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

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.

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

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

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

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.

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.

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.

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

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.

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

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

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

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)

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