This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Vitamin D to Prevent Autism in Newborn Siblings (NCT01366885), a na phase 2 study. The primary outcome is Number of Children Who Developed Autism.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01366885 |
| Phase | Phase 2 |
| Condition | Autistic Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Oregon Health and Science University |
| Results posted | Yes |
2. Clinical Question
Population
Pregnant mothers who already have at least one child with autism, and the newborn siblings whose later development was to be assessed. The record lists Autistic Disorder as the condition and describes screening the child during follow-up.
Intervention
A vitamin D3 regimen that begins during pregnancy and continues according to breastfeeding status and the child’s age. The regimen describes 5000 IU for the mother during pregnancy, 7000 IU during breastfeeding if breastfeeding, or 400 IU for the infant during the first year and then 1000 IU until the research trial is complete if not breastfeeding.
Comparator
No control group or like-for-like comparator is reported. The registry classifies the study as single-group and lists allocation as NA, so the study does not provide a randomized comparison of vitamin D3 with another treatment or with no intervention.
Primary question
The primary outcome asks how many children developed autism, with assessment at 3 years of age. The study’s stated purpose is to examine whether administering vitamin D to pregnant mothers who already have a child with autism could prevent recurrence in the newborn sibling. The primary outcome result is not reported in the registry record, so the posted information does not answer that question.
This clinical question concerns a prevention strategy in a specifically described family context. Its interpretation depends on distinguishing the study’s stated purpose from evidence of an effect: a purpose describes what investigators set out to examine, while a result requires outcome data and an analysis. The registry record describes the regimen and planned assessments, but does not report the number of children who developed autism or an estimate comparing outcomes with a control group.
3. Trial Design
The registry describes a completed Phase 2 study with a single-group model and enrollment of 20. Allocation is listed as NA, and masking is listed as none. These features mean the record does not describe a randomized, masked comparison between intervention and control groups. It also specifically cautions that the arms are not a like-for-like control comparison.
The intervention is vitamin D3 given in relation to pregnancy, breastfeeding, and the child’s age. The arm description specifies 5000 IU for the mother during pregnancy. It describes 7000 IU during breastfeeding if breastfeeding; if not breastfeeding, the infant is to receive 400 IU during the first year of age, then 1000 IU until completion of the research trial. The registry names the intervention as Vitamin D3.
The listed study dates are a start in 2008-02 and primary completion in 2016-02. The study status is completed. Those administrative details indicate the recorded study is no longer listed as ongoing, but they do not establish that outcome data were posted or that the stated primary question was answered.
The registry lists two outcome measures and zero analyses. Its primary outcome is the number of children who developed autism, assessed at 3 years of age. A secondary outcome concerns the number of mothers who developed side effects from vitamin D. The registry record does not report the outcome results, eligibility details beyond the described family context, recruitment flow, adherence, or the protocol’s sample-size justification. The record also does not describe an alternative comparator. In a single-group design, observations after treatment can describe what occurred among participants, but without a suitable comparison they cannot by themselves separate an intervention effect from other explanations for the observed outcomes.
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
| Stage | Intervention During Pregnancy |
|---|---|
| STARTED | 20 |
| COMPLETED | 19 |
| NOT COMPLETED | 1 |
Analysis population for the primary outcome, as defined in the registry: Children who developed autism
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: Mothers of at least one child with autism and pregnant before the third trimester
| Characteristic | Unit | Intervention During Pregnancy |
|---|---|---|
| Participants analysed | 20 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 20 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex/Gender, Customized: Females | participants | 20 |
| Region of Enrollment: United States | participants | 19 |
| Region of Enrollment: Israel | participants | 1 |
| Mothers with at least one child with autism, and pregnant before the third trimester | participants | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Children Who Developed Autism, measured over Child assessed at 3 years of age.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Children who developed autism |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of children who developed autism, with the child assessed at 3 years of age. The registry description says the child will be screened using a Modified Checklist for Autism in Toddlers (MCHAT) interview at 18 months of age and a Pervasive Developmental Disorder Behavioral Inventory (PDDBI) questionnaire at 3 years of age to determine whether the child has developed autism.
This endpoint is relevant to the study’s stated prevention question because it concerns the outcome the intervention is intended to address: whether autism develops in the newborn sibling. The staged assessment description names both an earlier screening measure and a later questionnaire. The record does not report how screening results were translated into a final outcome classification, whether any further clinical assessment was used, or how disagreements or missing assessments were handled. Those details are important for understanding how an outcome count was established, but are not reported in the registry record.
The endpoint is expressed as a number of children, rather than as a treatment contrast or an effect estimate. Because the registry record does not report the observed count, the primary result cannot be interpreted from the posted information. Nor does the record provide a comparator group against which to judge whether the count differs from what might have occurred without the intervention.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed study, but it does not report the primary outcome result. It lists the primary endpoint as the number of children who developed autism, assessed at 3 years of age, and provides planned screening details at 18 months and 3 years. The posted record therefore gives information about the question and measurement plan, but not the observed primary outcome. No conclusion about the number of children who developed autism can be drawn from the information reported.
The design further limits what a result could establish. The study is listed as single-group, with allocation NA and no masking; the record warns that the arms are not a like-for-like control comparison. Without a suitable comparator, an observed outcome count would describe the participants’ experience under the regimen, but would not establish what would have happened to similar children without it. A difference from an external expectation, if one were considered, would not be equivalent to a randomized treatment effect.
The enrollment is 20. This is a description of the study’s enrollment, not evidence that all enrolled participants completed follow-up or contributed data to the primary endpoint. The registry record does not report participant flow, the number assessed at the planned ages, exclusions, or missing endpoint data. It also lists zero analyses. The result and analysis details needed to assess the precision of any estimate are therefore not available in the record.
The safety information is distinct from the primary outcome. For the listed intervention group, the record reports 19 at risk and zero serious events, as well as 19 at risk and zero other events. These entries describe the recorded adverse-event counts in that group; they do not establish that no side effects occurred in every participant or that the regimen is free of risk. The secondary outcome about mothers who developed side effects is listed, but its result is not reported in the registry record. Deaths are not reported in the record.
In statistical terms, a missing estimate is not evidence of no effect, and a count without a comparator is not an estimate of comparative benefit. The posted information supports a description of the design, regimen, planned endpoint, and recorded adverse-event counts. It does not support a quantified claim about prevention, a measure of uncertainty around the primary outcome, or a comparison with usual care or another strategy.
9. Statistical Methods Explained
The registry describes a single-group Phase 2 study rather than a randomized comparison. Allocation is listed as NA, masking as none, and the model as single group. These design labels matter because they determine what kinds of statistical conclusions the data could support. A single-group study can record outcomes among participants who received an intervention, but it does not supply a concurrent control group for estimating a treatment contrast. The record itself notes that the arms are not a like-for-like control comparison.
What does the primary outcome count?
The primary measure is the number of children who developed autism, with assessment at 3 years of age. The endpoint description names an MCHAT interview at 18 months and a PDDBI questionnaire at 3 years. A count is a direct summary of how many recorded participants meet the outcome definition. By itself, however, a count does not show the uncertainty around the underlying risk, and it does not establish whether an intervention changed that risk. To estimate a comparative effect, a suitable comparator and an analysis designed for that contrast are needed.
The registry record does not report the observed primary count, a percentage, a confidence interval, or a statistical test. A confidence interval is a statistical range intended to express uncertainty around an estimate; its interpretation depends on the estimator and assumptions used. Since the outcome estimate is absent, there is no posted interval to interpret. The record also does not detail the final classification procedure following the named screens, or how unresolved or missing assessments would be treated.
Why does the design affect interpretation?
In a randomized study, allocation can make comparison groups more alike on average with respect to factors that influence outcomes. Here, allocation is NA and the study is single-group, so that randomized basis for comparison is not described. Even if an outcome count were available, the count would reflect the participants and their circumstances during follow-up. It would not isolate the effect of vitamin D3 from other influences, changes over time, or differences in who enrolled. This is a general limitation of uncontrolled comparisons, not a finding about what occurred in this study.
Masking is listed as none. Masking refers to keeping participants, investigators, or outcome assessors unaware of treatment assignment where applicable. In an unmasked setting, knowledge of the intervention may influence behavior, reporting, or assessment, depending on the outcome and procedures. The registry does not report who knew what during the assessments or describe safeguards intended to limit assessment bias. The measures named in the endpoint description do not, on their own, resolve those questions.
How should planning calculations be understood?
The record describes sample-size calculations as planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event calculations are expressed as participants per arm. Those assumptions describe a planning exercise; they are not the trial’s own design justification and are not evidence of achieved power. The trial itself is listed as single-group, so an equal-allocation two-arm planning setup should not be mistaken for the design actually recorded.
A sample-size calculation asks what enrollment might be needed under specified assumptions about an effect and statistical procedure. It does not show that an effect exists, and it does not establish the chance that the study’s finding is correct. “Observed power” is not a substitute for reporting an estimate and its uncertainty. Here, the registry does not report a primary outcome estimate or analysis, and the sample-size assumptions do not supply either. The protocol’s own sample-size justification is not reported in the registry record.
What can the adverse-event counts show?
The adverse-event record lists 19 participants at risk for serious events and zero serious events, and 19 at risk for other events and zero other events. These are counts, not a comparative safety estimate. The record also lists a secondary outcome concerning mothers who developed side effects from vitamin D, but does not report its result. General statistical interpretation requires attention to the population included, the observation period, event definitions, and ascertainment. The registry does not provide enough detail to infer those items beyond the entries it lists.
Over-dispersion is a general statistical concept in count analysis: it means observed variation exceeds what a chosen model expects. It can make model-based uncertainty too small if the analysis assumes less variation than the data contain. The registry lists the primary measure as a count but does not report an analysis or a dispersion estimate, so there is no basis for saying whether over-dispersion was assessed or affected inference in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary count of children who developed autism and a secondary measure concerning mothers who developed side effects from vitamin D. Considering multiple outcomes can raise multiplicity concerns because testing several questions increases the opportunity for a statistically notable result by chance. A prespecified hierarchy, adjustment procedure, or other strategy can help clarify how multiple outcomes are interpreted. Such a strategy is not reported in the registry record.
The registry lists zero analyses. It does not report hypothesis tests, confidence intervals, adjusted or unadjusted estimates, or a statistical analysis plan. It is therefore not possible to assess whether multiple outcome testing was addressed, whether analyses were prespecified, or which results were intended as confirmatory rather than descriptive.
Missing-data handling is also not reported in the registry record. The endpoint description specifies assessments at 18 months and 3 years, but does not state how many children completed each assessment, whether any data were missing, or how missing assessments would be handled. The enrollment of 20 does not by itself establish the number contributing primary outcome data. No imputation strategy, sensitivity analysis, or follow-up accounting is reported.
The analysis populations are not described. The record does not state whether analyses were planned for all enrolled participants, only those who received or adhered to the regimen, or another defined group. Without participant flow and population definitions, the relationship between enrollment, exposure, follow-up, and any outcome analysis cannot be evaluated. These omissions limit reproducibility and make it difficult to judge how representative an eventual analyzed group might be of those who enrolled.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Intervention During Pregnancy | 0 | 19 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Intervention During Pregnancy | 0 of 19 |
The adverse-event entries list 19 participants at risk for serious events and zero serious events in the intervention group. The entries also list 19 participants at risk for other events and zero other events. These figures describe what is recorded for the listed group; they should not be read as proof that no adverse effects occurred among all enrolled participants or as a comparison with an untreated group.
The enrollment is 20, while the adverse-event entries use 19 as the number at risk. The reason for this difference is not reported in the registry record, so it should not be inferred. The registry also lists a secondary outcome for the number of mothers who developed side effects from vitamin D, but does not report that outcome’s result. The serious adverse-event terms list is empty, and deaths are not reported in the record.
Safety interpretation depends on how events were defined, how long participants were observed, and how events were collected. Those details are not reported in the registry record. With a single group and no like-for-like comparator, the listed counts also cannot estimate whether event occurrence differed from what would have occurred under another approach. The counts are descriptive entries, not a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, single-group Phase 2 study of vitamin D3 was registered, with enrollment of 20 and a stated primary outcome concerning children who developed autism. It describes a regimen spanning pregnancy and early childhood, along with assessments planned at 18 months and 3 years. It also lists a secondary outcome concerning maternal side effects.
The posted record does not report the primary outcome count, the secondary outcome result, or any statistical analyses. Consequently, it does not provide an estimate of how often the primary outcome occurred, how precise such an estimate might be, or whether outcomes differed from a suitable comparison group. The study’s stated aim to examine prevention is not itself evidence that prevention occurred. Neither an effect nor a lack of effect can be concluded from an unreported outcome.
Even if an outcome count were available, this single-group design would not by itself establish what would have happened without the intervention. The lack of a like-for-like control comparison means that outcome experience among enrolled participants cannot be directly attributed to vitamin D3. A comparison with another population or an assumed expected rate would require additional information and assumptions not reported in the registry record.
The adverse-event entries record zero serious events and zero other events among 19 participants listed at risk in the intervention group. They provide a limited description of recorded events, not proof that the intervention has no risks. The listed maternal side-effect outcome has no reported result, and deaths are not reported in the record.
The appropriate statistical reading is therefore narrow: the registry documents the study design, intervention, planned measurement approach, and selected adverse-event counts, while leaving the main efficacy outcome and analysis unavailable. No treatment recommendation or conclusion about clinical effectiveness follows from the posted information alone.
13. Why This Trial Matters Statistically
This study matters statistically because it illustrates the difference between a clinical question and an analysis capable of answering it. The stated question is whether a vitamin D3 regimen could prevent autism in newborn siblings of children with autism. The registry describes the regimen and a planned primary assessment, but records a single-group design with allocation NA and no like-for-like control comparison. That design distinction determines how far an observed count could be interpreted.
It also highlights why outcome reporting is essential. A registry can describe an endpoint and its measurement schedule without reporting the result. In this record, the primary outcome is named and the assessment ages are stated, but the number of children who developed autism and any estimate of uncertainty are not reported. Without those results, readers cannot quantify even the observed outcome experience, much less evaluate a treatment contrast.
The record also shows why enrollment, analysis populations, and follow-up should not be treated as interchangeable. Enrollment is 20, whereas adverse-event entries list 19 at risk; the reason is not reported. The number contributing primary endpoint data is likewise not reported. Those distinctions are needed to understand who was followed and how complete the outcome information may be.
Finally, the sample-size assumptions describe planning illustrations based on an observed effect and a two-arm setup, whereas the recorded study is single-group. Such illustrations are not the trial’s design rationale, observed power, or evidence of a comparative effect. Reading design labels, outcome reporting, and planning calculations separately helps prevent statistical calculations from being mistaken for clinical findings.
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 central limitation for interpreting the registry record is that it does not report the primary outcome result or any analyses. Although the endpoint and assessment plan are described, the number of children who developed autism is absent. The secondary outcome about mothers who developed side effects is also listed without a reported result.
The single-group model, allocation listed as NA, and absence of masking constrain causal interpretation. The record does not describe a randomized control group, and it cautions that arms are not a like-for-like comparison. Thus, even a reported outcome count would not by itself show what difference the intervention made compared with no intervention or another strategy.
Enrollment is 20, but the number with complete primary follow-up is not reported. The adverse-event entries list 19 at risk, and the reason for the difference from enrollment is not reported. Participant flow, adherence, withdrawals, missing assessments, and analysis populations are not described. These gaps prevent assessment of whether outcome availability or participation affected the results.
The endpoint description names MCHAT screening at 18 months and PDDBI assessment at 3 years, but the record does not report how these measures were used to establish the final autism outcome, whether further assessment was required, or how missing or uncertain classifications were addressed. The analysis plan, multiplicity approach, uncertainty estimates, and protocol sample-size justification are also not reported in the registry record.
The safety entries are limited to the counts listed for the intervention group and do not provide a comparator or detailed event ascertainment information. Deaths are not reported. These limitations arise from what the registry record reports and should not be filled in by assuming procedures or results that are not described.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vitamin D to Prevent Autism in Newborn Siblings — NCT01366885.
- Registry record last updated 2016-06-14; status last verified 2016-05.
- Results first posted 2016-06-14.
- 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.
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18. Record Summary
The registry identifies NCT01366885 as a completed Phase 2 study titled “Vitamin D to Prevent Autism in Newborn Siblings,” sponsored by Oregon Health and Science University. The model is single-group, allocation is listed as NA, masking as none, and enrollment as 20. The recorded study dates are 2008-02 to 2016-02.
The intervention is Vitamin D3, with a regimen described for pregnancy, breastfeeding, and early childhood. The primary outcome is the number of children who developed autism, with assessment at 3 years of age and screening described at 18 months. A secondary outcome concerns mothers who developed side effects from vitamin D.
The registry lists zero analyses. It does not report the primary or secondary outcome results. For the intervention group, the adverse-event entries list 19 at risk and zero serious events, and 19 at risk and zero other events. Deaths are not reported in the record. The registry cautions that the arms are not a like-for-like control comparison.