EAL

Author and Year:

Manzoni P, Guardione R, et al 2013

PubMed ID:

Article Title:

Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: a multicenter randomized controlled trial.

Authors:

Manzoni P, Guardione R, Bonetti P, Priolo C, Maestri A, Mansoldo C, Mostert M, Anselmetti G, Sardei D, Bellettato M, Biban P, Farina D

Journal:

American Journal of Perinatology

Year of publication:

2013

Volume:

Issue:

Page numbers:

25-32

Study Design:

Randomized Controlled Trial

Risk of Bias Assessment Rating:

Positive

Inclusion Criteria:

Gestational age less than 32 weeks + 6 days born within the study period at one of the 3 NICUs of northern Italy.

Exclusion Criteria:

Parental refusal, admission after 48 hours of life, death prior to 72 hours of life, ophthalmologic disease already present at the time of randomization

Research Purpose:

The present study assesses the outcomes of preterm infants given supplemented carotenoids (lutein & zeaxanthin) during their stay in NICU as well as the safety and tolerability of these 2 supplements. Primary objective of the study was to evaluate the effectiveness of the lutein plus zeaxanthin supplementation, compared with placebo, in the prevention of threshold ROP, BPD, and NEC of surgical stage. Secondary objectives were the assessment of the incidence of ROP of all stages, NEC of all stages; of intestinal perforation; of late-onset sepsis; of mortality prior to discharge; of severe (grade 3 to 4) intraventricular hemorrhage; of need for transfusions; of liver failure defined as 3 times elevation of normal serum liver enzymes values.

Blinding efforts:

Infants were randomly allocated to one of two groups in a 1:1 ratio to receive carotenoids oral supplementation (group A) or placebo (group B). Randomization was stratified by center, and randomly permuted blocks of size 9 and 12 were used. The random allocation sequence was generated using ralloc.ado version 3.2.5 in Stata 9.2 (Stata-Corp, College Station, TX). The pharmacy at each center used these computer-generated randomization lists to form the two groups and prepared the drug doses in sealed opaque vials. Clinical and research staff remained unaware of study group assignments during the study.

Study Location:

S. Anna Hospital, Torino, Italy, Azienda Ospedaliera, Verona, Italy, City Hospital, Thiene, Italy

Source(s) of Funding:

SOOFT Italia

Please specify names of funders:

Partially funded by SOOFT Italia

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
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
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?	Yes
	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
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
	6.3.	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
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)?	Yes
	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