Preterm Infant Gut (PINGU) - a Norwegian Multi Centre Study

NCT ID: NCT02197468

Last Updated: 2019-03-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2015-11-30

Brief Summary

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria may contribute to the development of NEC.

Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age <28 weeks/birth weight <1000g).

The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.

Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity will be analysed with bioinformatic tools.

Study hypotheses:

• Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
• Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
• After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
• A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.

Detailed Description

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). Prematurity is the most important risk factor for NEC. The pathogenesis of NEC remains unclear, and prevention and treatment strategies are limited. It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria, is significant in the pathogenesis of NEC.

Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age (GA) <28 weeks/birth birth weight (BW) <1000 g).

The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.

Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity and taxonomy will be analysed using bioinformatic tools

Inclusion criteria:

• Preterm infants 24-27 weeks gestation/ birth weight < 1000 g receiving probiotics
• Preterm infants 28-31 weeks gestation/BW 1000-1500 g not receiving probiotics
• Healthy term infants

Exclusion criteria

• Preterm infants < 24 weeks gestation
• Preterm infants < 32 weeks with severe lethal complication/poor prognosis around 1 week of age
• Infants with severe congenital malformations

Fecal samples will be obtained:

• 1 week of age
• 4 weeks of age
• 4 months corrected age
• 12 months corrected age

Study hypotheses:

• Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
• Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
• After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
• A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.

This is an explorative study. No formal sample size assessment is possible. Sequencing costs will be substantial. We will limit the number of participants to 26 x 2 preterm infants and 10 control healthy infants.

Six Norwegian Neonatal Intensive care units wil participate in the study.

Conditions

Mixed Flora; Infection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Probiotics

Preterm infants given probiotics: GA 24-27 weeks/Birth weight < 1000 g

Preterm infants not given probiotics: GA 28-31 weeks/Birth weight 1000-1500 g

Full-term infants not given probiotics (control)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Preterm infants with gestational age 24-27 weeks/birth weight < 1000 g, treated with probiotics (target number 26)
• Preterm infants with gestational age 29-31 weeks/birth weight 1000-1500 g, not treated with probiotics (target number 26)
• Term infants (target number 10)

Exclusion Criteria

• Extremely preterm infants with gestational age below 24 weeks
• Preterm infants (24-31 weeks) with life threatening complications during 1 week of age
• Infants with congenital malformations

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Tromso

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: collaborator

Ullevaal University Hospital

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claus Klingenberg, MD.phD.Prof.

Role: STUDY_CHAIR

University Hospital of North Norway

Eirin Esaiassen, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of North-Noway

Locations

Haukeland Universtiy Hospital

Bergen, , Norway

Oslo University Hospital, Rikshospitalet

Oslo, , Norway

Oslo University Hospital, Ullevaal

Oslo, , Norway

Ahus University Hospital

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

University Hospital of North Norway

Tromsø, , Norway

St Olavs Hospital, Trondheim University Hospital

Trondheim, , Norway

Countries

Norway

References

Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Curr Opin Infect Dis. 2014 Jun;27(3):236-43. doi: 10.1097/QCO.0000000000000061.

Reference Type: BACKGROUND

PMID: 24751892 (View on PubMed)

Stewart CJ, Marrs EC, Magorrian S, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr. 2012 Nov;101(11):1121-7. doi: 10.1111/j.1651-2227.2012.02801.x. Epub 2012 Aug 31.

Reference Type: BACKGROUND

PMID: 22845166 (View on PubMed)

Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018.

Reference Type: DERIVED

PMID: 30505830 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

Publication from this study

View Document

Other Identifiers

2014/930 (REK)

Identifier Type: -

Identifier Source: org_study_id