Fig 2 - uploaded by Ana C. Hanlon-Dearman
Content may be subject to copyright.
Head circumference increased with age for both males (blue) and females (red) in both groups (A, B), and HC was lower in PAE than controls for males but not females (C). Brain volume did not change with age in either group (D,E), and was consistently reduced in PAE relative to controls for both males and females (F). IQ standard scores did not change with age in either group (G, H), and were again lower in the PAE group (I). Sex differences within groups were larger in the control group for both head circumference (C) and brain volume (F). ns = non-significant.
Source publication
Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumf...
Contexts in source publication
Context 1
... HC increased with age in both groups and sexes (male controls R = 0.53 p<0.001; female controls R = 0.51, p<0.001; male PAE R = 0.45, p<0.001; female PAE R = 0.44, p<0.001- Fig 2A and 2B), but raw brain volume did not change with age (Fig 2D and 2E). Raw HC was 2.2% lower in males with PAE versus male controls, but females with PAE did not differ from female controls (t = -3.81, ...
Context 2
... HC increased with age in both groups and sexes (male controls R = 0.53 p<0.001; female controls R = 0.51, p<0.001; male PAE R = 0.45, p<0.001; female PAE R = 0.44, p<0.001- Fig 2A and 2B), but raw brain volume did not change with age (Fig 2D and 2E). Raw HC was 2.2% lower in males with PAE versus male controls, but females with PAE did not differ from female controls (t = -3.81, ...
Context 3
... and t = -1.58, p = 0.117, respectively- Fig 2C). Conversely, raw brain volume was lower in both males (-8.8%) and females (-5.1%) with PAE relative to controls (t = -6.47, ...
Context 4
... and t = -3.32, p = 0.001, respectively- Fig 2F), though greater overlap between sexes can be seen in the PAE than control group (Fig 2D and 2E). In the sub- set of participants with IQ scores, IQ did not change with age (as expected for a standard score) and sex differences were not significant in either group (Fig 2G-2I), though the control group (IQ~112) significantly outperformed the PAE group (IQ~88) (t = -8.73, ...
Context 5
... and t = -3.32, p = 0.001, respectively- Fig 2F), though greater overlap between sexes can be seen in the PAE than control group (Fig 2D and 2E). In the sub- set of participants with IQ scores, IQ did not change with age (as expected for a standard score) and sex differences were not significant in either group (Fig 2G-2I), though the control group (IQ~112) significantly outperformed the PAE group (IQ~88) (t = -8.73, ...
Context 6
... = 0.001, respectively- Fig 2F), though greater overlap between sexes can be seen in the PAE than control group (Fig 2D and 2E). In the sub- set of participants with IQ scores, IQ did not change with age (as expected for a standard score) and sex differences were not significant in either group (Fig 2G-2I), though the control group (IQ~112) significantly outperformed the PAE group (IQ~88) (t = -8.73, p<0.001- ...
Context 7
... Table 1, Fig 2I). Likewise, the control group scored better than the PAE group on all other cognitive tests (t = -2.37-19.19, ...
Context 8
... greatest reductions of HC, IQ and brain volume were found in participants with dysmorphic features indicative of FAS/pFAS (data not shown) in keeping with previous literature [27]; however, subgroup analysis was not further explored given that IQ and HC are used in the sub-classification of FASD. Despite group differences, substantial overlap between the PAE and control groups is evident for all three metrics (Figs 2 and 3). ...
Context 9
... = 0.190-0.072). IQ was only available in 50 PAE and 66 control participants; however, this subsample had a similar age, sex and diagnostic sub-group distribution as the total sample ( Fig 2G and 2H), and demonstrated tight correlations between brain volume Z scores and normed HC (Fig 5C and 5D), indicating that these negative findings (no relationships between HC or brain volume and IQ) are unlikely to stem from sample bias. Likewise, no other cognitive scores correlated with normed HC or total brain volume Z scores in either group, despite larger sample sizes of n~90-140 in each group. ...
Context 10
... addition to group differences, sex effects were observed for both brain volume and HC in the control group, as expected [37], but were less prominent between males and females in the PAE group (Fig 2). Both males and females with PAE showed significant brain volume reduc- tions, albeit with a greater difference in males, in keeping with previous findings of more sub- stantial brain volume reductions in males with FASD [24,38]. ...
Citations
... Parent feeling variables were included in our selection as they may be relevant to determine if parental perceptions play a role in the diagnosis of FASD predicted by ML algorithms. For clinical variables were selected growth deficits (Astley et al., 2016;Hoyme et al., 2016;Treit et al., 2016), craniofacial dysmorphology (Smith et al., 2014;Hoyme et al., 2016), birth malformations (Dylag et al., 2023), neurodevelopmental disorders (Geier and Geier, 2022) and other physical features and medical history (Brennan and Giles, 2014;del Campo and Jones, 2017;Ninh et al., 2019). Lastly, related to neuropsychological domains, we selected variables significant for FASD diagnosis, including motor cognition (Bakoyiannis et al., 2014), language (Hendricks et al., 2019), academic achievement (Glass et al., 2017), memory (Rasmussen, 2005), attention (Young et al., 2016), executive functioning including impulse control and hyperactivity (Peadon and Elliott, 2010), affect regulation (Temple et al., 2019) and adaptive behavior, social skills, or social communication (Temple et al., 2019;Hammond et al., 2022). ...
Introduction
Fetal alcohol spectrum disorders include a variety of physical and neurocognitive disorders caused by prenatal alcohol exposure. Although their overall prevalence is around 0.77%, FASD remains underdiagnosed and little known, partly due to the complexity of their diagnosis, which shares some symptoms with other pathologies such as autism spectrum, depression or hyperactivity disorders.
Methods
This study included 73 control and 158 patients diagnosed with FASD. Variables selected were based on IOM classification from 2016, including sociodemographic, clinical, and psychological characteristics. Statistical analysis included Kruskal-Wallis test for quantitative factors, Chi-square test for qualitative variables, and Machine Learning (ML) algorithms for predictions.
Results
This study explores the application ML in diagnosing FASD and its subtypes: Fetal Alcohol Syndrome (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND). ML constructed a profile for FASD based on socio-demographic, clinical, and psychological data from children with FASD compared to a control group. Random Forest (RF) model was the most efficient for predicting FASD, achieving the highest metrics in accuracy (0.92), precision (0.96), sensitivity (0.92), F1 Score (0.94), specificity (0.92), and AUC (0.92). For FAS, XGBoost model obtained the highest accuracy (0.94), precision (0.91), sensitivity (0.91), F1 Score (0.91), specificity (0.96), and AUC (0.93). In the case of pFAS, RF model showed its effectiveness, with high levels of accuracy (0.90), precision (0.86), sensitivity (0.96), F1 Score (0.91), specificity (0.83), and AUC (0.90). For ARND, RF model obtained the best levels of accuracy (0.87), precision (0.76), sensitivity (0.93), F1 Score (0.84), specificity (0.83), and AUC (0.88). Our study identified key variables for efficient FASD screening, including traditional clinical characteristics like maternal alcohol consumption, lip-philtrum, microcephaly, height and weight impairment, as well as neuropsychological variables such as the Working Memory Index (WMI), aggressive behavior, IQ, somatic complaints, and depressive problems.
Discussion
Our findings emphasize the importance of ML analyses for early diagnoses of FASD, allowing a better understanding of FASD subtypes to potentially improve clinical practice and avoid misdiagnosis.
... Their birth sizes were relatively small, which is in line with previous literature [4,18,24]. In addition to maternal pharmacotherapy [4,25,26], several other factors may have contributed to the birth sizes, including fetal exposure to smoking [27]; alcohol [28]; polysubstance use, hepatitis C [29], and poor nutrition, either alone or in combination. Smoking was common, consistent with prior research [20,23,30]. ...
... Watkins et al. (2013) and Shelton et al. (2018) identify the need to engage in prevention work and noted intervention is critical to prevent further cases of FASD in the same family. Researchers in Canada indicate there are maternal as well as societal factors that contribute to the risk of giving birth to a child with FASD and that alcohol use during pregnancy is related to complex psychosocial histories (Treit et al., 2016). ...
Children and youth with fetal alcohol spectrum disorder (FASD) have limited access to assessment, diagnostic, and treatment resources – a distinct disadvantage in meeting their care needs in Australia. Limited knowledge exists on the intersection of FASD, Indigeneity, racism, trauma, and child welfare involvement. Notably, the lack of support for children with FASD increases the risk of adverse outcomes, including incarceration, homelessness, mental health problems, and early mortality. Children with FASD are often cared for in the child protection system by kinship carers, many without a diagnosis or the benefits of FASD informed care. Rarely considered is the Australian response to FASD or the Aboriginal worldview on disability. Qualitative research was utilized to conduct semi-structured interviews with six carers of Indigenous children with FASD–three foster carers and three relative or kinship carers. Seven core themes identified by carers included: FASD awareness, caregiver health, advocacy for the child, mothers of the children with FASD, loss and grief experienced by the carer, social costs, and children in child protection care. Carers identified that limited resources existed to address the disabilities and care needs of children, including training and respite. Financial disparity exists with relative carers receiving less income than foster carers. Carers demonstrated advocacy, resiliency, and resourcefulness in providing care. A lack of knowledge of FASD and core resources in child welfare services were identified as major challenges in providing care. This research examined the caregiving experiences of foster and Aboriginal kinship carers, caring for children with FASD in child protection.
... This result suggests that the geometric puzzle test was capable of distinguishing cognitive performance between stunting-indicated children and children with typically normal development by revealing expected different outcomes in children with SG, who showed greater difficulty in figuring different shapes into the example models than their peers with no indication of growth faltering. Head circumference was known for indicating neurological development in infancy and early childhood [23] and also reflected nutritional background [24]. As a result of inadequate nutrition during golden 1000 days, children may show lower intellectual ability which can be observed in cognitive performance [24]. ...
Children with stunting have been associated with delayed brain development and poor cognitive performance by a lack of attentional control. The aim of the present study was to determine characteristics of stunting children based on theta (4-8 Hz), alpha (8-12 Hz) and beta (12-30 Hz) oscillation at anterofrontal (AF) and temporoparietal (TP). This research involved two groups: Stunting Group (SG, N=14) and Control Group (C; N=8) from East Nusa Tenggara. EEG was recorded during an eyes-open condition at baseline and puzzle task. Our result revealed alteration of theta oscillation in SG AF8 and TP10 during puzzle task, supporting role of theta oscillation in higher working memory loads although it was not accompanied by proper TP connectivity. Higher alpha and beta AF7 activity in SG compared to control group implying decreasing attentional processing and higher arousal. According to Laterality Index (LI), we revealed alteration in temporoparietal SG during puzzle task. These findings provide new insights about theta, alpha, and beta oscillation in stunting children may reflect that declining attentional functioning during the puzzle task leads to poor cognitive performance.
... F etal alcohol spectrum disorders (FASD) are typically diagnosed on the basis of prenatal alcohol exposure (PAE), brain anomalies including microcephaly (small head size), physical growth restriction (height and weight), facial dysmorphology, and neurobehavioral impairment. 1 Microcephaly (as determined by occipitofrontal circumference [OFC]) was a core finding in the earliest descriptions of fetal alcohol syndrome (FAS) 2 and is known to be associated with the degree of alcohol exposure. 3 Commonly-applied current diagnostic criteria for atypical brain volume include OFC £ 10 th percentile 4,5 or £ third percentile 6 as determined by physical measurement of the head. ...
... In one study of youth (5-19 years) with and without PAE, researchers found that in 55-66 percent of youth with PAE who had total brain volumes £ third percentile (9.7% of PAE group) or £ 10 th percentile (15.3% of PAE group), OFC was in the average range (ie, ³ 11 th percentile). 3 In addition, studies comparing OFC and IQ in PAE samples have found inconsistent results. 3,12 Together, these factors highlight the need for alternative, complementary approaches to characterizing anomalous brain volume associated with PAE. ...
... 3 In addition, studies comparing OFC and IQ in PAE samples have found inconsistent results. 3,12 Together, these factors highlight the need for alternative, complementary approaches to characterizing anomalous brain volume associated with PAE. ...
... Fetal exposure to all three substances has overlapping effects including low birth weight, lower brain volumes and cognitive deficits (Ekblad et al., 2010;Rivkin et al., 2008;Treit et al., 2016). That alcohol and tobacco are legal does not mean that they are safer than illicit drugs (Ross et al., 2015). ...
Objective: The objective of the present study was to examine whether exposure to prenatal psychoactive substances is associated with psychological outcomes and deviant behaviour. Methods: This was a secondary analysis of 7,769 mother-child dyads in the Avon Longitudinal Study of Parents and Children (ALSPAC) who were followed until the children were aged approximately 12 years. Parental characteristics and maternal use of various substances were collected in pregnancy and entered as predictors of psychological outcomes in childhood and deviant behaviours in early adolescence. The psychological outcomes were IQ, social cognition, working memory and inhibition, while the deviant behaviours were threatening others, truancy and cruelty to animals. Weighted logistic regression models were used to predict deviant behaviours and weighted linear regression for the psychological outcomes. Results: High prenatal alcohol exposure predicted truancy and cruelty to animals. Tobacco exposure predicted lower IQ, a greater social communication deficit, lower working memory, truancy and threatening others. Illicit drugs predicted a higher social communication deficit and truancy. All prenatal substance exposures remained significant after adjustment for peer influences and covariate imbalance. Conclusion: Alcohol, tobacco and illicit drugs were associated with deviant behaviours in early adolescence and these behaviours were preceded by psychological deficits in childhood. The present study supports the guideline that no amount of alcohol is safe to consume in pregnancy and that tobacco and illicit drugs should be avoided.
... In the FASD population with brain growth deficiency (Archibald et al., 2001;Astley et al., 2009;Rajaprakash et al., 2014;Treit et al., 2016;Boronat et al., 2017), brain size must be properly considered Comparison of length and thicknesses of singular points. Group effect (control, FAS and NS-FASD) on ANOVA. ...
Introduction
Fetal alcohol spectrum disorders (FASD) range from fetal alcohol syndrome (FAS) to non-syndromic forms (NS-FASD). The neuroanatomical consequences of prenatal alcohol exposure are mainly the reduction in brain size, but also focal abnormalities such as those of the corpus callosum (CC). We previously showed a narrowing of the CC for brain size, using manual measurement and its usefulness to improve diagnostic certainty. Our aim was to automate these measurements of the CC and identify more recurrent abnormalities in FAS subjects, independently of brain size reduction.
Methods
We developed a fast, automated, and normalization-free method based on spectral analysis to generate thicknesses of the CC continuously and at singular points (genu, body, isthmus, and splenium), and its length (LCC). We applied it on midsagittal section of the CC extracted from T1-anatomical brain MRI of 89 subjects with FASD (52 FAS, 37 NS-FASD) and 126 with typically development (6–20 y-o). After adjusting for batch effect, we compared the mean profiles and thicknesses of the singular points across the 3 groups. For each parameter, we established variations with age (growth charts) and brain size in the control group (scaling charts), then identified participants with abnormal measurements (<10th percentile).
Results
We confirmed the slimming of the posterior half of the CC in both FASD groups, and of the genu section in the FAS group, compared to the control group. We found a significant group effect for the LCC, genu, median body, isthmus, and splenium thicknesses (p < 0.05). We described a body hump whose morphology did not differ between groups. According to the growth charts, there was an excess of FASD subjects with abnormal LCC and isthmus, and of FAS subjects with abnormal genu and splenium. According to the scaling charts, this excess remained only for LCC, isthmus and splenium, undersized for brain size.
Conclusion
We characterized size-independent anomalies of the posterior part of the CC in FASD, with an automated method, confirming and extending our previous study. Our new tool brings the use of a neuroanatomical criterion including CC damage closer to clinical practice. Our results suggest that an FAS signature identified in NS-FASD, could improve diagnosis specificity.
... The experimental pipeline used in this article, from the imaging techniques to the data analysis strategy, are applicable to any rodent model and potential therapeutic compound, allowing the integrated investigation of other therapeutic compounds and DS models that more faithfully replicate the genetic condition of DS, such as the TcHSA21rat and TcMAC21 mouse model (Kazuki et al., 2020 ;Kazuki et al., 2022 ). Furthermore, the simultaneous direct and indirect effects of potential therapeutic agents could be investigated in an integrated manner for other disorders and syndromes with multi-systemic alterations such as Apert, Pfeiffer and Crouzon craniosynostosis syndromes (Caputo et al., 2016 ;Fernandes et al., 2016 ;Monteagudo, 2020 ;Nopoulos et al., 2007 ;Pirozzi et al., 2018 ;Roberts et al., 2012 ;Treit et al., 2016 ;Vogels & Fryns, 2006 ;Wilhoit et al., 2017 ;Wozniak et al., 2019 ), considering the associated effects in different systems. ...
Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, reduced bone mineral density, neurodevelopmental delay, hyperactivity, and impaired long-term memory with altered hippocampal metabolite concentration and gene expression. However, Ts65Dn mice showed milder phenotypes than previously described, suggesting a drift of the mouse model. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.
... For example, Jacobson et al. (2017) reported significantly smaller corpus callosum in infants subsequently diagnosed with FAS (n = 43) relative to controls. Previous studies revealed total brain volume reductions in gray and white matter in individuals with PAE relative to controls (Archibald et al., 2001;Inkelis et al., 2020), with reports of total brain volume decreases in the pFAS/FAS groups (Archibald et al., 2001;Treit et al., 2016). In addition, Sowell et al. (2002b) showed regional increases in gray matter (GM) volumes in FASD participants. ...
... A strength of the current study is the almost equal representation of males and females and the equal distribution of FASD subtypes and control groups across age. Additionally, the participants were recruited from one site, which likely reduced variability in diagnostic criteria and variability in scanner protocols relative to prior multi-site studies (Roussotte et al., 2012;Yang et al., 2012a;Treit et al., 2016;Zhou et al., 2018). Despite being relatively large, the FASD sample size remains a limitation of the current study due in part to the inherent variability in alcohol exposure that is present in human studies of FASD. ...
Introduction
The teratogenic effects of prenatal alcohol exposure (PAE) have been examined in animal models and humans. The current study extends the prior literature by quantifying differences in brain structure for individuals with a fetal alcohol spectrum disorder (FASD) compared to typically developing controls, as well as examining FASD subtypes. We hypothesized the FASD group would reveal smaller brain volume, reduced cortical thickness, and reduced surface area compared to controls, with the partial fetal alcohol syndrome (pFAS)/fetal alcohol syndrome (FAS) subtypes showing the largest effects and the PAE/alcohol-related neurodevelopmental disorder (ARND) subtype revealing intermediate effects.
Methods
The sample consisted of 123 children and adolescents recruited from a single site including children with a diagnosis of FASD/PAE (26 males, 29 females) and controls (34 males, 34 females). Structural T1-weighted MRI scans were obtained on a 3T Trio TIM scanner and FreeSurfer v7.2 was used to quantify brain volume, cortical thickness, and surface area. Analyses examined effects by subgroup: pFAS/FAS (N = 32, Mage = 10.7 years, SEage = 0.79), PAE/ARND (N = 23, Mage = 10.8, SEage = 0.94), and controls (N = 68, Mage = 11.1, SEage = 0.54).
Results
Total brain volume in children with an FASD was smaller relative to controls, but subtype analysis revealed only the pFAS/FAS group differed significantly from controls. Regional analyses similarly revealed reduced brain volume in frontal and temporal regions for children with pFAS/FAS, yet children diagnosed with PAE/ARND generally had similar volumes as controls. Notable differences to this pattern occurred in the cerebellum, caudate, and pallidum where children with pFAS/FAS and PAE/ARND revealed lower volume relative to controls. In the subset of participants who had neuropsychological testing, correlations between volume and IQ scores were observed. Goodness-of-Fit analysis by age revealed differences in developmental patterns (linear vs. quadratic) between groups in some cases.
Discussion
This study confirmed prior results indicating decreased brain volume in children with an FASD and extended the results by demonstrating differential effects by structure for FASD subtypes. It provides further evidence for a complex role of PAE in structural brain development that is likely related to the cognitive and behavioral effects experienced by children with an FASD.
... Patients with alcoholism exhibited cognition deficits during alcohol withdrawal [3,4]. Moreover, extensive chronic alcohol consumption induced deficits in cognitive functions and morphology in the brain regardless of age [5,6]. Many studies using rodents also found that chronic alcohol administration induces deficits in spatial working memory and neuroinflammatory damage [7e10]. ...
Background:
Alcohol is one of the most commonly used psychoactive drugs. Due to its addictive characteristics, many people struggle with the side effects of alcohol. Korean Red Ginseng (KRG) is a traditional herbal medicine that is widely used to treat various health problems. However, the effects and mechanisms of KRG in alcohol-induced responses remain unclear. Therefore, the purpose of this study was to investigate the effects of KRG in alcohol-induced responses.
Methods:
We investigated two aspects: alcohol-induced addictive responses and spatial working memory impairments. To determine the effects of KRG in alcohol-induced addictive responses, we performed conditioned place preference tests and withdrawal symptom observations. To assess the effects of KRG in alcohol-induced spatial working memory impairment, Y-maze, Barnes maze, and novel object recognition tests were performed using mice after repeated alcohol and KRG exposure. To investigate the potential mechanism of KRG activity, gas chromatography-mass spectrometry and western blot analysis were performed. Results: KRG-treated mice showed dose-dependent restoration of impaired spatial working memory following repeated alcohol exposure. Furthermore, withdrawal symptoms to alcohol were reduced in mice treated with KRG and alcohol. The PKA-CREB signaling pathway was activated after alcohol administration, which was reduced by KRG. However, the levels of inflammatory cytokines were increased by alcohol and decreased by KRG.
Conclusion:
Taken together, KRG may alleviate alcohol-induced spatial working memory impairments and addictive responses through anti-neuroinflammatory activity rather than through the PKA-CREB signaling pathway.
