Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates (NCT01050660), a randomized na study. The primary outcome is The Presence of Cholestasis at Age of 28 Days or When Full Enteral Nutrition is Achieved, Whichever is Longer..

2. Clinical Question

The study concerns cholestasis associated with parenteral nutrition, abbreviated PNAC in the registry summary and PNALD in the primary outcome description. Its stated aim was to determine whether PNAC is related to the amount of parenteral, or intravenous, fat administered to premature babies until full enteral nutrition is achieved. The primary outcome records the number of participants who developed cholestasis over the stated assessment period.

The registry record describes a randomized comparison between the two fat-emulsion regimens. It lists 67 participants in the 3 gm/kg/Day arm and 69 in the restricted-emulsion arm. The primary outcome counts are 39 and 45, respectively. However, no statistical comparison, confidence interval, or analysis result for this primary endpoint is reported in the registry record. Those counts therefore describe the posted outcome data, but do not by themselves establish how precisely the groups differ or whether a statistical analysis supported a difference.

3. Trial Design

The registry record describes a randomized, open-label, parallel-group trial conducted by Yale University. It lists an enrollment of 136 and a completed status. The recorded start is 2009-06, and primary completion is 2012-11. The phase is listed as NA. The two groups were assigned different intravenous lipid-emulsion regimens: 3 gm/kg/Day intravenous lipid emulsion or intravenous fat emulsion restricted to 1 gm/kg/d. Masking is listed as none.

The primary endpoint was the number of participants who developed cholestasis, assessed at 28 days of age or when full enteral nutrition was achieved, whichever was longer. The registry summary frames the study objective as examining whether PNAC is related to the amount of intravenous fat administered to premature babies until full enteral nutrition is achieved. The arm descriptions themselves contain no further detail about treatment administration or participant management.

The primary outcome description says that PNALD incidence at Yale and UCLA NICU before the study was around 40%. It also states a goal of decreasing incidence by 50%, with an alpha of 5% and power of 80%, and a calculated sample size of 65 infants in each group. The registry record does not include a detailed statistical analysis plan, so it is not possible to tell from the record which planned analysis methods were intended for the primary comparison or how the stated planning assumptions were applied.

There are no reported analyses attached to the primary endpoint. The posted primary results give outcome counts for each arm, but not an estimated between-group effect or its uncertainty. The record includes secondary results for mortality and anthropometric measurements, while results for several other listed secondary outcomes are not reported in the registry record.

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: Incidence of PNALD at Yale and UCLA NICU prior to the start of the study was around 40%. Our goal was to decrease incidence by 50%/ Alpha of 5%/ Power of 80% We calculated a sample size of 65 infants in each group

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 The Presence of Cholestasis at Age of 28 Days or When Full Enteral Nutrition is Achieved, Whichever is Longer., measured over 28 days of age or when full enteral nutrition is acheived, whichever is longer.

The primary endpoint counts participants who developed cholestasis. Its assessment period is specified as 28 days of age or when full enteral nutrition is achieved, whichever is longer. This time definition ties the outcome to an early period of neonatal care while allowing the assessment to continue until the stated feeding milestone if that occurs later. The registry summary explains that the study was intended to examine whether PNAC is related to the amount of intravenous fat administered until full enteral nutrition is achieved.

A participant count is a binary-outcome summary: each participant either met the recorded outcome definition or did not. For a comparison between randomized groups, the counts are most informative when interpreted alongside the number of participants assessed in each group and an effect estimate with an uncertainty interval. The registry record lists 39 participants with cholestasis among 67 in the 3 gm/kg/Day group and 45 among 69 in the restricted group. It does not report a primary-endpoint effect estimate, confidence interval, or p-value.

The precise diagnostic criteria for cholestasis, how cases were confirmed, and how participants with incomplete outcome information were handled are not reported in the registry record. Without those details or a reported comparison, the posted counts cannot show the precision of the group contrast or resolve how the outcome was analyzed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a randomized, parallel-group design with no masking. Random assignment is intended to create groups that are comparable, on average, with respect to factors measured and unmeasured at baseline. That design can support a causal comparison when the trial is conducted and analyzed as planned, but the design label alone does not establish that all details of allocation, follow-up, and analysis are available. The sequence-generation and concealment methods are not reported in the registry record.

What does the primary outcome count tell us?

The primary measure is a count of participants who developed cholestasis. The registry record lists 39 such participants in the group assigned 3 gm/kg/Day and 45 in the restricted group. Counts need to be interpreted with their group sizes, which are 67 and 69. A count is not itself a comparative effect estimate. A formal comparison might express the contrast as a difference in risks, a relative measure, or another prespecified quantity; the primary comparison method and its estimate are not reported in the registry record.

For a binary endpoint, an uncertainty interval around a between-group effect helps distinguish a relatively precise estimate from one that remains compatible with a broad range of effects. A p-value, when reported, addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Neither a primary confidence interval nor a primary p-value is reported in the registry record, so neither the precision nor the statistical evidence for a primary contrast can be assessed from this entry.

How should the secondary comparisons be read?

The registry record gives unadjusted recalculated comparisons for several secondary results. For mortality, the recalculated risk difference is 0.012 with a confidence interval from -0.079 to 0.104 and an unadjusted p-value of 0.792. For body weight, the recalculated mean difference is -3.7 g/week, with a confidence interval from -15.99 to 8.587 and an unadjusted p-value of 0.555. For length, the recalculated mean difference is 0.1 cm/week, and the unadjusted p-value is 0.244. These are secondary summaries, not reported sponsor analyses; the registry record lists no reported analyses for these outcomes.

For a continuous outcome, a mean difference compares group averages. Its interpretation depends on the measurement and time frame: body weight is recorded in g/week, and length in cm/week, at age 28 days and at discharge. The reported standard deviations describe variability within groups. The confidence intervals indicate uncertainty around the recalculated mean differences. In general, when an interval includes the value representing no difference, the estimate is not precise enough to rule out that value using that interval. The posted secondary intervals for body weight and mortality include their respective no-difference values; the length comparison’s interval is also reported, but its exact limits are not repeated.

What do the planning illustrations mean?

Planning illustrations based on observed effects are hypothetical sample-size calculations, not observed power. They show how many participants per arm might be needed under stated assumptions to detect a specified fraction of an observed effect. The registry’s illustration assumptions specify a two-sided significance level of 0.05, equal allocation, and a normal approximation; they use the observed effect as a planning reference. Such calculations depend strongly on the effect size chosen. If a smaller effect is targeted, more participants are generally needed for the same nominal power. The illustration does not establish that the trial was designed around those post hoc values, nor does it explain a trial’s actual sample-size rationale.

The primary outcome description separately records a planning goal: decrease incidence by 50%, alpha of 5%, power of 80%, and 65 infants in each group. The full statistical plan, including how the primary endpoint was to be modeled and whether any interim analyses were planned, is not reported in the registry record. Those absent details should not be inferred from the observed results or from the planning illustration.

Why does over-dispersion matter?

In general, over-dispersion occurs when the variability in data is greater than a statistical model expects. If a model underestimates variability, it can make uncertainty intervals too narrow and statistical evidence appear stronger than it is. This concept can matter for count outcomes or clustered data, but the registry record does not report an over-dispersion assessment or a model for the primary endpoint. No conclusion about whether over-dispersion was relevant in this trial can be drawn from the entry.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes in addition to the primary cholestasis endpoint. These include mortality, neonatal complications, length of stay, and anthropometric measurements. Testing several outcomes can increase the chance of an apparently unusual result arising by chance. A prespecified multiplicity strategy can control or contextualize that risk, for example by defining a hierarchy of outcomes or adjusting inference across tests. Such a strategy is not reported in the registry record.

The recalculated secondary comparisons are unadjusted. Their p-values should not be interpreted as if they were protected against multiple testing. Nor does the record report a prespecified analysis hierarchy, so it is not possible to determine whether any secondary outcome was intended to support a confirmatory claim. The absence of this information does not show that no multiplicity approach was used; it means the approach is not reported in the registry record.

Missing-data handling is also not described. The record gives group sizes for the posted outcomes, but does not report whether all randomized participants were included in each analysis, whether any endpoint values were missing, or how missing measurements were treated. The analysis populations, including whether an intention-to-treat population was used, are not reported in the registry record. Details of exclusions after randomization and any sensitivity analyses are also not reported.

The registry entry does not provide a complete statistical analysis plan, including the intended primary comparison method, covariate adjustment, interim analyses, or procedures for handling deviations from assigned treatment. These details matter because analysis choices affect interpretation of estimates and their uncertainty. Their absence from the record limits reproducibility and prevents a full assessment of whether the posted outcome summaries match a prespecified plan.

11. Safety Results

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

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: mortality prior to discharge (8.7%).

The registry’s adverse-event record lists serious adverse events affecting 5 participants in the 3 gm/kg/Day group and 6 in the restricted-emulsion group. The numbers at risk are listed as 67 and 69, respectively. The record lists 0 other adverse events in each group. It also identifies “Mortality prior to discharge” as a serious-event term, with 8.7% recorded.

These entries describe reported event counts, not proof that an event was caused by the assigned regimen. The adverse-event record does not provide event-level descriptions, severity grading, timing, relatedness assessments, or explanations of how the serious-event term was defined. The deaths field in the adverse-event summary is not populated. Separately, the secondary mortality outcome lists 5 participants in the 3 gm/kg/Day arm and 6 in the restricted arm at discharge from the Newborn ICU. The record does not explain the relationship between that outcome and the serious-event listing, so they should be read as distinct registry entries rather than assumed to be identical measures.

Safety counts are most informative when accompanied by consistent definitions, follow-up periods, and detailed attribution. Those details are not reported in the registry record. The event counts alone do not establish a causal difference in safety between the groups.

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

The registry record establishes that the trial randomized preterm neonates to one of two intravenous lipid-emulsion regimens and posted primary outcome counts for cholestasis. It records 39 participants with the outcome in the 3 gm/kg/Day group and 45 in the restricted group. These counts answer a descriptive question about how many participants were recorded with cholestasis in each arm.

The counts do not, on their own, establish the size or precision of a treatment contrast. The primary endpoint has no posted effect estimate, confidence interval, or p-value, and no primary analysis is listed. As a result, the record does not support a precise statement about how the groups compare statistically. Nor should the absence of a reported analysis be interpreted as evidence of no difference.

The trial’s stated aim was to examine whether PNAC is related to the amount of intravenous fat administered until full enteral nutrition is achieved. The registry record includes a primary outcome description with planning assumptions, but it does not include enough detail to reconstruct the prespecified statistical approach. It also does not report the diagnostic criteria for cholestasis or missing-data procedures. Those limitations affect how confidently the posted counts can be interpreted as a complete comparison.

The secondary results offer additional observations, but they are unadjusted and come without a reported multiplicity strategy. They cannot fill the gap left by the missing primary comparison. General statistical interpretation distinguishes an observed point estimate from its uncertainty: an estimate describes the observed contrast, while an interval communicates how imprecise that estimate may be. Without those primary statistics, the uncertainty around the main comparison remains unknown.

These limitations concern what can be concluded from the registry record, not what might be found in other sources. Details or analyses beyond the registry entry are not reported in the registry record. No treatment recommendation follows from these descriptive counts.

13. Why This Trial Matters Statistically

This trial illustrates why reporting group counts is not enough for a complete statistical interpretation. A reader can identify the number of participants recorded with the primary outcome in each randomized group, but without an estimated contrast and its uncertainty, the strength and precision of the comparison remain unclear. Clear reporting of the primary effect estimate, confidence interval, and analysis method would make the central result more interpretable.

The entry also distinguishes study planning from observed evidence. The primary outcome description states a target decrease, alpha, power, and planned group size. Those statements communicate design intentions; they do not establish that the realized study achieved a particular degree of precision or that an observed effect is reliable. Planning calculations based on observed effects are illustrations for future design decisions, not observed power for the completed trial.

Finally, the registry demonstrates how a broad set of secondary outcomes can coexist with limited analysis reporting. Multiple outcomes may be useful for describing a trial, but unadjusted secondary results require caution when no multiplicity strategy or analysis hierarchy is reported. Transparent reporting of analysis populations, missing-data handling, endpoint definitions, and planned statistical methods would help readers judge whether findings are robust and how they relate to the primary question.

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 trial-specific limitations in interpretation arise from the registry record. The primary endpoint is posted as counts, but a between-group estimate, confidence interval, p-value, and analysis method are not reported in the registry record. This prevents assessment of the magnitude and precision of the primary comparison. The outcome description also does not state the diagnostic criteria or the procedures used to ascertain cholestasis.

The registry lists randomized, open-label, parallel-group allocation but does not report how the random sequence was generated or concealed. Masking is listed as none. The record does not explain whether outcome assessors were masked, or whether any safeguards were used to limit ascertainment differences. These details are particularly relevant when an outcome depends on clinical assessment, but their absence does not establish that ascertainment differed between groups.

The handling of missing outcome data, analysis populations, treatment adherence, and deviations from assigned regimens is not reported in the registry record. Nor are baseline characteristics or detailed arm descriptions available in the entry. The timing rule for the primary outcome allows assessment through 28 days of age or achievement of full enteral nutrition, whichever is longer, but participant-level follow-up duration is not reported.

Several listed secondary outcomes have no posted results, and the available secondary comparisons are unadjusted. A multiplicity strategy and full statistical analysis plan are not reported. The adverse-event record gives limited counts without event-level detail or relatedness information. Together, these gaps mean the registry entry supports a narrow descriptive reading of the posted outcomes, rather than a comprehensive evaluation of efficacy, safety, or analysis robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates — NCT01050660.
• Registry record last updated 2014-10-28; status last verified 2014-10.
• Results first posted 2014-10-28.
• 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

NCT01050660 is a completed randomized, open-label, parallel-group trial sponsored by Yale University. The registry record lists 136 participants and compares 3 gm/kg/Day intravenous lipid emulsion with intravenous fat emulsion restricted to 1 gm/kg/d in preterm neonates. The primary outcome is cholestasis at 28 days of age or when full enteral nutrition is achieved, whichever is longer.

The primary outcome counts are 39 of 67 in the 3 gm/kg/Day group and 45 of 69 in the restricted group. The registry record does not report a primary comparison or uncertainty estimate. Secondary results include mortality and anthropometric measures; other listed secondary outcomes do not have results reported in the registry record. A complete statistical plan, missing-data approach, and multiplicity strategy are not reported.