Probiotics in the Management of Necrotizing Enterocolitis in HIV-exposed Premature Infants

NCT01868737 | Completed Phase 3

• 1 other identifier: M10/09/035
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, double blind, placebo controlled clinical trial was conducted in the neonatal high care unit of Tygerberg Children's Hospital (TBCH) Cape Town, South Africa for the period July 2011 to August 2012. The primary objective of the study was to assess the effect of probiotics on the incidence of NEC in high risk infants born to HIV-positive and HIV-negative women. Throughout the study period, the standard of care protocol consisted of one dose (5 drops) probiotic/placebo daily for 4 weeks (28 days). This provided the study group with L. rhamnosus GG (0.35 x 109 colony-forming units \[CFU\]) and B. infantis (0.35 x 109 CFU) daily. The control group received placebo consisting of medium chain triglyceride (MCT) oil. Supplementation of the probiotic/placebo was initiated when enteral feeds started. Probiotic/ placebo supplementation was delayed/ halted in the event of: the infants being nill per os (NPO); when a query Necrotizing Enterocolitis (NEC) was suspected the infant continued with treatment until a confirmed a positive diagnosis of NEC I was made through abdominal X-ray; if the infant remained a query NEC and was NPO the infant did not receive probiotics/ placebo until the enteral feeds were commenced again. Supplementation was discontinued when HIV-exposed infants had a positive polymerase chain reaction (PCR) result on day 14 of life. All study participants received human breast milk. Both the probiotics and placebo were mixed with the mothers own breast milk or donor breast milk before administration via the orogastric tube or orally. The probiotic/ placebo was added to the breast milk by the researcher and two research assistants who were blinded and not involved in the routine care of the infants. Participants exited the study on day 28 after birth or upon discharge from the hospital.

Conditions

Necrotizing Enterocolitis

Keywords

Human Immunodeficiency Virus; Necrotizing Enterocolitis; Premature infant; Probiotic; Very Low Birth Weight

Outcome Measures

Primary Outcomes (1)

• Probiotics administration in reducing the incidence and severity of NEC (as per Bell's criteria19) in premature very-low birth weight infants that are exposed to HIV.

  Lactobacillus rhamnosus GG and Bifidobacterium infantis have been used as probiotics to reduce the incidence of NEC. The Product that was used is Pro-B2, it contains L. rhamnosus GG and B. infantis. The product was supplied by C Pharm. The study group received L. rhamnosus GG and B. infantis for 4 weeks (28 days). The control group received a placebo oil preparation, administered as drops of the oil vehicle used in manufacturing the Lactobacillus rhamnosus GG and Bifidobacterium infantis suspensions. A daily dose of 5 drops of the probiotic/ placebo was administered to the infants. The probiotics/ placebo was administered by the research assistant or investigator who only followed the assigned randomization of groups. The standard feeding protocol of the ward applied during the study. The breast milk of HIV positive mothers were pasteurised according to ward protocol.

  Each infant received supplementation for 28 days

Secondary Outcomes (1)

• The prebiotic quality known as oligosaccharides of pasteurised own mothers breast milk of HIV positive and HIV negative mothers

  3 milk samples in 38 days

Other Outcomes (2)

• The association between the prebiotic quality of breast milk and the incidence of NEC in premature very-low birth weight infants

  3 milk samples in 28 days

• Weight gain for both probiotic exposed and unexposed premature very-low birth weight infants

  Weight daily. Head circumfernce and length weekly. total follow-up was 28 days

Study Arms (4)

HIV exposed infants

EXPERIMENTAL

Probiotic: L. rhamnosus GG (0.35 x 109 colony-forming units \[CFU\]) and B. infantis (0.35 x 109 CFU) daily

Dietary Supplement: Probiotic

HIV- exposed infants

PLACEBO COMPARATOR

MCT oil

Dietary Supplement: Placebo

HIV-unexposed infants

PLACEBO COMPARATOR

MCT oil

Dietary Supplement: Placebo

HIV-unexposed

EXPERIMENTAL

Probiotic: L. rhamnosus GG (0.35 x 109 colony-forming units \[CFU\]) and B. infantis (0.35 x 109 CFU) daily

Dietary Supplement: Probiotic

Interventions

Probiotic DIETARY_SUPPLEMENT

Lactobacillus rhamnosus GG and Bifidobacterium infantis'

Also known as: Brand name: Pro-B2, Lactobacillus rhamnosus GG and Bifidobacterium infantis'

HIV exposed infants; HIV-unexposed

Placebo DIETARY_SUPPLEMENT

MCT oil

HIV- exposed infants; HIV-unexposed infants

Eligibility Criteria

• Age: 25 Weeks - 34 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Consecutive HIV positive or negative mothers, who gave birth to a premature, very-low birth weight infant at Tygerberg Childrens Hospital (TBCH) and consented to participate in the study.
• Only mothers who decided to breastfeed after counseling, regardless of their HIV status were included
• All HIV positive mothers are counseled routinely at TBCH about the risks and benefits of breastfeeding and bottle-feeding relating to the prevention of mother to child transmission scheme.
• HIV positive mothers that were on the PMTCT treatment regiment and if antiretroviral medication was prescribed. Mothers receiving Nevirapine and Zidovudine as well as those receiving highly active antiretroviral medication were included in the study.
• Premature/ low birth weight infants
• Admission or transfer's to wards G1, G2, J3 and G8 at TBCH
• Patients who were transferred to the kangaroo mother care unit in TBCH
• Birth weight \<1 250g
• Premature infant with a birth age of \<34 weeks gestation
• Male and female subjects
• Patients that received own mother's breast milk
• Patients that received donor breast milk due to the following circumstances:
• If donor breast milk was given as a supplemental feed due to insufficient breast milk supply from the mother
• When the mother was unavailable e.g. home visits over weekends, continuation of work
• If the mother was ill and unable to breastfeed the infant e.g. ICU admission

You may not qualify if:

• Mothers that received medications that is contra-indicated for breastfeeding
• These medications include the following drug classes: anticoagulants, cytotoxics and psychoactive drugs e.g. antidepressants , antipsychotics chlorpromazine and individual drugs detectable in breast milk that pose theoretical risk.
• Mothers with active Mycobacterium tuberculosis who were still potentially infectious and who should not have been in direct contact with the infant were be excluded from this study
• HIV positive mothers that presented clinically sick with a CD4 cell count \<200cells/µl
• Premature/ low birth weight infants
• Birth weight \< 500g
• Premature infant with a birth age of \<25 weeks gestation
• Prenatal/ postnatal diagnosis of gastroschisis, large omphalocele or congenital diaphragmatic hernia
• Infants with congenital intestinal obstruction or perforation
• Infants with major congenital malformations and/or developmental disabilities pertaining to the gastrointestinal tract
• Infants with perinatal asphyxia
• Infants with a positive diagnosis of a complex heart disease

Sponsors & Collaborators

• University of Stellenbosch: lead

Study Sites (1)

Tygerberg Hospital

Tygerberg, Cape Town, Western Cape, 7500, South Africa

Location

Related Publications (1)

• Van Niekerk E, Autran CA, Nel DG, Kirsten GF, Blaauw R, Bode L. Human milk oligosaccharides differ between HIV-infected and HIV-uninfected mothers and are related to necrotizing enterocolitis incidence in their preterm very-low-birth-weight infants. J Nutr. 2014 Aug;144(8):1227-33. doi: 10.3945/jn.113.187799. Epub 2014 Jun 11.

  PMID: 24919691 DERIVED

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Acquired Immunodeficiency Syndrome; Premature Birth

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Evette van Niekerk, M Dietetics

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: May 30, 2013
• First Posted: June 4, 2013
• Study Start: July 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: July 22, 2013

Record last verified: 2013-06

Locations

ZA (1)