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

Not Applicable

Active, not recruiting

• Conditions: Infant, Newborn, Diseases; Infant Development
• Interventions: Dietary Supplement: Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748

• Registration Number: NCT05945017
• Lead Sponsor: Fundacion Clinic per a la Recerca Biomédica

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-01
• Primary Completion: 2019-12-31
• Study First Submitted: 2023-05-19
• Study First Submitted QC: 2023-07-11
• Study First Posted: 2023-07-14
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-10
• Last Update Posted: 2023-08-14
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 233

Inclusion Criteria

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

Exclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748	Infloran® -Berne, Switzerland- (Bifidobacterium bifidum NCDO 2203 and Lactobacillus acidophilus NCDO 1748	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

Primary Outcome Measures

Name	Time	Method
Degree of neurodevelopment at 6 years of age	6 years	Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parent/teacher self reporting form.
Neuroplasticity biomarkers and intestinal permeability	6 years	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
Degree of neurodevelopment at 24 months corrected age	24 months	Severe impairment will be attributed to subjects with any of the following: spastic quadriplegia, choreoathetosis, ataxia, Bayley score \<50, blindness or severe hypoacusis

Secondary Outcome Measures

Name	Time	Method
Incidence of necrotising enterocolitis	40 weeks	cases fulfilling the stage II or above of the modified Bell's Criteria
Incidence of late onset sepsis	40 weeks	positive blood culture beyond 72 hours of life
Incidence of Intraventricular haemorrhage	40 weeks	Grade I-IV
Mortality	40 weeks	Proportion of dead participants before discharge
Intensive care length of stay	40 weeks	Days of intensive care

Trial Locations

Locations (1)

Neonataology Service, BCNatal Hospital Clinic Seu Maternitat; 🇪🇸 Barcelona, Spain