Clinical trial NCT04888377: ASPIRIN: Neurodevelopmental Follow-up Trial
Official title: Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN): Neurodevelopmental Follow-up Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neurodevelopmental Abnormality
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
Lead sponsor: NICHD Global Network for Women's and Children's Health
Sponsor class: NETWORK
Collaborators: name: Thomas Jefferson University
name: RTI International
name: Thrasher Research Fund
First posted: 2021-05-17
Enrollment: 666
Sex: ALL
Minimum age (years): 33
Maximum age (years): 39
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will consist of approximately 620 children, between 33 and 39 months of age, whose mothers were included in the ASPIRIN trial.

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.

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.

Primary outcomes:
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score
timeFrame: At a single visit occurring between 33-39 months corrected age
Secondary outcomes:
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 70
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Cognitive Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 70
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Language Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 70
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) Motor Composite Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Communication Total Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Gross Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Fine Motor Total Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Problem Solving Total Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score
timeFrame: At a single visit occurring between 33-39 months corrected age
measure: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) Personal Social Total Score Less Than 1 Standard Deviation (SD) Below the Mean
timeFrame: At a single visit occurring between 33-39 months corrected age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Newark
country: United States
facility: Christiana Care
state: Delaware
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina School of Medicine
state: North Carolina
city: Research Triangle Park
country: United States
facility: RTI International
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Kinshasa School of Public Health
city: Guatemala City
country: Guatemala
facility: INCAP
city: Belgaum
country: India
facility: Jawaharlal Nehru Medical College
city: Nagpur
country: India
facility: Lata Medical Research Foundation
city: Karachi
country: Pakistan
facility: Aga Khan University
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: RTI International
name: Elizabeth McClure, PhD
role: PRINCIPAL_INVESTIGATOR
References: