Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants

March 19, 2019 updated by: Sanford Health

The purpose of this study is to understand if the "DHA gap" can be corrected by giving a daily dose of DHA oil to preterm babies.

DHA is an essential omega-3 fatty acid, which means our body cannot make DHA. We have to take it in through our diet. DHA is important for normal brain and eye health and it may also decrease inflammation. This is important for premature babies because they are at a greater risk for getting diseases related to inflammation, especially in their lungs, eyes and intestines. Since DHA is so important for normal growth, you will find DHA naturally in breast milk and it is now added to infant formula. But the amount in breast milk and infant formula is about half of what your infant should expect to get in the womb (about 13-29mg per day in breast milk vs. 50-75mg per day in the womb). Very premature babies are at an even greater disadvantage because they cannot always eat very much right away and that is the only way they can get essential fatty acids in their body. This means premature babies are getting less DHA than they would in the womb and then the "DHA gap" continues for a longer period of time. This gap also comes at a time when their brain is growing most rapidly and their bodies need it the most. This trial is designed to see if giving DHA, even before the baby can take food orally, will raise his/her DHA blood levels to those of normal term babies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective is to develop a DHA supplementation strategy to overcome these barriers. This single-center, double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels will be analyzed at baseline, full feedings and near discharge in DHA or placebo supplemented preterm infants. Term peers will also have blood FA levels analyzed for comparison. Growth, feeding tolerance and adverse outcomes (NEC, intraventricular hemorrhage (IVH), thrombocytopenia, sepsis) will be evaluated. Study progress and safety will be monitored by an external Data Safety Monitoring Board (DSMB). Overall, the study aims to determine if daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57117
        • Sanford Health USD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 7 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Preterm infants between 24 and 33 6/7 weeks gestation
  • must be less than or equal to 1 week of age

Exclusion Criteria:

  • infants who are considered by the medical team to be non-viable
  • infants with multiple or severe congenital anomalies such as gastroschisis, congenital chylothorax or other illnesses that do not allow a feeding tube to be placed or utilized at 7 days of age.
  • term infants: who are born to mothers with diabetes or are small for gestational age (SGA-less than the 10th% for adjusted gestational age
  • All families consented for this study will need to be able to read and write English
  • Mother must be 18 years of age or older
  • Taking Omegaven

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: DHA oil
DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
Dietary supplement: DHA oil
Therapy Group:DHA oil administered at 50 mg/d (0.18ml) as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
Placebo Comparator: (MCT) control oil
MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
Dietary supplement: (MCT) Control oil
Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days to Reach Full Enteral Feedings and Days on Study Oil.
Time Frame: From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.
This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.
From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.
Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change
Time Frame: 30 days from birth
A linear mixed model was used to explore weight over time.
30 days from birth
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood
Time Frame: At baseline (enrollment, < 1 week of age), full feedings, discharge
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
At baseline (enrollment, < 1 week of age), full feedings, discharge
Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change
Time Frame: 30 days from birth
A linear mixed model was used to explore length over time.
30 days from birth
Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference
Time Frame: 30 days from birth
A linear mixed model was used to explore head circumference over time.
30 days from birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood
Time Frame: At baseline (enrollment, <1 week of age), full feedings and discharge
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
At baseline (enrollment, <1 week of age), full feedings and discharge

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
LCPUFA Levels - Alpha-linolenic Acid (ALA) in Whole Blood
Time Frame: Baseline (<1 week of age), full enteral feedings and discharge
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Baseline (<1 week of age), full enteral feedings and discharge
LCPUFA Levels - Linoleic Acid (LNA)
Time Frame: Baseline, full feedings and discharge
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Baseline, full feedings and discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanford Health

Collaborators

The Gerber Foundation

Investigators

  • Principal Investigator: Michelle L Baack, MD, Sanford Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

July 2, 2013

First Submitted That Met QC Criteria

July 23, 2013

First Posted (Estimate)

July 26, 2013

Study Record Updates

Last Update Posted (Actual)

March 21, 2019

Last Update Submitted That Met QC Criteria

March 19, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DHA Gap

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Individual participant data (IPD) will not be shared with other researchers. All data is de-identified for review by DSMB or others.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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