Post-Partum Immunization With Live Attenuated Influenza Vaccine (LAIV) or Trivalent Influenza Vaccine (TIV) in Post-Partum Breast Feeding Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-Partum Immunization With Live Attenuated Influenza Vaccine (LAIV) or Trivalent Influenza Vaccine (TIV) in Post-Partum Breast Feeding Women (NCT01181323), a randomized phase 2 study. The primary outcome is Number of Participants Reporting Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 trial. The registry lists triple masking; the official title describes the trial as double-blind. The registry record does not identify which roles were masked, so the difference in wording cannot be resolved from the record alone. The study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), and its status is completed.

The trial began in 2011-09, with primary completion in 2013-05. The registry describes a planned enrollment of 240. The brief description says participants were to be involved for about 6 months. Eligible women were assigned by chance to one of two vaccine approaches: nasal LAIV with a placebo shot, or an intramuscular TIV shot with a placebo nasal spray. Each maternal group description lists 120 maternal subjects.

The study addressed safety in mothers and infants and immunogenicity in mothers. Listed procedures included nasal swabs, blood samples, and memory aids. Secondary outcomes include maternal serum hemagglutination inhibition antibody geometric mean titers to vaccine strains, and detection of season-specific LAIV influenza strains in maternal and infant respiratory secretions at specified times. These outcomes help describe both the maternal immune response and whether vaccine strains were detected after vaccination.

The posted primary outcome is the number of participants reporting SAEs from Day 0 to Day 180 post vaccination. The registry lists outcomes for maternal and infant groups separately. The reported arm denominators are 124 for Maternal LAIV, 124 for Maternal TIV, 124 for Infant LAIV, and 125 for Infant TIV. The registry enrollment figure and these outcome denominators are not the same, and the record does not explain the difference.

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: Maternal participants and their infants were enrolled separately in the study for the purposes of data collection, analysis and reporting. For baseline measures, adverse events, and outcome measures as appropriate, the infants are defined as their own arms of the study based on the study product the mother received.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled participants are included in the analysis population for this outcome measure.

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: All enrolled subjects are included in the baseline analysis population.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Serious Adverse Events (SAEs), measured over Day 0 to Day 180 post vaccination.

The primary endpoint counts participants reporting serious adverse events (SAEs) from Day 0 to Day 180 post vaccination. It is a safety outcome: it records whether a participant experienced an event meeting the registry’s seriousness criteria, rather than measuring the frequency of all symptoms or the severity of every event.

The registry defines an SAE as an untoward medical occurrence that resulted in death, was life threatening, caused persistent or significant disability or incapacity, required inpatient hospitalization or prolongation of hospitalization, involved a congenital anomaly or birth defect, or may have jeopardized the participant or required intervention to prevent one of these outcomes. The definition applies regardless of the event’s relationship to the study product or study participation. Thus, the endpoint is not limited to events judged to have been caused by vaccination.

In general, counting participants with at least one serious event offers a way to summarize whether serious medical occurrences were reported during a specified follow-up period. It does not describe the total number of events when a participant may have had more than one, nor does it establish causation. The registry says all enrolled participants are included in the analysis population for this outcome. The posted arm results report counts and denominators; details about handling incomplete follow-up or missing outcome data are not reported in the registry record.

7. Results Posted in the Registry

• Maternal TIV: 0.0% (0/124) versus 0.8% (1/124) on control; risk difference -0.8 percentage points (95% CI -2.4 to 0.8); unadjusted two-proportion z-test p = 0.316.
• Infant LAIV: 1.6% (2/124) versus 0.8% (1/124) on control; risk difference 0.8 percentage points (95% CI -1.9 to 3.5), risk ratio 2.00 (0.18–21.77); unadjusted two-proportion z-test p = 0.561.
• Infant TIV: 0.8% (1/125) versus 0.8% (1/124) on control; risk difference -0.0 percentage points (95% CI -2.2 to 2.2), risk ratio 0.99 (0.06–15.68); unadjusted two-proportion z-test p = 0.995.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a risk difference describe? A risk difference subtracts the proportion with an outcome in one group from the proportion in a reference group. A negative estimate means the reported proportion was lower in the comparison group; a positive estimate means it was higher. For Maternal TIV versus Maternal LAIV, the posted estimate is -0.008. For Infant LAIV versus Maternal LAIV, it is 0.008. For Infant TIV versus Maternal LAIV, it is -< 0.001. These are unadjusted comparisons based on the posted counts and denominators. They should not be treated as adjusted for other participant characteristics.

The posted group counts make clear why the estimates need cautious interpretation: they are based on few SAE reports. With uncommon events, a small change in the count can materially alter an estimated group difference. The numerical estimate is not the only relevant information; the confidence interval shows the range of values compatible with the data under the method’s assumptions.

How should a confidence interval be read?

In general, a confidence interval expresses statistical uncertainty around an estimate. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not give a probability that the true effect lies within the particular interval. Here, all three risk-difference intervals cross zero, the value representing no difference between groups. Their endpoints also extend in both directions, so the results are compatible with either a lower or a higher SAE proportion in the comparison group. The intervals do not demonstrate equivalence.

The reported p-values are unadjusted: 0.316 for Maternal TIV, 0.561 for Infant LAIV, and 0.995 for Infant TIV, each compared with Maternal LAIV. In general, a p-value summarizes how surprising data at least as extreme as those observed would be under a specified null model. It is not the probability that a treatment is effective or safe, and it does not measure the size or clinical importance of an effect. A large p-value does not prove the groups are the same; it can occur when data are too sparse to distinguish plausible differences.

Why does the event count matter?

SAEs are clinically important but uncommon outcomes in this record. When counts are sparse, methods based on large-sample approximations can yield estimates and intervals with substantial uncertainty. General statistical practice treats sparse-event comparisons cautiously and may use specialized methods depending on the study plan. The registry record does not report the method used to calculate the posted intervals or p-values, so the precise computational approach cannot be assessed from this record.

The endpoint is a binary participant outcome: a participant is counted as having reported an SAE or not. This does not mean the clinical event itself is simple. The definition includes multiple seriousness categories, and the count does not show event duration, recurrence, or severity beyond meeting the SAE definition. The registry’s event-term list adds descriptions of reported categories, but does not replace the participant-level endpoint or provide causal assessments.

What do the planning illustrations mean?

The registry-linked planning illustrations use the observed effect as a starting point and show hypothetical participants per arm for 80% power and 90% power when planning for 100%, 75%, or 50% of the observed effect. These are planning illustrations, not observed power and not the trial’s original sample-size justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect.

For the Infant LAIV comparison, planning for 100% of the observed effect gives 2,884 participants per arm for 80% power and 3,860 participants per arm for 90% power. For 75% of the observed effect, the corresponding figures are 4,705 and 6,298; for 50% of the observed effect, they are 9,634 and 12,896. For the Infant TIV comparison, the corresponding figures are 30,049,431 and 40,227,662 for 100% of the observed effect; 53,474,413 and 71,587,066 for 75%; and 120,437,130 and 161,231,146 for 50%. These extreme illustrations reflect the very small observed risk difference in that comparison and should not be read as a recommendation or as evidence about the trial’s design.

The registry record does not report its original sample-size justification, any interim analyses, or a detailed statistical analysis plan. The record lists no analysis entries. Consequently, the posted unadjusted contrasts and the planning illustrations should be interpreted as descriptive statistical material, not as a complete account of the trial’s prespecified analysis.

10. Confidence Intervals and Precision

Precision is limited by the small number of posted SAE reports. The group counts are 1 for Maternal LAIV, 0 for Maternal TIV, 2 for Infant LAIV, and 1 for Infant TIV. The corresponding denominators are 124, 124, 124, and 125. With so few events, the estimates can change substantially with a small change in the observed count, and the confidence intervals are broad relative to the point estimates.

For Maternal TIV compared with Maternal LAIV, the risk difference is -0.008, and its 95% confidence interval runs from -0.024 to 0.008. For Infant LAIV compared with Maternal LAIV, the risk difference is 0.008, with a 95% confidence interval from -0.019 to 0.035. For Infant TIV compared with Maternal LAIV, the risk difference is -< 0.001, with a 95% confidence interval from -0.022 to 0.022. Every interval includes zero and permits values on either side of no difference.

In general, an interval is useful because it shows how uncertain an estimate is, not just which value is the point estimate. These intervals do not establish that risks are equal: they leave room for differences in either direction. Nor do they establish a clinically important difference. The registry record does not specify a threshold for what would count as clinically important, and the available data are not precise enough to rule out a range of possible effects.

The outcome period extends from Day 0 to Day 180 post vaccination, but precision about the event proportions should not be confused with precision about timing or causation. The posted summary does not provide time-to-event estimates, event-level follow-up detail, or an account of missing observations. The reported denominators and confidence intervals are therefore the available basis for judging statistical precision.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 22 outcome measures and 12 posted secondary outcomes. These include maternal antibody geometric mean titers, detection of vaccine strains in maternal and infant respiratory secretions at specified times, and other strain-specific outcomes. Assessing multiple outcomes can increase the chance of finding at least one apparently notable result by chance. In general, a prespecified multiplicity strategy can address this concern, but such a strategy is not reported in the registry record.

The three posted SAE comparisons each have an unadjusted p-value. The registry does not report whether these comparisons were prespecified, whether any adjustment for multiple comparisons was planned, or how the primary and secondary outcomes were prioritized for inference. The p-values should therefore be read as unadjusted statistical summaries, not as evidence that multiplicity has been addressed.

The primary outcome description says all enrolled participants are included in its analysis population. This identifies the intended population but does not explain how participants with missing follow-up, incomplete event reporting, or other unavailable outcome information were handled. Missing-data methods and the amount of missing data are not reported in the registry record. The record also does not say whether analyses followed an intention-to-treat approach or describe exclusions from the posted outcome groups.

The registry gives an enrollment figure of 240 and outcome denominators of 124, 124, 124, and 125 for the maternal and infant groups. It does not explain how these denominators relate to the enrollment figure, whether the same maternal participants contributed infant observations, or how the dependence between a mother and her infant was handled in analysis. This matters because outcomes from a mother and her infant may be related; the record does not report whether or how that relationship was considered.

The record lists no analysis entries. Details such as adjustment variables, the method for constructing confidence intervals, planned subgroup analyses, and sensitivity analyses are not reported in the registry record. Those omissions limit independent assessment of the statistical plan and of how the posted estimates should be interpreted alongside the many other outcomes.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: retained placenta or membranes (0.8%), congenital syphilis (0.8%), urinary tract infection (0.8%), respiratory syncytial virus bronchiolitis (0.8%).

The primary safety figures count participants with at least one reported SAE during Day 0 to Day 180 post vaccination. The posted counts are 1 of 124 for Maternal LAIV, 0 of 124 for Maternal TIV, 2 of 124 for Infant LAIV, and 1 of 125 for Infant TIV. They do not represent a total count of all events, and the endpoint includes events regardless of their relationship to study product or participation.

The registry’s SAE definition covers death, life-threatening events, persistent or significant disability or incapacity, hospitalization or its prolongation, congenital anomaly or birth defect, and events that may have jeopardized a participant or required intervention to prevent such outcomes. The serious-event terms listed are retained placenta or membranes, congenital syphilis, urinary tract infection, and respiratory syncytial virus bronchiolitis, each reported at 0.8%. These terms are descriptive entries; the record does not establish that vaccination caused them.

Death counts are not reported in the registry record. The small number of reported SAEs means that the between-group estimates are imprecise. A zero reported count in one group does not establish that the underlying risk is zero, and a difference in counts does not by itself establish a causal effect. The posted data describe what was recorded under the registry’s outcome definition.

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

The trial’s posted primary outcome provides a count of participants with serious adverse events during the defined follow-up period. The observed counts were low in each reported group, and the comparative risk-difference confidence intervals all include no difference. This means the posted data do not establish a clear difference in SAE proportions for any of the listed comparisons.

That finding is not the same as demonstrating that the vaccines have identical safety profiles or that either approach has no risk. Sparse events produce imprecise estimates, and the confidence intervals allow differences in either direction. The record does not report an equivalence or non-inferiority objective, a margin for such a conclusion, or an analysis establishing equivalence. The absence of a statistically clear difference should not be interpreted as proof of sameness.

The posted comparisons also need to be understood according to their reference group. Maternal TIV, Infant LAIV, and Infant TIV are each compared with Maternal LAIV. The listed infant contrasts are not direct comparisons of Infant LAIV with Infant TIV. The registry record does not explain the relationship between maternal and infant outcome observations or how that relationship was considered analytically.

The trial’s stated aims extend beyond the primary SAE count. The secondary outcomes address maternal antibody titers and detection of vaccine strains in respiratory secretions among mothers and infants. The primary safety result alone does not answer those immunogenicity or detection questions. Their full interpretation would depend on their own posted results and analysis details, which are not described by the SAE comparison.

In general, a randomized design can support comparisons between assigned groups, but the strength of an inference depends on the outcome data, the analysis, and the conduct of follow-up. The registry record does not report enough detail to assess missing observations, the original statistical plan, or the handling of maternal-infant dependence. The defensible conclusion is therefore limited: the registry reports the specified SAE counts and uncertain comparisons, not proof of no risk, causation, or equivalent safety.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difficulty of comparing uncommon safety outcomes. A randomized design can organize a comparison, but randomization does not ensure precise estimates when few participants experience the outcome. The SAE counts are sparse, and the confidence intervals show substantial uncertainty around the risk differences.

It also highlights the distinction between a point estimate and the information around it. The posted estimates are near zero, but each interval spans negative and positive values. Reading only the point estimates could make the groups appear similar; reading the intervals shows that the data do not precisely determine the direction or size of a difference. A non-significant unadjusted p-value is not proof of equal risks.

The mother-infant setting adds an important design and analysis consideration. The registry reports maternal and infant outcomes but does not explain whether the observations are linked in the analysis or how any dependence was handled. Statistical interpretation should attend to the unit of observation and the relationship between participants, not simply compare group labels.

The trial also includes outcomes beyond SAEs, including maternal immunogenicity and detection of vaccine strains in respiratory secretions. Considering multiple outcomes raises questions about prespecification and multiplicity, details that are not reported in the registry record. Likewise, the planning illustrations based on the observed effects show why rare-event comparisons can require very large samples to achieve a specified power under their stated assumptions. Those calculations are planning scenarios, not observed power or the trial’s original design justification.

Together, these features make the record a useful example of interpreting sparse events, wide uncertainty, multiple outcomes, and incomplete reporting without overstating what the data establish.

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 posted comparison structure limits straightforward interpretation. Each listed contrast uses Maternal LAIV as the reference, including the Infant LAIV and Infant TIV groups. The registry does not report a direct Infant LAIV-versus-Infant TIV contrast. It also does not explain how maternal and infant records are related, whether infant observations are paired with maternal observations, or how such dependence was handled.

The registry gives planned enrollment as 240, while the posted outcome denominators are 124, 124, 124, and 125. The record does not explain this difference or how the denominators were derived. Although the primary outcome description says all enrolled participants are in the analysis population, the handling of incomplete outcome data and the amount of missing follow-up are not reported in the registry record.

There are few SAE reports, limiting precision for uncommon safety outcomes. The record does not report a detailed statistical analysis plan, the method used for the posted intervals and p-values, adjustments for multiple outcomes, or the original sample-size justification. Death counts are not reported in the registry record. Event terms are listed, but the posted information does not establish causality or provide detailed event-level context.

The record describes triple masking, while the official title calls the study double-blind; it does not explain which participants or study personnel were masked. The trial’s completed status and planned follow-up are recorded, but details of adherence, withdrawals, and completeness of follow-up are not reported in the registry record. These reporting gaps do not change the posted counts, but they constrain assessment of their precision, comparability, and potential sources of bias.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Post-Partum Immunization With Live Attenuated Influenza Vaccine (LAIV) or Trivalent Influenza Vaccine (TIV) in Post-Partum Breast Feeding Women — NCT01181323.
• Registry record last updated 2015-01-28; status last verified 2013-04.
• Results first posted 2014-05-16.
• 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

This completed phase 2 trial randomized breastfeeding postpartum women to LAIV by nasal spray with a placebo shot or TIV by injection with a placebo nasal spray. The registry lists triple masking and a planned enrollment of 240. The primary outcome counted participants reporting SAEs from Day 0 to Day 180 post vaccination, regardless of relationship to study product or participation.

Posted SAE counts were 1 of 124 for Maternal LAIV, 0 of 124 for Maternal TIV, 2 of 124 for Infant LAIV, and 1 of 125 for Infant TIV. The three posted risk-difference comparisons use Maternal LAIV as the reference; each confidence interval includes no difference. These results are imprecise and do not establish equivalent safety or exclude meaningful differences. The registry record does not report the detailed analysis plan, missing-data handling, multiplicity strategy, or how maternal and infant observations were related in the analysis.