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

Study Overview
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Brief Summary
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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)

Detailed Description
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Preterm neonates with birth weight less than 1500 g are in higher risk to develop NEC. NEC is an inflammatory condition that: Is the medical urgency most frequent of gastrointestinal tube that requires neonatal intensive care may perforate infant´s bowel requiring surgery from 20% to 60% of the cases may cause infant's death in 20% to 42% of the cases. 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: 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 increased weight, length and fat mass gain in septic neonates decreased organic failures in surgical neonates, and 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

Official Title
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Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates

Conditions
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Necrotizing Enterocolitis

Intervention / Treatment
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* Dietary Supplement: Docosahexaenoic acid (DHA)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Minutes
Maximum Age: 2 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHA Group<br>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)<br>* Docosahexaenoic acid from algae source<br>* Other names: n-3 Fatty Acids;|
| Placebo Comparator: Control Group (Placebo)<br>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<br>* Placebo was designed to mimic the color and consistence of the oil that contains DHA<br>* Other names: Sunflower oil, Placebo for DHA intervention;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necrotizing enterocolitis (NEC) | 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. | Patients will be followed for the duration of hospital stay, an expected average of 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10 | 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. | At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria | 
| Hospital stay | 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. | The duration of hospital stay, an expected average of 6 weeks | 
| Growth velocity in weight | Gain of weight in g/kd/day, measured with an electronic scale every week until hospital discharge or 40 weeks of corrected gestational age | Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks | 
| Growth velocity in length and head circumference | 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. | Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks | 
| Growth velocity in skin folds | 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. | Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks | 
| Enteral tolerance | 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. | During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks | 
| Enteral intolerance | 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. | During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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docosahexaenoic acid, n-3 fatty acids, necrotizing enterocolitis, preterm infants