The Effects of Probiotic Supplementation on Extremely Low Birthweight Infants

NCT01788761 | Terminated

• 1 other identifier: pROBIOTICS11
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study that will look at the effects of giving two nutritional supplements on extremely low birth infants (infants weighing less than 1000 grams or weighing less than approximately 2 lbs 3 1/2 ounces at birth). The nutritional supplements that will be studied are Culturelle for Kids/Culturelle Kids and Align. They are nutritional supplements that each contain a different probiotic. In this study the investigators will mainly be looking at the effect that these supplements may have on how well babies tolerate their feedings and how long they require supplemental intravenous fluids for nutritional support. The investigators will also, however, look at many other factors such as rate of growth, rates of infection, survival rate and the length of time the infant needs to be in the hospital. The investigators will also look at its effect on conditions/complications of prematurity such as bronchopulmonary dysplasia and chronic lung disease (chronic diseases of the lung associated with prematurity), necrotizing enterocolitis and intestinal perforations (serious diseases of the infant's intestines), retinopathy of prematurity (eye disease associated with prematurity), intracranial hemorrhage (bleeding into the brain) and patent ductus arteriosus (a blood vessel connecting two main blood vessels coming out of the heart that does not close spontaneously (by itself).

Conditions

Feeding Tolerance

Keywords

Probiotics; Feeding Tolerance; Extremely Low Birthweight Infants

Outcome Measures

Primary Outcomes (1)

• Feeding Tolerance

  Feeding Tolerance as determined by the number of days infant is without enteral feedings due to feeding intolerance, number of days infant requires supplemental hyperalimentation/intravenous fluids for nutritional support and number of days to achieve full enteral feedings

  Evaluated on a daily basis until hospital discharge/transfer/death up until one year of age

Secondary Outcomes (9)

• Necrotizing Enterocolitis (Bell's Stage 2 or greater)

  Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until 1 year of age

• Culture proven sepsis without Necrotizing Enterocolitis

  Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age

• Chronic Lung Disease

  Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age

• Periventricular Leukomalacia

  Infant's entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age

• Mortality

  Infant's entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age

Study Arms (2)

Probiotic Supplemented Group

EXPERIMENTAL

500,000,0000 cells of Lactobacillus GG (utilizing either Culturelle for Kids or Kids Culturelle preparation) and 500,000,000 cells of Bifidobacterium Infantis (utilizing Align capsule) diluted in 3 ml breastmilk/formula and administered enterally from first day of enteral feeds until term gestation/discharge/transfer/death (whichever occurs first) every day infant is receives enteral feedings

Dietary Supplement: Probiotic Supplemented Group

Control Group

SHAM COMPARATOR

3 ml enteral feeding of breastmilk/formula administered once daily in addition to regularly prescribed enteral feedings from day of first feeding until term gestation/discharge/transfer/death (which ever occurs first) and administered every day that infant receives enteral feedings

Dietary Supplement: Control Group

Interventions

Probiotic Supplemented Group DIETARY_SUPPLEMENT

Also known as: Culture for Kids, Kids Culturelle, Align, Lactobacillus GG, Bifidobacter Infantis

Probiotic Supplemented Group

Control Group DIETARY_SUPPLEMENT

Also known as: Breastmilk, Formula

Control Group

Eligibility Criteria

• Age: Up to 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Birthweight between 500-999 grams
• Apgar score greater than or equal to 3 at 5 minutes
• Infant free from any known major congenital anomalies or chromosomal/genetic anomalies
• Infant without any known cyanotic or complex congenital heart disease
• Infant NPO or on trophic enteral feedings than have been started less than 24 hours previously
• Infant without prior history of necrotizing enterocolitis or gastrointestinal perforation
• Infant without previous exposure to probiotics
• Infant that will be ready to start trophic feedings within the first 14 days of life
• Infant less than or equal to 14 days of age
• Infant born to HIV negative mother
• Written informed consent obtained from mother

You may not qualify if:

• Infant born to HIV positive mother
• Infant with history of prior probiotic exposure
• Infant greater than 14 days of age
• Infant on enteral feedings for greater than 24 hours
• Infant with major congenital anomaly/chromosomal or genetic anomaly
• Infant with cyanotic/complex congenital heart disease
• Infant with previous gastrointestinal perforation/necrotizing enterocolitis
• minute Apgar score \< 3

Sponsors & Collaborators

• Mercy Health System: lead
• Rockford Memorial Hospital Development Foundation: collaborator

Study Sites (1)

Rockford Memorial Hospital

Rockford, Illinois, 61103, United States

Location

Related Publications (25)

• Alfaleh K, Anabrees J, Bassler D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: a meta-analysis. Neonatology. 2010;97(2):93-9. doi: 10.1159/000235684. Epub 2009 Aug 25.

  PMID: 19707025 BACKGROUND

• Amerifit Inc. Culturelle Probiotics for Kids. Packaging information 2010

  BACKGROUND

• Baldassarre ME, Laforgia N, Fanelli M, Laneve A, Grosso R, Lifschitz C. Lactobacillus GG improves recovery in infants with blood in the stools and presumptive allergic colitis compared with extensively hydrolyzed formula alone. J Pediatr. 2010 Mar;156(3):397-401. doi: 10.1016/j.jpeds.2009.09.012. Epub 2009 Nov 2.

  PMID: 19880141 BACKGROUND

• Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005 Aug;147(2):192-6. doi: 10.1016/j.jpeds.2005.03.054.

  PMID: 16126048 BACKGROUND

• Chou IC, Kuo HT, Chang JS, Wu SF, Chiu HY, Su BH, Lin HC. Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. J Pediatr. 2010 Mar;156(3):393-6. doi: 10.1016/j.jpeds.2009.09.051. Epub 2009 Nov 14.

  PMID: 19914635 BACKGROUND

• Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate. 2002 Aug;82(2):103-8. doi: 10.1159/000063096.

  PMID: 12169832 BACKGROUND

• Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010 May;125(5):921-30. doi: 10.1542/peds.2009-1301. Epub 2010 Apr 19.

  PMID: 20403939 BACKGROUND

• Guenther K, Straube E, Pfister W, Guenther A, Huebler A. Sever sepsis after probiotic treatment with Escherichia coli NISSLE 1917. Pediatr Infect Dis J. 2010 Feb;29(2):188-9. doi: 10.1097/INF.0b013e3181c36eb9. No abstract available.

  PMID: 20118747 BACKGROUND

• Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R. Effects of probiotic and prebiotic on gastrointestinal motility in newborns. J Physiol Pharmacol. 2009 Dec;60 Suppl 6:27-31.

  PMID: 20224148 BACKGROUND

• Hojsak I, Abdovic S, Szajewska H, Milosevic M, Krznaric Z, Kolacek S. Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics. 2010 May;125(5):e1171-7. doi: 10.1542/peds.2009-2568. Epub 2010 Apr 19.

  PMID: 20403940 BACKGROUND

• Kuitunen M, Kukkonen K, Savilahti E. Pro- and prebiotic supplementation induces a transient reduction in hemoglobin concentration in infants. J Pediatr Gastroenterol Nutr. 2009 Nov;49(5):626-30. doi: 10.1097/MPG.0b013e31819de849.

  PMID: 19644396 BACKGROUND

• Ladd N, Ngo T. The use of probiotics in the prevention of necrotizing enterocolitis in preterm infants. Proc (Bayl Univ Med Cent). 2009 Jul;22(3):287-91. doi: 10.1080/08998280.2009.11928535. No abstract available.

  PMID: 21240300 BACKGROUND

• Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2005 Jan;115(1):1-4. doi: 10.1542/peds.2004-1463.

  PMID: 15629973 BACKGROUND

• Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, Tsao LY, Chen CH, Su BH. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics. 2008 Oct;122(4):693-700. doi: 10.1542/peds.2007-3007.

  PMID: 18829790 BACKGROUND

• Luoto R, Isolauri E, Lehtonen L. Safety of Lactobacillus GG probiotic in infants with very low birth weight: twelve years of experience. Clin Infect Dis. 2010 May 1;50(9):1327-8. doi: 10.1086/651694. No abstract available.

  PMID: 20367236 BACKGROUND

• Ohishi A, Takahashi S, Ito Y, Ohishi Y, Tsukamoto K, Nanba Y, Ito N, Kakiuchi S, Saitoh A, Morotomi M, Nakamura T. Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele. J Pediatr. 2010 Apr;156(4):679-81. doi: 10.1016/j.jpeds.2009.11.041.

  PMID: 20303445 BACKGROUND

• Rinne M, Kalliomaki M, Arvilommi H, Salminen S, Isolauri E. Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses. J Pediatr. 2005 Aug;147(2):186-91. doi: 10.1016/j.jpeds.2005.03.053.

  PMID: 16126047 BACKGROUND

• Rouge C, Piloquet H, Butel MJ, Berger B, Rochat F, Ferraris L, Des Robert C, Legrand A, de la Cochetiere MF, N'Guyen JM, Vodovar M, Voyer M, Darmaun D, Roze JC. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2009 Jun;89(6):1828-35. doi: 10.3945/ajcn.2008.26919. Epub 2009 Apr 15.

  PMID: 19369375 BACKGROUND

• Salminen S, Collado MC, Isolauri E, Gueimonde M. Microbial-host interactions: selecting the right probiotics and prebiotics for infants. Nestle Nutr Workshop Ser Pediatr Program. 2009;64:201-13; discussion 213-7, 251-7. doi: 10.1159/000235792. Epub 2009 Aug 19.

  PMID: 19710524 BACKGROUND

• Samanta M, Sarkar M, Ghosh P, Ghosh Jk, Sinha Mk, Chatterjee S. Prophylactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns. J Trop Pediatr. 2009 Apr;55(2):128-31. doi: 10.1093/tropej/fmn091. Epub 2008 Oct 8.

  PMID: 18842610 BACKGROUND

• Scalabrin DM, Johnston WH, Hoffman DR, P'Pool VL, Harris CL, Mitmesser SH. Growth and tolerance of healthy term infants receiving hydrolyzed infant formulas supplemented with Lactobacillus rhamnosus GG: randomized, double-blind, controlled trial. Clin Pediatr (Phila). 2009 Sep;48(7):734-44. doi: 10.1177/0009922809332682. Epub 2009 Mar 4.

  PMID: 19264721 BACKGROUND

• Schanler RJ. Probiotics and necrotising enterocolitis in premature infants. Arch Dis Child Fetal Neonatal Ed. 2006 Nov;91(6):F395-7. doi: 10.1136/adc.2005.092742. No abstract available.

  PMID: 17056837 BACKGROUND

• Soll RF. Probiotics: are we ready for routine use? Pediatrics. 2010 May;125(5):1071-2. doi: 10.1542/peds.2010-0643. Epub 2010 Apr 26. No abstract available.

  PMID: 20421256 BACKGROUND

• Tarnow-Mordi WO, Wilkinson D, Trivedi A, Brok J. Probiotics reduce all-cause mortality and necrotizing enterocolitis: it is time to change practice. Pediatrics. 2010 May;125(5):1068-70. doi: 10.1542/peds.2009-2151. Epub 2010 Apr 19. No abstract available.

  PMID: 20403934 BACKGROUND

• Anderson, T., Lord, A., Shotkoski, N. and O'Keefe, C. The use of probioitics for the prevention of necrotizing enterocolitis in the premature infant. Infant, Child and Adolescent Nutrition 2009; October: 246-249.

  BACKGROUND

MeSH Terms

Interventions

Culture Techniques; Control Groups; Food, Formulated

Intervention Hierarchy (Ancestors)

In Vitro Techniques; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Foods, Specialized; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Kim M Schmidt, MS, APN, NNP

  Mercy Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 11, 2013
• Study Start: July 1, 2012
• Primary Completion: July 11, 2018
• Study Completion: July 11, 2018
• Last Updated: October 11, 2018

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)