Clinical trial NCT01745510: Enteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates
Official title: Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Necrotizing Enterocolitis
Keywords: docosahexaenoic acid
n-3 fatty acids
necrotizing enterocolitis
preterm infants
Lead sponsor: Coordinación de Investigación en Salud, Mexico
Sponsor class: OTHER_GOV
Collaborators: name: National Council of Science and Technology, Mexico
First posted: 2012-12-10
Enrollment: 225
Sex: ALL
Minimum age (years): 60
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.
Primary purpose: PREVENTION

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

Eligibility criteria: 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

Primary outcomes:
measure: Necrotizing enterocolitis (NEC)
timeFrame: Patients will be followed for the duration of hospital stay, an expected average of 6 weeks
Secondary outcomes:
measure: Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10
timeFrame: At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria
measure: Hospital stay
timeFrame: The duration of hospital stay, an expected average of 6 weeks
measure: Growth velocity in weight
timeFrame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
measure: Growth velocity in length and head circumference
timeFrame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
measure: Growth velocity in skin folds
timeFrame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
measure: Enteral tolerance
timeFrame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
measure: Enteral intolerance
timeFrame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS
state: Distrito Federal
Study officials:
affiliation: Instituto Mexicano del Seguro Social
name: Mariela Bernabe-Garcia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lopez-Alarcon M, Bernabe-Garcia M, Del Prado M, Rivera D, Ruiz G, Maldonado J, Villegas R. Docosahexaenoic acid administered in the acute phase protects the nutritional status of septic neonates. Nutrition. 2006 Jul-Aug;22(7-8):731-7. doi: 10.1016/j.nut.2006.04.002. Epub 2006 Jun 5.
citation: Lopez-Alarcon M, Bernabe-Garcia M, del Valle O, Gonzalez-Moreno G, Martinez-Basilea A, Villegas R. Oral administration of docosahexaenoic acid attenuates interleukin-1beta response and clinical course of septic neonates. Nutrition. 2012 Apr;28(4):384-90. doi: 10.1016/j.nut.2011.07.016. Epub 2011 Nov 12.
citation: Bernabe-Garcia M, Lopez-Alarcon M, Villegas-Silva R, Mancilla-Ramirez J, Rodriguez-Cruz M, Maldonado-Hernandez J, Chavez-Rueda KA, Blanco-Favela F, Espinoza-Garcia L, Lagunes-Salazar S. Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study. Ann Nutr Metab. 2016;69(1):15-23. doi: 10.1159/000447498. Epub 2016 Jul 9.
citation: Bernabe-Garcia M, Calder PC, Villegas-Silva R, Rodriguez-Cruz M, Chavez-Sanchez L, Cruz-Reynoso L, Mateos-Sanchez L, Lara-Flores G, Aguilera-Joaquin AR, Sanchez-Garcia L. Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial. Nutrients. 2021 Feb 17;13(2):648. doi: 10.3390/nu13020648.