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Sleep disturbances are commonly reported in children with persistent post-concussion symptoms (PPCS). Melatonin treatment is often recommended, yet supporting evidence is scarce. We aimed to evaluate the efficacy of treatment with... more
Sleep disturbances are commonly reported in children with persistent post-concussion symptoms (PPCS). Melatonin treatment is often recommended, yet supporting evidence is scarce. We aimed to evaluate the efficacy of treatment with Melatonin for sleep disturbance in youth with PPCS following mild traumatic brain injury (mTBI). Methods This paper is a secondary analysis of a clinical trial of Melatonin to treat PPCS compared to placebo. Youth (aged 8-18 years) with PPCS and significant sleep-related problems (SRPs) at 4-6 weeks post-injury were eligible. Exclusion criteria: significant medical/psychiatric history; previous concussion/mTBI within 3months. Treatment groups were: placebo, Melatonin 3mg, or Melatonin 10mg. Primary outcome was change in SRPs measured using the Post-Concussion Symptom Inventory (PCSI) after two weeks of treatment. Secondary outcomes included change in actigraphy sleep efficiency, duration, onset latency, and wake-after-sleep-onset. Behaviour was measured using Behaviour Assessment for Children (2nd edition). Results Seventy-two participants (mean age 14.0(SD=2.6) years; 60% female) with PPCS and significant sleep disturbance were included in the secondary analysis: placebo (n=22); Melatonin 3mg (n=25); Melatonin 10mg (n=25). Sixty-four participants had actigraphy data. SRPs decreased across all groups over time with a significant effect of Melatonin 3mg (3.7; 95%CI:2.1, 5.4) compared to placebo (7.4; 95%CI:4.2,10.6) and Melatonin 10mg (6.4; 95%CI:3.6,9.2). Sleep duration increased in Melatonin 3mg (43minutes; 95%CIs:6,93) and Melatonin 10mg groups (55minutes; 95%CIs:5,104) compared to placebo. A per protocol analysis demonstrated improved sleep efficiency in the Melatonin 10mg group (p=.029). No serious adverse events were reported. Depressive symptoms significantly decreased with Melatonin 3mg (EMD=-4.7; 95%CI:-9.2,-.2) but not Melatonin 10mg (-1.4, 95%CIs:-5.9,3.2) treatment compared to placebo. Changes in cognition or behaviour were otherwise not significantly different between treatment groups. Conclusions Short-term Melatonin is a well-tolerated treatment for sleep disturbance in youth with PPCS following mTBI. In this context, it may also be associated with a reduction in depressive symptoms.
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Reading disorders are common in children, and can impact academic success, mental health, and career prospects. Reading is supported by network of interconnected left hemisphere brain regions, including temporo-parietal,... more
Reading disorders are common in children, and can impact academic success, mental health, and career prospects. Reading is supported by network of interconnected left hemisphere brain regions, including temporo-parietal, occipito-temporal, and inferior-frontal circuits. Poor readers often show hypoactivation and reduced gray matter volumes in this reading network, with hyperactivation and increased volumes in the posterior right hemisphere. We assessed gray matter development longitudinally in pre-reading children aged 2-5 years using magnetic resonance imaging (MRI) (N = 32, 110 MRI scans; mean age: 4.40 ± 0.77 years), half of whom had a family history of reading disorder. The family history group showed slower proportional growth (relative to total brain volume) in the left supramarginal and inferior frontal gyri, and faster proportional growth in the right angular, right fusiform, and bilateral lingual gyri. This suggests delayed development of left hemisphere reading areas in children with a family history of dyslexia, along with faster growth in right homologues. This alternate development pattern may predispose the brain to later reading difficulties and may later manifest as the commonly noted compensatory mechanisms. The results of this study further our understanding of structural brain alterations that may form the neurological basis of reading difficulties. This article is protected by copyright. All rights reserved.
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Background Prenatal anxiety is associated with child behavioral problems. Prenatal anxiety is predictive of postnatal anxiety which can interfere with the security of maternal-child attachment and further raise the risk of child behavior... more
Background Prenatal anxiety is associated with child behavioral problems. Prenatal anxiety is predictive of postnatal anxiety which can interfere with the security of maternal-child attachment and further raise the risk of child behavior problems. Secure maternal-child attachment is essential for optimal emotional health. Sex influences the type of behavior problem experienced. There is a gap in understanding whether attachment security and the sex of the child can moderate association between prenatal anxiety and children’s behavioral problems. Purpose To examine the association between prenatal anxiety and child behavioral problems and to test the moderating effects of attachment security and child sex on the association between prenatal anxiety and child behavioral problems. Methods Secondary analysis of data from 182 mothers and their children, enrolled in the Alberta Pregnancy Outcomes and Nutrition Study using Hayes' (2013) conditional process modeling. Results Prenatal an...
Research Interests: Psychology and Nursing
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Caesarean section (C-section) deliveries account for nearly 30% of births annually with emergency C-sections accounting for 7–9% of all births. Studies have linked C-sections to postpartum depression (PPD). PPD is linked to reduced... more
Caesarean section (C-section) deliveries account for nearly 30% of births annually with emergency C-sections accounting for 7–9% of all births. Studies have linked C-sections to postpartum depression (PPD). PPD is linked to reduced quality of parent-child interaction, and adverse effects on maternal and child health. New mothers’ perceptions of more negative childbirth experiences, such as unplanned/emergency C-sections, are linked to post-traumatic stress disorder (PTSD), which in turn is related to PPD. Our objectives were to determine: (1) the association between C-section type (unplanned/emergency vs. planned) and PPD symptoms, and (2) if postnatal PTSD symptoms mediate this association. Employing secondary analysis of prospectively collected data from 354 mother-child dyads between 2009 and 2013 from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, conditional process modeling was employed. The Edinburgh Postnatal Depression Scale (EPDS) and the Psychiatric Diagnosti...
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Women’s nutritional status during pregnancy can have long-term effects on children’s brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal... more
Women’s nutritional status during pregnancy can have long-term effects on children’s brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal development. They have also been associated with brain and cognitive development in children. Animal studies have observed that prenatal folate and choline supplementation is associated with better cognitive outcomes in offspring and that these nutrients may have interactive effects on brain development. Although some human studies have reported associations between maternal folate and choline levels and child cognitive outcomes, results are not consistent, and no human studies have investigated the potential interactive effects of folate and choline. This lack of consistency could be due to differences in the methods used to assess folate and choline levels, the gestational trimester at which they were measured, and lack of consideration of potential confound...
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Much of our understanding of motor control deficits in children with developmental coordination disorder (DCD) comes from upper limb assessments focusing on the dominant limb. Here, using two robotic behavioural tasks, we investigated... more
Much of our understanding of motor control deficits in children with developmental coordination disorder (DCD) comes from upper limb assessments focusing on the dominant limb. Here, using two robotic behavioural tasks, we investigated motor control in both the dominant and non-dominant limbs of children with DCD. Twenty-six children with diagnosed DCD (20 males; mean age 10.6 years ± 1.3 years) and 155 controls were included in this cross-sectional study. Participants completed a visually guided reaching task with their dominant and non-dominant limbs and a bimanual object hitting task. Motor performance was quantified across nine parameters. We determined the number of children with DCD who fell outside of the typical performance range of the controls on these parameters and compared the DCD and control groups using ANCOVAs, accounting for age. Children with DCD demonstrated impairments in six out of nine parameters; deficits were more commonly noted in the non-dominant limb. Inter...
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Developmental coordination disorder (DCD) is a neurodevelopmental disorder occurring in 5–6% of school-aged children. Converging evidence suggests that dysfunction within cortico-striatal and cortico-cerebellar networks may contribute to... more
Developmental coordination disorder (DCD) is a neurodevelopmental disorder occurring in 5–6% of school-aged children. Converging evidence suggests that dysfunction within cortico-striatal and cortico-cerebellar networks may contribute to motor deficits in DCD, yet limited research has examined the brain morphology of these regions. Using T1-weighted magnetic resonance imaging the current study investigated cortical and subcortical volumes in 37 children with DCD, aged 8 to 12 years, and 48 controls of a similar age. Regional brain volumes of the thalamus, basal ganglia, cerebellum and primary motor and sensory cortices were extracted using the FreeSurfer recon-all pipeline and compared between groups. Reduced volumes within both the left and right pallidum (Left: F = 4.43, p = 0.039; Right: F = 5.24, p = 0.025) were observed in children with DCD; however, these results did not withstand correction for multiple comparisons. These findings provide preliminary evidence of altered subco...
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ABSTRACT The objective was to investigate whether perinatal maternal anxiety and depressive symptoms predicted child attention and executive function (EF). Mothers (N = 614) reported pregnancy and three-months postnatal anxiety and... more
ABSTRACT The objective was to investigate whether perinatal maternal anxiety and depressive symptoms predicted child attention and executive function (EF). Mothers (N = 614) reported pregnancy and three-months postnatal anxiety and depressive symptoms. Attention and EF were measured at two-years-of-age. Covariates were demographics, alcohol use, mood disorder history, and pregnancy factors. Higher prenatal anxiety, b(SE) =.020(.005), p<.001, and postnatal depressive symptoms, b(SE) =.009(.004), p=.04, predicted poorer child attention. A prenatal-by-postnatal depressive symptom interaction emerged, b(SE) = −.005(.003), p=.04: When pregnancy depressive symptoms were low, higher postnatal symptoms predicted poorer attention. No distress variables predicted EF, p’s>.22. Perinatal distress timing, kind, and change were important for child attention.
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The current study aimed to understand the mediating and/or moderating role of prenatal hypothalamic–pituitary–adrenal (HPA) axis function in the association between maternal adverse childhood experiences (ACEs) and child internalizing and... more
The current study aimed to understand the mediating and/or moderating role of prenatal hypothalamic–pituitary–adrenal (HPA) axis function in the association between maternal adverse childhood experiences (ACEs) and child internalizing and externalizing behavior problems at age 4. The influence of timing and child sex were also explored. Participants were 248 mother–child dyads enrolled in a prospective longitudinal cohort study (the Alberta Pregnancy Outcomes and Nutrition Study). Maternal ACEs were retrospectively assessed while maternal self-reported depression and diurnal salivary cortisol were assessed prospectively at 6–26 weeks gestation (T1) and 27–37 weeks gestation (T2). Maternal report of child internalizing and externalizing problems was assessed at 4 years (T3). Results revealed that there was a negative indirect association between maternal ACEs and child internalizing behavior via a higher maternal cortisol awakening response (CAR). Maternal diurnal cortisol slope mode...
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Background Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse... more
Background Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children’s brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior. Methods Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3–4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2–5 years...
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Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track longitudinal changes in... more
Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track longitudinal changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed 'fixels'. Fixel-based analysis and mixed-effects models were used to assess tract-wise changes in fiber density and bundle morphology in 73 girls scanned at baseline (ages 4.09-7.02, mean=5.47, SD=0.81), 6-month (N=7), and one-year follow-up (N=42). We also assessed changes in fractional anisotropy (FA) and mean diffusivity (MD). Maturational increases in fixel-metrics were seen in most major white matter tracts, with the most rapid increases in the corticospinal tract and slowest or non-significant increases in the genu of the corpus callosum and uncinate fasciculus. As expected, we observed developmental increases in FA and decrea...
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ObjectiveYoung children are often unable to remain still for magnetic resonance imaging (MRI). Various preparation methods have been reported to avoid sedation or anesthesia, with mixed success rates and feasibility. Here we describe a... more
ObjectiveYoung children are often unable to remain still for magnetic resonance imaging (MRI). Various preparation methods have been reported to avoid sedation or anesthesia, with mixed success rates and feasibility. Here we describe a time-efficient preparation method and factors associated with successful scanning in young chdilren.We recruited 134 children aged 2.0–5.0 years for an MRI study. Some children completed a training session on a mock scanner, and all children received a 15–20 minute introduction to scanning procedures immediately before their scan. We compared success between children receiving mock scanner training or not, and evaluated demographic or cognitive factors that predicted success.Results97 children (72%) completed at least one sequence successfully; 64 children provided high-quality data for all 3 sequences. Cognitive scores were higher in successful children, but children who received mock scanner training were less likely to be successful. A case-control...
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Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living in such areas may be exposed by various... more
Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living in such areas may be exposed by various routes, and prenatal exposure to arsenic and mercury has been associated with adverse birth outcomes and developmental delays. The aim of this study was to determine if levels of arsenic and mercury differed among pregnant women living in areas with and without ASGM activities in Northern Tanzania. This cross-sectional study is part of the ongoing Mining and Health prospective longitudinal study. Spot urine samples and dried blood spots were collected at the antenatal health clinics from pregnant women (n = 1056) at 16-27 weeks gestation. Urine samples were analyzed for total arsenic (T-As) and dried blood spots were analyzed for total mercury (T-Hg). Women in the ASGM cohort had median T-As levels (9.4 μg/L; IQR: 4.9-15.1) and T-Hg levels (1.2 μg/L; IQR: 0.8-1.86) that were significantly higher than the median T-As levels (6.28 μg/L; IQR: 3.7-14.1) and T-Hg levels (0.66 μg/L; IQR: 0.3-1.2) of women in the non-ASGM cohort (Mann-Whitney U test, T-As: z = -9.881, p = 0.0005; T-Hg: z = -3.502, p < 0.0001). Among pregnant women from ASGM areas, 25% had urinary T-As and 75% had blood T-Hg above the established human biomonitoring reference values of 15 and 0.80 μg/L. In the ASGM cohort, lower maternal education and low socioeconomic status increased the odds of higher T-As levels by 20% (p < 0.05) and 10% (p < 0.05), respectively. Women involved in mining activities and those of low socioeconomic status had increased odds of higher T-Hg by 70% (p < 0.001) and 10% (p < 0.05), respectively. Arsenic and mercury concentrations among women in non-ASGM areas suggest exposure sources beyond ASGM activities that need to be identified. Arsenic and mercury levels in women in Tanzania are of public health concern and their association with adverse birth and child developmental outcomes will be examined in future studies on this cohort.
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White matter development continues throughout childhood and into early adulthood, but few studies have examined early childhood, and the specific trajectories and regional variation in this age range remain unclear. The aim of this study... more
White matter development continues throughout childhood and into early adulthood, but few studies have examined early childhood, and the specific trajectories and regional variation in this age range remain unclear. The aim of this study was to characterize developmental trajectories and sex differences of white matter in typically developing young children. Three hundred and ninety-six diffusion tensor imaging datasets from 120 children (57 male) aged 2-8 years were analyzed using tractography. Fractional anisotropy (FA) increased and mean diffusivity (MD) decreased in all white matter tracts by 5-15% over the 6-year period, likely reflecting increases in myelination and axonal packing. Males showed steeper slopes in a number of brain areas. Overall, early childhood is associated with substantial development of all white matter and appears to be an important period for the development of occipital and limbic connections, which showed the largest changes. This study provides a detai...
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Purpose of the ReviewTo provide an overview of the concept of comorbidity, research that supports the common co-occurrence of neurodevelopmental disorders and directions for future research.Recent FindingsNeurodevelopmental disorders... more
Purpose of the ReviewTo provide an overview of the concept of comorbidity, research that supports the common co-occurrence of neurodevelopmental disorders and directions for future research.Recent FindingsNeurodevelopmental disorders including attention-deficit/hyperactivity disorder, developmental coordination disorder, autism spectrum disorder, and learning disorders co-occur more commonly than would be expected by chance. The potential causes for this comorbidity suggested in the research literature are genetic, epigenetic, neurobiological, and environmental.SummaryDirections for research such as imaging genetics and epidemiological studies examining prenatal environmental exposures could increase our understanding of the mechanism underlying the high rates of symptom comorbidity among neurodevelopmental disorders. This in turn could lead to improvements in diagnosis, a better understanding of the course of these disorders, and the development of more effective treatments.
Young children are often unable to remain still for magnetic resonance imaging (MRI), leading to unusable images. Various preparation methods may increase success, though it is unclear which factors best predict success. Here, in a... more
Young children are often unable to remain still for magnetic resonance imaging (MRI), leading to unusable images. Various preparation methods may increase success, though it is unclear which factors best predict success. Here, in a retrospective sample, we describe factors associated with successful scanning in unsedated young children. We hypothesized that the mock scanner training and fewer behavior problems would result in higher success rates. We recruited 134 children aged 2.0-5.0 years for an MRI study. We compared success between children whose parents opted for mock scanner training ( = 20) or not ( = 114), and evaluated demographic and cognitive factors that predicted success. Ninety-seven children (72%) completed at least one MRI sequence successfully on their first try; 64 children (48%) provided high-quality data for all 3 structural imaging sequences. Cognitive scores were higher in successful than unsuccessful children. Children who received mock scanner training were ...
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Diet is regarded as the main source of bisphenol A (BPA) exposure, but comparatively little is known about dietary sources of BPA-alternatives. Here we measured exposure of BPA and BPA-alternatives among pregnant women in Canada,... more
Diet is regarded as the main source of bisphenol A (BPA) exposure, but comparatively little is known about dietary sources of BPA-alternatives. Here we measured exposure of BPA and BPA-alternatives among pregnant women in Canada, estimated their 24-h intakes and examined the importance of various dietary sources. Free and total BPA, bisphenol S (BPS) and bisphenol F (BPF) were measured in 467 second trimester maternal urine samples, and in 455 paired samples collected at three months postpartum. Linear regression was used to evaluate associations between urinary concentrations of bisphenols and 24-h dietary recall data. The geometric means of total BPA in second trimester and postpartum urine (1.2 and 0.95 ng/mL, respectively) were 5-7 times higher than corresponding total BPS (0.16 and 0.17 ng/mL). The detection frequency of BPF was only 9% (i.e. >1.0 ng/mL). However, at both time points 95th percentiles of total BPF (7.3 and 4.2 ng/mL, respectively) were similar to total BPA (8...
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The aim of the study was to explore the relationship between repressive adaptive style and self-reports of social adjustment in survivors of pediatric cancer compared to their siblings. We hypothesized that there would be a greater... more
The aim of the study was to explore the relationship between repressive adaptive style and self-reports of social adjustment in survivors of pediatric cancer compared to their siblings. We hypothesized that there would be a greater proportion of repressors among survivors of pediatric cancer compared to siblings, and that repressive adaptive style would be significantly associated with more positive self-reports of social adjustment. We utilized a cross-sectional approach. Seventy-seven families participated. Survivors of pediatric cancer (n = 77, 48% male; 8-18 years of age) and one sibling (n = 50, 48% male; 8-18 years of age) completed measures assessing repressive adaptive style and social adjustment. As well, one parent from each family completed a socio-demographic questionnaire. Questionnaire packages were mailed to eligible families who agreed to participate, and were mailed back to investigators in a pre-addressed, pre-stamped envelope. Chi-square analyses revealed there wa...
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Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate... more
Caffeine is effective in the treatment of apnea of prematurity. Although caffeine therapy has a benefit on gross motor skills in school-aged children, effects on neurobehavioral outcomes are not fully understood. We aimed to investigate effects of neonatal caffeine therapy in very low birth weight (500-1250 g) infants on neurobehavioral outcomes in 11-year-old participants of the Caffeine for Apnea of Prematurity trial. Thirteen academic hospitals in Canada, Australia, Great Britain, and Sweden participated in this part of the 11-year follow-up of the double-blind, randomized, placebo-controlled trial. Measures of general intelligence, attention, executive function, visuomotor integration and perception, and behavior were obtained in up to 870 children. The effects of caffeine therapy were assessed by using regression models. Neurobehavioral outcomes were generally similar for both the caffeine and placebo group. The caffeine group performed better than the placebo group in fine mot...
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Adolescence is a unique developmental period, characterized by physical and emotional growth and significant maturation of cognitive and social skills. For individuals with Autism Spectrum Disorder (ASD), it is also a vulnerable period as... more
Adolescence is a unique developmental period, characterized by physical and emotional growth and significant maturation of cognitive and social skills. For individuals with Autism Spectrum Disorder (ASD), it is also a vulnerable period as cognitive and social skills can deteriorate. Circumscribed interests (CIs), idiosyncratic areas of intense interest and focus, are a core symptom of ASD that may be associated with social development. Yet, relatively little is known about the expression of CIs in adolescents with ASD. Many studies investigating CIs have used images depicting items of special interest; however, it is not clear how images should be customized for adolescent studies. The goal of this study was to gain insight into the types of images that may be appropriate for studies of CIs in adolescents with ASD. To this end, we used a mixed methods design that included, 1) one-on-one interviews with 10 adolescents (4 with ASD and 6 TD), to identify categories of images that were ...
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Introduction Due to the decline in physical activity documented during the transition to adulthood, as well as the powerful modeling effect parents have on their young children, parents of preschool-age children are a valuable population... more
Introduction Due to the decline in physical activity documented during the transition to adulthood, as well as the powerful modeling effect parents have on their young children, parents of preschool-age children are a valuable population sub-group to examine in physical activity research. Method In this investigation, 118 Canadian mothers and fathers of preschool-age children filled out three questionnaires: the Godin leisure-time physical activity participation [1] , Stage of motivational readiness to change [2] , and Exercise Benefits/Barriers Scale (EBBS) [3] . Results Consistent with previous research, the trans-theoretical model of behavior change was supported. That is, respondents classified in higher stages of motivational readiness to change reported higher levels of physical activity. This finding held for both exercising alone or with their children. Similarly, participants classified into higher stages of motivational readiness to change also reported greater perceived benefits and fewer perceived barriers to physical activity participation. Contrary to previous research, gender was not found to be a significant correlate of physical activity participation in this sample. Parental time demands emerged as a novel barrier to physical activity participation in the EBBS. Mothers in lower stages of motivational readiness to change were more likely to view parenting as a barrier to physical activity participation. Active parents, in higher stages of motivational readiness to change, were less likely to view parenting related time demands as barriers to physical activity participation and were more likely to engage in physical activity with their children. Conclusion The relationships between gender, parenting related time demands, physical activity participation and stage of motivational readiness to change are complex. However, since parenting has a unique effect on families’ daily physical activity engagement, a practical conclusion of the study is that healthy living interventions targeting families with young children need to incorporate the parental expectations and needs to perceived benefits and barriers.
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Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We... more
Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We studied 68 children aged 3.0-5.6 years who underwent diffusion tensor imaging and participated in assessments of Phonological Processing and Speeded Naming. Tract-based spatial statistics and tractography revealed relationships between Phonological Processing and fractional anisotropy and mean diffusivity in bilateral ventral white matter pathways, the corpus callosum, and corticospinal tracts. The relationships observed in left ventral pathways are consistent with studies in older children, and demonstrate that structural markers for language difficulties are apparent as young as 3 years of age. Our findings in right hemisphere areas that are not as commonly found in adult studies suggest that young children rely on a widespread network for language...
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Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are... more
Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010-2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize c...
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Hemorrhage into the brain of term newborns often results in major injury and lifelong disability. The clinical epidemiology of neonatal hemorrhagic stroke (NHS) remains undefined, hindering the development of strategies to improve... more
Hemorrhage into the brain of term newborns often results in major injury and lifelong disability. The clinical epidemiology of neonatal hemorrhagic stroke (NHS) remains undefined, hindering the development of strategies to improve outcomes. To characterize the incidence, types, presentations, associated factors, and outcomes of neonatal hemorrhagic stroke. Population-based, nested case-control study. The Alberta Perinatal Stroke Project, a provincial registry, ascertained NHS cases using exhaustive diagnostic code searching (1992-2010, >2500 medical record reviews). Prospective cases were captured through the Calgary Pediatric Stroke Program (2007-2014). Participants included term neonates with magnetic resonance imaging-confirmed NHS including primary and secondary intracerebral hemorrhage, hemorrhagic transformation of ischemic injury, and presumed perinatal hemorrhagic stroke. Control infants with common data were recruited from a population-based study (4 to 1 ratio). Infants...
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Vitamin D is important in promoting healthy pregnancy and fetal development. We undertook this study to measure 25-hydroxyvitamin D in maternal and cord blood and to identify maternal factors related to vitamin D status in Calgary. Blood... more
Vitamin D is important in promoting healthy pregnancy and fetal development. We undertook this study to measure 25-hydroxyvitamin D in maternal and cord blood and to identify maternal factors related to vitamin D status in Calgary. Blood samples collected at the time of delivery from the Alberta Pregnancy Outcomes and Nutrition study cohort (ApronStudy.ca) participants were processed for plasma and assayed using liquid chromatography mass spectrometry methodology for 25(OH)D3. Ninety-two pairs of maternal and cord blood samples were obtained. The prevalence of 25(OH)D3 insufficiency-25(OH)D3 <75 nmol/L-was 38% and 80% in women and neonates, respectively. Vitamin D supplementation was the only clinical factor associated with 25(OH)D3 sufficiency, and the odds of sufficiency were 3.75 (95% CI 1.00 to 14.07) higher for women and 5.27 (95% CI 1.37 to 20.27) when over 2000 IU/day were used. Using liquid chromatography mass spectrometry, we demonstrated a very high prevalence of vitami...
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Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years. To evaluate whether neonatal... more
Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years. To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later. A follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English- or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome. Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed. Functional impairment was a composite of poor academic performance (defined as at least 1 standard score greater tha...
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Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77... more
Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and glob...
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In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound... more
In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound heterozygosity for two rare variants: c.324G>C, p.Met108Ile and c.491dup, p.Ile165Aspfs*12. The pathogenicity of these variants was confirmed by molecular-level studies, which showed that c.491dup does not produce soluble protein and c.324G>C results in a catalytically less efficient Met108Ile enzyme that is prone to proteolytic degradation. The biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences.
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A major research limitation in investigating the validity of the TAIS has been the failure to distinguish when attentional style has an effect on the information processing system, early as in encoding or late after processing. Few... more
A major research limitation in investigating the validity of the TAIS has been the failure to distinguish when attentional style has an effect on the information processing system, early as in encoding or late after processing. Few investigations have examined the TAIS predictive validity in a controlled setting wherein task attention demands can be systematically and accurately varied. Does the general trait of attentional style really have anything to do with how attention related information is processed? The present study examined this question using a valid attention theory (Treisman's feature integration theory) and a visual search paradigm. When the TAIS attentional-style scales were correlated with visual search rate for attention demanding targets, no significant relationships were observed. Specifically, TAIS scales did not relate to visual search rate for an attention demanding target, the performance of subjects extreme in search rate, or the central to peripheral sl...
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Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking. To determine whether BPA exposure during pregnancy is associated with dysregulation of... more
Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking. To determine whether BPA exposure during pregnancy is associated with dysregulation of the HPA-axis, we examined the association between urinary BPA concentrations and diurnal salivary cortisol in pregnant women. Secondary analyses investigated whether the association between BPA and cortisol was dependent on fetal sex. Diurnal salivary cortisol and urinary BPA were collected during pregnancy from 174 women in a longitudinal cohort study, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Associations between BPA and daytime cortisol and the cortisol awakening response (CAR) were estimated using mixed models after adjusting for covariates. Higher concentrations of total BPA uncorrected for urinary creatinine were associated with dysregulation of the daytime cortisol pattern, including reduced cortisol at waking, β=-.055, 95%...
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Research Interests:
Developmental coordination disorder is a common neurodevelopment disorder that frequently co-occurs with other neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD). Copy-number variations (CNVs) have been... more
Developmental coordination disorder is a common neurodevelopment disorder that frequently co-occurs with other neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD). Copy-number variations (CNVs) have been implicated in a number of neurodevelopmental and psychiatric disorders; however, the proportion of heritability in developmental coordination disorder (DCD) attributed to CNVs has not been explored. This study aims to investigate how CNVs may contribute to the genetic architecture of DCD. CNV analysis was performed on 82 extensively phenotyped Canadian children with DCD, with or without co-occurring ADHD and/or reading disorder, and 2988 healthy European controls using identical genome-wide SNP microarrays and CNV calling algorithms. An increased rate of large and rare genic CNVs (p=0.009) was detected, and there was an enrichment of duplications spanning brain-expressed genes (p=0.039) and genes previously implicated in other neurodevelopmental disorders (p=0.043). Genes and loci of particular interest in this group included: GAP43, RBFOX1, PTPRN2, SHANK3, 16p11.2 and distal 22q11.2. Although no recurrent CNVs were identified, 26% of DCD cases, where sample availability permitted segregation analysis, were found to have a de novo rare CNV. Of the inherited CNVs, 64% were from a parent who also had a neurodevelopmental disorder. These findings suggest that there may be shared susceptibility genes for DCD and other neurodevelopmental disorders and highlight the need for thorough phenotyping when investigating the genetics of neurodevelopmental disorders. Furthermore, these data provide compelling evidence supporting a genetic basis for DCD, and further implicate rare CNVs in the aetiology of neurodevelopmental disorders.
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The biology of post-concussive symptoms is unclear. Symptoms are often increased during activities, and have been linked to decreased cerebrovascular reactivity and perfusion. The aim of this study was to examine cerebral blood flow (CBF)... more
The biology of post-concussive symptoms is unclear. Symptoms are often increased during activities, and have been linked to decreased cerebrovascular reactivity and perfusion. The aim of this study was to examine cerebral blood flow (CBF) in children with different clinical recovery patterns following mild traumatic brain injury (mTBI). This was a prospective controlled cohort study of children with mTBI (ages 8 to 18 years) who were symptomatic with post concussive symptoms at one month post-injury (symptomatic, n=27) and children who had recovered quickly (asymptomatic, n=24). Pseudocontinuous arterial spin labeling MRI was used to quantify CBF. The mTBI groups were imaged at 40 days post-injury. Global and regional CBF were compared to healthy controls of similar age and sex but without a history of mTBI (n=21). Seventy-two participants (mean age: 14.1years) underwent neuroimaging. Significant differences in CBF were found: global CBF was higher in the symptomatic group and lower...