Are attention-deficit/hyperactivity disorder (ADHD) medications associated with the risk of cardiovascular disease (CVD)?This systematic review and meta-analysis based on 19 observational studies with more than 3.9 million participants suggested that there was no statistically significant association between ADHD medications and the risk of cardiovascular events among children and adolescents, young and middle-aged adults, or older adults.Despite no statistically significant association between ADHD medications and CVD, more evidence is needed for the potential risk of cardiac arrest and tachyarrhythmias, the cardiovascular risk in female patients and in those with preexisting CVD, and long-term risk. This systematic review and meta-analysis provides an updated synthesis of evidence on whether attention-deficit/hyperactivity disorder (ADHD) medications are associated with the risk of a broad range of cardiovascular diseases (CVDs). Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.Nineteen studies , of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years . Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents , young or middle-aged adults , or older adults . No significant associations for stimulants  or nonstimulants  were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias , cerebrovascular diseases , or myocardial infarction . There was no associations with any CVD in female patients  and in those with preexisting CVD . Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use. Longitudinal observation studies evaluating serious cardiovascular outcomes associated with ADHD medication use have emerged during the last decade, but with mixed findings.12 A review paper incorporating five large population-based studies in the US reported no association between stimulants and serious cardiovascular events in children.13 A meta-analysis of only 3 studies14 found no increased risk of arrhythmic and ischemic cardiac events but a decreased risk of stroke. A more recent meta-analysis of 10 studies15 showed a positive association between ADHD medications and risk of sudden death or arrhythmia but not for stroke, myocardial infarction, or all-cause mortality. However, it had several methodology limitations . Moreover, several new original studies have been published after these meta-analyses.20 Thus, an updated synthesis is needed to address those limitations as well as to include a broader range of cardiovascular events  and conduct sub-analyses by type of cardiovascular events and ADHD medications. In addition, observational studies that evaluate the benefits or risks of medical treatments are prone to bias  if not conducted appropriately. It is therefore critical to make a rigorous quality assessment of the available studies and discuss common problems that future studies need to address. Understanding whether, and to what extent, ADHD medications are associated with CVD is highly relevant from both clinical and public health perspectives, as an increasing number of individuals are receiving ADHD medications globally. Findings of any significant association would prompt research on underlying causal mechanisms .21While evidence from randomized clinical trials (RCTs) suggests ADHD medications are efficacious in reducing core ADHD symptoms,The current study aims to provide a comprehensive and updated systematic review and meta-analysis to assess the associations between ADHD medications and risks of a broad range of cardiovascular events. In addition, we aim to examine whether there is any difference in the associations by types of ADHD medication, types of cardiovascular events, sex, age, and preexisting CVD conditions.MOOSE) checklist.22 Our protocol is registered in the International Prospective Register of Systematic Reviews (CRD42021283702).23This study was conducted and reported according to the Meta-analyses of Observational Studies in Epidemiology . Discrepancies were resolved through discussion with a senior investigator (L.L.).The following information was extracted from each study for the qualitative and quantitative synthesis: first author, year of publication, sample size, data source, study country, age and sex distribution, study design, year of original data collection, follow-up time, type of ADHD medication, measure of medication use, definition of CVD, relative risk, and covariate adjustment. Two investigators conducted the data extraction separately (L.Z. and H.Y.), and any disagreements were resolved through discussion with a senior investigator (L.L.).24 Unlike the commonly used Newcastle-Ottawa Scale,25 the GRACE checklist is tailored for evaluating the quality of observational studies that examine the outcomes of medical treatment. It evaluates the quality of observational research based on the use of concurrent comparators, equivalent measurement of outcomes in different groups, collection of data on confounders and effect modifiers, risk of immortal time bias, and reporting of sensitivity analysis.24 Eleven items in the GRACE Checklist are grouped into 2 groups reflecting the quality of data and methods (eTable 2 in the Good Research for Comparative Effectiveness (GRACE) checklist version 2 was used for quality assessment.27 We used random-effects models to account for heterogeneity between studies. The significance of heterogeneity across studies was examined using Cochran Q test, while the percentage of variation attributed to true heterogeneity was estimated using the inconsistency index (I2).28 The restricted maximum likelihood method was used to estimate between-study variability, with the Hartung-Knapp-Sidik-Jonkman confidence interval for the summary estimates.30The characteristics of all included studies were described. Hazard ratios (HRs) from Cox regression, incidence rate ratios (IRRs) from Poisson regression, and odds ratios (ORs) from logistic regression were combined as approximations to relative risks (RRs), because under rare event assumption, different effect measures would yield mathematically similar estimates.P < .05, and all tests were 2-tailed.We meta-analyzed adjusted RRs across all studies and by age groups . To evaluate each study’s influence on the pooled estimates, the leave-one-out analysis was conducted. Publication bias was first assessed through visual inspection of the funnel plot and then tested quantitatively with Egger test. Subgroup analyses were conducted to investigate the associations of (1) stimulant and nonstimulant medications with any CVD, (2) ADHD medications with specific CVD , (3) stimulant ADHD medications with specific CVD, (4) ADHD medications with any CVD in individuals with and without a history of CVD, and (5) ADHD medications with any CVD by sex. All analyses were performed with Stata version 16.0 (StataCorp). Statistical significance was set at 40 A total of 3 931 532 participants from 6 countries or regions  were included. The study samples included children, adolescents, and adults, and 60.9% of participants were male. Average follow-up time ranged from 0.25 to 9.5  years. Most studies (14) were cohort studies,40 followed by 3 nested case-control studies,31 and 2 self-controlled case series.38 The most common data source was insurance claims databases (15 studies).39 More than half of the studies (10) used incident users,39 while others included prevalent users.40 Most studies used International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision  to define CVD, except 1 study34 that used self-reported CVD and another40 without sufficient information on outcome measurement. Absolute risks of CVD in the included studies are shown in eTable 4 in the 38 further accounted for unmeasured confounders that are time invariant. The GRACE quality scores ranged from 5 to 11 . Immortal time bias and lack of meaningful sensitivity analyses were the most common limitations in studies with lower scores . When restricting to specific effect measurements, heterogeneity was not significant for the analysis with HR as effect measures, yet it was still significant in other subgroups , young and middle-aged adults , older adults  , or overubgroups . As showubgroups , the estubgroups .In subgroup analyses, we found no statistically significant associations of stimulant  and nonstimulant medications  with any CVD . When ex40 with long-term follow-up both showed elevated risk  in those with a history of CVD  and male  patients. . We founTo our knowledge, this is the most comprehensive systematic review and meta-analysis of longitudinal observational studies on the association between ADHD medication use and the risk of CVD. By pooling results of 19 studies, we found no statistically significant association between ADHD medication use and CVD among children and adolescents, young and middle-aged adults, or older adults, although the pooled RR did not exclude a modest risk increase, especially for the risk of cardiac arrest or tachyarrhythmias. We did not detect any difference in the cardiovascular risk between stimulant and nonstimulant ADHD medication use. There was no association between ADHD medication and any CVD among female patients and those with preexisting CVD, although further study may be needed in these populations.15 Unlike the previous meta-analyses, we did not include all-cause mortality in our primary outcome (but sudden cardiac death), as previous studies have shown that most of the mortality in patients with ADHD was due to unnatural causes .42 We examined a broad range of cardiovascular outcomes including important cardiovascular outcomes  in addition to those examined in previous meta-analyses . We found no statistically significant association between ADHD medication use and CVD among children and adolescents, young and middle-aged adults, or older adults, although the confidence interval could not exclude an increased risk. It should be noted that as the absolute risk is relatively low, even a significant RR of 22% risk increase in general would possibly be offset by the benefits of medications, eg, alleviating ADHD symptoms and reducing risky behavior.43 The trade-off between benefits and risks could be different in high-risk patients. Regarding specific cardiovascular outcomes, results from previous meta-analyses for specific cardiovascular outcomes  are inconsistent.15 We found that ADHD medication use seemed to be associated with an increased risk of cardiac arrest or tachyarrhythmias, but not with cerebrovascular disease and myocardial infarction.This updated meta-analysis enabled us to include 13 more studies than the previous meta-analyses.44 compared the cardiovascular risks of a stimulant ADHD medication (dexmethylphenidate) vs a nonstimulant ADHD medication guanfacine. The study found that dexmethylphenidate was associated with increased systolic blood pressure, while guanfacine was associated with decreased heart rate, but both returned to baseline value during the 1-year open-label extension phase. It suggests that there might be differences in cardiovascular risks between stimulants and nonstimulants, but these differences may attenuate over time, thus not leading to a significant difference in clinically relevant outcomes. Nevertheless, head-to-head comparison studies based on observational data are warranted to compare stimulant vs nonstimulant ADHD medications regarding the risk of specific CVD.We also reported several findings that were not explored in previous meta-analyses. In terms of types of ADHD medication, we found both stimulant and nonstimulant ADHD medications were not statistically significantly associated with any CVD, with similar pooled RRs. These would suggest similar null effects on CVD or similar degree of confounding in studies of both stimulants and nonstimulants. We were unable to compare stimulants vs nonstimulants for the risk of specific CVD due to the limited number of studies that examined nonstimulants. Of note, 1 previous open-label extension of an RCT study45 Despite the lack of data supporting CVD history as a contraindication for ADHD medications, the FDA labeling includes a warning on the use of ADHD medications among individuals with structural cardiac abnormalities or other serious heart problems. Current treatment guidelines generally recommend carefully assessing patients with ADHD  and identifying individuals at risk before initiating ADHD medications.45 Careful monitoring should also be performed after initiation.47 Further studies focusing on the potential modifying risk of preexisting CVD, ideally separating risks for congenital or acquired CVD, are warranted. Clinical guidelines on prescribing ADHD medications among high-risk individuals should be updated once further evidence is available. We also found the point estimates for risk of CVD seemed to be higher among female compared with male patients, although only 3 studies have examined the sex-specific association along with high heterogeneity between studies. Previous research has shown that females with ADHD have somewhat different patterns of comorbidities49 and response to stimulants50 than males, and additional research is needed to examine this potential sex difference.We found that the risk of cardiovascular events associated with ADHD medications seemed to be higher among those with preexisting CVD compared with no prior CVD, although the findings did not reach the threshold for statistical significance. This coincides with raising concerns that individuals with congenital or acquired CVD are predisposed to additional risk.51 One key issue is that treatment is not randomly assigned, which could result in confounded estimates. The included studies mainly reflected practice in clinical settings rather than controlled settings, so the prescription of ADHD medications is influenced by the clinician’s perception of CVD risk. Most studies adjusted for a range of measured confounders, but the included confounders varied across studies. Many studies adjusted for demographic characteristics, and several adjusted for baseline comorbid conditions  and comedications , yet few studies accounted for time-varying confounding factors. Moreover, several studies used general population control  as the comparison group, but only 1 study9 adjusted for ADHD status. Not accounting for ADHD status would lead to bias, as recent research found that ADHD itself is a risk factor for CVD independent from comorbid psychiatric and somatic conditions.52The analysis of observational data provides an emerging opportunity to generate evidence to inform clinical decisions, but there are important issues to consider to avoid biases.51 Nine of the 19 included studies40 used prevalent users instead of incident users, and 7 studies37 were at risk of immortal time bias. Misclassification and exclusion of the so-called immortality period would necessarily bias the results toward favoring the treatment.53 Unlike lack of randomization, these flaws can be easily prevented by study design, eg, explicitly emulating a pragmatic target trial.54 Moreover, most of the included studies (17 of 19) had an average follow-up time of up to 2 years. Only 2 studies had sufficient follow-up time to examine the long-term cardiovascular risk associated with ADHD medication, but these studies were only moderate in their quality . Thus, further studies with rigorous methods are needed to evaluate the long-term risk of CVD associated with ADHD medication use.In addition, other fundamental flaws, such as selection bias and immortal time bias, need to be considered carefully when interpreting results from observational studies.Overall, our meta-analysis provides reassuring data on the putative cardiovascular risk with ADHD medications, but the possible associations with cardiac arrest or tachyarrhythmias, among female patients, and among those with preexisting CVD warrants further investigation. Importantly, our findings are presented at the population level; in clinical practice, specific individuals with ADHD might be particularly prone to negative cardiovascular outcomes; therefore, clinicians should discuss with their patients and families the possible cardiovascular risk of ADHD medication in light of the latest evidence, and they should rigorously follow clinical guidelines that suggest monitoring of blood pressure and heart rate at baseline and each medication review.55 When restricting to specific cardiovascular outcomes, heterogeneity was not significant for the analysis on CVDs, yet it was still significant in the subgroup analyses by sex and preexisting CVD. Second, due to a lack of data, we were unable to compare the associations with specific ADHD medications. Third, as few studies have information on dosage and duration of medication use, investigation of the dose-response association was not possible. Fourth, although the GRACE checklist is validated for evaluating the quality of observational studies of medical treatment, a total score approach for risk of bias assessment needed to be validated. Additionally, most of the included studies were conducted in the United States and Europe, which means the results may not generalize to other settings.There are several limitations to consider when interpreting the results. First, heterogeneity was high and significant for most analyses. Although this heterogeneity does not invalidate our results, it indicates that the pooled RR cannot appropriately summarize results from all individual studies and should therefore be interpreted with caution.The results of this meta-analysis suggested no statistically significant association between ADHD medication use and the risk of any cardiovascular events across age groups, although a modest risk increase could not be excluded, especially for the risk of cardiac arrest or tachyarrhythmias. Our study also warrants future studies with rigorous study designs to investigate the risk of cardiovascular events among female patients and among those with preexisting CVD, as well as the long-term risk of ADHD medication use.


Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and heritable childhood behavioral disorders. Although a number of ADHD-susceptible regions had been identified, details about the variations of genes and their related patterns involved in ADHD are still lacking. In this study, we collected 25 Chinese parents–offspring trios, each of which consisted of a child diagnosed with ADHD and his/her unaffected parents, and analyzed the variations from whole-genome sequencing data. SNVs in reported ADHD-susceptible regions and on the genes whose functions were related to dopamine were screened, and we identified a set of variants with functional annotations which were specifically detected in ADHD children, including most SNVs in the gene coding region that might impair protein functions and a few SNVs in promoter or 3′ untranslated region (3′-UTR) that might affect the regulation of relative gene expression in a transcriptional or posttranscriptional level. All the information may further contribute to the understanding, prediction, prevention, and treatment of ADHD in clinical. Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and heritable childhood behavioral disorders, which affects 2%–6% of school-age children . ADHD isClassical genetic studies indicate that ADHD is strongly heritable, with an estimated heritability for childhood ADHD on an average of 75% . In the Apparently, the genetic basis of ADHD is highly heterogeneous. Although a number of ADHD-susceptible regions had been identified with more or less overlaps in several studies, details of the variations of genes and their related patterns involved in ADHD, particular in East Asian populations, are still lacking. In this study, a cohort of 25 Chinese parents–offspring trios, in which each trio consisted of a child diagnosed with ADHD and his/her unaffected parents, were collected, and whole-genome sequencing (WGS) was performed; a set of novel variants associated with ADHD were identified through the systematic screening on this cohort.The cohort consisted of 25 parents–offspring trios. Within each trio, the child was clinically diagnosed as an ADHD patient, while his/her parents were presented with no history of ADHD. All samples were collected from West China Mental Health Center. This study was approved by the Ethics Committee of Chongqing Ninth People’s Hospital. Informed consent for DNA analysis was obtained from each family in line with local institutional review board requirements at the time of collection.Genomic DNA extracted from peripheral blood of each sample was fragmented to an average size of ∼350 bp and subjected to DNA library construction using established Illumina paired-end protocols. The Illumina Novaseq 6000 platform  was utilized for genomic DNA sequencing in Novogene Bioinformatics Technology Co., Ltd.  to generate 150-bp paired-end reads, with a minimum coverage of 10× for ∼90% of the genome (mean coverage of 30×).After sequencing, conversion and demultiplexing of Illumina Base Call Files (bcl files) were performed with bcl2fastq software (Illumina). The resulting fastq data were submitted to in-house quality control software for removing low-quality reads and then were aligned to the reference human genome (GRCh37/hg19) using the Burrows–Wheeler Aligner , and dupSingle-nucleotide variants (SNVs) and indels were called with Samtools  to generhttps://www.encodeproject.org/). Gene enrichment assays were performed with the R clusterProfiler package  or form homozygotes (homo_inherit) in ADHD children, but were not found in certain genotypes of unaffected parents in the whole cohort, were kept and considered as the potentially ADHD-susceptible sites. The distribution of these sites in gene body regions and regulatory regions (promoters) is shown in As expected, none of the 25 ADHD children in the cohort carried any explicit pathologic or likely pathologic variants. Alternatively, the frequencies of all single-nucleotide variants (SNVs) located in the reported ADHD-susceptible regions in the human genome are shown in Among all the filtered SNVs, the influence of gene coding region (exons) variations on protein functions was predicted by the Polyphen2_DHIV program and annotated as benign, possibly damaging, or probably damaging . Genes ccis-element recognized by certain transcriptional regulators. Among all filtered SNVs in this cohort, only two variants in the promoter regions and one variant in 3′-UTR were annotated to impact certain cis-elements  may interfere with the motifs for mRNA–miRNA mutual recognition and variants in promoter region may change the elements  and the elements , respectelements , suggestelements . Other dcis-elements or miRNA-targeting sites. Detailed information of this part of SNVs is listed in On the other hand, the pathogenesis of ADHD has been closely associated with the dopamine-related processes . Herein,de novo and homozygous variants specifically detected in ADHD children are more likely to contribute to the pathogenesis of ADHD. With such criteria, we screened the SNVs in two sections: the SNVs in the reported ADHD-susceptible regions and the SNVs on genes that play dopamine-related functions (de novo variation events.Attention-deficit/hyperactivity disorder (ADHD) is generally described as a multifactorial genetic disorder; however, the genetic basis of its pathogenesis is less studied. Although a set of susceptible regions have been identified based on linkage analysis in several independent cohorts, such as 4p16.1, 5p12-13, 6q12-14, 10q26, 11p15.5, 11q25, 12q23, 16p13, 17p11, and 20q13 , the knounctions . Among ade novo variations in this cohort, and allele frequency (AF) of neither site was included in the Chinese or East Asian population in the 1000 Genomes database, implying the very low frequency of these variants. Particularly, the variant of rs866882393, which eliminates the PAX5-binding motif in the promoter region of WFS1, was recurrently detected in three ADHD children, and it has been reported that the expression of WFS1 is closely correlated with neuronal differentiation (In this study, identified functional SNVs in promoter regions contain rs67529412 and rs866882393 corresponding to ZNF598 and WFS1, respectively. Notably, both of these sites were ntiation . rs11734β-catenin-independent neurotransmitter release (de novo variations, and the gene functions are related to the dopaminergic neuron development and the dopamine receptor signaling pathway, respectively.Identified functional SNVs in gene coding regions that may impair protein functions are many. Among these sites, corresponding genes, CACNA1H, PKD1, DYNC2H1, LRP6, PPFIA4, TSPOAP1, ADCY6, FLNA, and LAMA2, are annotated to play central nervous system-related functions. Particularly, defects in synapse formation and function lead to various neurological diseases, and a recent study suggests that protein PKD1 functions upstream of N-cadherin, a classical synaptic adhesion molecule, to promote functional synapse formation . CACNA1H release , and a g release . MoreoveAlthough this study cannot give the full view of the genetic basis of ADHD, it provides a series of novel insights for the understanding of ADHD in the Chinese population. Taken together, in this study, in a cohort containing 25 ADHD trios, we identified a set of SNV variations specifically in ADHD children and annotated to be functional for gene expression regulation or protein function, and linked some of these sites to the reported ADHD-susceptible regions or dopamine-related functions based on the annotation of their corresponding genes. All the information may further contribute to the understanding, prediction, prevention, and treatment of ADHD in clinical.


A growing body of research has been focusing recently on the life and well-being of students with attention-deficit/hyperactivity disorder (ADHD) and also on the well-being of their teachers. However, there is a need for in-depth, qualitative insights into ADHD issues from the teachers’ perspectives. Therefore, the main aim of this qualitative study was to use thematic analysis to explore how teachers perceive the relationship with students with ADHD and the factors that influence the quality of this relationship. Sixteen teachers working with adolescent ADHD students were interviewed for this purpose. The results indicate that the quality of the teacher-ADHD student relationship is associated with the ADHD students related behaviours, ambivalent emotions of the teacher, the teacher’s beliefs about ADHD and the beliefs about the determinants of the behaviour of the students with ADHD and the teacher’s approaches and methods of work in the classroom. Furthermore, the results suggest that increasing the quality of the teachers’ well-being is associated with knowledge of ADHD determinants, regulation of ambivalent emotions, empathy, teachers’ ability to perceive positive qualities and the potentials of the students with ADHD and their motivation to teach ADHD students. Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children worldwide , which was developed by researchers at the University of Oxford  study of scientific literature, (b) compilation of interview schedule and advisory panel, (c) pilot study, (d) clarifying of interview schedule, study plan and participant recruitment strategy, (e) participant recruitment, (f) data collection, (g) data coding, data analysis , (h) production of the final report. The final report of DIPEx provides a thematically structured lived experience of participants, e.g., how the disease affects family life, work, education and leisure, how to manage the disease or how professional care can be improved. The acquired knowledge is used in health policy and can influence changes in health or social care.The present study followed the qualitative approach aiming to assess the experience of participants, as described by O’Connor and McNicholas . These aPrior to recruiting participants, a semi-structured interview schedule was developed. The interview schedule was designed as an aid to researchers to remind them of the important themes that the participants may not have mentioned on their own. Interview schedule items were constructed based on recent studies concerning ADHD  from all regions of the Czech Republic. For a detailed description of the study sample, see, The inclusion criteria for participation in the study were: teachers working with students with ADHD aged 12–14 years, at least 2 years of teaching experience in teaching students with ADHD, teachers were informed about the diagnosis of ADHD by the parents of the students with ADHD, ADHD in students diagnosed by clinical psychologists in accordance with DSM-5  and indirect  recruitment strategy. Direct recruitment was carried out through advertisements in periodicals of magazines. The indirect recruitment method was based on the snowball method Noy, . It was The snowball method was used in our research with full knowledge of its advantages, disadvantages , such as “working with a student with ADHD”, “students with ADHD”, “symptoms of ADHD”, etc. Some passages of the texts were marked with multiple codes because they contained multiple meanings. The resulting list of thematic codes and sub-codes was then assessed using the NVIVO 12 program. Researchers made a node of the same name for each thematic code and inserted the appropriate sub-nodes for each. For example, under the node “student with ADHD” there were sub-nodes “problems of a student with ADHD”, “self-perception of student with ADHD”, “relationships of students with ADHD”. In the second phase, the transcript files of the interviews were uploaded by researchers to the program NVIVO 12. Consequently, researchers sorted and inserted the text of the transcripts under the relevant nodes and sub-nodes. At this phase, the researchers continuously discovered some other sub-nodes (sub-codes) that enriched the already existing tree of sub-nodes. For a detailed description of the system of thematic codes (nodes) and sub-thematic codes (sub-nodes), see, Subsequently, the researchers read the texts assigned under the nodes and sub-nodes. They wrote the participants’ statements out on a clean paper and marked them with identification labels to visualize which participants were involved. Next, the statements were cut and, based on their relation, placed side by side. Thus, the researchers created several clusters and labelled them by abstracting a more general meaning of the statements. Furthermore, the researchers looked for thematic connections between the statements within one cluster and thematic connections between clusters and between the statements of different clusters. For a detailed description of the frequency of themes, see, The structure and content of the results were based on these themes. The starting point of the result´s structure was chosen on the basis of the theme “the teacher’s strong ambivalent bond with students with ADHD”, because this theme emerged explicitly and implicitly from all clusters. This theme also became the label of the first subsection of the results and included the themes “negative emotions in relation to students with ADHD” and “positive emotions in relation to students with ADHD”. The following subsections of the results are “ADHD as an excuse for inappropriate behaviour” and “the behaviours of children with ADHD perceived intentionally or unintentionally,” which present the content of the theme “experiences and beliefs influencing the quality of the teacher-student with ADHD relationship”. The final subsection of the results is the subsection “Improving the quality of the teacher-student with ADHD relationship”, which provides a description of the themes of the same name.The researchers compiled the structure of the results in such a way that the reader first gains insight into the factors that influence the ambivalent quality of the teacher-student with ADHD relationship and then into the factors that allow the improvement of the quality of the teacher-student with ADHD relationship.The research was guided by ethical rules and standards based on the DIPEX methodology of Oxford University. The ethical approach of the research was further ensured by the approval of the Ethics Committee of the Cyril and Methodius Faculty of Theology in Olomouc, number (2018/01), by training of all members of the research team on ethical issues, consulting on ethical issues with a supervisor, ethical experts at the university and the advisory panel. The advisory panel was also set up to help researchers refine participant recruitment strategies, interview schedules and the research process.First, the participants were informed of their rights in the research and they signed informed consent. Informed consent procedures involved written information sheets that were given to participants, verbal information, and opportunities to ask questions prior to participation in the study. Participants were also informed that they can withdraw from the study at any stage and that they will have an opportunity to authorize an anonymized version of texts. Next, the participants were given the researchers’ contact details and received reimbursement for their time.Regarding the handling of the information, the audio recordings and the transcripts were stored securely in accordance with relevant legal requirements and with current Czech and European legislation on personal data protection  with ADHD overused the diagnosis of ADHD. In a way, such labelling allows students diagnosed with ADHD not to accept guilt for the negative consequences of their disruptive behaviour because it is believed that ADHD causes the disruptive behaviour. Participant Milos complained that some parents and their children with ADHD constantly made excuses that their child cannot be blamed for inappropriate behaviour because it is caused by ADHD. Parents and ADHD students were also hiding in the role of victims of bad behaviour by classmates, bad teachers’ methods that cause their child to behave inappropriately so that their child would not have to be held responsible for his behaviour and his parents for poor parenting. Milos described his experience and beliefs about the abuse of ADHD by some ADHD students and parents as follows:“He knows everything about his diagnosis and acts as if his ADHD entitles him to do whatever he wants and not learn anything he doesn’t want. He thus successfully avoids school duties and learning.”Several participants, such as Ivana, also reported abusing the diagnosis of ADHD by a student:The participants with this type of experience and beliefs about the students with ADHD and their parents more often reported a feeling of less closeness and tolerance in their relationships with those students because they did not believe that disruptive ADHD students’ school behaviour was conditioned by ADHD. These participants considered the personality of ADHD students to be spoilt by poor parenting. This means that those students deliberately avoid responsibility and put intentional resistance to educational efforts because they are used to doing only entertaining activities that bring them immediate satisfaction.“I feel that they know me well and know what bothers me and what they should not do. I’m sure they know that if they do something wrong, trouble will come. To be honest, I’m not convinced they can’t help themselves. They have no emergency brake.”Some participants reported experiences and beliefs that ADHD students understood their instructions and knew that their behaviour was inappropriate, but they are not able to control the behaviour and to behave according to the rules due to a higher level of impulsivity. In this sense, Ivana reported:The participants with these types of experiences and beliefs reported more closeness in the teacher-student with ADHD relationship and their efforts to tolerate and understand the students with ADHD and to empathize with them, because they perceived the disruptive behaviour as unintentional and as a consequence of the disorder, not as part of the students’ personality.I know that his behaviour is a symptom of ADHD, usually only after the outburst of a stronger rage. This does not happen with my own children who do not have ADHD. But then I also know of an ADHD boy who abuses the diagnosis of ADHD and claims that he can’t do any work because of it.”“A few participants expressed the belief that certain behaviour in children with ADHD was undoubtedly the symptoms of ADHD, and different behaviour was completely intentional and the diagnosis of ADHD was misused as an excuse. Evelina commented on this matter as follows:The participants with this type of belief often tried to distinguish between the boundaries of the behaviour caused by ADHD, and the behaviour caused by poor parenting. According to the participants’ personal opinion on, the distinction between behaviour caused by ADHD and by poor parenting may help to reduce conflicts in the relationship between the participants and their ADHD students. The conflict was reduced because the teachers stopped blaming the ADHD students for the ADHD-conditioned behaviour.“Working with him (ADHD student) was frustrating. I gave him a thousand percent of my attention and that’s completely exhausting. It happened to me that I blew up in a rage a few times, because you are doing your best and there are still problems and incidents with him, and that is annoying.”Most of the participants reported that they experience ambivalent emotions towards students with ADHD. Negative emotions were often evoked by the fact that working with students with ADHD was demanding and consuming a considerable amount of energy. Petra expressed this as follows:Other participants reported that the desire of the students with ADHD for a teacher’s attention is bottomless. Some teachers pointed out that they often feel overwhelmed by this, because they also have to work with thirty other students in the classroom.“Children with ADHD often surprise me and I am upset, but I try to think ahead. When I go to this lesson to meet this child, I have to mentally prepare for it and I have to tell myself, the problem may come, stay calm, you have to solve it calmly. You can’t yell at him, it won’t help him anyway, it won’t help anyone.”The participants emphasized that despite the strong negative emotions that students with ADHD sometimes evoke, it is necessary for the teacher to try to remain calm and think a few steps ahead. Such a teacher’s approach has the advantage of not destroying the closeness of the teacher-student with ADHD relationship through excessive negative emotions of the teacher and acute conflict. One of these participants reporting in this sense was Marta:It was really challenging and exhausting with him. It helped that I told him that we spent more time at school together during the week than his parents spent at home with him, and that together we had to figure out how to do it to feel better and work better together.”“With this attitude, the teachers set their consciousness to a “standby mode” in which they expect that the disruptive behaviour of a student with ADHD to occur, and that such behaviour needs to be responded to quickly but calmly. This way of mental preparedness allows teachers to alleviate their own shock from unexpected events, to better regulate strong emotions and also prevent the stress of a student with ADHD from a possible over-emotional reaction of the teacher. Other participants reported that their relationship with a student with ADHD improved when they agreed with a student with ADHD on what to do in order for the collaboration to work better. Josef expressed this as follows:The number of conflicts reduced when I explained to him that ADHD did not cause him to be unable to perform his duties, but that ADHD was only about being inattentive and in inner tension. It is therefore necessary to find a way to work with inattention and tension. I also tried to be a role model for him and honestly perform my duties.”“Such teachers’ approach is characterized by an offer of closeness and mutual responsibility in the teacher-student with ADHD relationship, teacher acceptance of a student with ADHD and an offer of more equal cooperation. Several participants were able to reduce conflicts in the teacher-student with ADHD relationship by explaining to an ADHD student that it is possible to respond to ADHD symptoms with more adaptable behaviour and also by trying to be a positive role model. Josef reported in this sense as follows:It took us about two years to understand what we can expect from each other, what works, what doesn’t work, and where we need to refine our cooperation.”“Furthermore, the quality of the teacher-student with ADHD relationship improved when the participants allowed the student to communicate openly about current needs. For example, one participant entered into an agreement with a student with ADHD based on mutual trust that a student with ADHD could truthfully tell that he was already overwhelmed by learning. In this case, the participants allowed the student with ADHD to walk or run down the hall. When the student relaxed, he returned to class. Most participants also reported that the quality of the teacher-student with ADHD relationship tends to gradually improve after several years of mutual cooperation because the teacher and the student get to know each other’s strengths and weaknesses and thus can respect each other more. Alena also described this as follows:This mutual attitude presupposes the will to try to re-establish closeness despite recurring conflicts.I tried to focus not only on the bad, but above all on the good. Praise him for it. Point it out. Show him that you also notice what he can do. One of those ADHD boys could draw beautifully. So I used it. When we were discussing a topic in a subject, I asked him to draw something on that topic. And he drew it very beautifully. And then he knew that I was interested in him and also that I would exhibit the pictures. And thanks to that, he knew that he was not just the boy who was naughty, he already knew that he could do something, and his classmates began to take him seriously and appreciate him.”“Some participants sought to improve the relationship with the students with ADHD by deliberately drawing attention to the positive skills of the students with ADHD. When teachers were able to take advantage of the positive qualities of a student with ADHD in behaviour of teaching the whole class, the quality of the teacher-student with ADHD relationship improved. This teacher’s approach also improved the self-esteem of the students with ADHD and class social status of the student with ADHD. Marie reported in this sense as follows:I feel satisfaction from it. Although the result is never completely perfect, I enjoy the work. And every little success does me good. It makes me happy to be able to work with children with ADHD.”“Some participants reported that their motivation to work on a good relationship with a student with ADHD is based on the joy of being able to make some progress and success with these students. Furthermore, the motivation is based on the desire to manage the challenge of working with ADHD students, to better understand the hidden causes of ADHD and to be a good professional. Marika put it this way:“I graduated from three universities focused on special pedagogy and I work perfectly with children with ADHD, I do not have any problems. And how do I experience a relationship with students with ADHD? I don’t experience it. It doesn’t make sense to deal with emotions. All you have to do is to do things right.”Two participants described their experiences with children with ADHD very confidently and conceitedly. They argued that they mastered the teaching of students with ADHD flawlessly and reported that they excluded all emotionality from the relationship with the students with ADHD. They also did not mention any conflicts with students with ADHD. These participants gave the researcher the impression that they were trying to protect their low professional self-esteem. Matej reported this in this way:The aim of this study was to assess the teachers’ perceptions of quality of their relationship with ADHD students and to gain insight into the factors that influence the quality of this relationship. We found that teachers often perceive ambivalent emotions to their ADHD students. Furthermore, our findings suggest that the quality of the teacher-ADHD student relationship is mainly influenced by the students´ behaviour, teachers’ beliefs and knowledge of ADHD, special abilities and talents of ADHD students, teachers’ respect to special educational needs and teachers’ motivation and resilience.Although most participants in our study reported positive emotions in relation to students with ADHD, the strength of the negative emotions was tangible, which is in line with the findings of other authors Ewe, . Ewe 20, ZendarsNevertheless, in our study, the participants described their relationship with ADHD students also in positive terms, such as joy, compassion, and love. These testimonies described how the teachers enjoyed the liveliness, creativity, authenticity, sense of humour and artistic talent of the students with ADHD. This is consistent with Sedgwick et al. , who conAltogether, our findings suggest that teachers are not only experiencing either positive or negative emotions towards their ADHD students, but that they often simultaneously experience a mixture of these emotions. These findings are in accordance with Anderson et al. , who furThe findings of the present study also point out that despite the presence of ambivalent emotions in the relationship of the teacher and ADHD student, the core of this relationship often consists of a strong social bond which may reduce or increase the quality of the relationship. If negative emotions take control over a teacher’s behaviour, a strong social bond can lead to a vicious circle of mutual accusation, hatred, aggression, and bullying, because the teacher may begin to perceive a student with ADHD as bad and intentionally harmful. This may also later lead to school failure, peer rejection, exclusion, loneliness and low self-esteem of students with ADHD Ewe, . In contOur findings also suggest that the teachers’ attitudes towards ADHD students are often burdened by the teachers’ beliefs that some of those students justified their selfish and oppositional behaviour and the inability to learn by suffering from ADHD. In such cases, some participants were hesitant about whether the ADHD students’ behaviour was due to ADHD or poor parenting. At the same time, the teachers who understood ADHD better were also more tolerant towards their ADHD students. Thus, the participants considered this distinction to be important because it determines the degree of closeness and conflict in the teacher-ADHD student relationship.. Our finding of a conflict between two opposing views of the causes of behaviour in ADHD students is consistent with recent labelling theory  and to eliminate the teachers’ stress experienced in teaching ADHD students. These activities may involve the teachers´ education regarding ADHD and their own personal support.The educational activities may involve refining the teachers´ beliefs and emotional attitudes regarding ADHD students through seminars introducing and explaining the various determinants of ADHD and the relevant methods of working with ADHD students. Teachers may also reduce the level of stress and increase the quality of the relationship with the ADHD students by being prepared for the disruptive behaviour of ADHD students. They should be taught to respond to such behaviour quickly but calmly and to monitor their emotions during the lessons. During emotionally-aroused situations, teachers should try to focus their attention on a possible solution of the problem rather than on their own feelings or on further stirring up negative emotions. Pre-prepared alternatives for solving critical situations in the classroom can also be helpful. Furthermore, teachers should reframe the expectations related to the ADHD students’ school achievement. It cannot be in general expected that the quality and way of school work of students with ADHD can reach the quality of students without ADHD. This means that sometimes even a small school achievement of students with ADHD can be proof of a very efficient work of teachers. If teachers are aware of this, it can protect them from stress, disillusion and disappointments that can arise from holding unrealistic expectations.Teachers could acquire these skills by attending seminars that could take place one weekend a year at the regional level at selected schools. These seminars could be led by psychologists, teachers, psychotherapists, special pedagogues with many years of experience working with ADHD students and researchers who study ADHD. Those professionals should provide the teachers with theoretical knowledge of ADHD, but also skills on how to build a stable teacher-ADHD student relationship and what methods, approaches and interventions to use when working with those students. The seminar should include exercises in addressing the disruptive behaviour of ADHD students. Professionals in the field of ADHD could imitate the behaviour of ADHD students at school, and teachers should try to respond to this behaviour with skills acquired from the theoretical part of the seminar. At the end of each exercise, there should be a discussion on what the teachers did well and where their skills need to be improved. We are of the opinion that the costs of the seminars would pay off in various forms for the state and schools. The seminars would increase the well-being of teachers, ADHD students, classmates and thus could reduce the state’s financial costs for professional health, psychological and social care.Furthermore, teachers should be educated in line with European Union and national policies for the education of students with special educational needs (Ministry of Education 2020). These policies recommend the use of adapted textbooks, specific teaching materials, compensatory and rehabilitation equipment and tools, support and behaviour services, additional support staff and additional teaching in specific subjects.The second set of activities may be represented by the teachers’ psychotherapy, behaviour or supervision, where the teachers may foster their own secure attachment. A secure attachment of the teachers may increase the sense of security and safety of the teachers, which increases resilience in stressful situations in the classroom and thus opens up the teachers’ capacity for a closer and warmer relationship with students with ADHD. Through supervision, the teachers may also refine their motivation for working with ADHD students. This professional support may help teachers to serve as positive role models for ADHD students and to focus on positive skills, traits and talents of students with ADHD.Future research could focus on a more detailed exploration of the factors that determine the teachers’ ambivalent emotions and the factors that help them to regulate these emotions. Specifically, it can focus on the relationship between the teachers’ ambivalent emotions and contextual factors such as the self-esteem and sense of competence of students with ADHD and teachers.The findings of this study suggest that the relationship between a teacher and an ADHD student is characterized by a strong bond despite the presence of ambivalent emotions. Negative emotions were found to be usually caused by the students’ disruptive behaviours driven by ADHD symptoms, by the long-term overload and stress of the teachers and their belief that the disruptive behaviour of ADHD students is intentional, and by abusing the ADHD diagnosis by ADHD students.Positive emotions were mainly related to the teachers’ efforts to understand the symptoms of ADHD and their knowledge in this area and sometimes elicited by the liveliness and creativity of the students with ADHD. Furthermore, an important role was also played by the teachers’ regulation of the ambivalent emotions, their ability to perceive positive qualities, talents and potentials of students with ADHD, motivation to manage teaching students with ADHD, and interventions that respect special educational needs of students with ADHD.Based on our findings, we recommend that teachers should complete seminars and trainings focused on theoretical knowledge of ADHD and practical skills on how to work and build stable and warm relationships with ADHD students. Furthermore, teachers could be recommended counselling, supervision or psychotherapy, where they can strengthen their secure attachment.Click here for additional data file.


Low birth weight (LBW) predisposes physical and mental growth failure and premature death among infants. Studies report that LBW predominately explains infant mortality. However, existing studies rarely demonstrate the phenomenon of both observed and unobserved factors, which may influence the likelihood of birth and mortality outcomes simultaneously. In this study, we identified the spatial clustering of the prevalence of LBW along with its determinants. Further, the relationship between of LBW and infant mortality, considering the unobserved factors, has been explored in the study.Data for this study have been extracted from the National Family Health Survey (NFHS) round 5, 2019-21. We used the directed acyclic graph model to identify the potential predictors of LBW and infant mortality. Moran’s I statistics have been used to identify the high-risk areas of LBW. We applied conditional mixed process modelling in Stata software to account for the simultaneous nature of occurrences of the outcomes. The final model has been performed after imputing the missing data of LBW.Overall, in India, 53% of the mothers reported their babies’ birth weight by seeing health card, 36% reported by recall, and about 10% of the LBW information was observed as missing. The state/union territory of Punjab and Delhi were observed to have the highest levels of LBW (about 22%) which is much higher than the national level (18%). The effect of LBW was more than four times larger compared to the effect in the analysis which does not account for the simultaneous occurrence of LBW and infant mortality . Also, in a separate analysis, the imputation technique has been used to address the missing data. Covariates’ effects showed that female children, higher order births, births that occur in Muslim and non-poor families and literate mothers were negatively associated with infant mortality. However, a significant difference was observed in the impact of LBW before and after imputing the missing values.The current findings showed the significant association of LBW with infant deaths, highlighting the importance of prioritising policies that help improve the birth weight of new-born children that may significantly reduce the infant mortality in India. India plays a crucial role in ending premature deaths as the nation carries the highest number of child mortality globally . Infant In India, approximately 83% of neonatal deaths occur due to complications from low birth weight (LBW) . PprevioThe etiology of LBW is not clearly understood. A study in South Africa demonstrated that the lack of antenatal care, hypertensive disorder during pregnancy, and previous cesarean delivery are associated with LBW . Also, m1, ε2) of each equation allowed to be correlated. Failing to include potential observed covariates in the model might lead to an unobserved heterogeneity (unobserved variability) in the response variable. For instance, potential covariates of LBW such as ‘maternal smoking during pregnancy, hypertensive disorder during pregnancy, which we cannot enter in our LBW model because of unavailability; thus, it remains unobserved and included in the idiosyncratic error term. Similarly, these factors may influence the mother’s behavior, a shared factor that influences the death of her child in an unobserved way.The study investigates the association between LBW and infant mortality. In the conceptual model, Fig. The National Family Health Survey (NFHS), round 5 is a nationally representative survey that collected information on a wide range of socio-demographic and health indicators, conducted from June 2019 to April 2021 across 36 states and union territories. Census enumeration areas have been considered the primary sampling unit at the first stage of the sampling frame. In the second stage, households have been randomly selected from the sampling frame’s primary sampling unit, ‘cluster’. The details of the sampling technique are published elsewhere . In the The NHFS has been conducted under the authority of the International Institute for Population Sciences (IIPS), under the Ministry of Health and Family Welfare. Ethical approval for the survey has been taken from the research ethics committee of the Ministry of Health and Family Welfare. Further, informed consent has been taken from each respondent before enrolling in the survey.Based on the question on the information of birth weight collected by the NFHS survey, LBW was defined as per the definition of the World Health Organization (WHO); with weight at birth less than 2500 grams. We created a dichotomous variable of birth weight based on the definition: ‘1’ for LBW and ‘0’ for no LBW.Infant mortality is defined as a child’s death before completing the first year of life . The surThe DAG model was used to establish a causal inference in epidemiology to illustrate how associations translate into causal relationships. Epidemiologists mostly use DAG model to identify the mediators and moderators of the casual relationship between predictor and outcome variables that is also useful to identify the actual covariates. In the DAG model Fig. , the bluInsti_deli = Institutional delivery, Fath_edu = Father’s education, Mom_edu = Mother’s Education, wealth = Wealth status of the household, smok_alco = Consumption of alcohol or smoking, F_secur = Food security, Sani = Sanitation facility of the household, Drin_water = Sources of drinking water, LBW = Low birth weight, preg_comp = Pregnancy complication, PTB = Preterm birth, ANC = Antenatal care, weight_gain = Weight gain during pregnancy, Age_mother = Maternal age at birth, nutria_edu = Nutritional education during pregnancy. Using the DAG model, we selected the explanatory variables to adjust the confounding pathways for the present study.Thus, the potential risk factors of LBW and Infant mortality were selected from the DAG model. Preterm birth was defined as ‘live births before completing the gestational period of 37 weeks’, following the method given by Jana et al. . The prey1 = 1 if y *1 >  0, and y1 = 0, otherwise. We also observed the propensity that the mother found her birth (child) to death during infancy, born to her with LBW as y2 = 1 if y *2 >  0, and y2 = 0, otherwise. Below we defined the equations.1 = β1χThe study used Global Positioning System (GPS) point data to create the hotspot map of low birth weight. Local Moran’s I statistics has been used to identify the high-risk areas of low birth weight. Moran’s I provides five clustering categories, including high-high, low-low, low-high, high-low, and not significant. High-high cluster (HH) illustrates the high prevalence areas and high-risk clusters or hotspots. In contrast, low-low (LL) cluster indicates the areas of low prevalence and the low-risk clusters of incidence or cold spots . Further2 = δ y1 + β2χ. Both equations are (standard) probit equations. y1 in the y2 equation. We estimated the model by exploiting cmp  command in stata [Where, θin stata . FurtherTable 2), below 20 years old and illiterate mothers. LBW information was observed missing to some children and the missing cases varied by different background characteristics. Out of all sample children, 17% were observed as missing the information on their birth weight status. This leads to missing the cases for the outcome variable of LBW. By background characteristics, it is revealed that 50% of the children born at home were observed to have missing information on LBW. About 20% of all illiterate mothers did not report the birth weight information. The missing cases for LBW were observed more frequent in the female births, births that were in the higher birth order, births that occurred in rural areas and births by mothers who had no exposure to mass media.Table In the dataset, 3.4% infants died before completing their first year of age. However, this rate varied by different background characteristics. About 5.5% of infants died among children with LBW compared to 2% in children with no LBW (> 2500 g). The infant death was higher among children born at home (home delivery) (3.2%), with three or higher orders (3.3%), those born to adolescent mothers (3.4%) and those born as preterm (5.8%). Also, infant death was higher among children born to mothers belonging to the poorest households and mothers who were illiterate, who had no mass media exposure were observed.Further, we performed spatial analysis considering 30,198 clusters across all states and union territories to find out the spatial heterogeneity of LBW. Figure The study exploits the conditional mixed model, which is a general framework to estimate models with various link functions. The empirical model using cmp command was estimated in other research as well . We repoOur primary focus was to estimate the effects of LBW on the probability of child deaths during infancy (0-11 months old), taking into account the frailty that the child born with LBW and death was influenced by the shared time-invariant mother specific unobserved heterogeneity, shown in panel A. Being born with LBW significantly increased the probability of death during infancy. The findings show that children born with LBW had 200% higher risk of death in the first year of life compared to children born with normal birth weight . Accounting for the endogeneity of LBW  increased the estimated effects . Further, instead of case-wise deletion (model 2), the effect in a model  was estimated as less . We consider model 3 as our benchmark (main results) model, where LBW was positively associated with the likelihood of infant mortality, and also the associated standard errors were relatively smaller compared to model 2 . Covariates’ effects showed that female children, higher order births, births that occur in Muslim and non-poor families and to literate mothers were negatively associated with infant death. However, another set of covariates that increase the likelihood of infant deaths was: children being born to older mothers (aged 30 years and above), in rural area, and states from the Central and Eastern areas.Results of panel B showed that preterm birth was significantly associated with the reduction in birth weight across all models. However, we explain the covariates’ effects of our benchmark model 3. The likelihood that a child will be born with LBW was 37% more in the preterm group compared to the group with ordinary births. Children being born to undernourished or thin mother, born at higher birth order, born to mothers who were uneducated or belonged to poor economic status were found to be significantly associated with LBW, while institutional birth and being born to mothers who were exposed to mass media were negatively associated with LBW.Infant mortality in India has reduced from 37 per 1000 live births in 2015 to 30 per 1000 live births in 2019 at national level . HoweverEarlier studies on the effects of LBW and infant mortality rarely exploits the model where it accounts for the shared mother specific frailty that influences the occurrences of LBW and influences infant death simultaneously. The current study found that half of the mothers who gave birth at their home had missing data on LBW and the multivariable estimates attenuated in the model with imputations which corroborates the previous finding that the prevalence of LBW from only the sample of measured birth weight by ignoring missing data may result in underestimation , and higBringing down the prevalence of LBW remains an arduous task in India. As India will not only accomplish the SDG target of reducing child mortality by preventing LBW, it may also be a push factor for human capital development , 33. AltHowever, in line with our hypothesis, we noted a significant association between LBW and infant mortality. The chances of a baby dying were 53%  higher when the baby was born with LBW. This effect is observed about five times larger in the correlated benchmark model (model 3) compared to the effects (12%) in the uncorrelated model (model 1). A reduction of the effect is observed in the model with case-deletion (model 2) and it was 53%. The smaller marginal effect (by 5%) was observed in model 3, which may be the case that imputation for missing cases of LBW addresses the selection bias. This is shown in the covariates’ effects as well and confidence intervals (by comparing model 2 & model 3). These results evidence the importance of two steps modelling and imputation of missing observations for better conclusions.Regarding the mechanism, LBW may cause newborn complications such as asphyxia, improper physical growth, and respiratory and metabolic dysfunction, which can increase the probability of contracting infectious diseases and malnutrition during childhood , which iAlbeit the Indian government has launched Pradhan Mantri Matru Vandana Yojana (PMMVY), a conditional cash transfer scheme to improve antenatal care and institutional delivery , our stuThe educated and wealthy women are usually more aware of access to healthcare facilities and the risks of inadequate healthcare use than the uneducated . PreviouNotably, the study also found that adolescent maternal age (< 20 years) is linked with an increased risk of children being born with LBW. Adolescent mothers do not have proper biological development and might not be physically or emotionally prepared to carry the fetus during pregnancy , 61. A pThis study has several strengths. Firstly, it is based on the national-level data that used validated questionnaires and methodology. Secondly, this is one among the first studies in India that address the potential risk factors of LBW and simultaneously analyze its impact on infant mortality along with other risk factors using national representative data. Lastly, this study used the imputation technique to account for the missing information.This study had some limitations too. Firstly, the accuracy of self-reported data for the diagnosis of LBW is subject to recall and reporting bias. Secondly, as previous studies explored a strong correlation between multiple gestation and preterm birth, which has been also observed in the dataset used for the study, we could not include multiple births in the model to avoid the multicollinearity. Although maternal anemia is a good predictor of LBW, the study was not able to consider it due to the unavailability of the information.The findings of this study suggested a higher prevalence of LBW across India, which is higher in Northern India. Since LBW is shown to be associated with infant deaths in this study, it is important to prioritize the policies targeting risk factors of LBW to reduce significantly the infant mortality in India. Preterm birth is the most important predictor of LBW along with maternal factors such as delivery at home, nutritional status, age at birth and education. Measures should also be taken to improve the schemes such as iron supplementation, antenatal visit, and institutional delivery in India. The media can be used as a helpful tool for making people aware of the complications of LBW. Public-private partnerships that are recommended by the WHO in the health sector can strengthen survival outcomes of new-born babies with LBW. Through minimizing the burden of LBW, India might achieve the SDG target of reducing child mortality and malnutrition by 2030.


Executive function (EF) deficits are often associated with Autism Spectrum Disorder (ASD), even in the absence of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis. To date, no approved medication treatments exist for EF deficits associated with ASD.To assess the efficacy of transcranial photobiomodulation (tPBM) on EF in adults with ASD.Adults (18-59) with high-functioning (HF)-ASD received twice a week tPBM for 8 weeks in an open-label single group design. ASD and EF deficits were assessed by clinician-rated Clinical Global Impression Scale and patient-rated scales of Behavior Rating Inventory of Executive Function-Adult (BRIEF-A).Eleven participants were enrolled. Ten participants completed the study. Nine participants who completed the study had comorbid ADHD diagnosis. All 10 participants were included in efficacy analyses of EF deficits. Statistically significant improvements in executive function deficits were found in BRIEF-A total score and in subdomains of Inhibition, Emotional Control, Planning and Organization, Organization of Materials, Behavioral Regulation, Metacognitive Index and Global Executive Control. All participants were found to have mild to moderate improvement in their ADHD symptom severity per clinician rated CGIs. Statistically significant improvements in ADHD symptoms were noted in self-rated scales. No adverse events required changes in tPBM protocol.tPBM is a safe and feasible treatment approach that has the potential to treat core features of ASD. Further research is necessary and warranted.This work is funded by Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder and the MGH Pediatric Psychopharmacology Council Fund.


Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Although it has been well documented that children with ADHD are associated with impairment of executive functions including working memory (WM) and inhibitory control, there is not yet a consensus as to the relationship between ADHD and memory-driven attentional capture . The present study herein examined whether children with ADHD have sufficient cognitive control to modulate memory-driven attentional capture. 73 school-age children  children) were instructed to perform a visual search task while actively maintaining an item in WM. In such a paradigm, the modality and the validity of the memory sample were manipulated. The results showed that under the visual WM encoding condition, no memory-driven attentional capture was observed in TD children, but significant capture was found in children with ADHD. In addition, under the audiovisual WM encoding condition, memory-matched distractors did not capture the attention of both groups. The results indicate a deficit of cognitive control over memory-driven attentional capture in children with ADHD, which can be improved by multisensory WM encoding. These findings enrich the relationship between ADHD and cognitive control and provide new insight into the influence of cross-modal processing on attentional guidance. Attention deficit hyperactivity disorder (ADHD) is a common childhood mental health disorder that is characterized by a pattern of inappropriate levels of inattentiveness, hyperactivity, and impulsivity . The dysApart from inhibitory control, working memory (WM), as another essential component of executive function, has been found to be impaired in individuals with ADHD in many studies ,8. A metThe biased competition model suggests that there is a close relationship between WM and selective attention, with a stimulus that matches internal representations stored in WM prioritized for attentional selection as neural representations encoding memorized features are already preactivated . In lineMeanwhile, utilizing WM representations to guide attention away from memory-matched distractors requires sufficient cognitive control . The morPrevious studies have demonstrated that children with ADHD have weakened cognitive control and difficulty in filtering out interference by task-irrelevant information and they exhibit inefficient neurocognitive mechanisms during active suppression ,28,29. FTaken together, the present study investigated whether children with ADHD have sufficient cognitive control to modulate memory-driven attentional capture. A dual-task paradigm combining a visual search task and a change detection task was adopted. Participants were asked to perform a visual search task while maintaining the identity of a memory item that could either appear as a distractor or not in the search display. Critically, the task was designed to provide strong motivation to exert cognitive control. First, between the memory display and the search display, a cue display appeared that provided prior knowledge of both the identity and the location of subsequent search items to maximize the motivation to guide attention away from a memory-matched distractor. Second, we did not include valid search trials  to eliminate the motivation to attend to a memory-matched item.In addition, it has been demonstrated that semantically congruent bimodal presentation can enhance cognitive control and facilitate subsequent cognitive processing ,36. MoreN = 23 for each group was sufficient to achieve the desired effect size. A total of 73 children aged 7 to 12 years were enrolled in the study, including 36 children with ADHD and 37 age- and sex-matched TD children. Children with ADHD were recruited from the Children’s Hospital of Soochow University, and controls were enrolled from local primary schools. The diagnosis of ADHD was based on being clinically interviewed with the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) criteria by qualified psychiatrists. In addition, all children with ADHD met diagnostic criteria on the Swanson, Nolan, and Pelham-IV Rating Scale (SNAP-IV) completed by their parents [G*Power 3.1.9.7  was used parents . The SNA parents ,42. Thert68 = 0.46, p = 0.65) and sex ratios  were observed between groups.All children with ADHD met the following criteria: (a) ADHD diagnosis based on DSM-5 by qualified psychiatrists and moderate to severe scores on the SNAP-IV; (b) right-handed; (c) normal hearing and normal or corrected-to-normal visual acuity; (d) normal intelligence quotient (IQ > 25%) as estimated by the Raven Standard Reasoning Test (RSRT); (e) drug-naïve; and (f) no history of other neurological or psychiatric disorders. The inclusion criteria for the TD group were the same as for the ADHD group, with the exception of the ADHD diagnosis. None of the participants in the TD group had academic or behavioral problems based on parent and teacher reports. Of the 73 potential participants, 3 participants (1 ADHD child with ADHD and 2 TD children) were excluded due to poor performance (the z score of accuracy or RT was larger than 3). Therefore, 35 children with ADHD  and 35 TD children  were ultimately included. No significant group differences in age , were delivered binaurally via stereo headphones (model: ATH-WS990BT) and were standardized in amplitude.The visual stimuli were obtained from a standard set of outlined drawing pictures . The selThe experiment was programmed and executed using E-prime 3.0 software  and presented on a 32-inch LCD monitor  with a black background . Participants sat at a viewing distance of approximately 57 cm and provided their responses using two two-key customized keyboards.An example trial sequence is illustrated in The cue array consisted of four visual items presented at either 1, 4, 7, 10 or 2, 5, 8, 11 o’clock locations around an imaginary circle (with a radius of 13°), with no items overlapping. The cue array was presented between the memory display and the search display, providing prior knowledge of the identity and location of search items. The setting of the cue array is useful to facilitate cognitive control to avoid distractions from memory-matched distractors ,44.The visual search items were identical to the cue items except that they had gaps on the left and the right side of the square box. The distractor had an equal-size gap (0.3° × 1.1°), whereas the target had a slightly larger gap (0.3° × 1.6°) on either the left or the right side. Half of the search trials were invalid trials, in which the memory sample reappeared as one of the distractors in the search display. The remaining half were neutral trials, in which memory items did not reappear in the visual search task.Each trial began with a white fixation cross (1° × 1°) shown in the center of the center, after which the memory display was presented for a duration of 500 ms. Participants were required to memorize the memory item for a later memory test. After a blank interval of 500 ms, the cue display appeared for 750 ms. Following the cue display presentation, the search display appeared. Participants were required to judge which side of the target had a larger gap by pressing “F” for the left  and “J” for the right  with their left hands. Responses occurring outside the 5000 ms time interval following the search display onset were coded as incorrect. The memory test then appeared until the response. Participants needed to judge whether the probe stimulus was the same as the memory stimulus presented during the WM encoding stage with a key response . Participants received immediate feedback on accuracy. Each trial ended with a blank screen for a random duration ranging from 800 to 1000 ms. Participants were instructed to execute the search task as quickly and accurately as possible. The memory task had to be completed as accurately as possible, without time pressure.Taken together, the present experiment was a 2  × 2  × 2 (group: children with ADHD vs. TD children) three-factorial mixed design. Before the formal experiment, each participant was required to complete a practice block  to get familiar with the task. The total experiment consisted of 128 trials, which were presented in blocks of 32 trials each . The validity was mixed randomly within the block, whereas the memory modality varied between blocks. The participants completed two V and two AV blocks, whose order was chosen randomly with equal probability from ABBA and BAAB design. The entire experiment lasted for about 30 min. Participants were informed in advance that memory-matched stimulus would never be a target, and the cue stimuli had the same identity and location as the subsequent search items.p < 0.05 was considered significant for all statistical analyses. The participants’ response time (RT) and accuracy were recorded and analyzed. Before analyzing the RTs for the search task, trials with incorrect responses in either the search or the memory task were excluded, as were trials with RTs ± 3 SDs beyond the mean RT within each condition for each participant. To explore whether there was a difference between children with ADHD and TD children, we conducted a 2  × 2  × 2 (group: ADHD vs. TD) repeated-measures ANOVA on memory accuracy, search accuracy, and mean search RTs, respectively. After that, post hoc t tests based on Bonferroni correction were performed. Additionally, we conducted a 2  × 2 (group: children with ADHD vs. TD children) repeated-measures ANOVAs on memory-driven attentional capture effect to determine how the capture effect  was affected by the memory modality and the group. Effect sizes are reported in terms of partial eta squared (ηp2).Statistical analyses were performed using JASP (Version 16). A two-tailed F  = 41.85, p < 0.001, ηp2 = 0.38, demonstrating a higher memory accuracy under the audiovisual condition (93.3%) as compared to the visual condition (87.2%). The main effect of group was also significant, F  = 6.68, p = 0.012, ηp2 = 0.09, with lower accuracy for ADHD (88.5%) than for TD children (91.9%). Additionally, only significant two-way interaction between memory modality and group was found, F  = 4.35, p = 0.041, ηp2 = 0.06. For memory modality, a post hoc analysis with Bonferroni correction revealed a significant difference between children with ADHD and TD children under the visual condition . No significant difference under the audiovisual condition between the two groups was observed . For group, a similar analysis revealed significant differences between visual and audiovisual modalities were found in children with ADHD , as well as in TD children . No other significant main effects or interaction effects were observed (ps > 0.17). The results suggested that the participants’ memory performance was affected by the memory modality, and the memory accuracy was much greater under the audiovisual condition than under the visual condition. In addition, the memory accuracy of TD children was greater than that of the children with ADHD under the V condition, but no difference was observed under the AV condition.Regarding memory accuracy, an ANOVA with memory modality  and validity  as within-subject factors and group  as between-subject factors was conducted. The results revealed that the main effect of memory modality was significant, F  = 4.21, p = 0.044, ηp2 = 0.06, indicating a higher search accuracy in invalid trials (95.6%) than that in neutral trials (94.7%). The main effect of group was marginally significant, F  = 3.56, p = 0.064, ηp2 = 0.05, with lower accuracy for ADHD (94.1%) than for TD children (96.2%). However, the main effect of memory modality was not significant, F  = 0.32, p = 0.57. Moreover, all interaction effects were not significant (ps > 0.39). The details of the accuracy and RTs are shown in Regarding search accuracy, search performance reached a ceiling in all conditions (above 93%). A 2  × 2  × 2 (group: ADHD vs. TD) repeated-measures ANOVA on search accuracy was conducted. The results showed a significant main effect of validity, F  = 10.94, p = 0.002, ηp2 = 0.14, with a slower response for ADHD (2192 ms) than for TD children (1959 ms). However, the main effect of memory modality was not significant, F  = 0.92, p = 0.34, as was the main effect of validity, F  = 2.15, p = 0.15. There was significant two-way interaction between validity and group, F  = 4.82, p = 0.032, ηp2 = 0.07. Importantly, the interaction between the three factors was also significant, F  = 6.07, p = 0.016, ηp2 = 0.08. Neither the interaction between memory modality and group, F  = 0.01, p = 0.91, nor between memory modality and validity, F  = 3.22, p = 0.077, were significant. To test whether the pattern of interaction between memory modality and validity differed in ADHD and TD children, two separate 2  by 2  repeated measures ANOVA were conducted.A repeated measures ANOVA was conducted on mean search RTs with the factors of memory modality, validity, and group. The results showed a significant main effect of group, F  = 5.25, p = 0.028, ηp2 = 0.13, indicating that RTs on neutral trials (2158 ms) were faster than those on invalid trials (2226 ms). The main effect of memory modality was not significant, F  = 0.48, p = 0.49, ηp2 = 0.01. The interaction between memory modality and validity was also significant, F  = 8.59, p = 0.006, ηp2 = 0.20. A post hoc analysis with Bonferroni correction only revealed a significant difference between the invalid and neutral trials under the V condition , but not under the AV condition . For TD children, no significant main effect or interaction effects were observed (ps > 0.51).For ADHD children, the main effect of validity was significant, F  = 4.82, p = 0.032, ηp2 = 0.07, but not for the main effect of memory modality, F  = 3.22, p = 0.077, indicating a greater capture effect in the ADHD group (68 ms) than in the TD group (−14 ms). The interaction between memory modality and validity was also significant, F  = 6.07, p = 0.016, ηp2 = 0.08. For memory modality, a post hoc analysis with Bonferroni correction revealed a significant difference between children with ADHD and TD children because of the V condition . No significant difference under the AV condition between the two groups was observed . Regarding group, a similar analysis revealed a significant difference between the V and the AV condition in children with ADHD . No significant difference was found between the V and the AV condition in TD children .We performed additional analyses to determine how the memory-driven attentional capture effect  was affected by the memory modality and the group. A 2  × 2 (group: children with ADHD vs. TD children) repeated-measures ANOVA was conducted. The results revealed that the main effect of group was significant, Based on these results, children with ADHD took much longer to complete the visual search than TD children, regardless of whether the validity of the search trial was invalid or neutral. In addition, for children with ADHD, the memory-driven attentional capture effect was affected by the memory modality. The capture effect of children with ADHD was significant under the V condition, but not under the AV condition. For TD children, the capture effect was not significant regardless of whether the modality of the memory sample was visual or auditory. These results suggested that memory-matched distractors capture the attention of children with ADHD under the V encoding condition possibly due to their cognitive control impairments. Semantically congruent AV encoding could compensate for the lack of cognitive control, thereby allowing children with ADHD to guide attention away from memory-matched distractors.The present study aimed to investigate the modulation of cognitive control over memory-driven attentional capture in children with ADHD. The study employed a dual-task paradigm in which a cue display was presented between the memory display and the search display to maximize the motivation to exert cognitive control. Analysis of search performance revealed remarkable differences when comparing the children with ADHD and TD children. Most importantly, our data indicated that the cognitive control deficit in ADHD could be improved by semantically congruent multisensory WM encoding. Specifically, for the visual encoding condition, the responses were slower in invalid trials than in neutral trials, indicating memory-driven attentional capture. Such a result was found only in children with ADHD. However, for the multimodal (AV) encoding condition, no capture effect was observed in either children with ADHD or healthy controls.Under the unimodal (V) encoding condition, WM-related distractors captured the attention of children with ADHD but not of TD children. These contrasting effects suggested that children with ADHD had weaker cognitive control abilities than TD children and were more susceptible to the WM content matched with a distractor. This finding is consistent with previous studies. Some evidence has shown that ADHD is associated with marked difficulty in shifting and inhibition functions ,47. For Relatedly, it is also possible that the current results are due to energetic dysfunction in children with ADHD . AccordiAn interesting result of the present study was that the memory-driven attentional capture effect disappeared in children with ADHD under the condition with multisensory WM encoding, suggesting that such semantically congruent bimodal presentation could facilitate the establishment of cognitive control and then eliminate attentional capture by memory-matched distractors. The signal suppression hypothesis proposes that the actual deployment of attention depends on the relative strengths of priority signals and top-down control signals ,26,57. AThe ability of multisensory facilitation in distractor suppression could involve brain regions involved in inhibitory control, such as the dorsolateral prefrontal cortex. Neuroimaging studies have shown that children with ADHD exhibit abnormal activation of these brain regions specifically during demanding tasks associated with inhibitory control ,66,67. MIn the present study, no advantage of WM content-related distractors was observed, regardless of whether the modality of the memory sample was visual or audiovisual in TD children, which is usually reported in studies with healthy adults ,23. TherApart from poor search performance, children with ADHD performed worse than healthy controls regarding memory accuracy measures under the unimodal encoding condition. Previous studies have confirmed that WM impairment is a typical cognitive impairment in ADHD . IndividIn the present study, the robust difference in the memory-driven attentional capture effect between children with ADHD and TD children provided evidence that children with ADHD were deficient in resistance to proactive interference from WM. More importantly, their performance improved overall in the semantically congruent multisensory WM encoding condition. This work may extend our understandings of the relationship between ADHD and cognitive control and provide new insight into the influence of cross-modal processing on attentional guidance. On the other hand, this may have important practical implications, especially for the intervention/training of children with ADHD. For example, multisensory stimulation can be added to attentional control or working memory training to improve the cognitive control of children with ADHD.There are several limitations to the present study. First, the small sample size recruited for this study did not allow further analysis of the effects of ADHD subtypes and genders on cognitive control over memory-driven attentional capture. Second, we included a homogeneous sample of children with ADHD and with limited comorbidities . Therefore, it is possible that findings may be not generalizable to a more severe ADHD population. Third, due to the limitation of the experimental design, we could not analyze whether ADHD affects memory retrieval speed. Future studies need to separate the memory recognition and the visual search task.In summary, the present study investigated the modulation of cognitive control over memory-driven attentional capture in children with ADHD. The results showed robust between-group differences under the unimodal  WM encoding condition; that is, no memory-driven attentional capture was observed in TD children, but significant capture was found in children with ADHD. Moreover, under the semantically congruent bimodal  WM encoding condition, no capture was found in either children with ADHD or TD children. The present study provided evidence that children with ADHD were deficient in resistance to proactive interference from WM, and these deficits could be improved by semantically congruent multisensory WM encoding.