Prenatal Magnesium Sulfate and Functional Connectivity in Offspring at Term-Equivalent Age.

Importance: Understanding the effect of antenatal magnesium sulfate (MgSO4) treatment on functional connectivity will help elucidate the mechanism by which it reduces the risk of cerebral palsy and death. Objective: To determine whether MgSO4 administered to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks is associated with increased functional connectivity and measures of functional segregation and integration in infants at term-equivalent age, possibly reflecting a protective mechanism of MgSO4. Design, Setting, and Participants: This cohort study was nested within a randomized placebo-controlled trial performed across 24 tertiary maternity hospitals. Participants included infants born to women at risk of imminent preterm birth at a gestational age between 30 and 34 weeks who participated in the MAGENTA (Magnesium Sulphate at 30 to 34 Weeks' Gestational Age) trial and underwent magnetic resonance imaging (MRI) at term-equivalent age. Ineligibility criteria included illness precluding MRI, congenital or genetic disorders likely to affect brain structure, and living more than 1 hour from the MRI center. One hundred and fourteen of 159 eligible infants were excluded due to incomplete or motion-corrupted MRI. Recruitment occurred between October 22, 2014, and October 25, 2017. Participants were followed up to 2 years of age. Analysis was performed from February 1, 2021, to February 27, 2024. Observers were blind to patient groupings during data collection and processing. Exposures: Women received 4 g of MgSO4 or isotonic sodium chloride solution given intravenously over 30 minutes. Main Outcomes and Measures: Prior to data collection, it was hypothesized that infants who were exposed to MgSO4 would show enhanced functional connectivity compared with infants who were not exposed. Results: A total of 45 infants were included in the analysis: 24 receiving MgSO4 treatment and 21 receiving placebo; 23 (51.1%) were female and 22 (48.9%) were male; and the median gestational age at scan was 40.0 (IQR, 39.1-41.1) weeks. Treatment with MgSO4 was associated with greater voxelwise functional connectivity in the temporal and occipital lobes and deep gray matter structures and with significantly greater clustering coefficients (Hedge g, 0.47 [95% CI, -0.13 to 1.07]), transitivity (Hedge g, 0.51 [95% CI, -0.10 to 1.11]), local efficiency (Hedge g, 0.40 [95% CI, -0.20 to 0.99]), and global efficiency (Hedge g, 0.31 [95% CI, -0.29 to 0.90]), representing enhanced functional segregation and integration. Conclusions and Relevance: In this cohort study, infants exposed to MgSO4 had greater voxelwise functional connectivity and functional segregation, consistent with increased brain maturation. Enhanced functional connectivity is a possible mechanism by which MgSO4 protects against cerebral palsy and death.

Size at birth predicts later brain volumes.

We aimed to investigate whether gestation at birth, birth weight, and head circumference at birth are still associated with brain volume and white matter microstructure at 9-10 years in children born late-preterm and at term. One hundred and eleven children born at ≥ 36 weeks gestation from the CHYLD Study cohort underwent brain magnetic resonance imaging at 9 to 10 years. Images were analysed using FreeSurfer for volumetric data and tract-based spatial statistics for diffusion data. Of the cohort, 101 children were included for volumetric analysis [boys, 49(49%); median age, 9.5 (range: 8.9-12.4) years]. Shorter gestation at birth, lower birthweight, and smaller birth head circumference were associated with smaller brain volumes at 9 to 10 years, both globally and regionally. Amongst the perinatal factors studied, head circumference at birth was the strongest predictor of later brain volumes. Gestation at birth and absolute birthweight were not associated with diffusion metrics of white matter skeleton. However, lower birthweight z-score was associated with higher fractional anisotropy and lower radial diffusivity. Our findings suggest that even in children born late preterm and at term, growth before birth and timing of birth are still associated with brain development in mid-childhood.

Neurodevelopmental correlates of caudate volume in children born at risk of neonatal hypoglycaemia.

BACKGROUND: Neonatal hypoglycaemia can lead to brain damage and neurocognitive impairment. Neonatal hypoglycaemia is associated with smaller caudate volume in the mid-childhood. We investigated the relationship between neurodevelopmental outcomes and caudate volume and whether this relationship was influenced by neonatal hypoglycaemia. METHODS: Children born at risk of neonatal hypoglycaemia ≥36 weeks' gestation who participated in a prospective cohort study underwent neurodevelopmental assessment (executive function, academic achievement, and emotional-behavioural regulation) and MRI at age 9-10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (blood glucose concentration <2.6 mmol/L or at least 10 min of interstitial glucose concentrations <2.6 mmol/L). Caudate volume was computed using FreeSurfer. RESULTS: There were 101 children with MRI and neurodevelopmental data available, of whom 70 had experienced neonatal hypoglycaemia. Smaller caudate volume was associated with greater parent-reported emotional and behavioural difficulties, and poorer prosocial behaviour. Caudate volume was significantly associated with visual memory only in children who had not experienced neonatal hypoglycaemia (interaction p = 0.03), but there were no other significant interactions between caudate volume and neonatal hypoglycaemia. CONCLUSION: Smaller caudate volume is associated with emotional behaviour difficulties in the mid-childhood. Although neonatal hypoglycaemia is associated with smaller caudate volume, this appears not to contribute to clinically relevant neurodevelopmental deficits. IMPACT: At 9-10 years of age, caudate volume was inversely associated with emotional-behavioural difficulties and positively associated with prosocial behaviour but was not related to executive function or educational achievement. Previous studies have suggested that neonatal hypoglycaemia may contribute to smaller caudate volume but exposure to neonatal hypoglycaemia did not appear to influence the relationship between caudate volume and behaviour. Among children not exposed to neonatal hypoglycaemia, caudate volume was also positively associated with visual memory, but no such association was detected among those exposed to neonatal hypoglycaemia. Understanding early-life factors that affect caudate development may provide targets for improving behavioural function.

Associations between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure in mid-childhood: An MRI study.

Neonatal hypoglycaemia is a common metabolic disorder that may cause brain damage, most visible in parieto-occipital regions on MRI in the acute phase. However, the long term effects of neonatal hypoglycaemia on the brain are not well understood. We investigated the association between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure at 9-10 years. Children born at risk of neonatal hypoglycaemia at ≥ 36 weeks' gestation who took part in a prospective cohort study underwent brain MRI at 9-10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (at least one consecutive blood glucose concentration < 2.6 mmol/L) or interstitial episode (at least 10 min of interstitial glucose concentrations < 2.6 mmol/L). Brain volumes and cortical thickness were computed using Freesurfer. White matter microstructure was assessed using tract-based spatial statistics. Children who had (n = 75) and had not (n = 26) experienced neonatal hypoglycaemia had similar combined parietal and occipital lobe volumes and no differences in white matter microstructure at nine years of age. However, those who had experienced neonatal hypoglycaemia had smaller caudate volumes (mean difference: -557 mm3, 95% confidence interval (CI), -933 to -182, p = 0.004) and smaller thalamus (-0.03%, 95%CI, -0.06 to 0.00; p = 0.05) and subcortical grey matter (-0.10%, 95%CI -0.20 to 0.00, p = 0.05) volumes as percentage of total brain volume, and thinner occipital lobe cortex (-0.05 mm, 95%CI -0.10 to 0.00, p = 0.05) than those who had not. The finding of smaller caudate volumes after neonatal hypoglycaemia was consistent across analyses of pre-specified severity groups, clinically detected hypoglycaemic episodes, and severity and frequency of hypoglycaemic events. Neonatal hypoglycaemia is associated with smaller deep grey matter brain regions and thinner occipital lobe cortex but not altered white matter microstructure in mid-childhood.

Neurodevelopmental impairment is associated with altered white matter development in a cohort of school-aged children born very preterm.

Individuals born very preterm (<32 weeks gestation) have altered brain growth and white matter maturation relative to their full-term peers, and approximately 30% will experience neurodevelopmental impairment. We investigated the relationship between neurodevelopmental impairment and MRI measures of white matter microstructure and brain volume. Children born before 30 weeks' gestation or who had very low birthweight (< 1500 g) underwent neurodevelopmental assessment and MRI at age 7 years as part of the PIANO study, a New Zealand-based cohort study. Fractional anisotropy (FA) and diffusivity measures were derived from diffusion tensor imaging to index white matter microstructure. Volumes were derived from T1-weighted imaging. Neurodevelopmental impairment was defined as a score < 85 on the Wechsler Intelligence Scale for Children, <5th centile on the Movement Assessment Battery for Children or a diagnosis of cerebral palsy by a paediatrician. Relationships between MRI and neurodevelopmental impairment were assessed with general linear models adjusted for sex, gestational age at birth, birthweight z-score, age at assessment, New Zealand Deprivation index score and multiplicity. Children with neurodevelopmental impairment (n = 38) had smaller total brain, cortical grey matter and cerebral white matter volumes compared to children without neurodevelopmental impairment (n = 62) (p < 0.05, false discovery rate corrected), but the regional volume differences did not remain significant after adjustment for total brain volume. Lower FA and higher radial diffusivity were observed in the superior longitudinal fasciculi, uncinate fasciculi and right hemisphere corticospinal tract in children with neurodevelopmental impairment. This may reflect differences in cellular properties such as myelination or axonal packing. Neurodevelopmental impairment may reflect smaller overall brain volume and altered microstructure in white matter tracts that are important for language, cognitive and motor functioning.

Substance use, criminal behaviour and psychiatric symptoms following childhood traumatic brain injury: findings from the ALSPAC cohort.

Recent research suggests a link between traumatic brain injury (TBI) in youth and later risk behaviour. We explored the association between mild TBI and psychiatric symptoms, substance use and criminal behaviour using data from a longitudinal birth cohort. Participants with mild TBI (n = 800), orthopaedic injuries (n = 2305) and no injuries (n = 8307) were identified from self and parent reports up to age 16 years. Self-report measures of substance use (alcohol, tobacco and cannabis) and criminal behaviours, and parent-reported psychiatric symptoms were collected at age 17 years. Analyses were adjusted for pre-birth and early childhood confounders. Participants with a TBI showed increased odds of hazardous alcohol use compared to those with no injury and those with an orthopaedic injury. Relative to those with no injury, participants with a TBI showed increased odds of problematic use of tobacco and cannabis, being in trouble with the police and having more parent-reported conduct problems. Sustaining either a TBI or an orthopaedic injury increased the odds of offending behaviour compared to having no injuries. There was no clear evidence of association between orthopaedic injury and the other risk outcomes. The increased odds of risk behaviour associated with TBI relative to no injury replicated previous research. However, the inclusion of a non-brain-related injury group adds evidence for a possible causal pathway between mild TBI in youth and later hazardous alcohol use only. This highlights the importance of including an additional negative control injury group in mild TBI research.

Childhood Traumatic Brain Injury and the Associations With Risk Behavior in Adolescence and Young Adulthood: A Systematic Review.

OBJECTIVE: To systematically review the evidence that childhood traumatic brain injury (TBI) is associated with risk behavior in adolescence and young adulthood. Risk behavior included one or more of the following: use of substances, including alcohol, tobacco, and illicit substances; involvement in criminal behavior; and behavioral issues with conduct. METHODS: A literature search was conducted using these terms: child, pediatric, traumatic brain injury, head injury, adolescent, psychosocial, antisocial, conduct, substance use. Studies describing original research were included if they reported outcomes over the age of 13 years in participants who sustained a TBI between birth and age 13 years. RESULTS: Six journal articles were reviewed based on 4 separate studies. Three articles indicated a relationship between childhood TBI and increased problematic substance use in adolescence and young adulthood. Three articles supported an association between childhood TBI and later externalizing behavior; however, 2 articles did not support this link. CONCLUSION: More research is warranted to explore the association between childhood TBI and later risk behavior as the relationship is not currently understood. Future research should build on existing longitudinal research with continued use of medical records for identifying TBI and inclusion of a non-brain-related trauma group to control for general injury effects.

Networks offer new opportunities for diabetes research.

The incidence of diabetes continues to rise and demands on healthcare resources continue to grow. High quality research offers a way forward for developing new treatments and care options for people with this condition. The Diabetes Research Network represents a new approach to supporting collaborative research and has been at the vanguard of encouraging patients to get involved through its advocacy workstream. Since its inception more than 200 studies involving 25,000 volunteers have been registered in the network portfolio. An essential element for success is the involvement of primary care where benefits can accrue to patients and healthcare professionals alike.

Clinical benefits of remote versus transtelephonic monitoring of implanted pacemakers.

OBJECTIVES: The purpose of this study was to evaluate remote pacemaker interrogation for the earlier diagnosis of clinically actionable events compared with traditional transtelephonic monitoring and routine in-person evaluation. BACKGROUND: Pacemaker patient follow-up procedures have evolved from evaluating devices with little programmability and diagnostic information solely in person to transtelephonic rhythm strip recordings that allow monitoring of basic device function. More recently developed remote monitoring technology leverages expanded device capabilities, augmenting traditional transtelephonic monitoring to evaluate patients via full device interrogation. METHODS: The time to first diagnosis of a clinically actionable event was compared in patients who were followed by remote interrogation (Remote) and those who were followed per standard of care with office visits augmented by transtelephonic monitoring (Control). Patients were randomized 2:1. Remote arm patients transmitted pacemaker information at 3-month intervals. Control arm patients with a single-chamber pacemaker transmitted at 2-month intervals. Control arm patients with dual-chamber devices transmitted at 2-month intervals with an office visit at 6 months. All patients were seen in office at 12 months. RESULTS: The mean time to first diagnosis of clinically actionable events was earlier in the Remote arm (5.7 months) than in the Control arm (7.7 months). Three (2%) of the 190 events in the Control arm and 446 (66%) of 676 events in the Remote arm were identified remotely. CONCLUSIONS: The strategic use of remote pacemaker interrogation follow-up detects actionable events that are potentially important more quickly and more frequently than transtelephonic rhythm strip recordings. The use of transtelephonic rhythm strips for pacemaker follow-up is of little value except for battery status determinations. (PREFER [Pacemaker Remote Follow-up Evaluation and Review]; NCT00294645).