ASPIRIN: Neurodevelopmental Follow-up Trial

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

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).

Study Overview

• Status: Completed
• Conditions: Neurodevelopmental Abnormality
• Intervention / Treatment: Drug: Aspirin; Drug: Placebo

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.

• Study Type: Observational
• Enrollment (Actual): 666

Contacts and Locations

Study Locations

• Congo, The Democratic Republic of the
  • Kinshasa, Congo, The Democratic Republic of the
    • Kinshasa School of Public Health
• Guatemala
  • Guatemala City, Guatemala
    • INCAP
• India
  • Belgaum, India
    • Jawaharlal Nehru Medical College
  • Nagpur, India
    • Lata Medical Research Foundation
• Pakistan
  • Karachi, Pakistan
    • Aga Khan University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama, Birmingham
  • Colorado
    • Denver, Colorado, United States, 80208
      • University of Colorado Health Sciences Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina School of Medicine
    • Research Triangle Park, North Carolina, United States, 27709
      • RTI International
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
• Zambia
  • Lusaka, Zambia
    • University Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 3 years (Child)
• Accepts Healthy Volunteers: Yes

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Aspirin; Participant's mothers were administered 81mg of Aspirin throughout their pregnancy with the participant.
Antenatal exposure to Placebo; Mothers in the Global Networks ASPIRIN trial were given placebo throughout their pregnancy with the follow-up studies participant.	Drug: Placebo; Participant's mothers were administered placebo throughout their pregnancy with the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	At a single visit occurring between 33-39 months corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	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)	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	Mean of the Bayley-III Language Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)	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	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)	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	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)	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	Mean of the Bayley-III Motor Composite Score (standardized mean 100, SD 15, range 45-155) (lower scores indicating greater impairment)	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	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)	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	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)	At a single visit occurring between 33-39 months corrected age
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)	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	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)	At a single visit occurring between 33-39 months corrected age
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)	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	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)	At a single visit occurring between 33-39 months corrected age
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)	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	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)	At a single visit occurring between 33-39 months corrected age
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)	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	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)	At a single visit occurring between 33-39 months corrected age
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)	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	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)	At a single visit occurring between 33-39 months corrected age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant Feeding Index	Collection of information on breastfeeding history, feeding practices, food frequency, and recent dietary history. This is a questionnaire to determine the child's availability to basic food sources.	36 months
Family Care Indicators	Questionnaire to indicate the basic resources available to the participant (i.e. housing, medical care, etc).	36 months

Collaborators and Investigators

• Sponsor: NICHD Global Network for Women's and Children's Health
• Collaborators: Thomas Jefferson University; Thrasher Research Fund; RTI International
• Investigators: Principal Investigator: Elizabeth McClure, PhD, RTI International

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Pre-eclampsia; Global Network; LDA; Pre-term birth; Low Dose Aspirin; ASPIRIN Trail; NICHD Global Network; ASPRIN Follow Up; BSID-III; Family Resources and Context; ASQ-36; Neurodevelopmental delays; hypertensive disorders of pregnancy (HDP)
• Additional Relevant MeSH Terms: Congenital Abnormalities; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: GN ASPIRIN Follow Up

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The plan is to release primary results from the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No