Adherence to Care for Children With Congenital Zika Virus Infection in Puerto Rico: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adherence to Care for Children With Congenital Zika Virus Infection in Puerto Rico (NCT05041439), a randomized na study. The primary outcome is Number of Participants With Adherence to Pediatric Zika Care.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group study with single masking. The meaning of single masking, including which participants or study personnel were masked, is not reported in the registry record. The record lists the phase as NA and the status as completed. Enrollment was 50, with 25 participants listed in each arm for the posted primary outcome.

The study compared a Community Health Worker group with an Enhanced Care Condition. The intervention group was offered 5 one-on-one community health worker sessions over 6 months, along with a manual and written materials on child development. The enhanced care group received 5 outreach calls at the same interval and the written materials. Both groups had assessments at baseline and exit. The registry record does not describe additional procedures for assignment, allocation concealment, or delivery of the intervention.

The study start date was 2021-07-06, and primary completion was 2022-08-31. The primary endpoint concerned a pediatric developmental-exam visit within 6 months after randomization. The registry also lists secondary outcomes concerning detection of Zika-associated birth defects or neurodevelopmental abnormalities within 6 months and adherence to pediatric Zika care within 12 months. Detailed eligibility rules, recruitment methods, and the original trial design rationale are not reported in the registry record.

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: 60 participants were screened for eligibility and 50 were consented/enrolled.

Overall Study

Reasons for not completing this period:

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 Number of Participants With Adherence to Pediatric Zika Care, measured over Within the first 6 months.

The primary endpoint counts participants with at least one pediatric visit for a developmental exam with a pediatrician within 6 months post-randomization. It is a binary participant-level outcome: a participant either met the stated visit criterion during the specified period or did not. The registry reports counts for each arm, rather than a continuous measurement such as a score or a measure of how many visits each participant attended.

This endpoint is used to assess a concrete aspect of adherence to pediatric Zika care: whether a developmental-exam visit occurred within the follow-up window. A visit is an observable care process and is relevant to the study's focus on follow-up care. It does not, by itself, establish whether the visit included every recommended service, whether the exam found an abnormality, or whether a child's developmental status changed. Those are different questions from attendance.

The registry defines the timeframe as within the first 6 months and the population measure as a count of participants. It does not report additional detail on how visits were verified, what happened when visit information was unavailable, or whether care received outside the specified pediatric setting counted toward the endpoint.

7. Results Posted in the Registry

• Enhanced Care Condition (ECC): 60.0% (15/25) versus 56.0% (14/25) on control; risk difference 4.0 percentage points (95% CI -23.3 to 31.3), risk ratio 1.07 (0.67–1.72); unadjusted two-proportion z-test p = 0.774.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Detection of Zika-associated Birth Defect or Neurodevelopmental Abnormality

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Enhanced Care Condition (ECC): 12.0% (3/25) versus 4.0% (1/25) on control; risk difference 8.0 percentage points (95% CI -6.9 to 22.9), risk ratio 3.00 (0.33–26.92); unadjusted two-proportion z-test p = 0.297.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Enhanced Care Condition (ECC) and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Adherence to Pediatric Zika Care

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Enhanced Care Condition (ECC): 20.0% (5/25) versus 24.0% (6/25) on control; risk difference -4.0 percentage points (95% CI -26.9 to 18.9), risk ratio 0.83 (0.29–2.38); unadjusted two-proportion z-test p = 0.733.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Enhanced Care Condition (ECC) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary attendance question to detection of Zika-associated birth defects or neurodevelopmental abnormalities within 6 months and adherence to pediatric Zika care within 12 months. Across these outcomes, the direction of the arm contrasts is not uniform: the posted comparisons do not show a single consistent pattern favoring one arm across all measures. This variation is compatible with differences in outcome definition and follow-up window, as well as uncertainty in the arm summaries.

The secondary findings complement the primary result by describing other aspects of follow-up and detection, but they do not replace the primary endpoint. Detection of an abnormality is not the same measure as attending a developmental visit, and the longer-window adherence endpoint is not identical to the primary endpoint's shorter follow-up definition. Taken together, the secondary outcomes help characterize what was recorded, but they do not establish a coherent treatment effect across multiple dimensions of care.

Secondary comparisons generally warrant less weight when they are unadjusted, especially when several outcomes are considered. If many outcomes are tested, some apparently notable differences can arise by chance even when there is no underlying effect. A multiplicity plan is not reported in the registry record, and no reported secondary analysis results are listed. The arm summaries and unadjusted comparisons should therefore be treated as descriptive and exploratory rather than as independent confirmatory evidence.

The record also lists a repeated birth-defect/neurodevelopmental outcome title in its secondary outcome descriptions. It does not explain the relationship between those entries. That lack of detail makes it important to avoid assuming that each listed entry represents a distinct outcome or a separate confirmatory question.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Detection of Zika-associated Birth Defect or Neurodevelopmental Abnormality
• Number of Participants With Adherence to Pediatric Zika Care
• Number of Participants With Detection of Zika-associated Birth Defect or Neurodevelopmental Abnormality

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a participant count, with each participant classified according to whether the visit criterion was met. For such a binary outcome, an arm-level proportion can be used to describe the share meeting the criterion. The comparison reported as a risk difference expresses the difference between those arm-level proportions, with the Enhanced Care Condition compared against the Community Health Worker group. A positive estimate favors a higher observed proportion in the enhanced care arm on this measure; it is not, by itself, evidence of a causal benefit.

What does the confidence interval describe?

A confidence interval describes the statistical uncertainty around an estimated contrast under the assumptions of the method used. It is not a range containing a fixed percentage of individual outcomes, and it does not give the probability that the true effect lies inside the particular interval. For the primary risk difference, the interval runs from -0.233 to 0.313. Because it spans zero, the posted data are compatible with a range of contrasts that includes no difference as well as differences in either direction. Its width also indicates limited precision.

Why are risk ratios and odds ratios included?

Risk differences, risk ratios, and odds ratios describe contrasts on distinct scales. A risk difference compares proportions by subtraction; a risk ratio compares them as a ratio; an odds ratio compares the odds in each arm. The registry's primary comparison lists a risk ratio of 1.071, with a confidence interval from 0.668 to 1.718, and an odds ratio of 1.179, with a confidence interval from 0.383 to 3.627. These values are not interchangeable. For a practical interpretation, the endpoint definition and the scale of the reported estimate should be made explicit rather than treating one measure as a substitute for another.

What does the unadjusted p-value tell us?

The primary unadjusted p-value is 0.774. In general, a p-value measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a difference. The registry does not report a model-based or covariate-adjusted primary analysis, so the displayed p-value should be understood as an unadjusted comparison rather than evidence from an adjustment for participant characteristics.

Why does outcome type matter?

These outcomes are counts of participants with an event, not counts of repeated events per person or measurements over time. A participant with a qualifying visit contributes to the participant count under the endpoint definition; the posted result does not distinguish people with one qualifying visit from people with more than one. The binary summary is suited to the yes-or-no endpoint as defined, but it cannot convey the frequency or timing of visits beyond the stated window. Over-dispersion is especially relevant to count models when event counts vary more than a model assumes; it is not a separate quantity reported for this participant-level binary endpoint.

For the primary outcome, the registry reports arm-level event counts and an unadjusted comparison. The record does not report the statistical test or model details, confidence-interval construction method, handling of missing outcomes, or analysis population definition beyond the arm summaries. It also does not report whether there were interim analyses or what multiplicity procedure, if any, was planned. Those methodological details should not be inferred from the presence of estimates and p-values.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.04, with a 95% confidence interval from -0.233 to 0.313. The interval crosses zero and covers values on both sides of it. This means the observed estimate is not precise enough to rule out a range of possible differences under the method used. The interval is appreciably broader than the point estimate itself, so the point estimate should not be read as a highly precise description of the underlying contrast.

The ratio measures likewise have broad intervals: the risk ratio is 1.071 with a confidence interval from 0.668 to 1.718, and the odds ratio is 1.179 with a confidence interval from 0.383 to 3.627. Each interval includes its no-contrast value: 1 for a ratio measure and 0 for a difference measure. This is a way to describe compatibility with no contrast, not proof that the groups are equivalent. Equivalence would require a specified margin and an analysis designed to assess it; that information is not reported in the registry record.

Precision is affected by the amount of information in the data and the variability of the outcome. The posted primary summaries list 25 participants per arm, and the event counts are close. With this amount of information, the uncertainty around the contrast remains substantial. The registry record does not report a prespecified precision target or a confidence-interval method, so the intervals are best read as the uncertainty estimates posted with the arm comparison rather than as a complete account of all design considerations.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the original trial design. They are expressed as participants per arm for the binary outcomes in this study, not as total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial's own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions were correct. The 90% power column describes the corresponding planning target with a 90% chance. These are design probabilities under assumptions, not probabilities that the treatment will work and not measures of the probability that the posted finding is true.

Each planning scenario uses either 100%, 75%, or 50% of the observed effect as the effect to detect. Planning for 100% of the observed effect gives a different target from planning for a smaller fraction; as the effect to detect becomes smaller, more participants are needed to distinguish it from random variation under otherwise stated assumptions. The large changes across these scenarios illustrate how sensitive a planning calculation can be to the assumed effect size.

For example, for 100% of the observed primary effect, the listed targets are 2,389 participants per arm for 80% power and 3,198 participants per arm for 90% power. For 75% of the observed effect, the targets are 4,262 and 5,705 participants per arm, respectively. For 50% of the observed effect, they are 9,618 and 12,875 participants per arm. These figures are not observed power. They are planning illustrations calculated from the observed effect under the specified assumptions, and they should not be interpreted as the trial's original design targets or as evidence about the result's validity.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.560; treatment proportion p₁ = 0.600; average p̄ = 0.580.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6980 = 1.3680.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6974 = 0.5870.
4. n = (1.3680 + 0.5870)² / (0.0400)² = 2,388.8, rounded up to 2,389 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.56                          # control proportion
p1 <- 0.6                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5041439)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 2,389 (80% power), 3,198 (90% power)
 75% of observed effect: n per arm = 4,262 (80% power), 5,705 (90% power)
 50% of observed effect: n per arm = 9,618 (80% power), 12,875 (90% power)
power.prop.test: 2388.8 
Simulated power at n = 2,389 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes and more than one follow-up timeframe. It does not report a multiplicity adjustment, an outcome hierarchy, or a prespecified rule for interpreting the family of comparisons. When several outcomes are examined, the chance of at least one apparently unusual result can increase. Without a stated plan, individual unadjusted secondary p-values should not be treated as if each were the sole confirmatory test. The record lists no reported secondary analyses.

Information about missing data is also limited. The registry provides arm denominators and endpoint counts, but it does not report the amount or pattern of missing outcome information, how missingness was handled, or whether imputation or another method was used. It does not describe a missing-data sensitivity analysis. The posted denominators alone do not establish how participants with unavailable outcome information were treated.

The analysis population is not described beyond the arm summaries. The record does not specify whether the primary comparison followed an intention-to-treat approach, a per-protocol approach, or another population definition. It also does not report how deviations from assigned care, loss to follow-up, or incomplete intervention exposure were handled. Randomization is reported, but the details needed to assess analysis consistency with the randomized assignment are not reported in the registry record.

These omissions do not change the observed counts, but they limit assessment of the assumptions behind the comparisons and of how representative the posted outcome summaries are of all randomized participants. Protocol-level details, any interim analyses, and the trial's original statistical analysis plan are not reported in the registry record.

15. 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

Serious events with the highest arm-level rate: complications of diabetes (4.0%).

The registry reports serious adverse events affecting 1 participant in the Community Health Worker group and 0 participants in the Enhanced Care Condition. Other adverse events affected 0 participants in each arm. The death counts are 1 in the Community Health Worker group and 0 in the Enhanced Care Condition. These are descriptive counts; the record does not report an analysis attributing events to the intervention or comparing safety risks statistically.

The registry lists “Complications of diabetes” as a top serious adverse event term at 4.0%. The record does not provide enough context in this summary to determine the event's relationship to study participation or to either care condition. The counts should not be interpreted as evidence of causation, nor do they establish that no other safety events occurred beyond those captured and reported in the registry.

Safety interpretation is also limited by the small arm summaries and the lack of detailed event narratives, timing, severity classifications beyond the serious-event listing, or attribution information. No additional safety analysis is reported in the registry record.

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

The posted primary result describes a small observed difference between the arm summaries on the specific measure of having at least one pediatric developmental-exam visit within 6 months. The estimate and its confidence interval leave substantial uncertainty about the direction and size of the underlying contrast. The result does not establish that the care conditions are equivalent, nor does it demonstrate that one condition caused better adherence.

The endpoint is a measure of attendance within a defined period. It does not establish the quality or content of care, the number of visits, or whether a child experienced a developmental benefit. The secondary outcomes concern detection of abnormalities and adherence over a longer timeframe; those are related areas of follow-up but are not interchangeable with the primary visit measure. The registry record does not report enough methodological detail to resolve questions about missing data, analysis populations, or multiplicity.

Interpretation should remain tied to the study setting and design: children born to mothers with laboratory evidence of confirmed or possible congenital Zika virus infection during pregnancy, with a community health worker intervention compared against outreach calls and written materials. The posted results are not a basis for claims about other populations, other care models, or outcomes not measured in the registry. They also do not provide a basis for medical advice. They describe the recorded trial outcomes and the uncertainty around the reported comparisons.

17. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between an estimated effect and the precision of that estimate. A single point estimate can be close to no difference while its confidence interval remains compatible with contrasts in either direction. The primary comparison makes that distinction especially visible: the point estimate is modest on the reported scale, but the interval is broad. Reading the estimate without its interval would understate uncertainty.

The active comparison is also important for interpreting the question. The community health worker intervention was compared with scheduled outreach calls and written materials, not with an absence of contact. The result therefore concerns the contrast between these two care approaches as described in the registry, rather than the effect of contact versus no contact.

The study also illustrates why planning calculations based on an observed effect require caution. The planning figures change substantially when the target effect is set to a smaller fraction of the observed estimate. They are illustrative, assumption-dependent planning quantities rather than evidence that the trial had a particular level of power or that the observed contrast is stable.

Finally, the registry record contains arm-level outcomes but limited detail on the statistical analysis plan, missing data, and multiplicity. This makes careful separation of descriptive summaries, unadjusted comparisons, and confirmatory conclusions especially important. The study offers an informative example of how a clear outcome definition can coexist with considerable uncertainty and incomplete analysis documentation.

18. 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 limitations specific to this trial affect interpretation. The enrollment listed in the registry is 50, and the posted primary summaries list 25 participants in each arm. With these arm summaries, the primary confidence interval is broad. The data therefore provide limited precision for estimating the difference in the specified visit outcome.

The intervention and comparator both included structured contact and child-development materials. The observed contrast pertains to those two conditions as described; it cannot isolate the contribution of any single component of community health worker support. The registry record does not report intervention fidelity, actual session or call completion, or participant exposure to the materials. It also does not report whether participants received other relevant care outside the described study contacts.

The primary measure is limited to whether at least one qualifying visit occurred within 6 months. Details on visit ascertainment and the handling of unavailable records are not reported in the registry record. The record also does not report the analysis population, missing-data methods, allocation concealment, the identity of the masked party, or a detailed statistical analysis plan. These gaps limit assessment of potential bias and the robustness of the comparison.

The secondary outcomes add information about detection and a longer adherence window, but their multiplicity handling is not reported. The registry lists a repeated secondary outcome title without explaining its relationship to the other entries. The original sample-size justification and assumptions are also not reported, so the planning illustrations should not be mistaken for the trial's initial design rationale.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Adherence to Care for Children With Congenital Zika Virus Infection in Puerto Rico — NCT05041439.
• Registry record last updated 2023-12-15; status last verified 2023-11.
• Results first posted 2023-12-15.
• 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.

22. Record Summary

The registry record describes a completed randomized, single-masked, parallel-group study in Puerto Rico, with enrollment of 50. It compared 5 community health worker sessions over 6 months, a manual, and written child-development materials with 5 outreach calls and written materials. Both arms had baseline and exit assessments.

The primary outcome was the number of participants with at least one pediatric developmental-exam visit within 6 months after randomization. The posted arm counts were 14 of 25 in the Community Health Worker group and 15 of 25 in the Enhanced Care Condition. The risk-difference estimate was 0.04, with a confidence interval from -0.233 to 0.313. The interval indicates substantial uncertainty around the comparison.

Secondary outcomes concerned detection of Zika-associated birth defects or neurodevelopmental abnormalities and adherence to pediatric Zika care over a longer follow-up window. The registry record does not report detailed methods for missing data, analysis populations, multiplicity, or the original sample-size rationale.