lactoferrin and Developmental-Disabilities

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks' gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks' post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old.

Topics: Bronchopulmonary Dysplasia; Child, Preschool; Cost-Benefit Analysis; Developmental Disabilities; Dietary Supplements; Enteral Nutrition; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant; Infant Mortality; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lactoferrin; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian child with GDLD who also exhibited global developmental delay.. Bilateral lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for light and electron microscopy, including immunoelectronmicroscopy. The coding region of the M1S1 gene was screened for mutations in the affected proband and available relatives, using DNA extracted from mouthwashes.. Nodular deposits, which were present subepithelially and in the central superficial stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (betaig-h3), was present in the central superficial stroma, causing destruction of Bowman's layer and elevation of the thinned, degenerate epithelium. Around the deposit zone, the stroma exhibited large numbers of thick filamentous proteoglycan deposits. While the affected child was homozygous for a novel A1133 C single-nucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine substitution at position 173 of the M1S1 coding sequence, this polymorphism was also found at relatively high frequency in a sample of normal controls, enabling exclusion of the M1S1 gene as the disease locus.. Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeability of the superficial epithelial cells. An association with developmental delay has not been reported previously.

Topics: Amyloid; Antigens, Neoplasm; Base Sequence; Cell Adhesion Molecules; Cornea; Corneal Dystrophies, Hereditary; Developmental Disabilities; Extracellular Matrix Proteins; Female; Humans; Infant; Lactoferrin; Male; Microscopy, Immunoelectron; Pedigree; Polymorphism, Genetic; Sequence Analysis, DNA; Transforming Growth Factor beta