Probiotics and the Neurodevelopment in the Premature Infant <32 Weeks Gestational Age and <1500g

NCT05945017 | Active Not Recruiting

• 1 other identifier: HCB/2021/0454
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 1

Brief Summary

Unicentric, quasi-experimental, cohort study to evaluate the effect of combining two probiotics (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748) in the neurodevelopment of preterm neonates below 32 weeks' gestation and a birthweight under 1,500 g. This probiotic combination has shown to be safe and beneficial in premature neonates in the prevention of NEC. The investigators hypothesised that this mixture would contribute to better neurodevelopmental outcomes of preterm neonates when assessed at 24 months corrected age. Additionally, neurodevelopment improved would be more relevant at 6 years of age, together with a better pattern of neuronal plasticity biomarkers. Secondarily, this mixture of probiotics could reduce NEC, LOS, intraventricular haemorrhage and neonatal mortality in accordance with previous studies.

Conditions

Infant, Newborn, Diseases; Infant Development

Keywords

Probiotics; Bifidobacterium bifidum; Lactobacillus acidophilus; Neurodevelopment; Prematurity; Late-onset sepsis

Outcome Measures

Primary Outcomes (8)

• Degree of neurodevelopment at 24 months corrected age

  Normal neurodevelopment will be considered when no muscle tone changes, no impaired fine or gross motor coordination, Bayley scale score between above 84, no behaviour disorders or visual disability.

  24 months

• Degree of neurodevelopment at 24 months corrected age

  Mild impairment will be considered if any of the following: muscle tone changes, impaired fine or gross motor coordination, Bayley scale score between 71-84, moderate behaviour disorders or mild visual disability.

  24 months

• Degree of neurodevelopment at 24 months corrected age

  Moderate impairment will be diagnosed when suffering from any of the following: spastic diplegia, hemiplegia, seizures (non-febrile), Bayley scores between 50-70, severe behaviour disorders, moderate visual disability or mild-moderate hypoacusis.

  24 months

• Degree of neurodevelopment at 24 months corrected age

  Severe impairment will be attributed to subjects with any of the following: spastic quadriplegia, choreoathetosis, ataxia, Bayley score \<50, blindness or severe hypoacusis

  24 months

• Degree of neurodevelopment at 6 years of age

  Wechsler Intelligence Scale for Children - Fifth edition. Ranges from below 69 to above 130. Scores from 90-109 indicate average, above it indicates above average and below, below average performance.

  6 years

• Degree of neurodevelopment at 6 years of age

  Child behaviour checklist 6-18 years of age. 113 items about behaviour and social competence scored from 0 "absent" to 2 "occurs often"

  6 years

• Degree of neurodevelopment at 6 years of age

  Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parent/teacher self reporting form.

  6 years

• Neuroplasticity biomarkers and intestinal permeability

  NeuN, Doublecortin, GFAP, GDNF, Ki67, Nrf2, BDNF, NGF, neurotrophin-1 (NT-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), DYRK1A, HIF1α, S100B i GSK3B. IL1B, IL6, IL8, IL10, IL12, TNF- α

  6 years

Secondary Outcomes (5)

• Incidence of necrotising enterocolitis

  40 weeks

• Mortality

  40 weeks

• Incidence of late onset sepsis

  40 weeks

• Incidence of Intraventricular haemorrhage

  40 weeks

• Intensive care length of stay

  40 weeks

Study Arms (2)

Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748

EXPERIMENTAL

Daily dose of 6x109 UFC Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748) from 7 days of life until reaching a postmenstrual age of 34 weeks or discharge

Dietary Supplement: Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748

Control

NO INTERVENTION

Untreated control group

Interventions

Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748 DIETARY_SUPPLEMENT

Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748

Eligibility Criteria

• Age: Up to 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Premature infants under 32 weeks gestational age and less than 1500g birthweight.
• Born at BCNatal Hospital Clínic between years 2014-2019.

You may not qualify if:

• All neonates presenting with suspected congenital anomalies, inborn errors of metabolism, or genetic defects were excluded.
• Infants with a suspected syndrome, or who have suffered events beyond the neonatal period, not related to prematurity, that could entail impairment in neurodevelopment (severe cranioencephalic trauma, oncological process, meningitis, or exposure to toxic substances)

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead
• Hospital Clinic of Barcelona: collaborator

Study Sites (1)

Neonataology Service, BCNatal Hospital Clinic Seu Maternitat

Barcelona, 08028, Spain

Location

Related Publications (24)

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MeSH Terms

Conditions

Infant, Newborn, Diseases; Premature Birth

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Benjamin James Baucells, MD

  Neonataology Service, BCNatal Hospital Clínic

  PRINCIPAL INVESTIGATOR

• Giorgia Sebastiani

  Neonatology Service, BCNatal Hospital Clínic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sequential study with consecutive recruitment with a washout period of 12 months between groups

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: July 14, 2023
• Study Start: January 1, 2014
• Primary Completion: December 31, 2019
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)