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

Necrotizing Enterocolitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01745510
• Other study ID #: DHA-ECN
• Secondary ID: DHA, ECN and Pre
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2012
• Est. completion date: October 2017

Study information

• Verified date: March 2021
• Source: Coordinación de Investigación en Salud, Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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 information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis

Intervention

Dietary Supplement:
• Docosahexaenoic acid (DHA)
Docosahexaenoic acid from algae source
• Placebo
Placebo was designed to mimic the color and consistence of the oil that contains DHA

Locations

Country	Name	City	State
Mexico	Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS	Mexico City	Distrito Federal

Sponsors (2)

Lead Sponsor	Collaborator
Coordinación de Investigación en Salud, Mexico	National Council of Science and Technology, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (4)

Bernabe-García M, Calder PC, Villegas-Silva R, Rodríguez-Cruz M, Chávez-Sánchez L, Cruz-Reynoso L, Mateos-Sánchez L, Lara-Flores G, Aguilera-Joaquín AR, Sánchez-García L. Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in — View 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. — View Citation

López-Alarcón M, Bernabe-García 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. Epub 2006 Jun 5. — View Citation

López-Alarcón M, Bernabe-García M, del Valle O, González-Moreno G, Martínez-Basilea A, Villegas R. Oral administration of docosahexaenoic acid attenuates interleukin-1ß 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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