To Evaluate the Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Evaluate the Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older (NCT04754594), a randomized phase 2, phase 3 study. The primary outcome is Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 1.

2. Clinical Question

The study was designed to evaluate safety, tolerability, and immunogenicity. Its secondary outcomes also include COVID-19 incidence, asymptomatic SARS-CoV-2 infection, antibody concentrations and titers, changes in antibody measures after vaccination, and infant birth outcomes. These are distinct questions: the primary endpoint is a short-term measure of local reactions after the first dose, whereas the secondary outcomes address infection, immune response, and birth outcomes over their stated follow-up periods.

3. Trial Design

The registry identifies this as a Phase 2/3, randomized, placebo-controlled, observer-blind study with triple masking and a parallel design. Participants were assigned in a 1:1 allocation to BNT162b2 or placebo, according to the brief summary. The intervention description specifies 30 µg of BNT162b2 or saline placebo, given in 2 doses 21 days apart. The target population was healthy pregnant women 18 years of age and older, vaccinated at 24 to 34 weeks’ gestation.

The record lists enrollment as 726, while the brief summary describes approximately 350 pregnant women. It does not explain the difference between these figures. The study is marked completed. Its recorded start date is 2021-02-16, and its primary completion date is 2022-07-15. BioNTech SE is listed as the sponsor.

Blinding and random allocation are relevant to interpreting comparisons because they are intended to reduce the influence of participant or study-team expectations and systematic differences between assigned groups. The registry does not specify which roles were included in triple masking, how the randomization sequence was generated, or how allocation was concealed. Those procedural details are not reported in the registry record.

The primary endpoint concerns reported local reactions during the 7 days after dose 1. Other listed outcomes cover maternal COVID-19 incidence, asymptomatic infection, antibody measures, and infant birth outcomes. The brief summary notes that data are not yet available for all serology outcome measures. The registry record does not provide a numerical result for the primary endpoint.

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: A total of 726 participants were enrolled in this study. 391 were maternal participants who signed informed consent form and were enrolled out of which 41 were screen failures and 2 participants were not randomized. Eventually 348 maternal participants were randomized to receive treatment. 335 were infants born to maternal participants.

Blinded Period

Reasons for not completing this period:

Unblinded Period

Reasons for not completing this period:

Infant Participants

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: For maternal participants, safety population included all randomized participants who received at least 1 dose of the study intervention. Here, "Overall Number of Participants Analyzed" (N) signifies participants evaluable for this outcome measure. Human immunodeficiency virus (HIV) positive participants were excluded from analysis as pre-specified in the statistical analysis plan (SAP).

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: For maternal participants, safety population included all randomized participants who received at least 1 dose of the study intervention. For infant participants, safety population included all infant participants born to maternal participants who received at least 1 dose of the study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 1, measured over From Day 1 to Day 7 after dose 1.

The primary endpoint is the percentage of maternal participants reporting a local reaction from Day 1 to Day 7 after dose 1. The reactions specified are pain at the injection site, redness, and swelling. Participants recorded pain, redness, and swelling in an electronic diary. Redness and swelling were measured with a device and converted to centimeters, with severity categories defined in the record. Pain severity was classified according to whether it interfered with or prevented daily activity, or led to an emergency-room visit or hospitalization. Grade 4 reactions were classified by an investigator or medically qualified person. Reactions also reported as adverse events in the case report form during the same period were included.

A percentage gives the proportion of evaluable participants who experienced the defined event, making it a direct summary of how frequently local reactions were reported in each group. The registry specifies an exact, two-sided 95% confidence interval using the Clopper–Pearson method. Such an interval conveys uncertainty around an estimated percentage; it does not establish that any observed group difference is caused by the assigned intervention.

The record does not state the numerical percentages or confidence limits for this endpoint. Consequently, the endpoint definition can be described, but its observed frequency and comparative precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary event measure: each evaluable maternal participant either met the definition of reporting a local reaction during the specified period or did not. The reported statistic is a percentage of participants. In general, a percentage describes the observed frequency of an event in the analyzed group; it does not, by itself, describe the severity of every event or establish a causal effect.

What does the confidence interval communicate?

The registry specifies an exact, two-sided 95% confidence interval based on the Clopper–Pearson method. In general, a confidence interval expresses the uncertainty associated with an estimate under the statistical method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval is not a guarantee that the true value lies within its limits, nor does it show whether a difference between groups is clinically important. Since the endpoint percentages and interval limits are not reported in the registry record, their precision cannot be evaluated.

Why use an exact method for a percentage?

For a binary outcome, the estimate is based on the number of participants with the event relative to the number analyzed. The Clopper–Pearson method constructs confidence limits for a binomial proportion. It is called an exact method because its coverage is based on the binomial distribution rather than relying on a normal approximation to that distribution. In general, exact methods can be useful when the event count is limited or the estimated proportion is near a boundary. The registry does not report the primary endpoint event counts or analyzed denominators, so the behavior of the interval in this particular endpoint cannot be assessed.

Why does the denominator matter?

The registry distinguishes the safety population from the participants evaluable for the outcome. The safety population is described as all randomized participants who received at least one dose, while the outcome’s analyzed number signifies participants evaluable for that measure. These definitions matter because a percentage depends on which participants are included in its denominator. If participants with unavailable diary information or other missing outcome data are excluded, the analyzed group may differ from the safety population. The registry record does not explain the missing-data rules or provide the primary endpoint denominators.

What can randomization contribute?

In general, random assignment aims to make the comparison groups similar, on average, with respect to characteristics that could influence outcomes. A placebo-controlled, parallel design permits a comparison between groups assigned to different interventions over the study period. Blinding can reduce some sources of bias in outcome reporting or assessment. The registry describes randomization, placebo control, observer blinding, triple masking, and parallel groups, but does not report the random sequence procedure, allocation concealment, or the roles included in triple masking. The design description alone does not demonstrate that all potential biases were eliminated.

How should planning illustrations be read?

The registry’s planning assumptions describe illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations are framed around detecting a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm; time-to-event planning uses a total number of events. These are planning illustrations, not observed power and not evidence that the original trial was designed using those assumptions. Numerical illustration results are not reported in the registry record. No sample-size justification or original statistical plan is reported.

In general, over-dispersion matters when observed variability exceeds what a chosen probability model expects. If it is ignored, uncertainty can be understated and intervals or tests can be misleading. The listed primary endpoint is a participant-level percentage, and the registry specifies a binomial confidence-interval method. The registry does not report an over-dispersion analysis for this endpoint, so there is no basis to claim that such an adjustment was used or needed.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 21 outcome measures and 6 analyses. The outcomes span local reactions, adverse events, COVID-19 incidence, asymptomatic infection, antibody measures, and infant birth outcomes. When a study evaluates multiple outcomes or performs multiple analyses, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can address this issue through a prespecified hierarchy or adjustment. The registry record does not report whether any such procedure was planned or used, nor does it identify a hierarchy of outcomes. The presence of multiple listed outcomes alone does not establish how their results should be interpreted jointly.

For the primary endpoint, the record describes the safety population as randomized participants who received at least one dose and says the analyzed number represents participants evaluable for the outcome. It does not provide the actual analyzed denominators or the numerical outcome estimates. The record does not report how missing diary entries, incomplete follow-up, or other missing outcome data were handled. Without those details, it is not possible to determine whether participants with missing information were excluded, treated as having no event, or handled by another approach.

The brief summary states that data are not yet available for all serology outcome measures. The registry record does not describe imputation, sensitivity analyses, or other methods for missing serology data. It also does not report whether analyses were adjusted for baseline factors or how analysis populations were defined for each secondary outcome. Those details are not reported in the registry record and should not be inferred from the outcome titles.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (11.1%), neonatal pneumonia (11.1%), gastroenteritis (11.1%), dehydration (11.1%), superior sagittal sinus thrombosis (11.1%).

The adverse-event record separates serious events, other adverse events, and deaths. In the maternal blinded-phase groups, serious events are listed for 21 of 161 participants assigned to BNT162b2 and 23 of 163 assigned to placebo. Other adverse events are listed for 143 of 161 and 119 of 163, respectively. In the maternal placebo-then-BNT162b2 unblinded-phase group, the record lists 0 serious events among 144 participants and 21 with other adverse events among 144.

For infants, the BNT162b2 group lists 21 serious events among 156 and 29 with other adverse events among 156; the placebo group lists 24 serious events among 159 and 33 with other adverse events among 159. The record lists 0 deaths in the maternal groups, 1 death in the infant placebo group, and 0 in the infant BNT162b2 group. The HIV-positive maternal and infant groups are separately listed subgroups, not additional groups to combine with the broader categories.

The record also names serious-event terms with percentages, including Urinary tract infection at 11.1% and Cephalo-pelvic disproportion at 10.0%. It does not give the event counts or denominators for these terms in the registry record, so those percentages should be read as registry-listed values rather than recalculated. Event counts alone do not establish causation or comparative risk, particularly across groups from different phases or populations.

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

The registry record establishes that a randomized, placebo-controlled study was conducted to evaluate safety, tolerability, and immunogenicity of BNT162b2 in healthy pregnant women. It describes the intervention schedule, target population, primary local-reaction endpoint, and several secondary outcome areas. It also reports adverse-event counts for maternal and infant groups. These details help define what the study set out to examine and which types of events were recorded.

They do not establish the numerical result for the primary local-reaction endpoint. The registry record does not provide its percentages or confidence intervals. Nor do the listed adverse-event counts, by themselves, answer the primary endpoint question: serious and other adverse events are not interchangeable with the endpoint’s specified local reactions during the 7 days after dose 1.

The record also does not provide numerical estimates for the listed infection, antibody, or infant birth outcomes in the registry record for this analysis. The brief summary cautions that data are not yet available for all serology measures. Therefore, the outcome list should not be mistaken for results, and the trial’s completed status should not be taken as evidence that every outcome estimate is present in the registry record.

In general, a group comparison requires estimates for the outcome, clear denominators, and an account of uncertainty and analysis choices. A difference in observed percentages, if reported, would not alone establish a causal or clinically meaningful effect. Interpretation would also depend on missing data, multiplicity, follow-up, and the prespecified analysis. Several of these details are not reported in the registry record. No conclusion about whether the intervention works or does not work follows from the available details.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are important when studying outcomes during pregnancy. The population, timing of vaccination, comparator, and follow-up define which participants and events the results could describe. The primary endpoint is a short-term participant-reported outcome, while the secondary outcomes include infection incidence, immune measurements, and infant birth outcomes. These measures differ in meaning and in the way their uncertainty should be assessed.

The design uses randomization and placebo control, which provide a framework for comparative inference. Blinding is also relevant when outcomes include participant-reported reactions. At the same time, the registry’s brief design description does not report the randomization procedure or the specific roles covered by triple masking. Statistical interpretation must distinguish design features that are recorded from procedural details that are not reported.

The record also illustrates why a named endpoint is not enough to interpret a result. The local-reaction endpoint specifies a time window, reaction types, grading rules, and a confidence-interval method, but its numerical estimates and analyzed denominators are absent. Without those, the frequency and precision of the primary endpoint cannot be assessed. The safety counts add information about recorded adverse events, but they address different measures.

Finally, the record lists numerous outcome measures and analyses, while leaving multiplicity and missing-data methods unspecified. These are not minor technicalities: they affect how estimates across outcomes should be evaluated. The record’s note about unavailable serology data and the differing enrollment figures in the record and brief summary further emphasize the need to state clearly which data and populations support each conclusion.

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.

The principal limitation for interpreting the stated primary question is that the registry record does not report the primary endpoint percentages, confidence intervals, or analyzed denominators. As a result, neither the observed frequency of local reactions nor the precision of its estimate can be assessed. The adverse-event counts do not fill this gap because they summarize different event categories.

The registry reports enrollment as 726, while the brief summary describes approximately 350 participants. It does not explain the difference, so the figures cannot be reconciled from the registry record. The primary endpoint population text is also incomplete after describing the safety population and evaluable participants; additional eligibility details are not reported in the registry record.

The record lists 21 outcome measures and 6 analyses but does not report a multiplicity strategy, a statistical analysis plan, or methods for missing data. It does not provide the primary endpoint results, numerical estimates for the listed secondary outcomes, or all serology data. The brief summary explicitly notes that data are not yet available for all serology outcome measures.

Adverse-event counts are reported across blinded and unblinded phases, maternal and infant groups, and HIV-positive subgroups. These groupings do not all represent the same population or comparison. The record does not supply enough detail to treat every listed group as part of a single direct randomized comparison. The serious-event terms are listed with percentages, but their corresponding counts and denominators are not included in the registry record for this analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Evaluate the Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older — NCT04754594.
• Registry record last updated 2024-12-06; status last verified 2024-11.
• Results first posted 2024-12-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed randomized, placebo-controlled Phase 2/3 study of BNT162b2 in healthy pregnant women 18 years of age and older. The brief summary specifies vaccination at 24 to 34 weeks’ gestation, with 2 doses 21 days apart, and placebo as the comparator. BioNTech SE is listed as sponsor.

The primary outcome is the percentage of maternal participants reporting local reactions within 7 days after dose 1. The registry specifies an exact, two-sided 95% Clopper–Pearson confidence interval, but does not report the primary outcome estimates or analyzed denominators. Adverse-event counts are listed for maternal and infant groups, including separate HIV-positive subgroups. The record lists 21 outcome measures and 6 analyses, and the brief summary notes that data are not yet available for all serology outcome measures.