Benjamin Clayden

Background: Brain development is altered in neonates with congenital heart disease (CHD), with well‐characterised reductions in regional brain volumes and enlargement of CSF spaces. However, perioperative morphological changes remain incompletely understood. Purpose: To identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and controls, assess perioperative changes and effects of perioperative risk factors, using Structural Covariance Component (SCC) analysis. Study Type: Prospective. Population: Forty‐one neonates with CHD (male = 20) who underwent cardiac surgery or catheterization and 359 healthy neonates (male = 185). Field Strength and Sequence: 3T T2‐weighted turbo‐spin‐echo sequence. Assessment: Images were motion‐corrected and reconstructed using a neonatal algorithm. Jacobian determinants calculated from non‐linear image registration to a template were input into an Independent Component Analysis to identify SCCs ( N = 40). SCC weightings were extracted, reflecting the degree to which the covariance pattern is expressed per neonate. Statistical Tests: Postoperative SCC weightings were compared to those of controls using a general linear model or robust regression. Perioperative change was assessed using a linear mixed effects model, and associations between perioperative differences and age at surgery, cardiopulmonary bypass duration, and postoperative pediatric intensive care unit stay were assessed using partial Spearman's rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate, significant at p < 0.05. Results: Sixteen of the 40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical‐ and deep gray matter, brainstem, and CSF ( f ² _partial = 0.02–0.04), with seven also showing significant perioperative change ( f ² _partial < 0.01–0.27). An additional nine SCCs only showed significant perioperative change ( f ² _partial < 0.01–0.14). Perioperative risk factors were not associated with perioperative change ( p > 0.463). Data Conclusion: This work highlights region‐specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. Evidence Level: 1. Technical Efficacy: Stage 3.

Temporal relationships between the recreational use of alcohol, tobacco and cannabis with mental health challenges have been extensively reviewed. However, this is not the case for other widely consumed drugs. Between 7/6/23 and 3/12/23 we searched Web of Science, EMBASE, PsychINFO and MEDLINE databases for studies investigating temporal relationships between recreational drug use (RDU) and mental health (MH). From N=8,759 publications originally identified, we systematically reviewed 69 studies fulfilling four criteria; 1) studying the general population, 2) investigating cocaine, ketamine, psychedelics, opioids, 3,4-methylenedioxymethamphetamine (MDMA/ecstasy) or amphetamines, 3) prospective/longitudinal designs measuring RDU and MH on at least two separate occasions, 4) measuring symptoms of either depression or anxiety. Studies were placed into seven outcome categories: RDU was followed by worse MH (N1), worse MH was followed by increased RDU (N2), RDU was followed by better MH (P1), better MH was followed by decreased RDU (P2), as well as bidirectional, mixed or no relationships seen. Whilst the most commonly identified relationships were N2 (N=16, 23.2%) or N1 (N=15, 21.7%) these were seen in under half of the studies included. We identified a number of contributing factors, including patterns of drug use, socioeconomic factors, definitions of MH and RDU employed, and direction of relationship tested. Our results reveal a nuanced picture, suggesting blanket statements on RDU-MH temporal relationships may be misleading. We discuss these factors and offer suggestions that future studies may incorporate to better understand the relationship between these domains.

Background: Brain development is altered in neonates with congenital heart disease (CHD). However, development in the perioperative period remains incompletely understood. Purpose: This study used Structural Covariance Component (SCC) analysis to identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and healthy controls, as well as pre-to postoperative changes and effects of perioperative risk factors. Study type: Prospective. Population: The cohort included 41 neonates with CHD who underwent cardiac surgery or catheterization and 359 healthy neonates. Field strength and sequence: 3 Tesla T2-weighted turbo-spin-echo sequence. Assessment: Brain MRI were motion-corrected and reconstructed using an established neonatal algorithm. Jacobian determinants calculated from non-linear registration of MRI to a neonatal template were input into an Independent Component Analysis to identify SCCs (N=40). SCC weightings were extracted, reflecting the degree to which the pattern of covariance is expressed in each neonate. Statistical tests: Postoperative SCC weightings were compared to healthy neonates using a general linear model or robust regression. Pre- and postoperative SCC weightings were compared using a linear mixed effect model. Pre- to postoperative differences were calculated and associations with age at surgery, cardiopulmonary bypass duration, and postoperative paediatric intensive care unit stay were assessed using partial spearman’s rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate. Results: 16/40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep grey matter, brainstem, and CSF regions, with seven also showing significant perioperative change. A further nine SCCs only showed significant perioperative change. Perioperative risk factors were not associated with perioperative change. Data conclusion: This data-driven approach highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. Evidence level. 1. Technical Efficacy: Stage 3.