Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)

NCT ID: NCT04394910

Last Updated: 2023-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-16
• Study Completion Date: 2022-02-26

Brief Summary

Infants diagnosed with intrauterine growth restriction are at increased risk for brain injury in the neonatal period, and eventually increased risk for adverse long-term neurodevelopmental outcomes. This kind of growth restriction is often caused by long-term placental insufficiency leading to chronic lack of oxygen in the brain during development. Pomegranate juice is one of the highest polyphenol-containing dietary supplements commercially available. Previous studies have shown that pomegranate-derived polyphenols are potent neuroprotective antioxidants with no proven side effects. The investigators hypothesize that maternal dietary supplementation with pomegranate juice during the last trimester of pregnancy will reduce the effects of exogenous stimuli contributing to placental insufficiency, and will enhance brain growth and development in the IUGR population.

Detailed Description

The current study seeks to investigate the impact of maternal dietary supplementation with pomegranate juice on placental morphology and on subsequent newborn brain development and function. A total of 99 consenting women carrying fetuses with a diagnosis of intrauterine growth restriction (IUGR) in the third trimester were randomized to one of two arms.

Treatment Group: Expecting mothers in this group will be randomized to consume 8oz of pomegranate juice daily. Participants will keep a daily diary documenting compliance with the regimen. Participants will continue daily intake until delivery.

Placebo group: Expecting mothers will be randomized to consume an 8oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. Participants will keep a diary of daily intake to help ensure compliance similar to the treatment group. Participants will continue to placebo until delivery.

Both groups: Maternal blood and urine samples will be collected prior to starting the juice regimen in order to establish baseline metabolite status. For the first 84 mothers enrolled, a fetal MRI was scheduled prior to beginning the juice regimen. Phase I participants will undergo two fetal echocardiograms: one before starting the juice regimen, and a second two weeks into the juice regimen to establish the safety of high polyphenol intake on fetal heart development. All women will be contacted on a weekly basis to assess compliance. At the time of delivery, maternal blood and urine, and cord blood will be collected and sent for analysis to test for the presence of dimethylellagic acid glucuronide (DMEAG) and urolithin A glucuronide (UAG), polyphenic components of pomegranate juice. Placental material will be sent for formal pathological exam.

If clinically stable, MRI will be undertaken without sedation at term equivalent (38-41 weeks CGA). Infants will undergo testing of cognitive, gross and fine motor, and speech skills at around 2 years of age.

Conditions

Intrauterine Growth Restriction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pomegranate Juice

Dietary supplementation with 8 oz. commercially-available pomegranate juice consumed daily.

Group Type: EXPERIMENTAL

Pomegranate Juice

Intervention Type: DIETARY_SUPPLEMENT

Placebo Juice

Dietary supplementation with 8 oz. placebo juice (identical to pomegranate juice but lacking polyphenols) consumed daily.

Group Type: PLACEBO_COMPARATOR

Placebo Juice

Intervention Type: DIETARY_SUPPLEMENT

Interventions

Pomegranate Juice

Intervention Type: DIETARY_SUPPLEMENT

Placebo Juice

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Expecting mother with a fetal diagnosis of less than 5th percentile on the Doubilet fetal growth curve

Exclusion Criteria

• Multiple congenital abnormalities
• Known fetal chromosomal disorder
• Maternal illicit drug or alcohol intake

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

POM Wonderful LLC

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Terrie Inder

Chair, Department of Pediatric Newborn Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Terrie E Inder, MD, MBChB

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Ross MM, Cherkerzian S, Mikulis ND, Turner D, Robinson J, Inder TE, Matthews LG. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021 Feb 11;11(1):3569. doi: 10.1038/s41598-021-82144-0.

Reference Type: DERIVED

PMID: 33574371 (View on PubMed)

Other Identifiers

2014P000870

Identifier Type: -

Identifier Source: org_study_id