Neurodevelopmental Delay

Study Hypothesis/Question In infants born very preterm, advancing enteral feeds after 24 hours from birth (limited trophic feeds) versus after 72 hours (extended trophic feeds) reduces the risk of all-cause late onset sepsis (LOS) without increasing the risk of other adverse outcomes. Study Design Type This is a multi-center, open-label, parallel-group, individual randomized controlled trial comparing two different trophic feeding regimens in preterm infants born between 25w0d and 31w6d. These infants will be randomly assigned to either the intervention group, receiving limited trophic feeding (20 to 25 mL/kg/day for one day) or the control group, receiving extended trophic feeding (20 to 25 mL/kg/day for three days) prior to advancing enteral feeds until full feeding volume (140 mL/kg/day) is achieved. Eligibility Criteria Preterm infants with gestational ages between 25 0/7 and 31 6/7 weeks and a birthweight of \<1500 grams who are admitted to six participating neonatal units will be eligible for inclusion. Infants with \<5th percentile for weight at birth, vasopressor use within first 24 hours of life major congenital/genetic anomalies affecting enteral feeding, growth, or mortality, and those with a terminal illness in which decisions to withhold or limit support have been made will be excluded. Infants of parents or legal guardians who are unable to provide consent within 36 hours of birth will also be excluded. Study Intervention/Methods Written parental informed consent will be obtained prenatally or within the first 36 hours of birth. Infants will be randomized to receive limited trophic feeds of 24 to 36 hours or extended trophic feeds for 72 hours prior to the advancement of enteral feeds. Infants will be fed parent's own milk (POM) with donor human milk as the alternative if POM is unavailable. Primary Outcome Late-onset sepsis, defined as positive blood, urine, and/or cerebrospinal fluid (CSF) cultures in the presence of compatible clinical signs of sepsis, occurring after postnatal day 3 and before hospital discharge, and treated with antibiotics for 5 days or more. Secondary Outcome(s) The trial will assess various secondary outcomes including length of hospital stay, all-cause in-hospital mortality, duration of IV fluids and central line utilization, necrotizing enterocolitis (Bell's stage IIa or higher), severe intraventricular hemorrhage (grade III or IV either unilaterally or bilaterally), bronchopulmonary dysplasia (oxygen requirement or positive pressure ventilation at 36 weeks corrected gestational age), or retinopathy of prematurity requiring intervention. Additionally, growth metrics throughout hospitalization will be evaluated using change in weight, length, and head circumference z-scores from birth to 36 weeks' corrected gestational age between infants in the limited and extended trophic feeding groups. We will also evaluate the 2 year developmental outcomes of a subset of participants who consent to follow up. This will include the Bayley Scales of Infant and Toddler Development-4th edition Language, Cognitive, and Motor domain scores at 2 years corrected age.

The PLUSS (Mental health, learning, development, collaboration around preschool children) is a collaborative project involving guardians, Jönköping County´s health care, preschools and social services. The project studies the implementation of a "One way in"-model that provides coordinated services to screen, evaluate and treat toddlers with behavioral problems. The project also provides parental interventions and education for preschool teachers. The study aims to investigate a) implementation of the PLUSS model, b) effectiveness of the model and the included parental training program on behavioral problem and their longitudinal development among preschool children, c) parental wellbeing and satisfaction. In the long term, the goal is to reduce mental health problems among children, adolescents and their families and to provide support for a functioning everyday life.

International large-scale clinical studies have found that prolonged or repeated exposure to general anesthesia drugs in infancy and early childhood can lead to an increased risk of long-term neurodevelopmental abnormalities in children. The study of neurodevelopmental toxicity of general anesthesia drugs is of great social significance. We have established a rhesus monkey model to study the neurodevelopmental toxicity of general anesthetic drugs, the first time to make a preliminary exploration of the mechanism of myelin developmental toxicity of general anesthetic drugs. Several studies using magnetic resonance scanning found a positive correlation between the number of anesthesia exposures and the maturity of distant brain white matter development in juvenile non-human primates. Clinical evidence for myelin developmental toxicity induced by general anesthetic drugs needs to be collected by conducting multicenter and large-sample clinical studies. Earlier studies have either had low sample sizes, which do not allow for better control of confounding factors; or the study population has been limited to specific disease populations, and the results cannot be extrapolated to normal children. In view of this, based on the applicant's earlier study, this project proposes to recruit children who underwent general anesthesia surgery between 0-3 years of age and are now 12-15 years old; children who did not experience surgery between 0-3 years of age were matched by age-sex to serve as a control group. MRI will be used to assess their brain white matter development, to explore the correlation between anesthesia and anesthesia-related factors and brain white matter development and related neurobehavioral development, and to clarify the effects of anesthesia and surgery on children's brain white matter and related neuropsychological development.