ASPIRIN: Neurodevelopmental Follow-up Trial

• ClinicalTrials.gov Identifier: NCT04888377
• Recruitment Status: Completed
• First Posted: May 17, 2021
• Last Update Posted: June 27, 2022
• Sponsor: NICHD Global Network for Women's and Children's Health
• Collaborators: Thomas Jefferson University; RTI International; Thrasher Research Fund
• Information provided by (Responsible Party): NICHD Global Network for Women's and Children's Health

Tracking Information

• First Submitted Date: April 28, 2021
• First Posted Date: May 17, 2021
• Last Update Posted Date: June 27, 2022
• Actual Study Start Date: September 1, 2021
• Actual Primary Completion Date: June 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 12, 2021)

BSID-III Examination [ Time Frame: 36 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 12, 2021)

ASQ-3 [ Time Frame: 36 months ]

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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 12, 2021)

• Infant Feeding Index [ Time Frame: 36 months ]
  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.
• Family Care Indicators [ Time Frame: 36 months ]
  Questionnaire to indicate the basic resources available to the participant (i.e. housing, medical care, etc).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: ASPIRIN: Neurodevelopmental Follow-up Trial
• Official Title: Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN): Neurodevelopmental Follow-up 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 (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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: Neurodevelopmental Abnormality

Intervention

• Drug: Aspirin
  Participant's mothers were administered 81mg of Aspirin throughout their pregnancy with the participant.
• Drug: Placebo
  Participant's mothers were administered placebo throughout their pregnancy with the participant.

Study Groups/Cohorts

• 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: Drug: 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: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 24, 2022): 666
• Original Estimated Enrollment (submitted: May 12, 2021): 620
• Actual Study Completion Date: June 15, 2022
• Actual Primary Completion Date: June 15, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 33 Months to 39 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Congo, The Democratic Republic of the, Guatemala, India, Pakistan, United States, Zambia

Administrative Information

• NCT Number: NCT04888377
• Other Study ID Numbers: GN ASPIRIN Follow Up
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: The plan is to release primary results from the study.

• Current Responsible Party: NICHD Global Network for Women's and Children's Health
• Original Responsible Party: Same as current
• Current Study Sponsor: NICHD Global Network for Women's and Children's Health
• Original Study Sponsor: Same as current

Collaborators

• Thomas Jefferson University
• RTI International
• Thrasher Research Fund

Investigators

• Principal Investigator: Elizabeth McClure, PhD; RTI International

• PRS Account: NICHD Global Network for Women's and Children's Health
• Verification Date: June 2022