ASPIRIN: Neurodevelopmental Follow-up Trial

Sponsor

NICHD Global Network for Women's and Children's Health (Other)

Overall Status

Completed

CT.gov ID

NCT04888377

Collaborator

Thomas Jefferson University (Other), RTI International (Other), Thrasher Research Fund (Other)

666

Enrollment

Locations

9.4

Actual Duration (Months)

47.6

Patients Per Site

Patients Per Site Per Month

Study Details

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	Phase
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 :

Sep 1, 2021

Actual Primary Completion Date :

Jun 15, 2022

Actual Study Completion Date :

Jun 15, 2022

Arms and Interventions

Arm	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.

Arm

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

BSID-III Examination [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

ASQ-3 [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

Infant Feeding Index [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 [36 months]
Questionnaire to indicate the basic resources available to the participant (i.e. housing, medical care, etc).

Eligibility Criteria

Criteria

Ages Eligible for Study:

33 Months to 39 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35233
2	University of Colorado Health Sciences Center	Denver	Colorado	United States	80208
3	Christiana Care	Newark	Delaware	United States	19718
4	Boston University	Boston	Massachusetts	United States	02115
5	Columbia University	New York	New York	United States	10032
6	University of North Carolina School of Medicine	Chapel Hill	North Carolina	United States	27599
7	RTI International	Research Triangle Park	North Carolina	United States	27709
8	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
9	Kinshasa School of Public Health	Kinshasa		Congo, The Democratic Republic of the
10	INCAP	Guatemala City		Guatemala
11	Jawaharlal Nehru Medical College	Belgaum		India
12	Lata Medical Research Foundation	Nagpur		India
13	Aga Khan University	Karachi		Pakistan
14	University Teaching Hospital	Lusaka		Zambia