Effect of Colostrum on Mucosal Immunity in Very Low Birth Weight (VLBWs) Premature Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Colostrum on Mucosal Immunity in Very Low Birth Weight (VLBWs) Premature Infants (NCT01776268), a randomized na study. The primary outcome is Concentration of APPs Before Oral Priming.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. It lists an enrollment of 99 and a completed status. The trial's phase is listed as not applicable. Vanderbilt University Medical Center is identified as the sponsor.

The intervention was oral priming with the mother's own colostrum. The protocol description specifies 0.1 mL to each cheek every 6 hours for 5 days, beginning when colostrum is available from the mother. It says this timing was independent of when enteral feedings began. The comparison group received no oral priming. Details of any other care shared by the groups are not reported in the registry record.

The registry describes the study objective as measuring antimicrobial proteins and peptides in colostrum, human milk, and preterm infant saliva, and testing hypotheses about changes over time, concentrations in colostrum compared with human milk, and saliva concentrations in infants who did or did not receive oral colostrum. The stated primary outcome, however, is a saliva concentration measurement before oral priming on days 1-2 of life. These descriptions establish the biological focus but do not provide results for the broader objectives.

The registry record does not report details of sequence generation, concealment of allocation, or procedures used to maintain the assigned intervention. It also does not describe whether participants could cross over between groups, how adherence was assessed, or how deviations from the assigned regimen were handled. The absence of masking is recorded, but who knew the assignment and how that knowledge might have affected measurement or conduct are not specified. The study start is listed as 2013-02 and primary completion as 2015-03.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Concentration of APPs Before Oral Priming, measured over days 1-2 of life.

The primary outcome is titled “Concentration of APPs Before Oral Priming.” It refers to measuring antimicrobial proteins and peptides in saliva before the oral priming intervention, with sampling described on days 1-2 of life. The unit is femtomole (fmol); the planned summary is a mean with an inter-quartile range. The registry description says investigators were assessing saliva for a change in antimicrobial protein concentration.

These measurements address a biological question: whether concentrations of immune-related antimicrobial substances in saliva differ in the context of oral exposure to colostrum. As a general statistical point, a concentration endpoint can help characterize a biological response directly, while remaining distinct from clinical outcomes such as infection. A change in a measured concentration alone would not establish a change in infection risk or other health outcomes.

The registry does not provide numerical values for the primary outcome, group-specific summaries, or an estimated treatment contrast. It also does not identify the specific APP measures in the primary outcome description. The outcome is noted as having several categories or time points and is not reduced to one comparison. Consequently, the posted record does not support a quantitative interpretation of the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies randomization, no masking, and a parallel-group model. It does not report the detailed statistical methods used to analyze the outcomes. The concepts below are general explanations of how such methods are often interpreted, not claims about the methods used in this trial.

What does random assignment contribute?

In general, random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics at the start of a trial. This supports a causal interpretation when the allocation process is implemented as intended and subsequent analysis preserves the comparison created by assignment. The registry record does not describe the randomization sequence, allocation concealment, or the analysis population, so those implementation details cannot be assessed from the record.

What does no masking mean for interpretation?

The record lists masking as none. In general, lack of masking means treatment assignment is not concealed through a blinding procedure, but the registry does not say which individuals knew assignments. Knowledge of assignment can influence behavior, co-interventions, or outcome assessment, depending on the setting and how outcomes are measured. The record does not describe safeguards against such influences or whether the laboratory assessment was masked.

How should a mean and inter-quartile range be understood?

The primary outcome is described using a mean and inter-quartile range, with concentrations expressed in fmol. In general, the mean represents the arithmetic average of the measured values. The inter-quartile range describes the spread of the middle portion of a distribution and is less sensitive to extreme observations than the range from the smallest to the largest value. Reporting both can convey a measure of average concentration alongside information about dispersion. The registry record does not give either summary for the trial's groups, so these measures cannot be interpreted numerically for this study.

Why does the endpoint structure matter?

The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. In general, multiple outcomes or repeated measurements can create several possible comparisons. The interpretation depends on which comparisons were specified in advance, how measurements over time were handled, and whether multiplicity was addressed. These details are not reported in the registry record. A single summary result would not necessarily capture patterns across all categories or time points, while selecting a result after inspecting multiple comparisons can make nominal statistical evidence harder to interpret.

What would an effect estimate and confidence interval show?

In general, an effect estimate describes the size and direction of a contrast between groups. A confidence interval expresses uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but precision is not the same as clinical importance. The registry record does not report an effect estimate or confidence interval for the primary outcome. It also does not report a p-value, so neither the magnitude nor the statistical uncertainty of the primary comparison can be evaluated.

What does the absence of a posted analysis mean?

The registry lists zero analyses. In general, a registry may describe a trial without posting outcome analyses; the absence of analysis results in the record does not by itself show whether investigators performed analyses elsewhere. Here, the record does not specify the statistical model, covariates, handling of repeated measures, missing-data approach, or criteria for including participants in each analysis. Those choices can affect estimates and their uncertainty, so the registry description is not enough to reproduce or appraise an analysis.

How should any planning illustration be read?

As a general principle, sample-size calculations are planning tools, not estimates of treatment effect. The record's stated assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect, and distinguishes between total events for time-to-event outcomes and participants per arm for other outcomes. Such assumptions do not reveal the trial's original design rationale. The registry record does not report the protocol's sample-size justification, and planning illustrations must not be interpreted as observed power or as evidence that a treatment effect was present.

Because outcome estimates are not reported, recalculating an unadjusted comparison from summary statistics is not possible from the registry record. No numerical treatment effect, precision measure, or statistical significance assessment should be inferred from the design description or adverse-event counts.

10. Multiplicity, Missing Data and Analysis Populations

The record states that the primary outcome has several categories or time points and is not reduced to one comparison. It does not identify the number or names of those categories or time points in the posted results, and it does not provide a set of outcome estimates to compare. The registry record also does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment procedure, or distinction between confirmatory and exploratory comparisons.

As a general statistical matter, examining multiple outcomes, time points, or group contrasts can increase the chance that at least one result appears unusual by chance. The effect on interpretation depends on the comparisons planned and the methods used to account for them. Without the prespecified analysis plan and the complete set of results, readers cannot determine how multiplicity was handled or whether a selected comparison represents the intended primary question.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how missing saliva samples or unavailable measurements were treated, whether participants were analyzed according to randomized assignment, or whether any per-protocol or other population was used. It also does not give the number of participants contributing primary outcome measurements in either group. These details matter because incomplete measurements or exclusions can affect both the estimates and their precision.

The record lists enrollment and adverse-event counts, but those figures do not establish how many participants contributed data to the primary endpoint. Nor do they identify reasons for missing outcome measurements. The posted record therefore does not permit assessment of missingness, population definitions, or the robustness of any primary analysis.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: death (2.1%).

The registry lists one serious adverse event among 48 participants at risk in the oral-priming group and zero among 51 participants at risk in the no-oral-priming group. It lists zero other adverse events in both groups. Death is the serious-event term reported, with a percentage of 2.1% listed for that term. The group-level death counts are one in the oral-priming group and zero in the no-oral-priming group.

These are descriptive registry counts, not an estimate of a causal effect. A difference in event counts does not by itself show that the intervention caused an event or that the groups had different underlying risks. The record does not report a statistical comparison, an adjudication process, or further detail about the circumstances or timing of the event. The figures should therefore be read as the safety information posted in the registry, not as a definitive comparison of safety between groups.

The registry record also does not provide a broader account of adverse-event definitions, severity grading, or follow-up duration for these events. The serious-event counts should be considered separately from the unreported primary saliva concentration results.

12. What the Result Does, and Does Not, Mean

This record describes a randomized study of oral colostrum priming in very premature infants, with an interest in antimicrobial proteins and peptides measured in saliva. The primary outcome is described as a concentration measurement before priming on days 1-2 of life. The registry also lays out broader hypotheses about changes over time and comparisons involving colostrum, human milk, and saliva.

The record does not report numerical results for the primary outcome, group contrasts, confidence intervals, or p-values. It therefore cannot show how salivary APP concentrations differed between the groups, how large any difference was, or how precisely it was estimated. The absence of a posted result is not evidence of no effect, nor is it evidence that an effect was present. It indicates that the relevant outcome analysis is not reported in the registry record.

Even if a concentration difference were reported, it would answer a biological measurement question rather than directly establish an effect on infection or other clinical outcomes. As a general point, an immune-related biomarker can provide information about a proposed biological pathway, but a biomarker result alone does not demonstrate a change in clinical outcomes. The registry's background discusses infection and the potential protective properties of human milk; the available primary outcome description does not report infection results.

The serious-event information is limited to the listed counts and term. Those observations should not be interpreted as proof of causation or as a comprehensive safety assessment. Likewise, the completed status and enrollment figure describe trial conduct, not the outcome of the primary comparison.

The appropriate statistical conclusion is therefore limited: the registry documents the question, randomized design, intervention description, and some adverse-event counts, but does not report the numerical primary outcome or its analysis. Any claim about the direction, magnitude, or certainty of an effect on saliva concentrations would go beyond the posted results.

13. Why This Trial Matters Statistically

The trial illustrates why an outcome definition and a result are different kinds of information. The registry specifies a biological measurement, its unit, summary format, and timing, but does not provide the concentration values or an estimated contrast. Without those estimates, a reader cannot judge the magnitude or precision of the comparison, even when the trial's intervention and randomization are described.

It also highlights how outcome structure affects interpretation. The record says the primary outcome involves several categories or time points and is not reduced to one comparison. Repeated measurements and multiple categories can raise questions about which comparison is primary, how measurements are modeled, and how multiplicity is handled. The statistical plan needed to answer those questions is not reported in the registry record.

The distinction between a biological endpoint and a clinical outcome is also central. Measuring APP concentrations can address a proposed immune mechanism, but it is not equivalent to measuring infection outcomes. The registry's background gives the biological motivation; the posted primary outcome does not show whether any clinical outcome changed.

Finally, the record demonstrates the limits of reading design and safety counts in isolation. Randomization is an important design feature, and the adverse-event counts are useful descriptive information, but neither supplies the missing primary outcome estimates. For clinical researchers and statisticians, transparent reporting of analysis populations, missing-data handling, prespecified comparisons, effect estimates, and uncertainty is needed to connect a trial's question to an interpretable result.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for statistical interpretation is that numerical results for the primary outcome are not reported in the registry record. There are no group-specific concentrations, treatment-effect estimates, confidence intervals, or p-values available to assess direction, magnitude, or precision. The record also lists zero analyses, so it does not permit evaluation of the methods actually used or reproduction of a primary comparison.

The primary outcome is described as involving several categories or time points and is not reduced to one comparison. The record does not specify the categories, identify how repeated measurements were handled, or state which comparisons were prespecified. The statistical plan, multiplicity approach, and any distinction between confirmatory and exploratory analyses are not reported in the registry record.

Details needed to assess the analysis population are also absent. The record does not describe missing saliva measurements, exclusions, adherence, crossovers, or how deviations from the assigned intervention were handled. It does not give the number of participants contributing primary outcome data in each arm. Although the trial is listed as randomized and unmasked, the record does not provide details of sequence generation, allocation concealment, or whether laboratory outcome assessment was masked.

The registry describes the intervention and comparator but does not report further details about shared care or the handling of colostrum availability. The serious-event information is limited to the posted counts and term; further detail about event ascertainment and timing is not reported. These limitations restrict both assessment of the primary biological question and interpretation of the safety observations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Colostrum on Mucosal Immunity in Very Low Birth Weight (VLBWs) Premature Infants — NCT01776268.
• Registry record last updated 2017-07-07; status last verified 2017-06.
• Results first posted 2017-07-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, randomized, parallel-group trial with no masking and an enrollment of 99. It compares oral priming with the mother's own colostrum against no oral priming in very premature infants. The regimen is described as 0.1 mL to each cheek every 6 hours for 5 days, starting when colostrum is available from the mother.

The primary outcome is concentration of APPs before oral priming, measured in saliva on days 1-2 of life and summarized as a mean with an inter-quartile range in fmol. Numerical primary outcome results and statistical analyses are not reported in the registry record. The record flags the outcome as involving several categories or time points and not reduced to one comparison.

The registry lists one serious event and one death in the oral-priming group, and none in the no-oral-priming group. These counts are descriptive and do not establish causation.