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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Use of Probiotics in the Management of Necrotizing Enterocolitis in HIV-exposed Premature and Very-low Birth Weight Infants

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.


Detailed 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. All mothers and infants pairs that conformed to the inclusion criteria and provided written informed consent were included into the study. Premature (<34 weeks' gestation) and very-low birth weight (<1 250g) HIV-exposed and unexposed infants were randomized into the study or control groups by a random-number table sequence assigned by a statistician. Sample size was determined by a statistician according to the life birth statistics form the institution. Participants were enrolled and assigned to the respective groups by the researcher and two research assistants. Inclusion criteria for the mothers included: (1) HIV-positive or-negative mothers who gave birth to a premature and low birth weight baby at TBCH and consented to participate in the study; (2) Only breastfeeding mothers, regardless of their HIV status and (3) HIV-positive mothers that were on the prevention of mother to child transmission (PMTCT) treatment schedule and received nevirapine and zidovudine (AZT) as well as those that received highly active antiretroviral (HAART) medication were included in the study Babies were included if they were (1) born prematurely with a birth weight of of ≥500g and ≤1250g; (2) were HIV exposed or unexposed; (3) HIV-exposed infants and received antiretroviral (ARV) medication and (4) received breast milk (either from their mothers or donor breast milk). Breast milk of HIV-positive mothers was pasteurized (according to ward protocol) before it was administered to the infants. Infants were excluded if they had major abnormalities such as ga
Sponsor: University of Stellenbosch

Current Primary Outcome: 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. [ Time Frame: Each infant received supplementation for 28 days ]

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.


Original Primary Outcome: To evaluate the efficacy of probiotics 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. [ Time Frame: Each infant received supplementation for 28 days ]

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.


Current Secondary Outcome: The prebiotic quality known as oligosaccharides of pasteurised own mothers breast milk of HIV positive and HIV negative mothers [ Time Frame: 3 milk samples in 38 days ]

Breast milk samples of HIV positive and HIV negative breast milk was tested. All breast milk samples were raw untreated specimens therefore milk samples did not undergo any pasteurization procedures Breast milk was collected in sterilised containers with lids Each sample contained a volume of 5-10ml of breast milk for the analysis

Sample 1 The first milk sample was collected on day four of lactation Sample 2 The second milk sample was collected on the tenth day of lactation Sample 3 The third sample was collected on the final day of the study

Day 28 after birth and the end of the neonatal period If a mother was unavailable during the breast milk sample collection the breast milk samples were collected during the first available time All milk samples were collected by the investigator or research assistant who was standardized for all protocol procedures



Original Secondary Outcome: To determine the prebiotic quality known as oligosaccharides of pasteurised own mothers breast milk of HIV positive and HIV negative mothers [ Time Frame: 3 milk samples in 38 days ]

Breast milk samples of HIV positive and HIV negative breast milk was tested. All breast milk samples were raw untreated specimens therefore milk samples did not undergo any pasteurization procedures Breast milk was collected in sterilised containers with lids Each sample contained a volume of 5-10ml of breast milk for the analysis

Sample 1 The first milk sample was collected on day four of lactation Sample 2 The second milk sample was collected on the tenth day of lactation Sample 3 The third sample was collected on the final day of the study

Day 28 after birth and the end of the neonatal period If a mother was unavailable during the breast milk sample collection the breast milk samples were collected during the first available time All milk samples were collected by the investigator or research assistant who was standardized for all protocol procedures



Information By: University of Stellenbosch

Dates:
Date Received: May 30, 2013
Date Started: July 2011
Date Completion:
Last Updated: July 19, 2013
Last Verified: June 2013