Enteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates
- 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)
|Necrotizing Enterocolitis||Dietary Supplement: Docosahexaenoic acid (DHA) Dietary Supplement: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (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|
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||October 2017 (Final data collection date for primary outcome measure)|
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
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01745510
|Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS|
|Mexico City, Distrito Federal, Mexico, 06720|
|Principal Investigator:||Mariela Bernabe-Garcia, PhD||Instituto Mexicano del Seguro Social|