Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Growth and Neurodevelopmental Outcomes of Preterm Infants Born < 26 Weeks Gestation before and after Implementation of a Nutrition-Care Bundle.

BACKGROUND: This study aimed to assess the impact of a nutrition-care bundle on growth and neurodevelopmental outcomes of micro-preterm infants born in a level III neonatal intensive care unit (NICU) by two years corrected age. METHODS: A nutrition-care bundle emphasizing the prompt initiation of parenteral nutrition at birth, initiation of enteral feeds within 6 h after birth, and early addition of human milk fortifiers was implemented in 2015 for infants born < 26 weeks gestation. This before-and-after study evaluated growth and neurodevelopmental outcomes in infants born between 2012-2013 (before-nutrition-bundle, BNB) and 2016-2017 (after-nutrition-bundle, ANB). RESULTS: A total of 145 infants were included in the study. Infants in the ANB group (n = 73) were smaller (birthweight and gestational age), and there were more male infants and multiples included compared to the BNB group (n = 72). Enteral feeds and fortifiers started earlier in the ANB group. Growth velocity and weight z-score changes were similar in both groups during NICU stay and post-discharge. Systemic steroid use, but not cohort, was linked to lower Bayley scores across all domains. CONCLUSIONS: Implementing a nutrition-care bundle was not consistently associated with improved weight gain and neurodevelopmental outcomes in the micro-preterm infant population, possibly due to ongoing high-quality nutritional care by the clinical team.

Association of low hemoglobin at birth and neurodevelopmental outcomes in preterm neonates ≤28 weeks' gestation: a retrospective cohort study.

OBJECTIVE: To compare neurodevelopmental outcomes at 18-24 months corrected age (CA) for preterm infants who had hemoglobin levels <120 g/l versus those with hemoglobin level ≥120 g/l at birth. METHODS: We included infants of ≤28 weeks gestational age (GA) born between January 2009 and June 2018. The primary outcome was neurodevelopmental impairment (NDI) at 18-24 months. Multivariable logistic regression was applied to determine the association. RESULTS: Of the 2351 eligible neonates, 351 (14.9%) had hemoglobin levels <120 g/L at birth. Of the 2113 surviving infants, 1534 (72.5%) underwent developmental follow-up at 18-24 months CA. There was no statistically significant difference in ND outcomes between the two groups. The composite outcome of death or NDI was significantly higher in the low hemoglobin group. CONCLUSION: In preterm infants ≤28 weeks GA, initial hemoglobin <120 g/L at birth was not associated with neurodevelopmental impairment at 18-24 months CA among survivors.