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

Study Description

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).

Condition or disease	Intervention/treatment
Neurodevelopmental Abnormality	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 (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 Design

• Study Type: Observational
• Actual Enrollment: 666 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN): Neurodevelopmental Follow-up Trial
• Actual Study Start Date: September 1, 2021
• Actual Primary Completion Date: June 15, 2022
• Actual Study Completion Date: June 15, 2022

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Other Outcome Measures:

1. 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.
2. Family Care Indicators [ Time Frame: 36 months ]
   Questionnaire to indicate the basic resources available to the participant (i.e. housing, medical care, etc).

Eligibility Criteria

• Ages Eligible for Study: 33 Months to 39 Months (Child)
• Sexes Eligible for Study: All
• 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.

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama, Birmingham

Birmingham, Alabama, United States, 35233

United States, Colorado

University of Colorado Health Sciences Center

Denver, Colorado, United States, 80208

United States, Delaware

Christiana Care

Newark, Delaware, United States, 19718

United States, Massachusetts

Boston University

Boston, Massachusetts, United States, 02115

United States, New York

Columbia University

New York, New York, United States, 10032

United States, North Carolina

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States, 27599

RTI International

Research Triangle Park, North Carolina, United States, 27709

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Congo, The Democratic Republic of the

Kinshasa School of Public Health

Kinshasa, Congo, The Democratic Republic of the

Guatemala

INCAP

Guatemala City, Guatemala

India

Jawaharlal Nehru Medical College

Belgaum, India

Lata Medical Research Foundation

Nagpur, India

Pakistan

Aga Khan University

Karachi, Pakistan

Zambia

University Teaching Hospital

Lusaka, Zambia

Sponsors and Collaborators

NICHD Global Network for Women's and Children's Health

Thomas Jefferson University

RTI International

Thrasher Research Fund

Investigators

• Principal Investigator: Elizabeth McClure, PhD; RTI International

More Information

• Responsible Party: NICHD Global Network for Women's and Children's Health
• ClinicalTrials.gov Identifier: NCT04888377
• Other Study ID Numbers: GN ASPIRIN Follow Up
• First Posted: May 17, 2021
• Last Update Posted: June 27, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

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

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

Keywords provided by NICHD Global Network for Women's and Children's Health:

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

Additional relevant MeSH terms:

Congenital Abnormalities; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics