DHA & ARA Supplementation for Prematurity

Recruiting at 6 trial locations

Overseen By Diana Anzueto Guerra

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center at San Antonio

Disqualifiers: Congenital anomalies, Surgery, Imminent death

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks

328 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how adding DHA and ARA, two important nutrients, to the diet of premature babies affects their metabolism and inflammation. Researchers will test different schedules for administering these supplements to observe their impact on growth and health. The study focuses on babies born very early, between 25 and 29 weeks of pregnancy, who are less than two days old when they begin receiving the supplements. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve the health outcomes of premature infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that DHA and ARA are important for brain and eye development in babies, and these nutrients are often added to baby formulas. Enfamil's DHA & ARA supplement addresses special dietary needs and has been part of baby nutrition for years.

The FDA has stated that DHA and ARA are safe for use in baby formulas, although they once requested more information to ensure their safety. Despite this, many babies have used these supplements without issues. No widespread reports of serious side effects have been directly linked to DHA and ARA in baby formulas.

In summary, while the FDA previously sought more data, these supplements have been widely used without major safety concerns, suggesting they are generally safe for babies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the DHA & ARA supplementation for prematurity because these long-chain polyunsaturated fatty acids (LCPUFAs) might play a crucial role in the development of preterm infants. Unlike standard nutritional support that often lacks these specific fatty acids, this supplementation could provide essential building blocks for brain and eye development. By testing different timing and duration strategies of DHA & ARA administration, researchers aim to find the optimal approach to boost developmental outcomes in premature babies.

What evidence suggests that this trial's treatments could be effective for prematurity?

Research has shown that giving premature babies DHA and ARA can aid the development of their brain, eyes, and nervous system. Studies have found that these essential fatty acids support the growth of vision and mental abilities in babies born early. DHA and ARA are crucial for developing key body functions, which is why they are often added to baby formulas. Early findings suggest these nutrients also assist with metabolism and inflammation, important for overall health. This trial will evaluate different supplementation strategies: some participants will receive DHA/ARA supplements throughout the study, while others will receive them only during specific periods, or not at all. This evidence supports the idea that DHA and ARA can benefit premature infants. ^{2 3 4 6 7}

Who Is on the Research Team?

Cynthia Blanco, MD, MSCI-TS

Principal Investigator

University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

This trial is for preterm infants born between 25 and just under 30 weeks of gestation, who are less than 48 hours old when they receive their first lipid dose. Infants needing surgery before discharge or anticipated to require withdrawal from intensive care within the first 72 hours, as well as those with serious congenital anomalies, cannot participate.

Inclusion Criteria

My baby received their first lipid dose before they were 2 days old.

I was born between 25 and 29 weeks of pregnancy.

Exclusion Criteria

Serious congenital anomalies

Imminent death such that withdrawal of intensive care support is anticipated within the first 72 hours after birth

My newborn needs surgery before leaving the hospital.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Infants receive DHA/ARA supplementation from within the first 48 hours after birth to 36 weeks postmenstrual age

Up to 36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enfamil® DHA & ARA Supplement for Special Dietary Use

Trial Overview The study is examining how a special dietary supplement called Enfamil® DHA & ARA affects fat metabolism in premature babies. It looks at whether these supplements influence biological processes like metabolism, inflammation response, and development of organs.

How Is the Trial Designed?

Group I: No supplement initially then DHA/ARA supplement Experimental Treatment 1 Intervention

No DHA/ARA supplement till 31 6/7 weeks' then long-chain polyunsaturated fatty acids (LCPUFA) supplement from 32 to 36 weeks PMA, "x-off/on"

Group II: DHA/ARA supplement Experimental Treatment 1 Intervention

DHA/ARA supplement throughout the duration of the protocol, "d-on"

Group III: DHA/ARA initially then no supplement Experimental Treatment 1 Intervention

DHA/ARA supplement from enrollment to 31 6/7 weeks post-menstrual age (PMA) then no supplement from 32 to 36 weeks' PMA, "x- on/off"

Group IV: No DHA/ARA supplement Active Control 1 Intervention

no DHA/ARA supplement throughout the duration of the protocol, "d-off"

Enfamil® DHA & ARA Supplement for Special Dietary Use is already approved in United States, Canada for the following indications:

Approved in United States as Enfamil DHA-in-sol for:

• Dietary supplement for infants and toddlers to support brain and eye development

Approved in Canada as Enfamil DHA & ARA Supplement for Special Dietary Use for:

• Dietary supplement for infants and toddlers to support brain and eye development

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

DHA and arachidonic acid (ARA) are crucial for brain, immune, and cardiovascular health in early life, yet there is no consensus on dietary intake recommendations, especially in low-income countries where these nutrients are often lacking.

The review advocates for mandatory inclusion of DHA and ARA in infant and follow-on formulas at levels comparable to those found in breast milk, to ensure adequate intake during the critical growth period of 6-36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of dietary DHA and ARA in early life: a public health perspective. Forsyth, S., Gautier, S., Salem, N.[2018]

In a study involving 121 preterm infants, those receiving enhanced supplementation of arachidonic acid (ARA) and docosahexaenoic acid (DHA) showed significantly better linear growth compared to a control group, with a mean difference in length z score of 0.74.

While the ARA:DHA group demonstrated improved growth up to term equivalent age, there were no significant differences in growth and body composition outcomes at 3 months corrected age, indicating that early supplementation may support initial growth but does not necessarily affect long-term body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial. Rossholt, ME., Bratlie, M., Wendel, K., et al.[2023]

In a study involving lactating mothers who delivered preterm, higher DHA supplementation (1000 mg/d) significantly altered the expression of inflammation-related genes in the mammary gland compared to standard supplementation (200 mg/d), suggesting potential benefits for both mother and infant.

The analysis revealed that increased DHA led to upregulation of inflammation-inhibiting genes and downregulation of proinflammatory genes, indicating a shift towards improved immune regulation and reduced inflammation in the milk composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm. Adams, JM., Valentine, CJ., Karns, RA., et al.[2023]

DHA and ARA, important fatty acids found in breast milk, are crucial for infant development, and their supplementation in infant formula can lead to positive developmental outcomes, making formula-fed infants closer to breast-fed infants in terms of cognition, visual acuity, and immune responses.

Future research should focus on specific cognitive outcomes and immune function related to DHA and ARA supplementation, while also considering factors like genetic variations that may affect fatty acid metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DHA and ARA addition to infant formula: Current status and future research directions. Lien, EL., Richard, C., Hoffman, DR.[2021]

In a study involving 120 very preterm infants, supplementation with arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly reduced the duration of respiratory support needed and lowered oxygen demand compared to a control group receiving medium chain triglycerides (MCT) oil.

The supplementation was found to be safe, with no significant differences in the incidence of bronchopulmonary dysplasia (BPD) or other major morbidities between the treatment and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants. Wendel, K., Aas, MF., Gunnarsdottir, G., et al.[2023]

In developing countries, infants aged 6-36 months have low dietary intakes of arachidonic acid (ARA) and docosahexaenoic acid (DHA) from complementary foods, which is concerning given the importance of these nutrients for growth and development.

The low intake of ARA is linked to higher rates of childhood stunting, infant mortality, and other health issues, highlighting the need for public health strategies to improve nutritional support for vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Intakes of Arachidonic Acid and Docosahexaenoic Acid in Early Life - With a Special Focus on Complementary Feeding in Developing Countries. Forsyth, S., Gautier, S., Salem, N.[2018]

Preterm infants fed formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) showed significantly greater weight and length growth compared to those on unsupplemented formulas, with growth metrics comparable to term infants by 118 weeks postmenstrual age (PMA).

The supplemented groups also achieved higher mental and psychomotor development scores at 118 weeks PMA without an increase in adverse events, indicating that DHA and ARA supplementation is both safe and beneficial for developmental outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. Clandinin, MT., Van Aerde, JE., Merkel, KL., et al.[2013]

This study aims to determine if early supplementation of essential fatty acids (ARA and DHA) improves brain maturation and neonatal outcomes in very preterm infants born before 29 weeks of gestation, with a target sample size of 120 infants.

The primary outcome will be assessed using MRI to evaluate brain maturation, and the study could inform future nutritional guidelines for preterm infants, potentially reducing inflammation-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT). Wendel, K., Pfeiffer, HCV., Fugelseth, DM., et al.[2021]

A study involving 60 preterm infants (24-34 weeks gestational age) showed that daily enteral DHA supplementation (50 mg/day) significantly increased blood DHA levels over time, addressing the deficiency commonly seen in these infants.

The supplementation was found to be safe, with no differences in adverse events between the DHA and placebo groups, although preterm infants still had lower DHA levels compared to term peers at discharge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants. Baack, ML., Puumala, SE., Messier, SE., et al.[2018]

Preterm infants who were fed formula supplemented with DHA showed improved visual acuity and higher mental development scores at 12 months, indicating that DHA is beneficial for their early development.

While DHA appears to be conditionally essential for preterm infants, further research is needed to understand the balance of long-chain fatty acids required for optimal growth and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-chain fatty acids and early visual and cognitive development of preterm infants. Carlson, SE., Werkman, SH., Peeples, JM., et al.[2013]

Citations

1. withpower.com withpower.com/trial/phase-premature-6-2022-a8d93

DHA & ARA Supplementation for Prematurity Research shows that supplementing premature infants with DHA (an important fatty acid for brain and eye development) can improve visual and mental development.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05380401?tab=history&a=3

Record History | ver. 3: 2023-01-09 | NCT05380401 Infants will be randomized to receive the combined enteral DHA/ARA supplement within the first 48 hours after birth to 36 weeks postmenstrual age. The ...

3. enfamil.com enfamil.com/articles/importance-of-dha-and-ara-for-babies-and-toddlers/

Importance of DHA & ARA in Baby Formula DHA and ARA not only help support their brain development but their eyes and nervous system too. DHA and ARA supplements for infants can be a great way to help ...

4. clinicaltrial.be clinicaltrial.be/en/details/17035?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Metabolic Mechanisms Induced by Enteral DHA and ARA ... Infants will be randomized to receive the combined enteral DHA/ARA supplement within the first 48 hours after birth to 36 weeks ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11679688/

A Comparative In Vitro Digestion Study of Three Lipid ... This study compares the following three formulations in an in vitro digestion model to assess bioaccessibility: Enfamil® DHA & ARA (Mead Johnson ...

6. hcp.meadjohnson.com hcp.meadjohnson.com/s/product/a4R4J000000PpQoUAK/enfamil-dha-ara-supplement

Enfamil® DHA & ARA Supplement | Mead Johnson HCP Enfamil DHA & ARA Supplement is a commercially sterile, emulsified liquid that provides 20 mg DHA and 40 mg ARA per 0.5 mL.

7. flca.info flca.info/HTMLobj-156/DHA_article.pdf

DHA/ARA Supplemented Infant Formulas In 1999, the FDA determined that Wyeth Nutritionals'. GRAS notice for use of these fatty acids did not provide sufficient data to assure safety of their use in.