The Effects of Aspirin in Gestation and Reproduction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Aspirin in Gestation and Reproduction (NCT00467363), a randomized na study. The primary outcome is Live Birth.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with quadruple masking. Its official title calls it a multi-center, controlled, double-blind randomized trial. Those descriptions differ in their masking terminology; the record does not explain how the masking labels were assigned or which roles were masked. The study is listed as completed and has no phase classification beyond “NA.”

The two arms were Aspirin and Placebo. The Aspirin arm received 81mg of low-dose aspirin plus 400micrograms of folic acid; the Placebo arm received 400micrograms of folic acid. This design makes the added aspirin component the intended difference between the groups, while folic acid is common to both. The registry records enrollment of 1228. The analyzed group sizes vary by outcome, and the primary outcome description says that participants lost to follow-up were excluded from the intention-to-treat analyses.

The primary objective was to examine live births and spontaneous abortions among women who become pregnant. Live birth was assessed after delivery using maternal report and abstraction from medical records by trained staff. The record lists additional outcomes such as recognized pregnancy, early pregnancy loss, fetal pregnancy loss, stillbirth, ectopic pregnancy, and molar pregnancy. The record does not report the randomization procedure, allocation concealment, treatment adherence, crossover, or detailed eligibility criteria. Those details should not be inferred from the randomized and masked design labels alone.

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: Out of the 1397 women with confirmed eligibility, consented, and expressed initial interest in the study, 60 (4.3%) chose to discontinue the enrolment process. An additional 109 (7.8%) tested positive for pregnancy at the baseline visit or became pregnant before their randomisation visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analyses were based on the intention-to-treat principle (excluding participants lost to follow-up).

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 women who consented and underwent randomization were included in baseline analyses.

6. Primary Endpoint

The registry lists the primary outcome as Live Birth, measured over after delivery.

The primary endpoint was Live Birth, recorded as the number of live births after delivery. The registry says the information was obtained prospectively through maternal report and abstraction from medical records by trained staff. Using both sources can support outcome ascertainment, although the record does not describe how disagreements between sources were handled or how a live birth was defined in the study procedures.

Live birth is directly aligned with the study’s stated objective, which concerns the incidence of live births and spontaneous abortions among women who become pregnant. It is also an outcome that can be recorded after pregnancy and delivery, rather than an intermediate measure of pregnancy recognition. For the posted primary outcome, the arm summaries report 309 live births among 535 participants in the Aspirin group and 286 among 543 in the Placebo group. The sponsor’s reported comparison is a risk ratio.

As a general statistical point, an endpoint is useful when its definition corresponds to the question a trial is designed to address and when it can be measured consistently. The registry’s description identifies the sources used to ascertain live birth, but the full operational definition and procedures are not reported in the registry record. The stated analysis population is intention-to-treat excluding participants lost to follow-up, so the endpoint summaries should be interpreted in light of that qualification.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is reported as a risk ratio, using a Fisher Exact method. A risk ratio compares the probability of an outcome between groups; its no-difference value is the value at which the two group probabilities are equal. The reported primary estimate is 1.10, with a 95% confidence interval from 0.98 to 1.22. In general, a confidence interval describes a range of estimates compatible with the data and the method’s assumptions. Its width conveys precision: a wider interval indicates less precision. Because the primary interval covers the no-difference value, the estimate does not distinguish clearly between a small difference in either direction and no difference.

The registry’s displayed primary outcome is a count of live births, with a number of participants in each arm. The sponsor nevertheless reports a risk ratio, a measure based on group risks rather than a difference in raw counts. The record does not provide the sponsor’s full computational details, a complete statistical analysis plan, or the handling of every data issue. The arm counts and reported risk ratio therefore should be presented as recorded rather than used to reverse-engineer undocumented procedures.

For binary secondary outcomes, the recalculated summaries include risk differences and risk ratios. A risk difference expresses the contrast between group risks on an absolute scale, while a risk ratio expresses it on a relative scale. These measures answer related but distinct questions. A small absolute difference can coexist with a relative estimate that is less intuitively close to no difference, especially when an outcome is uncommon. General interpretation should consider the scale, the underlying event frequency, and the uncertainty interval together. The registry also reports sponsor comparisons for these outcomes; those analyses take priority as the trial’s own reported results, and recalculated results are explicitly unadjusted.

For the continuous secondary outcome, the arm summaries are means and standard deviations. A mean difference compares the groups’ average values, while the standard deviation describes variability among observations within a group. The recalculated mean difference is 12.0 grams, with a confidence interval from -51.95 to 75.95. In general, a t-test assesses whether a mean difference is distinguishable from no difference under its assumptions. The sponsor reports a two-sided t-test. The record does not report whether this analysis was adjusted for other variables or whether any transformations or other model choices were used.

General statistical explanation: confidence intervals are not guarantees that the true effect lies within the displayed range. They are calculated using a method whose interpretation depends on assumptions about the data and analysis. A confidence interval that spans the no-difference value does not prove equivalence. Showing that groups are sufficiently similar would require a prespecified equivalence or noninferiority framework and suitable margins; those are not reported in the registry record.

The planning illustrations are based on the observed effect and use a two-sided significance level of 0.05, equal allocation, and a normal approximation. Their rows consider detecting stated fractions of the observed effect. These are planning illustrations, not the trial’s own design justification and not observed power. They should not be used to infer what the investigators planned or to reinterpret the trial as having been designed around those assumptions. The record does not report the original sample-size justification.

General explanation: over-dispersion matters when count data vary more than the model assumes. A model that understates variability can produce confidence intervals that are too narrow and tests that are too optimistic. The primary outcome is recorded as a count, but the registry supplies no dispersion estimate and reports a Fisher Exact comparison for a risk ratio. There is no basis in the record for claiming that over-dispersion was present or that a count model was fitted. This general issue is relevant to count outcomes, but it should not be mistaken for a description of the trial’s actual analysis.

Finally, the record describes an intention-to-treat approach for the primary analyses, excluding participants lost to follow-up. In general, intention-to-treat analysis aims to preserve the randomized comparison by analyzing participants according to assigned group. The stated exclusion for loss to follow-up qualifies that label: the record does not say how missing outcomes were handled, whether follow-up differed by group, or how many participants were lost. Without those details, the consequences of missing data cannot be quantified.

10. Analyses Reported by the Sponsor

The registry’s primary analysis reports a risk ratio of 1.10 for live birth, with a 95% confidence interval from 0.98 to 1.22. The primary result is reported by the sponsor using a Fisher Exact method. No discrepancy is flagged between the sponsor analysis and a recalculation for this primary endpoint; a recalculated primary comparison is not available in the posted comparison data. The sponsor’s reported analysis is therefore the relevant primary estimate to quote, rather than substituting a newly derived figure.

For the secondary outcomes with comparisons, sponsor results are also listed. For stillbirth, the sponsor reports a risk ratio of 1.03 and a 95% confidence interval from .15 to 7.26. For preeclampsia, the sponsor reports a risk ratio of 1.08 and a 95% confidence interval from .67 to 1.76. For the continuous birth-weight outcome, the sponsor reports a two-sided t-test, without a reported test statistic or confidence interval in that analysis entry. Recalculated summaries use posted arm-level statistics and are simple, unadjusted calculations; they are not the sponsor’s analysis and should not be presented as if they were.

The registry record does not provide enough detail to reconstruct every sponsor procedure, including any covariate adjustment or missing-data sensitivity analysis. A match or lack of a flagged discrepancy does not establish that all underlying assumptions are identical. The sponsor analysis remains the primary reference for the trial’s reported result.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, 13 analyses, and 14 posted secondary outcomes. The outcomes span different clinical events and measurement types. Assessing many outcomes raises a general multiplicity issue: the more comparisons considered, the greater the possibility of observing an apparently unusual result by chance. This does not show that any particular finding is false, but it affects how much confirmatory weight should be placed on isolated secondary results.

A prespecified outcome hierarchy, family-wise error adjustment, false-discovery procedure, or other multiplicity plan could clarify how multiple tests were intended to be interpreted. Such a plan is not reported in the registry record. The record also does not report whether the outcomes or analyses changed over time, which outcomes were primary at the protocol stage, or whether any analyses were designated exploratory. Without that information, the posted secondary comparisons should be regarded cautiously and not treated as a set of independent confirmations.

For the primary endpoint, the population description states that analyses followed the intention-to-treat principle while excluding participants lost to follow-up. The record does not report how many participants were lost, the reasons for loss, the timing of loss, or whether missingness differed between groups. It does not say whether missing outcomes were imputed, whether participants with incomplete records were handled in another way, or whether sensitivity analyses were conducted. These omissions prevent assessment of how missing outcomes may have influenced the comparison.

Analysis populations for the secondary endpoints are not uniformly described in the registry entries. Arm sizes differ across outcomes, but the record does not explain each difference. The record also does not report a complete protocol, statistical analysis plan, interim-analysis procedures, stopping rules, or sample-size justification. Those elements should not be inferred from the planning illustrations, which are explicitly based on observed effects rather than the trial’s own design assumptions.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: minor birth defects (0.7%), neonatal death (0.3%), transient pulmonary hypertension (0.2%).

The adverse-event summary reports serious events among 615 participants at risk in the Aspirin group and 613 in the Placebo group. It records 7 serious events for Aspirin and 5 for Placebo. For other, non-serious adverse events, the record lists 24 among 615 at risk in the Aspirin group and 8 among 613 at risk in the Placebo group. These are the registry’s event counts and denominators; they do not by themselves establish whether an event was caused by the assigned intervention.

The record lists Minor Birth Defects at 0.7%, Neonatal Death at 0.3%, and Transient Pulmonary Hypertension at 0.2% among the top serious terms. It does not identify group-specific percentages for those terms in the registry record used. Death counts are not reported in the registry record. The record does not provide enough detail to assess event timing, severity definitions, relatedness assessments, or whether participants could contribute more than one event.

Safety figures should be interpreted as descriptive reporting rather than as a definitive comparative safety analysis. The different event counts do not establish a treatment effect, and sparse events can leave considerable uncertainty. The available registry information does not support a causal attribution or a complete account of all safety procedures.

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

The primary result estimates the relative frequency of live birth in the Aspirin group compared with the Placebo group. Its point estimate is 1.10, but the 95% confidence interval from 0.98 to 1.22 includes the no-difference value. The posted result therefore leaves uncertainty about whether the groups differed and, if so, about the size and direction of that difference. It is not a demonstration of equivalence, and it is not proof that no effect exists.

Nor should the point estimate be read as a causal promise about an individual pregnancy. A randomized trial can support a group comparison under its design and analysis assumptions, but the registry account does not supply all details needed to assess those assumptions. The stated primary analysis excludes participants lost to follow-up, and the extent and handling of missing data are not reported. The record also does not describe adherence, crossover, or the full eligibility criteria.

The intervention contrast is aspirin plus folic acid versus folic acid alone. The results therefore concern the added aspirin component within that trial comparison; they are not a comparison of aspirin against no treatment or of folic acid against no folic acid. The population is described in the objective as women who become pregnant, but the full characteristics of participants are not reported in the registry record.

The secondary outcomes add context but are not a substitute for the primary endpoint. Their estimates differ in scale, event frequency, and precision, and the registry does not report a multiplicity plan. For these reasons, neither the primary estimate nor a selection of secondary results should be generalized beyond the outcomes and comparison recorded. No medical conclusion about an individual’s care follows from these registry statistics alone.

14. Why This Trial Matters Statistically

This trial is statistically informative because its comparison separates the contribution of aspirin from folic acid more directly than a design in which the groups receive different combinations of both. Both arms received 400micrograms of folic acid, while the Aspirin arm also received 81mg of low-dose aspirin. The randomized, parallel-group design is suited to comparing group outcomes, and the masking description indicates an effort to limit some forms of bias, although the registry record does not detail implementation.

The primary endpoint also matters because it captures a consequential outcome aligned with the stated objective, rather than relying only on an intermediate measure such as pregnancy recognition. The registry describes prospective ascertainment through maternal report and medical-record abstraction by trained staff. That description provides useful information about measurement, while leaving the full endpoint definition and reconciliation procedures unreported.

At the same time, the result illustrates why point estimates must be paired with precision. A risk ratio of 1.10 can look like a clear numerical contrast when read alone, but its confidence interval extends across the no-difference value. The interval is compatible with materially different interpretations, so the evidence should be described as uncertain rather than reduced to the direction of the point estimate.

The record also illustrates the limits of registry-level reporting. A completed trial can have posted outcome results without the public record containing a full statistical plan, missing-data account, multiplicity strategy, or detailed population description. Those omissions matter when interpreting secondary findings and assessing reproducibility. The appropriate statistical reading is therefore specific: the posted primary estimate is imprecise, and the additional outcomes provide context with their own limitations rather than a definitive resolution.

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.

Several trial-specific details needed for a fuller assessment are not reported in the registry record. The full inclusion and exclusion criteria, participant characteristics, randomization procedure, allocation concealment, and implementation of masking are not described in the registry record used. The official title uses “double-blind,” while the masking classification is “quadruple”; the record does not explain this difference. It would be inappropriate to infer which participants or staff were masked.

The primary analysis is described as intention-to-treat with participants lost to follow-up excluded. The number lost, reasons for loss, group distribution, and missing-outcome methods are not reported in the registry record. The outcome-specific arm sizes also vary, with no complete explanation of those differences. Consequently, the impact of missingness or changes in analysis populations cannot be evaluated from the posted information.

The full statistical analysis plan, original sample-size justification, interim analyses, stopping rules, and any prespecified multiplicity procedure are not reported. The sample-size illustrations based on observed effects should not be mistaken for the trial’s own design plan. Secondary outcomes are numerous and do not all have posted comparisons, and the record does not clarify which were confirmatory. This limits the strength of conclusions drawn from selected secondary findings.

For safety, the record gives event counts and selected serious-event terms but does not report event relatedness, timing, detailed definitions, group-specific percentages for the listed terms, or death counts. For the primary endpoint, the measurement sources are described, but the operational definition and handling of disagreement between sources are not. These limitations concern what can be established from the registry record; they do not establish that a procedure was or was not used in the trial.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effects of Aspirin in Gestation and Reproduction — NCT00467363.
• Registry record last updated 2017-02-03; status last verified 2016-12.
• Results first posted 2014-05-14.
• 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

The record describes a completed randomized, parallel-group trial of low-dose aspirin plus folic acid versus folic acid alone. It lists quadruple masking and enrollment of 1228. The primary endpoint was live birth after delivery, ascertained by maternal report and medical-record abstraction. The reported risk ratio is 1.10, with a 95% confidence interval from 0.98 to 1.22.

The primary analysis is described as intention-to-treat excluding participants lost to follow-up. The record lists a range of pregnancy-related secondary outcomes and adverse-event summaries, but does not report a complete multiplicity plan, missing-data account, or full statistical analysis plan. The primary estimate is uncertain, and the registry information does not support treating the secondary findings as definitive confirmation.