8 counts at first measurement, infant birth weight, gestational age at birth, infant HIV infection status at 14 weeks, whether they were ever breastfed, current feeding, current weight and overall health since the last visit
Sample size was based on 30% mother-to-child HIV transmission, but transmission ended up only being 21%.

Data Collection Summary:

Timing of Measurements

Mothers were asked to return to follow-up clinics when their infants were one, six and 14 weeks old.

Dependent Variables

Infant gut function investigated using the lactulose/mannitol dual sugar permeability test
Weight
Data about feeding: Exclusive breastfeeding, no breast milk, breast milk plus water or mixed breast milk and other foods
Morbidity history: Overall morbidity since the previous visit and specific questions about the presence of diarrhea, fever, rapid breathing or other illness in the past three days.

Independent Variables

Infant HIV status determined through venous blood draws.

Control Variables

Maternal plasma retinol
Blood CD4 and CD8 counts at first measurement
Infant birth weight
Gestational age at birth
Infant HIV infection status at 14 weeks
Whether they were ever breastfed
Current feeding
Current weight
Overall health since the last visit.

Description of Actual Data Sample:

Initial N: 238 infants of HIV-infected South African women participating in a RCT
Attrition (final N): 238 infants; 26 HIV-infected infants from the vitamin A group and 29 in the placebo group
Age: Maternal age 26.2 years in vitamin A group, 26.8 years in placebo group
Anthropometrics: The vitamin A and placebo groups were largely comparable except for the higher blood CD8 counts among the vitamin A group women at first measurement and the greater proportion of female infants in the placebo group
Location: South Africa.

Summary of Results:

Maternal vitamin A supplementation did not significantly affect gut permeability in the group as a whole at any time.

By multiple regression analysis, HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both six and 14 weeks.

After controlling for birth weight, gestational age, current weight, feeding mode and recent morbidity, there was a trend toward an interaction between vitamin A supplementation and HIV infection (P=0.086) at 14 weeks.

Vitamin A made no difference to gut permeability of uninfected infants (lactulose/mannitol ratio for vitamin A group: 0.11, 95% CI 0.08, 0.15, N=73 and for placebo group; 0.09, 95% CI 0.06, 0.12, N=76), but largely prevented the increase in the ratio of HIV-infected infants (vitamin A group: 0.17, 95% CI 0.13, 0.23, N=23). Placebo group: 0.50, 95% CI 0.37, 0.68, N=20).

The effects on the lactulose/mannitol ratio were related to changes in lactulose, not mannitol, excretion.

Vitamin A supplementation was associated with significantly lower lactulose excretion at one and 14 weeks, suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions.

Author Conclusion:

Vitamin A supplementation (using both retinyl palmitate and beta-carotene) of HIV-infected pregnant women appeared to prevent the increased gut permeability seen in the subgroup of infants who themselves became HIV-infected. Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity.

Funding Source:

Industry:

Reviewer Comments:

Inclusion and exclusion criteria were not defined. Groups had statistically significant differences in terms of gender. Vitamin A status was not measured in the infants. The authors note that in a previous subsample from the main trial, plasma retinol did not differ between vitamin A-supplemented and placebo-treated mothers at any time up to six months of age. Authors also note the decreased study power due to lower-than-expected mother-to-child transmission rate.

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?		???
	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?	No
	2.2.	Were criteria applied equally to all study groups?	???
	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?	???
3.	Were study groups comparable?		???
	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?	No
	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?	N/A
	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?	Yes
	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?	Yes
	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?	Yes
	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?	Yes
	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?	Yes
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