Multisensory Early Oral Administration of Human Milk in Preterm Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multisensory Early Oral Administration of Human Milk in Preterm Infants (NCT06230848), a randomized na study. The primary outcome is Feasibility of Intervention.

2. Clinical Question

The central question is whether the M-MILK intervention can be delivered to preterm infants often enough to meet a prespecified feasibility threshold during their NICU stay. The posted primary outcome counts participants in the intervention arm who received M-MILK in at least 50% of their scheduled administrations. The registry also lists secondary outcomes concerning parent stress and discharge readiness, breastmilk pumping and breastfeeding, and maternal postnatal depression.

This is a feasibility question, not a direct test of whether M-MILK reduces stress or changes infant development. The trial description says the pilot aims to assess feasibility and acceptability, recruitment and retention, and to obtain information for sample-size estimation. The registry record does not report a primary efficacy comparison between M-MILK and control.

3. Trial Design

The study is listed as a completed randomized controlled pilot study with a parallel-group design and no masking. The registry lists the phase as NA and enrollment as 14. The study start date is 2023-10-23, and the primary completion date is 2024-10-23. The sponsor is Loyola University.

The intervention is M-MILK, classified in the record as an “OTHER” intervention. Infants assigned to M-MILK receive the intervention in addition to standard of care. The control arm description says that infants receive standard of care; the posted arm title is Attention Control. The registry does not give further details on allocation procedures, sequence generation, concealment, or what the Attention Control label entails. Although allocation is identified as randomized, the method used to randomize participants is not reported in the registry record.

The study is described as a pilot intended to assess feasibility and acceptability, recruitment and retention, and to obtain information for sample-size estimation. Its stated future purpose is to inform an R01 randomized controlled trial examining M-MILK’s efficacy in relation to early-life toxic stress in preterm infants. The registry record does not report a protocol-based efficacy objective for this pilot or a statistical analysis plan for a treatment comparison.

The registry lists 19 outcome measures, including the primary feasibility outcome and secondary outcomes related to parent stressor and discharge readiness scores, breastmilk pumping and breastfeeding rates, and maternal Edinburgh Postnatal Depression Scale score. The posted primary result reports 10 participants in the M-MILK arm and a feasibility count of 7. The primary outcome is assessed only in the intervention arm, so the control arm’s posted zero for this outcome is not a control-group feasibility result. The record does not explain the difference between overall enrollment of 14 and the number assessed for this primary outcome.

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

Analysis population for the primary outcome, as defined in the registry: Only the intervention arm is assessed for feasibility.

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.

Population: Enrolled and completed baseline assessments

6. Primary Endpoint

The registry lists the primary outcome as Feasibility of Intervention, measured over At the time of discharge from NICU, which is typically 10 to 16 weeks from birth..

The primary endpoint is titled “Feasibility of Intervention” and is measured as a count of participants. It counts M-MILK participants who received the intervention in at least 50% of their scheduled M-MILK administrations. The registry’s operational definition says implementation is considered feasible if nurses or parents deliver M-MILK after every hands-on care and during the beginning of a full gavage feeding at least 50% of the time. The assessment is made at NICU discharge, typically 10 to 16 weeks from birth.

This endpoint is useful for a pilot because it focuses on whether the intervention can be delivered with the frequency specified by the registry, rather than on whether a clinical outcome differs between groups. A participant-level count also makes the threshold interpretable: the posted result identifies how many assessed intervention participants met the criterion. It does not describe how far below or above the threshold other participants were, or how administrations were distributed across individuals.

The registry reports 7 participants meeting the criterion among 10 assessed in the M-MILK arm. The primary endpoint is not assessed in the control arm. Accordingly, the control arm’s zero in the primary outcome listing should not be read as a finding that no control participants met the intervention criterion; the registry explicitly limits this feasibility assessment to the intervention arm. Further details about how scheduled administrations were recorded or how incomplete records were handled are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group study with no masking. In a parallel design, participants are assigned to one group and remain in that group for the study rather than crossing over between interventions. Randomization is intended, in general, to make treatment groups comparable on average at assignment. It does not guarantee that groups will be identical, particularly in a pilot with limited enrollment. The registry record does not report the randomization procedure, allocation concealment, stratification, or details of how assignment was implemented.

What does the primary count represent?

The primary outcome is a participant count, not a continuous measurement or a treatment contrast. The count includes M-MILK participants who received at least 50% of scheduled administrations. The accompanying denominator is 10 participants in the M-MILK arm, and the posted count meeting the threshold is 7. This summarizes whether each assessed participant crossed a defined feasibility threshold. It does not show the administration-level data or each participant’s distance from that threshold.

For a binary outcome, a common statistical summary is the number meeting a criterion relative to the number assessed. When comparing groups, analysts may estimate a difference or ratio and quantify uncertainty. Those comparisons require outcome information in both groups and an analysis plan. Here, the primary measure is explicitly assessed only in the intervention arm, so the posted primary outcome does not support a randomized between-arm comparison. The record lists no analyses for this measure.

What does uncertainty mean for a count?

A confidence interval is a range calculated from data under a statistical method. In general, it represents uncertainty about an underlying quantity, such as a population proportion, rather than a range containing a specified share of individual participant outcomes. The registry does not post a confidence interval for the feasibility result. A reader therefore has the observed count and denominator, but not a registry-reported interval describing sampling uncertainty. No new interval can be inferred from the posted count without selecting an estimation method and calculating it.

The threshold itself is operational: it defines what counts as feasible for this outcome. Changing the threshold or the definition of a scheduled administration could change the classification, but the registry record does not report alternative thresholds or sensitivity analyses. The endpoint also relies on recording whether administrations occurred in specified care contexts. The record does not describe the data collection process, verification procedures, or handling of missing administration records.

Why is there no treatment-effect estimate?

The primary endpoint is not defined for the control arm, and the record reports 0 analyses. The control arm’s zero entry for this endpoint is not an observed estimate of control-group feasibility; it reflects that the outcome is assessed only in the intervention arm. A treatment-effect estimate would require a clearly defined outcome measured comparably in the groups and an analysis that accounts for the design. No such primary comparison is reported.

In general, a pilot feasibility count is often used to assess whether a larger study is practical and to inform its planning. It is not equivalent to a definitive efficacy test. The registry description says the pilot is intended to obtain information for sample-size estimation, but the record does not report the sample-size justification, planning target, or any statistical plan for estimating an efficacy effect.

How should planning calculations be understood?

General sample-size illustrations are conditional on assumptions about the effect to detect, allocation, significance level, and statistical approximation. The registry’s stated planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such planning values are hypothetical design illustrations, not observations from participants and not observed power. The record does not report that these assumptions were the trial’s original design plan, nor does it provide a trial-specific sample-size justification. The pilot’s posted feasibility count should not be treated as evidence that the study had adequate power for efficacy outcomes.

Over-dispersion is a general issue for count outcomes: it occurs when observed counts vary more than a chosen model expects, making standard errors from that model too small if the extra variation is ignored. It is not possible to assess over-dispersion from this participant-level feasibility count, and the registry does not report a count model or dispersion estimate. More broadly, no model, covariate adjustment, missing-data method, or inferential procedure is specified in the registry record. Interpretation should therefore remain descriptive and confined to the count and denominator that are posted.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("M-MILK")
n      <- c(10)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  M-MILK  10  7  70.0  34.8  93.3  39.7  89.2  39.0  89.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and identifies 5 secondary outcomes: Parent Stressor Scale: NICU Score, Parent Discharge Readiness Score, Breastmilk Pumping Rate, Breastfeeding Rate, and Maternal Edinburgh Postnatal Depression Scale Score. The record lists 0 analyses. It does not post results for those secondary outcomes in the registry record for this account, nor does it state how many hypotheses were planned for formal testing.

When a study evaluates multiple outcomes, the chance of at least one apparently unusual finding can increase if each result is tested separately. Statistical approaches can address multiplicity, for example by adjusting significance thresholds or by specifying a hierarchy of outcomes. Whether an adjustment is appropriate depends on the study aims and analysis plan. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or planned contrasts. No claim about adjusted or unadjusted secondary-outcome inference can therefore be made.

The record does not report a missing-data method, an analysis population definition, or participant flow by outcome. Overall enrollment is 14, and 10 M-MILK participants are listed for the primary feasibility endpoint; the registry does not reconcile those figures or state why the remaining enrolled participants do not appear in that endpoint denominator. The control arm is not assessed for the primary feasibility outcome, which is a design feature of the endpoint rather than evidence that control participants had missing feasibility measurements.

Information on withdrawal, loss to follow-up, protocol deviations, and the handling of incomplete administration logs is not reported in the registry record. It is also not reported whether secondary outcomes were analyzed for all randomized participants, for participants with available data, or under another population definition. These omissions limit assessment of potential bias from missing outcomes and prevent reconstruction of the analysis population.

12. 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.

The adverse-event listing reports 0 serious adverse events among 4 control participants at risk and 0 among 10 M-MILK participants at risk. Deaths are listed as 0 in both groups. Other adverse events are also listed as 0 among the same at-risk group counts. No serious-event terms are listed.

These are event counts, not evidence that the intervention is risk-free. A zero count means that no events in the listed category were recorded for the listed at-risk group in the registry results. It does not establish that an event could not occur, and it does not describe the precision of an underlying event rate. No confidence interval or statistical comparison of safety outcomes is posted.

The listed at-risk groups differ in size, and the adverse-event entry should be read using its own denominators. The control count of 4 is not the same as the control arm’s zero entry for the intervention-specific feasibility outcome. The registry does not report the safety definitions, ascertainment schedule, follow-up completeness, or details about how events were classified. The absence of listed serious-event terms should not be taken to mean that every possible adverse event was evaluated in the same way.

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

The result shows that 7 of the 10 M-MILK participants assessed for the primary outcome met the registry’s criterion for receiving the intervention in at least 50% of scheduled administrations. It is a descriptive measure of implementation in this pilot. It does not show how often M-MILK was administered overall, because the result is a participant count based on a threshold rather than an administration count.

The finding does not establish that M-MILK changes stress, epigenetic modifications, dysbiosis, infant development, or any other clinical outcome. Those topics appear in the trial title and rationale, but the posted primary endpoint is feasibility. The registry lists secondary outcomes related to parent stress and discharge readiness, breastfeeding, breastmilk pumping, and maternal postnatal depression; results for those outcomes are not reported in the record summarized by these registry entries.

The result also does not demonstrate that the intervention is more feasible than standard of care, since the primary endpoint is assessed only in the intervention arm. Nor does it establish that the observed feasibility will be reproduced in a different NICU, with a different implementation process, or in a larger study. The record does not supply uncertainty estimates for the count.

The study’s stated purpose is pilot work to inform a future efficacy trial and obtain data for sample-size estimation. The feasibility result may be relevant to those planning aims, but the record does not provide the planning calculations or justify a particular future sample size. It should be interpreted as an initial implementation observation rather than a definitive conclusion about efficacy or safety.

14. Why This Trial Matters Statistically

Feasibility is a distinct statistical and scientific objective from efficacy. A trial can measure whether an intervention was delivered as intended without being designed to estimate a clinical treatment effect. For a pilot that aims to inform a later randomized trial, documenting how often participants meet a delivery threshold can help clarify whether the intervention and its measurement are workable enough to study further.

This registry record makes that distinction important. The primary endpoint is a count of intervention participants who met a defined administration threshold, while the study description identifies future efficacy evaluation as a goal for a later R01 randomized controlled trial. Treating the pilot count as an efficacy result would conflate implementation with clinical effect. Keeping the estimand clear avoids attributing conclusions to the study that its posted primary outcome does not measure.

The record also illustrates why denominators and endpoint scope matter. Overall enrollment is 14, whereas the primary outcome lists 10 intervention participants and does not assess the control arm. The count is interpretable only in relation to that endpoint-specific population. The registry does not explain the enrollment-to-outcome accounting, so the result cannot be extended to all enrolled participants without additional information.

For statisticians and clinical researchers, a pilot record can therefore be informative even when it does not report inferential analyses. It can identify the operational threshold used, the observed count, and the kind of information the investigators say they sought for future planning. At the same time, the absence of a posted analysis plan, uncertainty interval, and participant-flow details places clear limits on the conclusions that can be drawn.

15. 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 primary limitation for interpretation is that the posted endpoint is intervention-specific. It counts M-MILK participants meeting a feasibility threshold, but does not provide a corresponding control outcome or a between-group estimate. The control arm’s zero in the primary outcome listing is not a measured control result. As a result, the primary outcome cannot be used to estimate a randomized treatment contrast.

The registry reports overall enrollment of 14 but lists 10 M-MILK participants for the primary outcome. It does not explain how these figures relate, provide a participant-flow account, or describe exclusions or missing outcome data. This makes it difficult to assess the representativeness of the assessed intervention participants. The record also does not explain the 4 control participants listed as at risk for adverse events in relation to the arm allocation and overall enrollment.

No confidence interval, inferential test, or analysis method is posted for the primary outcome, and the registry lists 0 analyses. The record does not report the sample-size justification, missing-data procedures, analysis populations, or a multiplicity plan. It also does not describe how intervention delivery was recorded, how scheduled administrations were defined, or how incomplete records were handled.

Further details about eligibility criteria, randomization implementation, control procedures, intervention fidelity, and safety ascertainment are not reported in the registry record. The study is a pilot, and its stated aims concern feasibility and planning rather than a definitive efficacy test. These limitations mean the posted count should be interpreted narrowly as the observed threshold count among the listed M-MILK participants, not as proof of comparative efficacy, generalizability, or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multisensory Early Oral Administration of Human Milk in Preterm Infants — NCT06230848.
• Registry record last updated 2026-01-08; status last verified 2025-12.
• Results first posted 2026-01-08.
• 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.

19. Record Summary

NCT06230848 is a completed randomized, parallel-group pilot study with no masking, sponsored by Loyola University. Enrollment is listed as 14. The study dates in the registry are 2023-10-23 for start and 2024-10-23 for primary completion.

The intervention is M-MILK in addition to standard of care; the control arm description states standard of care. The primary outcome is an intervention feasibility count assessed at NICU discharge, typically 10 to 16 weeks from birth. The registry reports 7 participants meeting the threshold among 10 in the M-MILK arm, with the primary outcome assessed only in that arm.

The trial description identifies feasibility and acceptability, recruitment and retention, and sample-size estimation as pilot aims. The registry lists 5 secondary outcomes and 19 outcome measures, but 0 analyses. It does not report a primary efficacy comparison or explain the relationship between total enrollment and the primary-outcome denominator.