ASPIRIN: Neurodevelopmental Follow-up Trial

Study Overview
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Brief Summary
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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
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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 (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.

Official Title
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Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN): Neurodevelopmental Follow-up Trial

Conditions
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Neurodevelopmental Abnormality

Intervention / Treatment
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* Drug: Aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 33 Months
Maximum Age: 39 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Antenatal exposure to low dose aspirin<br>Mothers in the Global Networks ASPIRIN trial were given 81 mg of Aspirin throughout their pregnancy with the follow-up studies participant. | Drug: Aspirin<br>* Participant's mothers were administered 81mg of Aspirin throughout their pregnancy with the participant.<br>|
| Antenatal exposure to Placebo<br>Mothers in the Global Networks ASPIRIN trial were given placebo throughout their pregnancy with the follow-up studies participant. | Drug: Placebo<br>* Participant's mothers were administered placebo throughout their pregnancy with the participant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BSID-III Examination | BSID-III examination at 36 months of life (+/-3months) with margins of 0-4 points. Minimum score of 1 and maximum score of 130. The lower score is a bad outcome and a higher score is good outcome. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASQ-3 | Accepted and Validated screening tool for neurodevelopment at 36 months of life (+/-3months). Minimum score of 0 and maximum score of 60. The lower score is a bad outcome and a higher score is good outcome. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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