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

Phase 1
Completed
Conditions
Necrotizing Enterocolitis
Interventions
Dietary Supplement: Docosahexaenoic acid (DHA)
Dietary Supplement: Placebo
Registration Number
NCT01745510
Lead Sponsor
Coordinación de Investigación en Salud, Mexico
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)

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
225
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DHA GroupDocosahexaenoic acid (DHA)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
Control Group (Placebo)PlaceboControl 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.
Primary Outcome Measures
NameTimeMethod
Necrotizing enterocolitis (NEC)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
NameTimeMethod
Enteral intoleranceDuring 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.

Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10At 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.

Hospital stayThe 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.

Enteral toleranceDuring 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.

Growth velocity in skin foldsThroughout 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.

Growth velocity in weightThroughout 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

Growth velocity in length and head circumferenceThroughout 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.

Trial Locations

Locations (1)

Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS

🇲🇽

Mexico City, Distrito Federal, Mexico

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