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Enteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01745510
Recruitment Status : Completed
First Posted : December 10, 2012
Last Update Posted : January 17, 2018
Information provided by (Responsible Party):

Study Description
Brief Summary:
  • The purpose of this study is to determine whether docosahexaenoic acid is effective in the prevention or reducing severity of necrotizing enterocolitis (NEC) in preterm neonates < 1500 g at birth who are starting enteral feeding.
  • if NEC is prevented, this study will measure whether hospital stay is also reduced in neonates who receive Docosahexaenoic acid (DHA)

Condition or disease Intervention/treatment Phase
Necrotizing Enterocolitis Dietary Supplement: Docosahexaenoic acid (DHA) Dietary Supplement: Placebo Phase 1 Phase 2

Detailed Description:
  • Preterm neonates with birth weight less than 1500 g are in higher risk to develop NEC.
  • NEC is an inflammatory condition that:

    1. Is the medical urgency most frequent of gastrointestinal tube that requires neonatal intensive care
    2. may perforate infant´s bowel requiring surgery from 20% to 60% of the cases
    3. may cause infant's death in 20% to 42% of the cases.
    4. has no adequate treatment worldwide, therefore prevention is needed
  • DHA by enteral feeding has been administrated by our research group to attenuate inflammatory response in septic and surgical neonates.
  • Our results showed:

    1. lower Interleukin(IL)-1 beta in septic neonates, but in surgical neonates, they also showed less IL-6 and anti-inflammatory cytokines IL-10 and IL-1ra, after adjusting by confounders
    2. increased weight, length and fat mass gain in septic neonates
    3. decreased organic failures in surgical neonates, and
    4. lower stay at neonatal intensive care in surgical neonates

DHA has not been used as unique intervention at a high but physiological dose; in addition, our previous results found an anti-inflammatory effect in neonates.Therefore, we expect that preterm infants may have a reduced bowel inflammatory response and lower NEC events and or severity

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates
Study Start Date : October 2012
Primary Completion Date : October 2017
Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: DHA Group

DHA Group will receive 75 milligrams of docosahexaenoic acid (DHA) per kilogram of their baseline weight.

They will receive one dose, administered by enteral feeding every 24 h during 14 days

Dietary Supplement: Docosahexaenoic acid (DHA)
Docosahexaenoic acid from algae source
Other Name: n-3 Fatty Acids
Placebo Comparator: Control Group (Placebo)

Control group will receive sunflower oil which is the excipient of the DHA in this study.

They will receive one dose every 24 h during 14 days.

Dietary Supplement: Placebo
Placebo was designed to mimic the color and consistence of the oil that contains DHA
Other Name: Sunflower oil, Placebo for DHA intervention

Outcome Measures

Primary Outcome Measures :
  1. Necrotizing enterocolitis (NEC) [ Time Frame: Patients will be followed for the duration of hospital stay, an expected average of 6 weeks ]
    Neonates will receive enteral DHA at beginning of their first enteral feeding and NEC will be diagnosed during hospital stay, measured as presence or absence, as well as severity of NEC by Bell's score.

Secondary Outcome Measures :
  1. Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10 [ Time Frame: At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria ]
    Plasma cytokines will be determined before to the beginning of the enteral feeding (baseline) and if the infant develop confirmed or severe NEC. Cytokines will be measured by a multiplex kit in picograms/mL.

  2. Hospital stay [ Time Frame: The duration of hospital stay, an expected average of 6 weeks ]
    Hospital stay includes intensive stay care and preterm service (where clinically stable babies are attended) until they are discharged from the hospital to home, in days.

  3. Growth velocity in weight [ Time Frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks ]
    Gain of weight in g/kd/day, measured with an electronic scale every week until hospital discharge or 40 weeks of corrected gestational age

  4. Growth velocity in length and head circumference [ Time Frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks ]
    Gain of recumbent length and and head circumference in cm/week measured every 2 weeks until hospital discharge or 40 weeks of corrected gestational age. For measuring length we will use an infantometer and for head circumference we will use a glass fiber tape.

  5. Growth velocity in skin folds [ Time Frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks ]
    Gain of bicipital, tricipital, suprailiac and subscapular skin folds in mm/week measured every 2 weeks, until hospital discharge or 40 weeks of corrected gestational age. We will use a glass fiber tape to measure it.

  6. Enteral tolerance [ Time Frame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks ]
    Registration of volume of the enteral intake every 24 h (ml/kg/day) until reach 150 ml/kg/day and being sustained or increased by enteral feeding with human milk or formula.

  7. Enteral intolerance [ Time Frame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks ]
    Registration of number of patients with clinical signs of intolerance such as vomit, abnormal number of stool loss, abdominal distension, number of patients with medical indication to withdraw enteral feeding due clinical unstability and number of patients with use of medications related to enteral tolerance such as omeprazole, ranitidine, vitamins, iron, etc.

Eligibility Criteria

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Ages Eligible for Study:   up to 2 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Birth weight lower than 1500 g
  • Adequate weight for gestational age
  • Clinically stable to begin enteral feeding
  • Written informed consent by both parents plus the sign of two witnesses

Exclusion Criteria:

  • Clinical and biochemical data of inflammatory response such as body core temperature altered, cardiac and respiratory frequency -low or high according to age-, leucocytosis or leucopenia, taking into account the thresholds reported by Goldstein in Pediatric Critical Care Medicine 2005 Vol 6 N°1.
  • Persistent bleeding at any level
  • Mother taking n-3 supplements and planning to breastfed
  • Parents who decline the authorization for participating in the study
  • Early discharge to other hospital outside the metropolitan area
  • Persistent vomiting
  • Receiving medication to avoid coagulation
  • Gastrointestinal malformations
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01745510

Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS
Mexico City, Distrito Federal, Mexico, 06720
Sponsors and Collaborators
Coordinación de Investigación en Salud, Mexico
National Council of Science and Technology, Mexico
Principal Investigator: Mariela Bernabe-Garcia, PhD Instituto Mexicano del Seguro Social
More Information

Responsible Party: Mariela Bernabe García, Principal investigator, Coordinación de Investigación en Salud, Mexico
ClinicalTrials.gov Identifier: NCT01745510     History of Changes
Other Study ID Numbers: DHA-ECN
DHA, ECN and Preterm ( Other Grant/Funding Number: CONACYT 161643 )
First Posted: December 10, 2012    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Mariela Bernabe García, Coordinación de Investigación en Salud, Mexico:
docosahexaenoic acid
n-3 fatty acids
necrotizing enterocolitis
preterm infants

Additional relevant MeSH terms:
Enterocolitis, Necrotizing
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases