VLBW: Mothers Milk vs Exclusive Formula (2020)

Author and Year:
Manzoni P, Stolfi I, et al 2013
PubMed ID:
Article Title:
Human milk feeding prevents retinopathy of prematurity (ROP) in preterm VLBW neonates.
Manzoni P,Stolfi I, Pedicino R, Vagnarelli F, Mosca F, Pugni L, Bollani L, Pozzi M, Gomez K, Tzialla C, Borghesi A, Decembrino L, Mostert M, Latino M, Priolo C, Galletto P, Gallo E, Rizzollo S, Tavella E, Luparia M, Corona G, Barberi I, Tridapalli E, Faldella G, Vetrano G, Memo L, Saia O, Bordignon L, Messner H, Cattani S, Della Casa E, Laforgia N, Quercia M, Romeo M, Betta P, Rinaldi M, Magaldi R, Maule M, Stronati M, Farina D
Early Human Development
Year of publication:
Page numbers:
Study Design:
Retrospective Cohort Study
Risk of Bias Assessment Rating:
Inclusion Criteria:
All infants from two previously conducted randomized control trials looking at the effectiveness of fluconzole prophylaxes and bovine lactoferrin supplementation in prevention of invasive fungal infection and of late-onset sepsis, respectively, in preterm very low birth weight infants prior to discharge from the NICU were eligible for this secondary data analysis. Inclusion criteria from original studies: Very-low-birth-weight neonates who were admitted to the NICU before day 3 of life were eligible for enrollment.
Exclusion Criteria:
Exclusion criteria for this study were incomplete data on ophtalmological follow-up, or on the type of nutrition and milk intake during their stay in the NICU. Exclusion criteria for fluconazole study: a lack of parental consent and liver failure (levels of aspartate aminotransferase and alanine aminotransferase that were three times the upper limit of the range of normal values). Exclusion criteria for bovine lactoferrin study: parental consent lacking/refused, ongoing antifungal prophylaxis, early onset sepsis (before the third day of life), or liver failure (aspartate aminotransferase, alanine aminotransferase, ?-glutamyl transferase, and direct bilirubin serum values 3-fold higher than reference range).
Research Purpose:
In the present study, we aimed to test the hypothesis that exclusive feeding with fresh human, maternal milk may prevent retinopathy of prematurity (ROP) of any stage in very low birth weight (VLBW) neonates, compared to preterm formula feeding.
Blinding efforts:
Ophtalmologists were always unaware of treatment assignment as well as of type of feeding and intakes of the enrolled infants.
Study Location:
Source(s) of Funding:
Please specify names of funders:
This study is a secondary analysis of the data from two trials that were partially supported by grants from Pfizer Italia, and from Dicofarm SpA, respectively.
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? No
  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? No
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) N/A
  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.) N/A
  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? Yes
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  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
5. Was blinding used to prevent introduction of bias? 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.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? 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? N/A
  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? No
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? No
  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