EAL

VLBW: Type of Fat (2020)

Author and Year:

Makrides M, Gibson R, et al. 2009

PubMed ID:

19141765

Article Title:

Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial.

Authors:

Makrides M, Gibson R, McPhee A, Collins C, Davis P, Doyle L, Simmer K, Colditz P, Morris S, Smithers L, Willson K, Ryan P

Journal:

The Journal of the American Medical Association

Year of publication:

2009

Volume:

301

Issue:

Page numbers:

175-82

Study Design:

Randomized Controlled Trial

Risk of Bias Assessment Rating:

Positive

Inclusion Criteria:

Infants born before 33 weeks’ gestation were eligible.

Exclusion Criteria:

Infants were excluded if they had major congenital or chromosomal abnormalities, were from a multiple birth in which not all live-born infants were eligible, or were in other trials of fatty acid supplementation. Lactating mothers in whom tuna oil was contraindicated (for example, because of bleeding disorders or therapy with anticoagulants) were also excluded.

Research Purpose:

We conducted a randomized controlled trial to study the long-term efficacy of high-dose dietary DHA in preterm infants. The intervention was designed to reflect the feeding practices of most neonatal units, where expressed breast milk is the nutrition of choice. Lactating women received tuna oil supplements to increase the DHA concentration of their milk,22 and preterm infant formula with a matching DHA composition was used if there was insufficient breast milk. We hypothesized that high-dose DHA supplementation would improve developmental quotient at 18 months’ corrected age.

Blinding efforts:

Double-blind. To facilitate blinding, each treatment group was separately color coded into 2 groups. All capsules were similar in size, shape, and color and were donated by Clover Corporation, Sydney, Australia. If formula was required in the pilot phase, 2 drops of oil from capsules in matching color-coded containers were added to each 90-mL jar of formula. For the remainder of the trial, Mead Johnson Nutritionals, Evansville, Indiana, specifically manufactured ready-to-feed preterm formula to trial specifications and packaged the formula according to the color codes. Parents, clinicians, and all research personnel were blinded to participant study group.

Study Location:

Australia

Source(s) of Funding:

Government, Industry, Not-for-profit

Please specify names of funders:

The Australian National Health and Medical Research Council (grant 250322) and by the Channel 7 Children’s Research Foundation of South Australia Inc. Treatment and placebo capsules were donated by Clover Corp and infant formula was donated by Mead Johnson Nutritionals and Nutricia Australasia.

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?	???
	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?	No
	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?	???
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
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