Neonatal Warming to Prevent Hypothermia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neonatal Warming to Prevent Hypothermia (NCT04827394), a randomized na study. The primary outcome is Temperature at Arrival to Warmer.

2. Clinical Question

The clinical focus is the temperature measured soon after birth, rather than a later measure of temperature or a broader assessment of hospital course. The registry also lists secondary outcomes addressing temperature at other locations or times, respiratory support, bilirubin, hospital stay, cord-clamping duration, and related measures. Those outcomes can add context, but they do not change what the primary endpoint asks.

The trial is identified as a pilot randomized controlled trial. The registry record gives an enrollment of 52. The primary outcome summaries report 25 participants in each group. The record does not provide a more detailed description of eligibility criteria beyond the population described in the trial summary, so other inclusion or exclusion rules are not reported in the registry record.

3. Trial Design

This was a randomized, parallel-group pilot trial with no masking. The registry lists University of Oklahoma as the sponsor, the status as completed, and the phase as NA. The recorded start date is 2020-12-01 and the primary completion date is 2023-02-21. The registry enrollment is 52.

Participants were assigned to an intervention group or a control group. The intervention used a neonatal warming mattress and sterile polyethylene wrap. The control group received standard care, described as delivery onto the sterile field. The brief summary additionally describes delayed clamping of the umbilical cord at cesarean delivery as part of the approach under study. The registry record does not give further detail about how this aspect was implemented, so the procedural specifics are not reported in the registry record.

The primary outcome was temperature at arrival to the warmer, measured at 3 minutes. It was summarized as a median and full range. The primary outcome record does not include a statistical comparison, confidence interval, or p-value. Secondary outcomes include temperature measures at other points, hypothermia measures, and several measures of clinical course. Numerical results are posted for some of these outcomes, while the remaining outcome values are not reported in the registry record.

The registry lists 15 outcome measures and 14 secondary outcomes posted. It records no analyses, and no reported analyses accompany the secondary outcome entries. The record does not describe the randomization procedure, allocation concealment, a prespecified statistical analysis plan, or a sample-size justification. These details are not reported in the registry record, and should not be inferred from the fact that the study was randomized or designated a pilot.

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.

Before assignment: The values reported reflect the total number of unique participants (mothers) assigned to each Arm.

Overall Study

Reasons for not completing this period:

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 Temperature at Arrival to Warmer, measured over 3 minutes.

The primary endpoint is temperature at arrival to the warmer, expressed in degrees Celsius and measured at 3 minutes. It is reported as a median with a full range for each group. The intervention group’s median was 36.9, with a range from 36.5 to 37.3. The control group’s median was 37.0, with a range from 36.8 to 37.1. Each group’s reported outcome summary includes 25 participants.

Temperature is a direct measure of the condition the trial set out to address: hypothermia in moderate and late preterm neonates. Measuring it soon after birth gives an early outcome relevant to the immediate warming strategy. It is not, by itself, a complete account of temperature over the subsequent hospital course or of other clinical outcomes.

In general, a median describes the midpoint of observed values, while a full range gives the lowest and highest values. These summaries describe the recorded temperatures but do not show the precision of an estimated difference between groups. A confidence interval or formal comparison for the primary endpoint is not reported in the registry record. The posted summaries therefore support a descriptive reading of this endpoint, not a claim about a statistically established group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary endpoint as a median and full range. In general, a median is the central value after observations are ordered, and the full range describes the smallest and largest observed values. These statistics are useful for describing the distribution without assuming that measurements follow a particular symmetric shape. They do not, on their own, quantify the uncertainty in the difference between groups. The primary endpoint’s confidence interval and formal comparison are not reported in the registry record.

What does a risk difference mean?

For the binary secondary outcomes, a risk difference compares the proportion with the outcome in the intervention group with the proportion in the control group. In general, a positive risk difference means the observed proportion is higher in the intervention group under the comparison’s stated direction; a negative value means it is lower. The recalculated risk differences in the registry-based summaries are 0.16 for hypothermia at the warmer, 0.12 for hypothermia at completion of resuscitation, and -0.16 for hypothermia at NICU or recovery. These are unadjusted re-calculations from the posted counts, not analyses reported by the trial.

A confidence interval expresses a range of values compatible with the data under a specified statistical method. In general, wider intervals indicate greater uncertainty about the size and direction of an effect. For each of these secondary risk differences, the posted interval includes zero, meaning the data are compatible with no difference as well as with differences in either direction. The intervals are broad, so the estimates do not precisely determine the size of a group difference.

How should the p-values be read?

The unadjusted p-values for the three secondary comparisons are 0.123, 0.269, and 0.239. In general, a p-value measures how unusual data at least as extreme as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. A p-value should be interpreted alongside the estimate, its uncertainty, study design, and analysis plan. These values come from recalculated comparisons; the registry record lists no reported analyses. The registry’s planning assumptions specify a two-sided significance level of 0.05 for the sample-size illustrations, but a threshold alone does not make an unadjusted exploratory result confirmatory.

Why does the pilot sample size matter?

In general, estimates based on limited data tend to be less precise, particularly when outcomes are binary and event counts are small. This is reflected in the broad confidence intervals for the posted secondary risk differences. The enrollment record is 52, and the outcome summaries report 25 participants per group. The registry does not explain why the enrollment was selected or report a formal sample-size justification. It would therefore be inappropriate to treat the planning illustrations as evidence that the original trial was designed to detect a particular effect.

The posted planning illustrations use the observed effect, two-sided significance level 0.05, equal allocation between groups, and a normal approximation. For hypothermia at the warmer, planning for 100% of the observed effect gives 82 participants per arm for 80% power and 109 for 90% power; planning for 75% gives 131 and 174; planning for 50% gives 258 and 345. These are prospective planning illustrations based on observed results. They are not observed power, do not show the probability that the trial detected an effect, and should not be interpreted as the trial’s original enrollment target.

What does “unadjusted” imply?

In general, an unadjusted comparison uses the observed group summaries without accounting for other variables or for the number of outcomes being examined. Adjustment can refer to controlling for covariates, accounting for a study design feature, or addressing multiple comparisons; those are different choices and require a specified analysis plan. The registry record does not report adjusted analyses or explain whether any adjustment was planned. Since the secondary outcomes include several measures, unadjusted findings are best treated as exploratory rather than as a set of independent confirmatory tests.

Randomization supports a comparison between assigned groups in principle, but interpretation also depends on implementation, follow-up, and the analysis population. The registry identifies the design as randomized and parallel, but details of sequence generation, allocation concealment, adherence, missing outcome data, and analysis population are not reported in the registry record. No particular approach to these issues should be assumed. The absence of those details limits how fully the posted outcome summaries can be evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including one primary outcome and a range of secondary outcomes. The record reports no analyses, and it does not describe a multiplicity strategy or any adjusted secondary analyses. It is therefore not reported in the registry record whether the trial planned to control the chance of false-positive findings across multiple outcome tests.

In general, when several outcomes are examined, the chance of at least one apparently unusual result can increase. A prespecified hierarchy, adjustment procedure, or clear separation between confirmatory and exploratory outcomes can help readers interpret such findings. Without a reported approach, the recalculated secondary p-values should not be treated as a set of independent confirmatory tests. Their estimates and intervals remain useful descriptive information, but they carry less weight than a prespecified primary analysis with a reported analysis method.

Missing-data handling is not reported in the registry record. The record does not say whether outcome measurements were missing, how missing values were handled, or whether any participants were excluded from particular analyses. The posted outcome summaries report 25 participants per group, while the registry enrollment is 52; the reason for the difference between the enrollment record and the displayed outcome denominators is not reported in the registry record. These figures should not be reconciled by assuming exclusions, missing data, or any other explanation.

The analysis population is also not reported in the registry record. The record does not state whether analyses followed assigned groups regardless of treatment received, were limited to participants who received the assigned intervention, or used another population definition. Details about intention-to-treat analysis, protocol deviations, or per-protocol analyses are not reported. These omissions do not establish that the trial mishandled missingness or assignment; they mean that the relevant analysis choices cannot be evaluated from the registry record.

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 non-serious adverse event terms

The adverse-event record reports no serious adverse events among mothers in either group and no serious adverse events among infants in either group. Each maternal group lists 25 at risk, and each infant group lists 25 at risk. The registry also reports no deaths in the maternal groups. For infants, one death is recorded in each group.

For non-serious adverse events, the maternal groups each have zero affected. The intervention-group infants have 2 affected, and the control-group infants have 1 affected. The registry does not list serious adverse-event terms. It does not provide event descriptions, causes, timing, or an assessment of whether events were related to the intervention. The record also does not explain the circumstances of the infant deaths, so no causal attribution can be made from these counts.

In general, adverse-event counts are descriptive safety information, not proof that an intervention caused or did not cause an event. The limited group sizes and absence of further event details constrain interpretation. The reported zero serious adverse events should be read as the registry’s recorded count, not as evidence that uncommon harms are ruled out. Likewise, the deaths are listed separately from serious adverse-event counts and cannot be interpreted as intervention-related on the basis of the registry record alone.

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

The posted primary results describe temperature at arrival to the warmer: the intervention group median was 36.9 and the control group median was 37.0, with the stated full ranges. These figures allow a descriptive comparison of the observed temperatures. They do not establish a statistical difference because the registry record does not report a primary-outcome comparison, confidence interval, or p-value.

The secondary outcome summaries show different directions across measurement points and have broad intervals. Their unadjusted p-values do not establish that a difference exists, and their failure to provide strong evidence against a null model does not establish equivalence. The record does not report a prespecified multiplicity strategy or adjusted analyses, so these secondary recalculations should be considered exploratory.

The results also do not answer every question about the intervention. The primary endpoint is an early temperature measure, and the posted registry information does not provide numerical results for every named secondary outcome. Details about missing data, analysis populations, allocation methods, and the statistical plan are not reported in the registry record. These gaps limit conclusions about precision and robustness.

In general, a pilot trial can describe observed outcomes and help identify uncertainties for future evaluation, but results from a small pilot should not be treated as definitive evidence of benefit or lack of benefit. The registry information supports a cautious reading of the measured outcomes, not medical advice or a treatment recommendation. It does not show that the intervention works or does not work; it reports group summaries and limited exploratory comparisons whose uncertainty is substantial.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between a descriptive result and an inferential conclusion. The primary outcome is reported with medians and full ranges, but no between-group confidence interval or p-value. Readers can inspect the observed temperatures, yet cannot assess the precision of an estimated primary difference using the registry record alone.

The secondary results illustrate why effect estimates and uncertainty should be read together. The reported risk differences vary in direction across measurement points, and their intervals include no difference. A point estimate alone can give an overly definite impression, especially when the number of outcome observations is limited. The registry-based recalculations are explicitly unadjusted, and the record has no reported analyses.

The planning illustrations also show how assumptions affect future sample-size planning. They are based on observed secondary effects and specify two-sided significance level 0.05, equal allocation, and a normal approximation. Different fractions of the observed effect produce different planning estimates. Those figures are not observed power and do not establish the trial’s original sample-size rationale, which is not reported in the registry record.

Finally, the record highlights the importance of transparent reporting. Information about missing outcomes, analysis populations, multiplicity, and the statistical plan would help readers assess how robustly the data answer the primary question. Their absence does not invalidate the reported observations, but it narrows what can be concluded from them. For clinical researchers, this is a useful reminder that clear reporting of estimates, uncertainty, and analysis decisions is central to interpreting randomized trial results.

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.

Several limitations specific to this trial affect interpretation. The registry identifies the study as a pilot and records enrollment of 52, while the outcome summaries report 25 participants per group. The registry does not explain this relationship. The displayed numbers should therefore be reported as recorded rather than reconciled by assuming a reason for the difference.

The primary outcome is reported descriptively, without a confidence interval or formal group comparison. This leaves the precision of the primary result unclear. The secondary risk-difference calculations have broad confidence intervals and are unadjusted; their estimates vary in direction across measurement points. Multiple outcome measures are listed, but the registry record does not report a multiplicity approach or a hierarchy for interpreting them.

Important design and analysis details are not reported in the registry record, including the randomization procedure, allocation concealment, analysis population, handling of missing data, and statistical analysis plan. The record also does not explain the sample-size rationale. These omissions limit assessment of potential bias, robustness, and the intended role of secondary outcomes.

The intervention description combines a warming mattress and wrap, while the brief summary also describes delayed cord clamping. The registry record does not provide enough detail to distinguish the contribution of each component or describe procedural implementation further. The study therefore does not provide a component-specific comparison in the posted information. Finally, adverse-event counts are given without event descriptions or attribution, limiting safety interpretation. These limitations apply to what can be concluded from the registry record, not necessarily to information that may exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Neonatal Warming to Prevent Hypothermia — NCT04827394.
• Registry record last updated 2024-05-01; status last verified 2024-04.
• Results first posted 2024-05-01.
• 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 identifies NCT04827394, titled “Neonatal Warming to Prevent Hypothermia,” as a completed, randomized, parallel-group pilot trial sponsored by University of Oklahoma. The record lists no masking and an enrollment of 52. The intended population was moderate and late preterm neonates born between 32 and 36 weeks during cesarean delivery.

The intervention used a neonatal warming mattress and sterile polyethylene wrap; the control group received standard care. The primary outcome was temperature at arrival to the warmer at 3 minutes, reported as a median and full range. The record posts secondary outcomes, including hypothermia measures at several points, but does not report analyses or a primary inferential comparison.

Some secondary comparisons are recalculated as unadjusted summaries, with considerable uncertainty. Statistical analysis details, missing-data handling, analysis populations, and a sample-size justification are not reported in the registry record. The posted results are therefore descriptive and exploratory rather than a complete inferential assessment.