Growth and risk of adverse neuro-developmental outcome in newborns with congenital heart disease: A single-centre retrospective study.

BACKGROUND: Mortality in infants with CHD is decreasing and focus has shifted to improving long-term outcomes. Growth and neurodevelopmental outcomes are important long-term endpoints for both clinicians and parents. OBJECTIVE: To evaluate growth and determine the impact of growth on neurodevelopmental outcomes at one year of age in infants who had an operative or therapeutic catheter procedure for CHD in neonatal period. METHODS: This was a single-centre retrospective cohort study of infants born at term gestation with CHD. Demographic details, measurements of growth, and scores of Bayley Scales of Infant and Toddler Assessment (third edition), were collected. Enrolled study participants were categorised in subgroups based on the procedures required prior to one-year assessment. Regression analysis was performed to explore predictive ability of anthropometric measurements on mean scores of developmental assessment. RESULTS: A total of 184 infants were included in the study. Mean z-scores for weight and head circumference at birth were age-appropriate. Mean scores for various developmental domains ranged from borderline to normal except for infants with single ventricular physiology who had gross motor delay concomitant with growth failure. In this group, z-score of weight at one-year-assessment predicted mean score of cognition (p-value 0.02), fine motor (p-value 0.03) and gross motor nearly (p-value 0.06). CONCLUSIONS: Infants born at term gestation, with CHD, without genetic diagnosis had normal fetal growth. Postnatal growth restriction and developmental delay was most marked in infants with single ventricle physiology, suggesting careful nutritional and developmental monitoring.

Growth and risk of adverse neuro-developmental outcome in infants with congenital heart disease: A systematic review.

AIM: Congenital heart disease (CHD) is one of the most common birth defects affecting around 1:100 infants. In this systematic review, we aimed to determine impact of growth on neurodevelopmental outcomes of infants with CHD. METHODS: Studies that reported association of growth with developmental outcomes in infants with CHD who had surgery, were included. The search strategy was prospectively registered. Relevant studies were identified by electronic searches. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched from their earliest date to February 2022. RESULTS: Twenty studies met inclusion criteria. Choice of growth measures, developmental assessment tools and timing of assessment varied widely precluding conduct of a meta-analysis. Seventeen studies reported on infants who had cardio-pulmonary bypass. Birth weight was reported in thirteen studies and was associated with adverse outcome in nine. Head circumference at birth and later predicted developmental outcomes in five. Impaired postnatal growth was associated with adverse developmental outcome in seven studies. CONCLUSION: Growth in infants with congenital heart disease, specifically single ventricle physiology can predict adverse neurodevelopmental outcome. Included studies showed significant clinical heterogeneity. Uniformity should be agreed by various data registries with routine prospective collection of growth and developmental data.

Growth and risk of adverse neurodevelopmental outcome in infants with congenital surgical anomalies: a systematic review.

Survival of infants with congenital anomalies requiring surgical correction has increased dramatically, shifting the focus of clinical care and research toward optimising growth and neurodevelopment.To determine the impact of growth on neurodevelopmental outcomes of infants with congenital surgical anomalies. Studies that reported association of growth with developmental outcomes in infants with congenital anomalies who had surgery, were eligible for inclusion. The search strategy was prospectively drafted, and relevant studies were identified by electronic searches. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2022, issue 1), MEDLINE and EMBASE from their earliest date to February 2022 were searched. Seven studies met the inclusion criteria. Variability in selection of growth measures, developmental assessment tools and assessment endpoints for neurodevelopment, precluded a meta-analysis. Four studies reported the association between growth and neurodevelopmental outcomes in infants with gastroschisis with two noting adverse outcomes in infants who were small for gestational age. Birthweight, reported in four studies, was not associated with adverse developmental outcomes. Postnatal growth, reported in three studies, was associated with adverse outcome. The data linking growth restriction in infants with congenital surgical anomalies and neurodevelopmental outcome is limited. There is limited published research examining the longitudinal effects of intra- and extra-uterine growth parameters on neurodevelopmental outcomes.

BRD2 inhibition blocks SARS-CoV-2 infection in vitro by reducing transcription of the host cell receptor ACE2

SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia. Moreover, pharmacological BRD2 inhibition with the drug ABBV-744 inhibited SARS-CoV-2 replication in Syrian hamsters. We also found that BRD2 controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates the antiviral response. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a novel therapeutic target for COVID-19.

The Evolution of an Interdisciplinary Developmental Round in a Surgical Neonatal Intensive Care Unit.

BACKGROUND: Developmentally supportive environments are known to improve medical outcomes for hospitalized neonates and are considered the overarching philosophy for practice in the neonatal setting. Developmental rounds are a strategy incorporated by multidisciplinary teams to support development within and beyond the neonatal unit. Typically, they consist of bedside consultations and individualized developmentally supportive recommendations for families and clinicians. Globally, the use of developmental rounds has been described since the early 1990s. They are viewed as a measure to counter some of the barriers to developmental care implementation while buffering against the effect of an intensive care admission. To date, their use in the surgical neonatal intensive care unit (sNICU) has been minimally reported in literature. PURPOSE: This article describes the focus and work of a developmental round team and strategy in the sNICU. METHOD: A retrospective audit of developmental round key performance criteria undertaken over a 4-year period (2015-2018). FINDINGS/RESULTS: More than 300 developmental consults and 2000 individualized developmental recommendations occurred annually. Parental presence during the developmental round increased by 10%, from 48% to 58%, during the audit period. IMPLICATIONS FOR PRACTICE/IMPLICATIONS FOR RESEARCH: Literature has supported the use of developmental round interventions; however, minimal data have been reported to date. This article provides retrospective audit data of a developmental round intervention in the sNICU with a focus on data over 4 years to highlight key areas, including the structure and process, recommended educational standards for team members, and parental engagement, as key markers for developmental round efficacy. Future research should focus on the link between the developmental round intervention and long-term neonatal outcomes.