Delayed Cord Clamping for Congenital Diaphragmatic Hernia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Delayed Cord Clamping for Congenital Diaphragmatic Hernia (NCT03314233), a na na study. The primary outcome is Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping.

2. Clinical Question

The clinical rationale concerns the timing of lung aeration relative to cord clamping. The registry summary explains that infants with CDH may experience hypoxemia and acidosis during neonatal transition. It describes animal-model evidence and trials in preterm infants as background for considering respiratory support before clamping, while also stating that this approach had not been studied in infants with CDH at the time described.

The research question is therefore primarily one of feasibility and observed delivery-room practice in this population: can intubation and ventilation be initiated before clamping, and how often does the defined endpoint occur? Because the record describes a single-group study, it cannot by itself provide a randomized estimate of how outcomes compare with immediate clamping. The primary endpoint result is not reported in the registry record, so its frequency cannot be stated.

3. Trial Design

The registry identifies NCT03314233 as a completed study titled “Delayed Cord Clamping for Congenital Diaphragmatic Hernia.” Its official title specifies delayed cord clamping for intubation and gentle ventilation in infants with CDH. The listed condition is congenital diaphragmatic hernia, and the intervention is a procedure named DING, described as delayed cord clamping.

The design is listed as single-group. Allocation is recorded as NA, and masking is listed as none. The record does not describe a concurrent control arm or a randomized comparison. The registry summary discusses immediate umbilical cord clamping followed by intubation and mechanical ventilation as the standard approach, but that background description is not evidence of a control group in this study.

Enrollment is recorded as 21. The study start date is 2017-10-12, primary completion is recorded as 2018-10-01, and status is completed. The phase is listed as NA. These registry entries describe the study record; they do not establish which participants contributed data to each outcome or analysis.

The primary outcome is the proportion of infants intubated before umbilical cord clamping, assessed at 3 minutes of life. The listed definition requires both intubation and ventilation initiation before clamping. The registry also lists secondary outcomes involving arterial blood pH, arterial oxygen partial pressure, oxygenation index, vasopressor use, severe pulmonary hypertension, ECMO treatment, and mortality in the first 7 days of life. The record lists eight outcome measures and zero analyses.

The statistical analysis plan, sample-size justification, interim analyses, and analysis populations are not reported in the registry record. The sample-size assumptions associated with planning illustrations are not described as the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. Those assumptions should not be mistaken for a randomized design or evidence that a particular analysis was conducted.

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

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 Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping, measured over 3 minutes of life.

The primary endpoint asks whether an infant was intubated and had ventilation initiated before umbilical cord clamping. It is assessed at 3 minutes of life. The outcome title frames this as a proportion, while the registry describes its parameter as a count of participants. The endpoint definition is about the occurrence of the specified sequence, rather than a measurement of later respiratory status.

This outcome is relevant to the intervention’s central procedural question: whether respiratory support can be started before clamping in infants with CDH. The registry summary provides a physiological rationale for studying that timing. It describes potential circulatory effects of lung aeration before clamping and notes that CDH infants may be vulnerable to pulmonary hypertension and systemic hypotension. That rationale motivates the question; it does not establish that the procedure changes those conditions.

For a binary endpoint, each participant is classified according to whether the defined event occurred. A count or proportion can describe how often the event was recorded in the study group. A proportion needs both an event count and a denominator from the relevant analysis population. The primary outcome count, denominator, and estimate are not reported in the registry record. Consequently, the endpoint’s observed frequency and its precision cannot be assessed from the reported primary results.

The record also does not report how timing was documented, how cases with incomplete timing information were handled, or whether any exceptions to the endpoint definition were permitted. Without those details, the endpoint definition is clear at a high level, but its implementation and completeness cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, the direct descriptive target is the outcome observed among participants who received the study intervention. For a binary outcome such as the primary endpoint, an analysis might report the number meeting the definition and the denominator assessed, then express that event frequency as a proportion. The registry does not report the primary count, denominator, or estimate, so none can be interpreted for this study.

A single-group estimate is different from a treatment contrast. A contrast requires outcomes under at least two conditions, such as intervention and control, measured in a way that supports comparison. This registry record lists no concurrent comparator and no randomized allocation. The background description of usual practice does not create a trial control group. Comparisons with historical or external data, if any, are not reported in the registry record.

What does a binary endpoint mean?

A binary outcome places each assessed participant into an event or no-event category according to a definition. Here, the event is intubation with ventilation initiated before umbilical cord clamping, assessed at 3 minutes of life. Clear classification depends on applying the same timing and event rules consistently. The registry definition states the essential sequence, but operational details such as how timing was recorded and how uncertain cases were treated are not reported in the registry record.

A count is the number of participants recorded with the event; a proportion relates that count to an analysis denominator. Counts alone cannot communicate the frequency without knowing how many participants were assessed. A proportion alone is also difficult to evaluate without its denominator and uncertainty. Neither the primary count nor the denominator is reported in the registry record.

How should uncertainty be understood?

General statistical explanation: a confidence interval gives a range of values compatible with the observed data under a specified statistical method and its assumptions. It indicates precision, not certainty that the true value lies within the interval. Wider intervals generally indicate less precision, while narrower intervals generally indicate more. The primary confidence interval is not reported in the registry record, so the precision of the primary outcome cannot be assessed.

A p-value, when used, quantifies how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the stated model. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. No primary p-value or inferential analysis is reported in the registry record. The registry lists zero analyses, which describes the analyses recorded in the registry and does not establish whether analyses were conducted outside that record.

What can planning illustrations tell readers?

The stated planning assumptions describe illustrations computed from an observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For non-time-to-event outcomes, the assumptions describe results in terms of participants per arm for 80% power or another stated planning level; time-to-event illustrations use a total event count. These calculations are planning aids, not observed outcomes and not observed power.

General statistical explanation: a sample-size calculation depends on the target effect, variability or event frequency, chosen error rate, allocation, and analysis method. If an observed effect is used to construct an illustration, the resulting sample size should not be treated as proof that the study was adequately powered or that its result is reliable. The registry does not report the study’s own sample-size justification, so the reason for its enrollment target is not reported in the registry record.

Why do the analysis details matter?

Analysis choices determine which participants contribute to an estimate, how missing observations are handled, and what assumptions connect the data to the reported result. A prespecified method can also reduce the risk of choosing an analysis after seeing the findings. The statistical plan, analysis population definitions, handling of missing data, and interim analyses are not reported in the registry record.

General statistical explanation: binary outcomes can be analyzed with methods that estimate event frequencies or compare them across groups. The appropriate method depends on the design, data structure, and question. Over-dispersion matters when observed variability exceeds what a chosen model assumes; if unaddressed, model-based uncertainty can be understated. The registry record does not report a model or a variance assessment, and the single-group design means that a between-arm model cannot be assumed.

When multiple outcomes are assessed, separate tests can increase the chance of finding an apparently notable result by chance if no adjustment or hierarchy is specified. A prespecified primary endpoint can help distinguish the main question from secondary or exploratory questions, but the registry record does not describe a multiplicity strategy. The reported outcome list alone does not reveal whether any adjustment was planned or performed.

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("DING Intervention")
n      <- c(20)
events <- c(17)
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  DING Intervention  20  17  85.0  62.1  96.8  64.0  94.8  63.7  94.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary endpoint and secondary measures of arterial blood pH, arterial oxygen partial pressure, oxygenation index, vasopressor use, severe pulmonary hypertension, ECMO treatment, and mortality in the first 7 days of life. The registry record does not report results for these outcomes or describe a multiplicity strategy. It is therefore not possible to determine whether the outcomes were tested, whether any adjustment was applied, or how findings across outcomes were interpreted.

General statistical context: testing multiple outcomes can increase the chance that at least one result appears notable by chance. A prespecified hierarchy, adjustment procedure, or clearly descriptive interpretation can address this issue, but none is reported in the registry record. The existence of one designated primary outcome does not establish that secondary analyses were adjusted or that the primary analysis followed a prespecified plan.

Missing-data handling and analysis populations are also not reported in the registry record. The record does not specify how many participants contributed to each outcome, whether any measurements were unavailable, how missing observations were treated, or whether analyses followed an intention-to-treat or other population definition. Enrollment alone does not show the denominator used for an outcome.

The registry lists zero analyses. This should be read as a registry entry, not as proof that no statistical work was done. A detailed statistical analysis plan, interim analyses, and sensitivity analyses are not reported in the registry record. These omissions limit assessment of how outcomes were selected, how uncertainty was handled, and whether the reported analyses—if conducted—were prespecified.

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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: pneumothorax (15.0%).

The registry’s safety entries distinguish serious adverse events, other adverse events, and deaths. For the DING intervention group, the serious-event fields list 20 at risk and 3 affected. The other-event fields list 20 at risk and 0 affected. Deaths are listed as 0. The record also identifies pneumothorax as a leading serious term at 15.0%.

These are registry safety fields, not a comparative risk estimate. The study is listed as single-group, so the entries do not show how the same events would have occurred under a concurrent alternative. The record does not explain the event-collection period, definitions used for each category, or the method used to produce the pneumothorax percentage. Avoid deriving additional rates from these entries.

The presence of an event term does not by itself establish that the intervention caused the event. Likewise, zero deaths recorded in these fields does not establish the absence of other safety concerns or describe outcomes beyond the registry’s reporting. The safety entries should be read as a limited account of events captured in the record; broader interpretation requires context that is not reported in the registry record.

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

The study addresses a clinically specific procedural question: whether intubation and ventilation can be initiated before umbilical cord clamping for infants with CDH. The registry defines a primary endpoint around that sequence and identifies delayed cord clamping as the intervention. It also records a completed, single-group study with enrollment of 21.

The primary outcome result is not reported in the registry record. As a result, readers cannot determine from the registry how often the defined event occurred, how precise an estimate might be, or whether the endpoint was achieved in the study group. The secondary outcome results are also not reported in the registry record, so no conclusions about blood gas measures, oxygenation, support requirements, pulmonary hypertension, ECMO, or early mortality can be drawn from the listed outcome titles.

The study design also limits what an observed result could establish. A single-group study can describe outcomes in the intervention group, but it does not create a randomized comparison with immediate clamping. The summary’s explanation of usual practice and physiological rationale provides context; it does not demonstrate a treatment effect. Even a complete single-group outcome estimate would not, by itself, establish what would have happened to the same population under another approach.

General statistical explanation: statistical significance and clinical importance are distinct questions. An inferential result concerns compatibility with a statistical model and null hypothesis, while clinical importance depends on the size and relevance of an effect in context. Neither can be assessed for the primary endpoint because its estimate and inferential results are not reported in the registry record.

The registry record is informative about the question the study was designed to address and the outcomes it intended to assess. It is not sufficient to establish efficacy, lack of efficacy, or comparative safety. The appropriate interpretation is limited to the registered design and the reported safety entries, with the central primary result remaining unreported.

14. Why This Trial Matters Statistically

This study is statistically interesting because it targets a tightly defined event at a clinically important transition: intubation and ventilation before umbilical cord clamping in infants with CDH. A clearly timed procedural endpoint can make a feasibility question concrete. It also connects an intervention sequence to a physiological rationale described in the registry summary, without assuming that the rationale guarantees an outcome.

The single-group design defines the kind of evidence available. It can characterize whether the specified sequence was observed among participants, but it cannot separate the intervention’s effect from other influences through a randomized comparison. This distinction is especially important when the background describes a usual-care approach that is not represented as a concurrent trial arm.

The registry record also illustrates why outcome definitions and analysis details matter. A primary endpoint framed as a proportion requires an event count and a relevant denominator to interpret frequency, while uncertainty requires an estimate and an appropriate measure of precision. Those primary results are not reported in the registry record. Without them, the central quantitative question remains unresolved in the available registry information.

Finally, the listed secondary outcomes and safety fields show the breadth of issues considered in the record, but outcome listings are not results. Multiplicity handling, analysis populations, missing-data methods, and the statistical plan are not reported in the registry record. These gaps constrain reproducibility and make it difficult to assess how planned questions were translated into analyses. The case underscores the value of reporting both outcome estimates and the methods used to obtain them, while keeping descriptive findings distinct from causal claims.

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 is that the primary endpoint result is not reported in the registry record. The event count, denominator, estimate, and uncertainty are unavailable, preventing assessment of the endpoint’s observed frequency and precision. Secondary outcome results are also not reported in the registry record.

The study is listed as single-group, with allocation recorded as NA and masking as none. No concurrent comparator is described. This means the record cannot support a randomized comparison with immediate clamping, which is discussed only as background usual practice. The design also limits causal interpretation of any group-level observations.

The registry does not report the statistical analysis plan, the sample-size justification, interim analyses, analysis populations, or missing-data methods. It is not possible to assess whether the outcome definitions and analyses were prespecified in detail, how incomplete records were handled, or which participants contributed to each outcome. The planning assumptions associated with sample-size illustrations are not the trial’s own design justification.

Outcome measurement details are limited. The primary definition specifies intubation and ventilation before clamping, but the record does not report how event timing was measured or how uncertain or incomplete observations were classified. The record also does not describe the collection period and definitions for the safety fields.

Finally, the registry lists zero analyses, but that entry does not establish whether analyses occurred outside the registry. The recorded status is completed, yet the absence of posted results leaves the principal efficacy-related endpoint and the listed secondary outcomes uninterpretable from this record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Delayed Cord Clamping for Congenital Diaphragmatic Hernia — NCT03314233.
• Registry record last updated 2020-01-21; status last verified 2020-01.
• Results first posted 2019-12-10.
• 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

NCT03314233 is a completed, single-group study of delayed cord clamping in infants with congenital diaphragmatic hernia. Enrollment is recorded as 21. The study started on 2017-10-12, and primary completion is recorded as 2018-10-01. Allocation is listed as NA, masking as none, and phase as NA.

The primary endpoint is the proportion of infants intubated with ventilation initiated before umbilical cord clamping, assessed at 3 minutes of life. The primary result is not reported in the registry record. The registry lists eight outcome measures and zero analyses.

Safety fields list 20 at risk and 3 affected for serious events, 20 at risk and 0 affected for other events, and 0 deaths. Pneumothorax is listed at 15.0% among serious terms. These entries do not provide a comparison with another treatment group.

The registry record describes the study question and design, but does not report the primary or secondary outcome results, statistical plan, missing-data methods, or analysis populations.