Neurodevelopmental Abnormality
Conditions
Keywords
Pre-eclampsia, Low Dose Aspirin, ASPIRIN Trail, NICHD Global Network, Global Network, ASPRIN Follow Up, BSID-III, Family Resources and Context, ASQ-36, Neurodevelopmental delays, hypertensive disorders of pregnancy (HDP), Pre-term birth, LDA
Brief summary
A total of 620 children will be enrolled in this study from six sites in sub-Saharan Africa, South Asia, and Latin America. Half of the children's mothers will have taken aspirin and half will have taken placebo. This will allow the researchers to compare results of the two groups of children and determine if children exposed antenatally to low dose aspirin will have scores on the Bayley Scales of Infant Development-III (BSID-III) examination at 36 months of life (+/-3months) that are not inferior to the child's peers who were not exposed (i.e., by no more than a margin of 4 points).
Detailed description
An estimated 250 million children under the age of 511 worldwide are at risk for not achieving their developmental potential; 52.9 million children under five years of age in low- and middle-income country (LMIC) settings have neurodevelopmental delays. Compounding the issue is preterm birth (more common in LMICs) which has consistently been identified as a cause of neurodevelopmental delay. A recent review reported that out of the estimated 13 million preterm infants who survive beyond the first month, 0.9 million will suffer long term neurodevelopmental impairment, with 345,000 moderately or severely affected. This burden places a significant strain on the families, healthcare systems and societies that provide care for these children. Data from other Global Network participating sites (Guatemala, Democratic Republic of Congo, Zambia and Pakistan) also found strikingly high rates of stunting ranging from 44% to 66%, among infants and toddlers. Poverty additionally contributes to the attainment of optimal neurodevelopment. As such, any study of neurodevelopment should at least document these potential confounders. Aspirin has been shown to predominantly affect both the COX-1 pathway which is involved in thrombosis and the COX-2 pathway, which affects inflammation through the production of Aspirin Triggered Lipoxins. More specifically, aspirin has been shown to inhibit the production of IL-6, IL-1B, CRP and TNF-α all of which have been shown to negatively affect child neurodevelopment and be involved in preeclampsia and preterm birth. This will be a prospective masked matched cohort study of children between 33 and 39 months (mean 36 months) of age whose mothers were randomized in the ASPIRIN trial \*NCT02409680\* (1:1 Aspirin-Placebo), who will be evaluated using the BSID-III. Additionally, the Family Resources and Context questionnaire will be performed to adjust for the local context and the ASQ-3 will be administered as a secondary screen. Recognizing the significant role that preterm birth plays in neurodevelopment, the investigators will include 100 (50 in each group) children who were delivered before 37 weeks.
Interventions
DRUGAspirin
Participant's mothers were administered 81mg of Aspirin throughout their pregnancy with the participant.
DRUGPlacebo
Participant's mothers were administered placebo throughout their pregnancy with the participant.
Sponsors
Thomas Jefferson University
RTI International
Thrasher Research Fund
NICHD Global Network for Women's and Children's Health
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
33 Months to 39 Months
Healthy volunteers
Yes
Inclusion criteria
* Mother was enrolled in the GN ASPIRIN trial * Mother consented to be recontacted * Child's parents or guardians are willing and able to give consent * Child is between 33-39 months of age * Child does not have significant congenital anomaly (blind or deaf) that would affect them from completing study assessments * Child does not have other medical conditions that would preclude the child from completing study assessments.
Exclusion criteria
* The child does not meet the inclusion criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score | At a single visit occurring between 33-39 months corrected age | Mean of the Bayley-III Cognitive Composite Score (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Cognitive Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score | At a single visit occurring between 33-39 months corrected age | Mean of the Bayley-III Language Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70 | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Language Composite score less than 70 (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Language Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score | At a single visit occurring between 33-39 months corrected age | Mean of the Bayley-III Motor Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70 | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Motor Composite score less than 70 (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Motor Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score | At a single visit occurring between 33-39 months corrected age | Mean of the ASQ Communication Total Score (range 0-60) (lower scores indicating greater impairment) |
| Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70 | At a single visit occurring between 33-39 months corrected age | Number of participants with the Bayley-III Cognitive Composite score less than 70 (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score | At a single visit occurring between 33-39 months corrected age | Mean of the ASQ Gross Motor Total Score (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the ASQ Gross Motor Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score | At a single visit occurring between 33-39 months corrected age | Mean of the ASQ Fine Motor Total Score (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the ASQ Fine Motor Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score | At a single visit occurring between 33-39 months corrected age | Mean of the ASQ Problem Solving Total Score (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the ASQ Problem Solving Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score | At a single visit occurring between 33-39 months corrected age | Mean of the ASQ Personal Social Total Score (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the ASQ Personal Social Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment) |
| Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean | At a single visit occurring between 33-39 months corrected age | Number of participants with the ASQ Communication Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment) |
Countries
Democratic Republic of the Congo, Guatemala, India, Pakistan, United States, Zambia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Children of mothers who received 81mg low-dose aspirin daily beginning between 6 weeks 0 days and 13 weeks 6 days, until 37 weeks or delivery. | 343 |
| Placebo Children of mothers who received placebo daily beginning between 6 weeks 0 days and 13 weeks 6 days, until 37 weeks or delivery. | 323 |
| Total | 666 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incomplete Follow-up or No Study Data | 1 | 3 |
| Overall Study | Physician Decision | 6 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Aspirin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.5 months STANDARD_DEVIATION 1 | 37.5 months STANDARD_DEVIATION 0.9 | 37.5 months STANDARD_DEVIATION 0.9 |
| Maternal education No formal schooling | 52 Participants | 44 Participants | 96 Participants |
| Maternal education Years of schooling: 13 years or more | 34 Participants | 41 Participants | 75 Participants |
| Maternal education Years of schooling: 7-12 | 196 Participants | 177 Participants | 373 Participants |
| Maternal education Years of schooling: Less than 7 | 61 Participants | 61 Participants | 122 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 71 Participants | 65 Participants | 136 Participants |
| Race/Ethnicity, Customized Asian | 175 Participants | 159 Participants | 334 Participants |
| Race/Ethnicity, Customized Black or African American | 97 Participants | 99 Participants | 196 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 71 Participants | 65 Participants | 136 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 272 Participants | 258 Participants | 530 Participants |
| Sex: Female, Male Female | 173 Participants | 155 Participants | 328 Participants |
| Sex: Female, Male Male | 170 Participants | 168 Participants | 338 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 329 | 0 / 311 |
| other Total, other adverse events | 0 / 329 | 0 / 311 |
| serious Total, serious adverse events | 0 / 329 | 0 / 311 |
Outcome results
Primary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score
Mean of the Bayley-III Cognitive Composite Score (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score | 96 score on a scale | Standard Deviation 9.9 |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score | 96.8 score on a scale | Standard Deviation 10.4 |
Comparison: Assuming a non-inferiority margin of 4 points in the BSID-III cognitive score as clinically significant, and a true effect of LDA of not more than a 1 point decrease, a total sample size of 620 was determined to provide 80% power for a one-sided test for non-inferiority with a type I error of 5%. To test this secondary hypothesis, the sample size also provided over 90% power, at a two-sided type I error of 5%, to detect a difference of 4 points between LDA and placebo based on a two-sided test.p-value: 0.2595% CI: [-2.2, 0.6]ANCOVA
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score
Mean of the ASQ Communication Total Score (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score | 52 score on a scale | Standard Deviation 8.9 |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score | 50.7 score on a scale | Standard Deviation 10.2 |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the ASQ Communication Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 277 Participants |
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 53 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 256 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 58 Participants |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score
Mean of the ASQ Fine Motor Total Score (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score | 39.6 score on a scale | Standard Deviation 16.6 |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score | 38.3 score on a scale | Standard Deviation 16 |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the ASQ Fine Motor Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 255 Participants |
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 75 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 246 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 68 Participants |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score
Mean of the ASQ Gross Motor Total Score (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score | 47.8 score on a scale | Standard Deviation 12 |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score | 48.3 score on a scale | Standard Deviation 12.6 |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the ASQ Gross Motor Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 270 Participants |
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 60 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 253 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 61 Participants |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score
Mean of the ASQ Personal Social Total Score (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score | 45.5 score on a scale | Standard Deviation 9.8 |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score | 45.3 score on a scale | Standard Deviation 10 |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the ASQ Personal Social Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 273 Participants |
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 57 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 252 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 62 Participants |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score
Mean of the ASQ Problem Solving Total Score (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score | 40.2 score on a scale | Standard Deviation 13.7 |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score | 40.2 score on a scale | Standard Deviation 13.7 |
Secondary
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the ASQ Problem Solving Total score less than 1 SD below the sample mean (range 0-60) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 265 Participants |
| Aspirin | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 65 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 256 Participants |
| Placebo | Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 58 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the Bayley-III Cognitive Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 297 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 32 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 285 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 26 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70
Number of participants with the Bayley-III Cognitive Composite score less than 70 (standardized mean 100, SD 15, range 55-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 327 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70 | Participants with Score Less than 70 | 2 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 309 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70 | Participants with Score Less than 70 | 2 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score
Mean of the Bayley-III Language Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score | 101.2 score on a scale | Standard Deviation 13.2 |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score | 100.4 score on a scale | Standard Deviation 13.6 |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the Bayley-III Language Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 290 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 38 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 273 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 33 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70
Number of participants with the Bayley-III Language Composite score less than 70 (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 327 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70 | Participants with Score Less than 70 | 1 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 302 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70 | Participants with Score Less than 70 | 4 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score
Mean of the Bayley-III Motor Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score | 99.4 score on a scale | Standard Deviation 13.2 |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score | 100.1 score on a scale | Standard Deviation 13.9 |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
Number of participants with the Bayley-III Motor Composite score less than 1 SD below the sample mean (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 281 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 45 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Greater than or Equal to 1 Standard Deviation (SD) Below the Mean | 264 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean | Participants with Scores Less than 1 Standard Deviation (SD) Below the Mean | 44 Participants |
Secondary
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70
Number of participants with the Bayley-III Motor Composite score less than 70 (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)
Time frame: At a single visit occurring between 33-39 months corrected age
Population: The analysis population includes all randomized infants with available data for the primary outcome.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70 | Participants with Score Less than 70 | 3 Participants |
| Aspirin | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 323 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70 | Participants with Score Greater than or Equal to 70 | 305 Participants |
| Placebo | Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70 | Participants with Score Less than 70 | 3 Participants |