Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN): Neurodevelopmental Follow-up Trial
Overview
- Phase
- Not Applicable
- Intervention
- Aspirin
- Conditions
- Neurodevelopmental Abnormality
- Sponsor
- NICHD Global Network for Women's and Children's Health
- Enrollment
- 666
- Locations
- 14
- Primary Endpoint
- Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Antenatal exposure to low dose aspirin
Mothers in the Global Networks ASPIRIN trial were given 81 mg of Aspirin throughout their pregnancy with the follow-up studies participant.
Intervention: Aspirin
Antenatal exposure to Placebo
Mothers in the Global Networks ASPIRIN trial were given placebo throughout their pregnancy with the follow-up studies participant.
Intervention: Placebo
Outcomes
Primary Outcomes
Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score(At a single visit occurring between 33-39 months corrected age)
- 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)
- Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score(At a single visit occurring between 33-39 months corrected age)
- 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)
- Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score(At a single visit occurring between 33-39 months corrected age)
- 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)
- Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score(At a single visit occurring between 33-39 months corrected age)
- 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)
- Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score(At a single visit occurring between 33-39 months corrected age)
- 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)