Fetal and Infant Effects of Maternal Buprenorphine Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fetal and Infant Effects of Maternal Buprenorphine Treatment (NCT01561079), a na phase 2, phase 3 study. The primary outcome is Fetal Heart Rate.

2. Clinical Question

3. Trial Design

The registry record describes a Phase 2 and Phase 3 study titled “Fetal and Infant Effects of Maternal Buprenorphine Treatment.” It is marked completed, with a recorded enrollment of 127. The study began in 2012-02 and its primary completion was 2016-06. The condition listed is Neonatal Abstinence Syndrome.

The design is classified as single-group. The intervention is buprenorphine, described as maternal maintenance during pregnancy. Allocation is recorded as not applicable, and masking is recorded as none. These design features mean that the primary endpoint is not framed as a randomized comparison between treatment groups. The registry summary says comparisons with results from a similar project in methadone-exposed pregnancies will be made; it does not describe that project as a concurrent control arm.

The primary endpoint concerns fetal heart rate in beats per minute at trough and peak maternal buprenorphine levels. Measurements are specified at 24, 28, 32 and 36 weeks of gestation. The endpoint population is described as participants active in the protocol at each of those gestational visits, respectively. This wording identifies visit-specific populations rather than guaranteeing that every participant contributed a measurement at every visit.

The broader study description says the research will track fetal neurobehavioral development across gestation through 1 month of age. It also describes aims related to maternal physiologic changes, newborn functioning, and potential fetal markers of Neonatal Abstinence Syndrome expression and infant neurobehavioral outcome. These are stated research aims; the registry record does not report results for those aims in the registry record for interpretation. The record identifies five outcome measures and five analyses, but does not report their individual results or the analysis methods used for them.

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: Participants must have an opioid use disorder, a singleton, generally uncomplicated pregnancy, be between 18 and 40 years of age, have accurate gestational age dating of less than 34 weeks, willing to receive obstetric care at the center and deliver their infant at the hospital affiliated with the treatment facility.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants active in the protocol at 24, 28, 32 and 36 weeks, respectively

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 Fetal Heart Rate, measured over 24, 28, 32 and 36 weeks of gestation.

The primary endpoint is fetal heart rate, measured in beats per minute at trough and peak maternal buprenorphine levels. It is assessed at 24, 28, 32 and 36 weeks of gestation. The registry identifies the summary measure as a mean and the measure of variability as a standard deviation. These specify how the outcome is intended to be described; they do not provide the observed means or standard deviations.

Fetal heart rate is a continuous measure: its values can vary across a range rather than being limited to categories such as event or no event. A mean describes the central level of the measurements, while a standard deviation describes how spread out observations are around that mean. Reporting both can help readers understand the observed level and variability, but neither alone establishes why values differ or whether a difference is clinically meaningful.

Measurements at trough and peak maternal levels are intended to characterize fetal heart rate in relation to those maternal treatment-level contexts. The registry description does not state the precise timing or procedures used to define or measure trough and peak. It also does not report the endpoint values, the number of observations contributing at each visit, or uncertainty estimates. Consequently, the endpoint definition can be described, but its observed pattern and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

For a continuous outcome such as fetal heart rate, the mean is a measure of the central level of observed values. The standard deviation describes their spread around that level. Together, these statistics can communicate both the average and the variability in a group. They do not show the full shape of a distribution, and they do not indicate whether an observed difference is attributable to treatment or another factor.

The registry specifies a mean and standard deviation for the primary endpoint, but does not report their values. It also does not report confidence intervals or another measure of uncertainty for fetal heart rate. In general, a confidence interval conveys uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but precision is distinct from clinical importance. Without reported estimates and uncertainty, neither can be evaluated for this endpoint.

Why do the visit and treatment-level descriptions matter?

The endpoint is defined at four gestational visits, with fetal heart rate assessed at trough and peak maternal buprenorphine levels. Repeated measurements can describe how an outcome varies over time and across measurement contexts. They also create analysis choices: an analyst might describe each visit separately or model the correlation among observations from the same participant. The registry record does not report which approach was used, how trough and peak were defined operationally, or how measurements from different visits were handled.

The endpoint population is described as participants active in the protocol at 24, 28, 32 and 36 weeks, respectively. This makes the visit-specific population relevant to interpretation. If the people contributing data differ across visits, apparent variation over time may reflect both changes within participants and changes in who remains observed. The registry record does not report visit-specific participant counts, reasons for unavailable measurements, or an approach to missing observations.

What can a single-group design establish?

A single-group study can describe outcomes observed among participants receiving the intervention. In general, a concurrent randomized comparator helps distinguish a treatment contrast from changes associated with time, participant characteristics, or other influences. This record classifies the model as single-group and allocation as not applicable; it does not describe a concurrent randomized control arm. Thus the design description does not establish a randomized treatment effect.

The summary refers to comparisons with results from a similar project in methadone-exposed pregnancies. Such a comparison may provide context, but interpretation depends on the comparability of participants, measurements, follow-up, and analysis. Those details are not reported in the registry record. The external comparison should not be treated as equivalent to a control group unless comparability is established.

How should planning illustrations be read?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes detecting a stated fraction of an observed effect. These are planning assumptions, not a description of the trial's own design: the study is classified as single-group. The illustration is not observed power and does not show that the study had a particular probability of detecting its actual effect. Sample-size illustrations depend on assumed effects and other design inputs; they do not substitute for observed estimates or their uncertainty.

The record does not report the effect estimate used for the illustration in the registry record for interpretation, or a justification showing how the study's enrollment was chosen. The registry record therefore does not support a judgment about whether the completed study was adequately sized for its primary endpoint. Any planning values should be understood as hypothetical illustrations under their assumptions, rather than as evidence about what the study found.

What is the role of adverse-event counts?

Adverse-event summaries count participants or events according to the categories defined by the record. A serious adverse event count is not a measure of the primary fetal heart rate endpoint. Counts also do not on their own establish that treatment caused an event. Interpretation depends on definitions, observation windows, ascertainment, and comparison groups. The registry record gives selected counts and serious-event terms, but does not report enough detail to resolve those issues.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("FHR 24 Weeks Trough", "FHR 28 Weeks Trough", "FHR 32 Weeks Trough", "FHR 36 Weeks Trough", "FHR 24 Weeks Peak", "FHR 28 Weeks Peak")
n   <- c(20, 30, 42, 40, 20, 30)
m   <- c(145.7, 143.3, 138.6, 136.3, 143.9, 141)
sp  <- c(5.8, 5.4, 6, 7.1, 6.4, 4.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  FHR 24 Weeks Trough  20  145.700  5.800  142.986  148.414
CARM  FHR 28 Weeks Trough  30  143.300  5.400  141.284  145.316
CARM  FHR 32 Weeks Trough  42  138.600  6.000  136.730  140.470
CARM  FHR 36 Weeks Trough  40  136.300  7.100  134.029  138.571
CARM  FHR 24 Weeks Peak  20  143.900  6.400  140.905  146.895
CARM  FHR 28 Weeks Peak  30  141.000  4.800  139.208  142.792

11. Multiplicity, Missing Data and Analysis Populations

The record identifies five outcome measures and five analyses. The primary endpoint is fetal heart rate, but the available record does not describe the analysis hierarchy for the other outcomes, whether any were designated secondary, or which analyses correspond to which measures. It also does not report whether the analysis plan adjusted for multiple outcomes, visits, or comparisons. When many hypotheses are tested, the chance of at least one apparently unusual result can increase; methods that address multiplicity can help control that issue. Whether any such method was used is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary endpoint population is defined as participants active in the protocol at 24, 28, 32 and 36 weeks, respectively. That wording leaves open how many measurements were available at each visit and why any were absent. It does not establish whether missing observations were excluded, imputed, or handled through a repeated-measures model. The record does not report sensitivity analyses for missing data.

The analysis population is not described beyond the visit-specific active-participant wording. The registry record does not report whether analyses followed an intention-to-treat principle, used only participants with available measurements, or applied another population definition. It also does not report interim analyses or the statistical analysis plan. These omissions limit assessment of selection, multiplicity, and the relationship between planned and reported analyses; they are not evidence that a particular method was or was not used.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: severe adverse event (2.0%), congenital heart disease (2.0%).

For the listed maternal buprenorphine treatment group, the registry records 49 at risk for serious adverse events and 1 affected by a serious adverse event. It records 49 at risk for other adverse events and 15 affected. Deaths are recorded as 0. These are safety counts for the group and should be read separately from the fetal heart rate endpoint.

The listed serious adverse event terms include “Severe adverse event” at 2.0% and “congenital heart disease” at 2.0%. The registry record does not give further detail in the registry record about event timing, overlap between terms, or whether the terms refer to participants or event occurrences. The percentages should therefore be understood as the recorded term summaries, not converted into additional counts.

Adverse-event counts describe what was recorded under the study's categories; by themselves, they do not establish that buprenorphine caused an event. Nor do counts from a single-group study provide a direct estimate of excess risk relative to an untreated or alternative-treatment group. Definitions, follow-up, ascertainment, and comparator data all matter to a fuller safety interpretation, and those details are not reported in the registry record.

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

The registry record establishes that this completed study examined maternal buprenorphine maintenance in a single-group design and specified fetal heart rate as its primary endpoint. It identifies the measurement contexts and gestational visits, and it describes broader interests in fetal and infant neurobehavioral development and Neonatal Abstinence Syndrome. It also reports selected adverse-event counts for the maternal buprenorphine treatment group.

The record does not report the observed fetal heart rate means, standard deviations, or uncertainty estimates. It therefore does not show the endpoint's level, variability, or precision. It does not report results for the broader neurobehavioral aims in the registry record for interpretation. The stated aims cannot be treated as evidence that fetal markers predicted Neonatal Abstinence Syndrome or that maternal physiologic changes were associated with newborn functioning.

The single-group design is important to the scope of interpretation. Outcomes observed during buprenorphine maintenance can be described, but the design information does not support a randomized comparison with another treatment. The summary's reference to a similar methadone-exposed project indicates an intended comparison of results, not a concurrent control group; the methods and findings for that comparison are not reported in the registry record.

The adverse-event figures are descriptive counts and term summaries. They do not establish causation or comparative risk. The record does not report enough information to determine how events were assessed, whether categories overlap, or how the findings compare with another group.

Accordingly, the posted information supports a description of the study's question, design, endpoint definition, and selected safety figures. It does not support a conclusion about the size or precision of the primary endpoint findings, a causal treatment effect, or the comparative safety of buprenorphine. Those questions require results and methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a statistically important challenge: describing measurements collected repeatedly during pregnancy while avoiding conclusions that exceed the design. Fetal heart rate is specified at trough and peak maternal buprenorphine levels across four gestational visits. Such a structure calls for attention to within-participant dependence, visit-specific data availability, and the definition of each measurement context. The registry record does not report how those analysis issues were addressed.

The single-group classification also clarifies the difference between describing outcomes under treatment and estimating a treatment contrast. Without a concurrent randomized comparator, observed measurements cannot by themselves separate treatment-related change from other influences. The stated intention to compare with a similar methadone-exposed project makes comparability of participants and methods especially relevant, but those details are not reported in the registry record.

Multiplicity is another consideration because the record identifies five outcome measures and five analyses. Multiple outcomes and repeated measurement contexts can create many possible comparisons. A clear analysis plan and reporting of how those comparisons were handled would help readers distinguish primary questions from exploratory ones. Those details are not reported in the registry record.

Finally, endpoint results and uncertainty are essential to judging what the data show. The endpoint definition alone cannot reveal its observed level, variability, or precision. The registry's design and safety information can orient readers to the research question, but without primary endpoint estimates and analysis details, statistical conclusions must remain limited.

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 main limitation for interpreting the primary endpoint is that its observed means and standard deviations are not reported in the registry record. No uncertainty estimate is reported either. As a result, the endpoint's magnitude, variation, and precision cannot be evaluated.

The study is classified as single-group, with allocation not applicable and no masking. The registry summary mentions comparison with a similar project in methadone-exposed pregnancies, but the registry entries available do not describe a concurrent comparator or provide the comparison methods and results. This limits conclusions about treatment contrasts and comparability.

The primary endpoint is defined at trough and peak maternal buprenorphine levels at 24, 28, 32 and 36 weeks of gestation. The record does not report the procedures used to define those levels, visit-specific data counts, or how measurements within participants were analyzed. Although the endpoint population is described as participants active in the protocol at each visit, the handling of missing measurements and changes in the observed population is not reported.

The registry identifies five outcomes and five analyses, but does not report their analysis hierarchy, multiplicity approach, or the statistical analysis plan. It also does not report interim analyses or the method used to select analysis populations. These gaps limit appraisal of the analysis decisions and the relationship between planned and reported results.

The adverse-event information is limited to the recorded at-risk and affected counts, deaths, and selected serious-event terms. Further event definitions, timing, ascertainment details, and comparative safety results are not reported in the registry record. The broader neurobehavioral aims are described, but results for them are not included in the registry record for interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fetal and Infant Effects of Maternal Buprenorphine Treatment — NCT01561079.
• Registry record last updated 2017-09-26; status last verified 2017-08.
• Results first posted 2017-08-28.
• 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.

19. Record Summary

NCT01561079, “Fetal and Infant Effects of Maternal Buprenorphine Treatment,” is recorded as a completed Phase 2 and Phase 3, single-group study with enrollment of 127. The intervention is maternal buprenorphine maintenance during pregnancy. The record lists Neonatal Abstinence Syndrome as the condition and describes fetal and infant neurobehavioral research through 1 month of age.

The primary endpoint is fetal heart rate in beats per minute at trough and peak maternal buprenorphine levels at 24, 28, 32 and 36 weeks of gestation. It is specified as a mean with standard deviation. The registry record does not report the endpoint results or their uncertainty. The summary mentions comparison with a similar methadone-exposed project, not a concurrent randomized control group.

For the listed treatment group, the record reports 1 serious adverse event among 49 at risk, 15 with other adverse events among 49 at risk, and 0 deaths. These descriptive figures do not establish causation or comparative risk.