VLBW: Breast Milk Fortifier Type (2020)

Author and Year:
Porcelli P, Schanler R, et al. 2000
PubMed ID:
Article Title:
Growth in human milk-fed very low birth weight infants receiving a new human milk fortifier.
Porcelli P, Schanler R, Greer F, Chan G, Gross S, Mehta N, Spear M, Kerner J, Euler A
Annals of Nutrition and Metabolism
Year of publication:
Page numbers:
Study Design:
Randomized Controlled Trial
Risk of Bias Assessment Rating:
Inclusion Criteria:
Very low birth weight (VLBW) infants were enrolled in the study if they were medically stable; had a gestational age between 25 and 32 weeks, a birth weight between 600 and 1,500 g, were appropriate for gestational age, had an enteral intake of 150 ml/kg/day of human milk, and were being fed human milk exclusively.
Exclusion Criteria:
Infants were excluded for the following reasons: receiving parenteral nutrition or infant formulas; significant acute or chronic illnesses; systemic infections; major congenital mal- formations; receiving corticosteroids, diuretics, or mother’s milk that was ! 14 days postpartum.
Research Purpose:
Efforts are currently underway to develop new human milk fortifiers that provide more favorable nutritional support for growth and bone mineralization in the VLBW infant. A new powdered human milk fortifier (HMF) was developed that we hypothesized would allow better growth than a currently available reference HMF. This clinical trial was designed to evaluate the efficacy and safety of this new HMF, in comparison with a reference fortifier, in the growth and nutritional status of VLBW infants.
Blinding efforts:
The study was single-blinded. The design was not double-blind because the reference HMF required 4 sachets to be added to 100 ml of human milk to provide the same caloric density as 2 sachets of the new HMF. To have blinded the latter would have required a placebo in 2 sachets, which would have changed the caloric density, and thereby invalidated all comparisons of growth between the study groups, besides introducing an additional risk and, therefore, invalidating safety comparisons between the study groups if lactose, starch, or another substance was chosen as the placebo. Repackaging the reference HMF so as to have it in only 2 sachets was logistically impossible because of the loss incurred when sachets were opened, emptied, and then their contents repacked into new sachets. The investigators were blinded as to which HMF the infants were receiving. All infants were identified by only a randomization number.
Study Location:
United States
Source(s) of Funding:
Please specify names of funders:
Wyeth Nutritionals International (Pharmaceutical Company), Philadelphia, Pa., USA
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? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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) No
  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? ???
  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? No
  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? 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? ???
  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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  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? No
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???