The presence of attention deficit hyperactive disorder (ADHD) causes great impairment in social and professional activities as well as in the quality of life (QOL) and increases level of parental stress.This study aimed to compare the QOL, self-competence, and self-liking among the caregivers of ADHD and non-ADHD children.A descriptive cross-sectional study was conducted on 216 caregivers. They were divided into two groups: caregivers of children with ADHD and caregivers of children without ADHD.This study was conducted in the Elsinbellawin City at Dakahlia Governorate in Egypt. Tools used were socio-demographic data sheet and WHO Quality of Life Scale-Brief (WHOQOL-Brief) and self-liking/self-competence scale.Our results showed that all QOL dimensions of the caregivers of ADHD children were markedly deteriorated, if compared to those of non-ADHD children, and two thirds of caregivers of ADHD children suffered from poor level quality of life (QOL). Caregivers of non-ADHD children had fair level of self-competence but a good level of self-liking. Caregiver of ADHD children who had no work or history of medical diseases has a fair level of QOL and self-competence but a good level of self-liking.We found that caregivers of ADHD children have fair levels of QOL, self-liking, and self-competence, if compared to those of non-ADHD children. There are statistically significant correlations between QOL, self-competence, and self-liking among both caregivers of both non-ADHD children and ADHD children. According to the American Psychiatric Association, attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by a cluster of symptoms of inattention and disorganization, with or without hyperactivity-impulsivity . ADHD isQOL is defined as the expected well-being and satisfaction of one’s life achievements in the social and culture contexts. It is a subjective and multidimensional construct consisting of physical, emotional, and social domains including both cognitive (satisfaction) and an emotional (happiness) component . EvidencA lower QOL was associated with the child’s functioning impairment, and the few social support received the use of non-adaptive coping mechanisms, and emotional conduct, physical health, and coordination problems as well as maternal and paternal mental health problems. Parents of children with ADHD reported more family problems and are at a higher risk for developing physical or psychological problems .Self-esteem is composed of both self-liking and self-competence. Self-competence refers to seeing oneself qualified, successful, and skillful in achieving goals. It is important for the development of the personality and for learning in general via its ability to motivate oneself, cope with failure, and handle one’s emotions. Self-liking refers to self-worth and value due to an individual’s place estimation in the social setting, irrespective of their success, reflecting his self-acceptance that perceived by himself. It is affected significantly by accepting or rejecting attitudes, and acceptance of positive or negative interpretations perceived by oneself or received from peers . IndividBehavioral parent training (BPT) is the predominant mode of behavior management treatment targeting home-based problems for school-age youth with ADHD. BPT programs tend to cover a set of topics. Psychoeducation about ADHD and the behavioral model for treatment is often covered first. Thereafter, most BPT programs begin with teaching parents positive attending skills to improve the parent-child relationship and promote a positive family climate, as well as contingent positive consequences  to encourage appropriate child behavior. Positive strategies are discussed first because they can interrupt the coercive cycle often displayed in families of children with ADHD , 10.This study aim to compare the QOL, self-competence, and self-liking among the caregivers of ADHD and non-ADHD children.Does self-competence of caregivers of ADHD and non-ADHD children predict being liked and disliked by themselves in a statistically significant way?Does self-competence of caregivers of ADHD and non-ADHD children predict their QOL in a statistically significant way?Does self-liking of caregivers of ADHD and non-ADHD children predict their QOL in a statistically significant way?Does self-competence of caregivers of ADHD and non-ADHD children predict their self-liking in a statistically significant way?A comparative research design was utilized in this study and was conducted between 20th of June and 21th of July 2020.This study was conducted in the early intervention center for children with special needs and learning disorders in Elsinbellawin City at Dakahlia Governorate in Egypt. This center helps the children with special needs to make adaptation to their condition and helps them to learn academically and socially in contact with others in the community. The center contains 5 floors which consist of 15 rooms for children with autism, ADHD, mental retardation, and children with learning disorders; 1 room for the director; 1 room for the staff; 1 room for workers; 1 room for activity; and 1 room for play. According to the following inclusion criteria, both genders, between the ages of less than 30 and more than 40 years and free from any chronic disease, are included.The samples were collected from 216 caregivers and were divided into two groups; caregivers of 108 children diagnosed to have ADHD according to DSM IV-T international criteria and with a minimum IQ ≥ 70 (investigator-estimated) were eligible for the study. General information and questionnaires were filled in by patents. The exclusion criteria comprised abnormal laboratory findings, acute or unstable medical conditions, cardiovascular disorder, history of seizures, psychosis, bipolar disorder, suicidal ideation, any medical condition that might increase sympathetic nervous system activity, or the need for psychotropic medication other than study drug. The second sample was composed of 108 normal children with the following inclusion criteria: normal children’s development not having any previous use of drugs for chronic diseases and not being treated for any psychiatric disorders. The groups were both genders. In the control group, according to caregivers, included the following criteria: agreed to contribute in the study, each of the two genders  were represented in the sample, and the mean age of the caregivers was 20–60 years.Mean ± SD of QOL among ADAH group was 64.97 ± 31.92 and 76.78 ± 29.89 of control group (pilot study), and confidence level is at 95% with power of study 80%. Sample size was calculated using Open Epi and 108 caregiver for each group.After obtaining the required permission to conduct the study, the researchers inter-viewed the caregivers in their center in order to attain their verbal consent to participate in the study after being informed about its aim. The selected caregivers were divided into groups (5 to 10 caregivers for each group). The researchers interviewed caregivers, explained each statement to them, and then asked them to complete the questionnaire. Each group required about 30–45 min to be completed. As a result of pandemic COVID-19, the necessity of taking safety precautions such as physical distancing, wearing a mask, keeping rooms well ventilated, avoiding crowds, cleaning hands, and data collection was completed in about 1 month.Questionnaire was established by researchers including questions about population age, gender, the level of education, marital status, job, and medical history of diseases.The shortened version of the original instrument WHOQOL-100, comprises of 26 questions. Two are related to an individual’s overall perception about QOL. The remaining 24 represent four domains of the original instrument; I—physical, II—psychological; III—social; and IV—environment domain [The scale was designed by  and consValidity of tools II and III were tested for their content by a jury of five experts in the field of psychiatric and mental health nursing to ascertain relevance and completeness of the tools and the needed modifications were done. Tools II and III reliability were assessed by Cronbach’s alpha through measuring their internal consistency. They show good level of reliability as follows: QOL score (α = 0.737), self-competence score (α = 0.742), and self-liking score (α = 0.741).The researchers conducted a pilot study on 10% of the study sample  to test the applicability of the data collection tool and the feasibility of the study. It was done to assess the study questionnaire clearness, easiness, and feasibility, as well as to estimate the required time to complete the questionnaire. Based on the pilot study results, some changes made to the questionnaire were mostly rephrasing and using simpler semantic for the statements, and adding some modifications was made to the instruments. Self-liking/self-competence scale (consisting of 16 items). The experts in the field of psychiatric and mental health nursing recommended classifying into two dimensions of self-esteem (8-point self-liking and 8-point self-competence). Also, define the three items need to be reversed before scoring regarding WHOQOL-Brief scale. Sample who took part in the pilot study were not included in the main study.P value < 0.05 was considered statistically significant (S), and p value ≥ 0.05 was considered statistically insignificant (NS).All data were collected, tabulated and statistically analyzed using SPSS 20.0 for windows . Quantitative data were expressed as the mean ± SD and (range), and qualitative data were expressed as absolute frequencies (number) and relative frequencies (percentage). Percent of categorical variables were compared using chi-square test. Spearman correlation coefficient was calculated to assess relationship between various study variables, (+) sign indicate direct correlation and (−) sign indicate inverse correlation, also values near to 1 indicate strong correlation and values near 0 indicate weak correlation. All tests were two sided. Figure p > 0.05) difference between both groups.Comparing between caregivers of non-ADHD children and ADHD children and regarding their socio-demographic characters, Table p < 0. 001) between both groups. It is apparent that all QOL dimensions of the caregivers of ADHD children were markedly deteriorated, if compared to those of non-ADHD children. The most affected QOL dimension was the psychological health (73.14%), physical health (69.45%), followed by the social relationships (66.67%), the overall QOL and general health (62.04%), and the least affected dimension was the environment dimension (60.19%). Moreover, two-third of caregivers of ADHD children suffered from poor level QOL (66.67).Table p < 0.001) difference between caregivers of non-ADHD children and ADHD children. It is obvious that caregivers of non-ADHD children had good level of self-competence and self-liking.Comparing between caregivers of non-ADHD children and ADHD children regarding self-competence and self-liking, Table p = 0.031), sex (p = 0.001), marital status (p = 0.007), and the medical history of diseases (p = 0.0001). Also, that there is statistically significant relations between self-competence of caregivers of non-ADHD children and their education (p = 0.048), and medical history of diseases (p = 0.009) only. Concerning relation between self-liking of caregivers of non-ADHD children and their socio-demographic characters, there is a statistically significant relations between self-liking of caregivers of non-ADHD children and their age (p = 0.003), marital status (p = 0.002), and medical history of diseases (p = 0.001).Regarding relation between QOL, self-competence, and self-liking of caregivers of non-ADHD children and their socio-demographic characters, Table p = 0.038), and medical history of diseases (p = 0.005). It seems that caregivers of ADHD children who had no work or history of medical diseases reveal fair level of QOL. As regards the relation between self-competence of caregivers of ADHD and their socio-demographic characters, there is statistically significant relation between self-competence of caregivers of ADHD children, their occupation (p = 0.008), and medical history of diseases (p = 0.008). It is obvious that the caregiver of ADHD children who works and had no history of medical diseases has a fair level of self-competence. As regards the relation between self-liking of caregivers of ADHD and their socio-demographic characters, there is a statistically significant relation between self-liking of caregivers of ADHD children, their occupation (p = 0.0001), and medical history of diseases (p = 0.003). It is evident that caregivers of ADHD children who had no work or history of medical diseases have a fair level of self-liking.As regards the relation between QOL of caregivers of ADHD children and their socio-demographic characters, Table p < 0.05) correlations between QOL, self-competence, and self-liking among both caregivers of both non-ADHD children and ADHD children.Table To the best of our knowledge, this is the first study comparing the QOL, self-competence, and self-liking scores between ADHD and non-ADHD children caregivers. Although previous studies have recommended that ADHD affects both the patients and their caregivers QOL, and a larger number of investigations have pointed out that of ADHD children’s behaviors lead to increased parental stress, anxiety, and negative parenting styles which upsurge those children’s problems. Thus, we aimed to compare the impacts of ADHD on QOL, self-competence, and self-liking levels of their caregivers against those of non-ADHD children, in addition to investigation of the relationships between these personality traits. Regarding the caregivers’ socio-demographic characters, our study showed that there is no statistically significant difference between both groups of non-ADHD children and ADHD children.By comparing QOL of the caregivers, the current study displayed a statistically significant difference between caregivers of non-ADHD children and those of ADHD children, and that two third of caregivers of ADHD children suffered from poor level QOL. As hypothesized, our results demonstrated marked impairments in all QOL dimensions in ADHD caregivers versus non-ADHD children, emphasizing how ADHD can affect the caregivers and the relevance of addressing this issue with them during treatment.This result is matched with results found by  who statThe present study demonstrates that QOL of caregivers of non-ADHD children is significantly correlated with their age, sex, marital status, and their medical history of diseases. It was noticed that married female caregivers of non-ADHD children with age less than or equal 30 years who had no history of medical diseases enjoy good level of QOL. Mothers are the primary care providers for their kids due to spending most of their time with them and occupying most traditional roles, increasing the effective parenting of mothers, such as being responsive to children’s needs and being more involved in child care. When she do most of these duties, she feel happy and satisfied when she sees her children’s love and happiness. On the contrary, our present study establishes that QOL of caregivers of ADHD children is significantly correlated only with their occupation and their medical history of diseases. We detected that non-working caregivers of ADHD children who had no history of medical diseases live fair level of QOL. Work is a critical factor for parenting behaviors; as working hours, workload, and complexity increase, parents cannot fulfill the requirements of their role as both an employee and a parent, work-family conflicts appear causing psychological problems due to emotional exhaustion. Perceived satisfaction with social support availability in caregivers of children with ADHD is inversely related to parenting stress due to decrease threatening. This social support from the primary networks as families or friends to the professional networks as health care professionals, education professionals, or social services help to cope with stressful events, improving QOL .In the current work, self-competence of caregivers of non-ADHD children is significantly correlated only to their education and medical history of diseases and that post-graduated caregivers of non-ADHD children who have no history of medical diseases and have a good level of self-competence, seeing that oneself is skilled, successful, and proficient in achieving goals. Seeing oneself as successful and effective in achieving goals motivates him to grow his personality and learning. Also, coping with failure and handling one’s emotions keep his development and continuous knowledge gain and education. Individuals who perceive themselves as competent and skillful of dealing with their stressful conditions or troubles are likely to take on problem-solving strategies rather than escaping strategies . On the Additionally, this study reveals that self-liking of caregivers of non-ADHD children is significantly correlated with their age, sex, marital status, and their medical history of diseases. We remarked that married female caregivers of non-ADHD children with age less than or equal 30 years who had no history of medical diseases enjoys good level of self-liking. Since the same married female caregivers of non-ADHD children with age less than or equal 30 years who had no history of medical diseases enjoys good level of both self-liking and QOL, so self-liking positively correlated with QOL, as we shall mention after. Children often told their mother that they love her and she is the best person in their world, and then she believes that she is good enough. Thus, she perceives self-worth and value, accepts herself, and be calmer, comfortable, and safe in their social life. Conversely, self-liking of caregivers of ADHD children is significantly correlated only with their working status and their medical history of diseases, similar to their self-competence. This may be attributed to marked impairments in all QOL dimensions in ADHD caregivers versus non-ADHD children due to internalizing or externalizing problems and impaired social skills or maladaptive behavior. Furthermore, we remarked that non-working caregivers of ADHD children who had no history of medical diseases reveal a fair level of self-liking beside self-competence. Non-working parents are reported to be more affected since they often experience greater feelings of guilt and responsibility for achieving their child’s needs than working parents . FinallyCollectively, we found that caregiver of ADHD children have fair levels of QOL, self-liking, and self-competence. We observed also that those non-ADHD children enjoy good levels of QOL, self-liking, and self-competence, emphasizing our results of presence of a statistically significant correlation between QOL, self-competence, and self-liking among both caregivers of both non-ADHD children and ADHD children. Also, these outcomes highlight the need for including the caregivers in the treatment strategies for ADHD patients to improve their QOL, self-competence, and self-liking results and promote positive outcomes.Small sample sizes may limit the generalization of the results. Furthermore, we did not evaluate the impact of the child’s ADHD symptom severity on the QOL self-competence, and self-liking of their caregivers since these symptoms may affect them. Despite these limitations, our current study support that ADHD impacts the children caregivers’ QOL, self-competence, and self-liking. Therefore, a need for future studies with larger sample sizes including the impact of the child’s ADHD symptom. Also, we did not use a semi-structured interview to confirm the diagnosis, because the diagnosis and treatment are carried out inside the center by the treating doctor, and this center is specific to those children with specific needs which are internally divided into groups according to every disease and diagnosis; thus, the children of the study sample with ADHD were easily reached by the director of the center without using the semi-structured interview.We suggest a need to increase the awareness of health professionals to identify high-risk ADHD caregivers for QOL, self-competence, and self-liking impairment. We advise also provision of design programs for families of children with ADHD in the clinical practice treatment, including family- and community-based services, besides the child behavioral training. In addition, intersectional involvement between health care system, education system, and social well-being system may decrease parents’ anxiety, depression, and sense of conflict between work and family or social isolation. In addition, intersectional involvement between health care system, education system and social wellbeing system may decrease caregivers’ anxiety, depression, and sense of conflict between work and family or social isolation, improving their QOL, self-competence, and self-liking results and promoting positive outcomes


The present study aims to investigate the prevalence of lower tract urinary symptoms (LUTS) and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents and their association in a community setting using validated scoring instruments.A cross-sectional study was carried out from February 2015 to December 2019, during which the parents or guardians of 431 children and adolescents from 5 to 13 years of age, attending a general pediatric outpatient clinic were interviewed.The prevalence of ADHD symptoms and LUTS were 19.9% and 17.9%, respectively. Of the 82 children and adolescents with ADHD, 28%  had LUTSChildren and adolescents with ADHD symptoms are 2.3 times more likely to have LUTS. The combined type of ADHD was the most prevalent among them. Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental condition and the second most frequent chronic disorder in children –3. ADHD Lower urinary tract symptoms (LUTS) are characterized by changes in the bladder emptying and/or storage phase and, if it there is coexistence with functional constipation it is named bladder bowel dysfunction (BBD) , 11. LUTADHD and LUTS are not only common disorders in childhood, but also has a high co-existence and interaction with each other –18. The We hypothesize that, in a general pediatrics clinics population, a significative association between these disorders can also be found. This study aims to investigate the prevalence of LUTS and ADHD symptoms in children and adolescents and the association between these two conditions in our population.A prospective cross-sectional study was carried out from February 2015 to December 2019, during which 431 children and adolescents from 5 to 13 years of age attending a general pediatric outpatient clinic were evaluated. Children and adolescents with moderate to severe intellectual disability of any cause, urogenital malformation or diseases that may impair the function of the bladder or urethral sphincter, were not included in the study. A complete physical exam and standard assessment was performed on all subjects.The study was approved by Institutional Review Committee (IRB), protocol number 2.625.013, and all parents or guardians of the patients signed an informed consent.Gestational age at birth  was investigated, based on the data recorded on the child's health card. The screening of ADHD symptoms and LUTS was performed through the application of MTA-SNAP-IV  and the The MTA-SNAP-IV  includesEach subject, with the help of their parents or guardians, answered the ten questions of the DVSS questionnaire . The firThe presence of functional constipation was assessed according to the Rome IV criteria  Appendi. The BriQuantitative data was expressed as mean±standard deviation (SD) while qualitative variables were expressed as absolute values, percentages, or proportions. The Student t-test or the Mann-Whitney test was used to compare continuous variables, while the categorical variables were compared using the Fisher exact test. Odds ratio and 95% confidence intervals were used to describe the magnitude of association between LUTS and ADHD symptoms. All tests were 2-sided with p <0.05 considered statistically significant. Analysis was performed using commercially available statistical software .All patients with confirmed LUTS and/or ADHD symptoms were referred for diagnosis, treatment and follow-up, in specialized outpatient clinics in these disorders.Four hundred twelve patients out of the 431 recruited were included in the study. Twelve parents refused to participate, three patients were diagnosed with severe intellectual disability, two had occult spinal dysraphism, and two had hypospadias with surgical complications. The mean age of participants was 7.26±1.84 years, being 53.4% males (220/412).The overall prevalence of LUTS estimated by DVSS was 17.9% (74/412). Of those, fifteen (3.6%) of the 412 had the diagnosis of LUTS prior to the study.ADHD symptoms were present in 19.9% (82/412) of children. Of those, a total of 24 patients (5.8% of 412) had neurodevelopmental disorders symptoms, specifically ADHD and six of them (25%) had a diagnosis and were receiving treatment with partial response. Of the patients presenting ADHD, 6.1% (5/82) had inattention type, 9.8% (8/82) hyperactivity/impulsivity type, and 84.1% (69/82) combined type of ADHD. When compared by gender, ADHD symptoms were present in 59.7% (49/82) of the boys .Of the 82 children and adolescents with ADHD symptoms, 28% (23/82) had LUTS , being 56% (13/23) males. The combined type of ADHD was present in 91.3% (21/23) and hyperactivity/impulsivity type in 8.7% (2/23) of the subjects with LUTS . None of those with the inattention type presented LUTS .The average DVSS total score in children and adolescents with ADHD symptoms was significantly higher than in those without . Urgency was the most common LUTS, being more frequent in those with ADHD symptoms . When we analyzed the average score of all DVSS subscales, responses to the items “When your child wants to pee, can't he wait?” and “Does your child hold the pee by crossing his legs, crouching or dancing?” were higher in those with symptoms of ADHD  .The overall prevalence of functional constipation (characterized according to the Rome IV criteria) was 31% (129/412), being 36.4% (27/74) with LUTS and 20.7% (70/338) in the ones without LUTS (OR 4.3 95% CI 1-5.3 p=0.001). Ninety-five percent of the individuals with functional constipation had stool types 1 and 2 of the Bristol Stool Form Scale modified for children. There was no statistical difference in the prevalence of functional constipation between those subjects with and without ADHD symptoms, both associated with LUTS (p=0.74).Among the children who had symptoms of LUTS and ADHD, 78% (18/23) were full-term, and 22% (5/23) were premature  (p=0.6).The present study demonstrated that children with ADHD have 2.3 times more chance of presenting LUTS, and that the most common voiding symptom in this population is urgency. The overall prevalence of ADHD symptoms in this study was in accordance to that previously reported. A recent review showed variability in the worldwide prevalence of ADHD symptoms around 5 to 29% in community samples of children and adolescents. This variability in the prevalence of ADHD was attributed to methodological differences between the studies, specifically in the diagnostic criteria and sources of information between different countries , 3. AlthIn the present study, we have found a high prevalence of LUTS (28%) in children and adolescents with ADHD symptoms. Individuals diagnosed with ADHD symptoms by MTA-SNAP-IV questionnaire were more likely to have LUTS, been the combined type the most frequent type, while hyperactivity/impulsivity type present in less than 10% of the patients with LUTS. Contrasting with our findings, Crimmins et al. showed that children with hyperactivity/impulsivity type ADHD is approximately 4.5 times more likely to have LUTS .β-adrenergic effect leads to contraction of detrusor, while an increase leads to relaxation of the detrusor  and inattentive symptoms were associated with daytime urinary incontinence with increased odds of enuresis at 10 years and adolescents . Therefodetrusor . Regardldetrusor , 28, 29.Two instruments validated for the Brazilian population to assess LUTS  and ADHDThe assessment of bowel habits is recommended as an approach for children and adolescents with LUTS to diagnose BBD , 12. In Regarding gestational age, 78% of participants with LUTS and ADHD symptoms were full term. A recent study reported that prematurity is independently associated with the diagnosis of neurological development disorders. Also, it showed that 19.5% of premature infants have ADHD, with a prevalence inversely proportional to gestational age . No studThis study has some limitations. Due to its configuration and design, the patient teacher's report on the MTA-SNAP-IV data was not included, which could increase its screening power . Also, tOn the other hand, some features of this study may increase the strength of our findings, such as sample size and the use of standardized questionnaires. Most studies examine risk factors for nocturnal enuresis, with very few studies examining daytime voiding symptoms.Children and adolescents, recruited in a general pediatric outpatient clinic, with ADHD symptoms are 2.3 times more likely to have LUTS. The combined type of ADHD was the most commonly associated with LUTS. Urgency and holding maneuvers were most prevalent symptoms in children and adolescents with ADHD symptoms. These findings support that all children with ADHD should be addressed for LUTS and vice versa.


Objective: To investigate the association between various injuries and attention-deficit hyperactivity disorder (ADHD) and distinguish ADHD from non-ADHD with regards to risk of various injuries among children in Taiwan. Method: Using the data from the National Health Insurance Research Database, we selected a total of 1802 subjects under the age of 18 who were diagnosed with ADHD as well as an additional 7208 subjects as a comparison group. Results: Compared with children who were not diagnosed with ADHD, children diagnosed with ADHD were more likely to intentionally injure themselves. During the school year, ADHD children were injured less frequently than were non-ADHD children on traffic-related incidents. The adjusted hazard ratio of injury for the ADHD children was 2.493 times higher than that of comparison subjects. The ADHD children had a greater length of stay and medical cost when compared to those of the non-ADHD children. Age showed a significant inverse relationship with injury. Among the ADHD children, the injury rate was evidently higher for the low-income group than for the non-low-income group. Conclusions: Age, cause of injuries, low-income household status, and school season all have a significant connection to the risk of injury for ADHD children.  Attention-deficit hyperactivity disorder (ADHD) is a cerebral dysfunction that results in problems with concentration and impulse control in about half of the adults who were diagnosed with ADHD as child . The estIn 2011, the prevalence of ADHD diagnoses in U.S. children ages 4–17 years) was approximately 8%, and children affected by ADHD were more vulnerable to physical injuries such as physical trauma, accidental poisoning, burns, etc. . Other s years waThe lack of long-term follow-up and comparisons among different causes of injuries in ADHD children could lead to inconsistent results. Therefore, the purpose of this study was to examine the association between ADHD and various injuries and to distinguish ADHD from non-ADHD children with regards to risk of various injuries with long-term follow-up from 2000 to 2010 in Taiwan’s medical environment. Approximately 20 years ago, the Taiwanese government initiated a single-insurer National Health Insurance (NHI) program and over 23 million people were enrolled in the National Health Insurance Research Database (NHIRD) after the program was implemented. The NHIRD allowed researchers access to a large amount of long-term data for analysis. Taiwan implemented National Health Insurance on 1 March 1995, and the health insurance coverage rate currently exceeds 99%. The NHIRD collects nationwide medical data including inpatient, outpatient, and emergency room services, and the law requires that all hospitals and clinics report all medical expenses to the Bureau of National Health Insurance on a monthly basis. Consequently, National Health Insurance information can serve as representative empirical data in medical- and health-related research fields . ResearcIn this study, we selected patients under the age of 18 who were diagnosed with ADHD based on the International Classification of Diseases Ninth Revision (ICD-9) codes 314 between January 2000 and December 2010 from the NHIRD. The study design is of a cohort study. The case group consisted of minors under the age of 18 who suffered from ADHD with injury and who joined the National Health Insurance for medical treatment. The control group consisted of children who did not suffer from ADHD with injury. People in the case and control groups were matched in terms of index date, gender, and age at the ratio of 1:4. The following variables were included in the comparison: gender, age, income level (two groups consisting of patients from low-income and non-low-income families), catastrophic illness , Charlson Comorbidity Index (CCI), circumstance characteristics, injury type, injury severity, and cause of injury.Characteristics of circumstance included season of admission, urbanization level , level of care , and department of visit . CCI selects the first five diagnostic codes (ICD-9-CM N-Code), weighs these 5 codes according to 19 disease scoring criteria defined by Charlson, and calculates the total score. The higher the score, the greater number of complications or the more severe the diagnosis [The severity of injury was measured by length of stay (days), medical cost (USD), and prognosis . Injury types were classified into 13 groups in accordance with the ICD-9-CM  and the p < 0.05).The SPSS 20.0 statistical software was utilized in this research. The chi-square test/Fisher exact test, the independent samples t-test, and the percentage test were used to compare the differences between the ADHD children and non-ADHD children in demographics, cause of injury, CCI, and inpatient season. Furthermore, we used Cox regression to examine the injury rate of each independent variable .The two groups were also significantly different on the injury type . Open wop < 0.001). ADHD children in low-income families also show a significantly higher probability of getting hurt than their non-low-income family counterparts (p < 0.001). p = 0.031). In addition, not all patients had data available on their cause of injury because the NHIRD does not require medical institutions to provide that information. In this study, a total of 476 patients provided information on the cause of the injury; 68 were ADHD children and 408 were non-ADHD children . Based op < 0.031); ADHD is positively associated with an increased risk of injuries. Moreover, the literature also found that the severity of trauma was directly associated with ADHD [Previous studies have seldom reported the injury characteristics and severity of ADHD with long-term follow-up. This study attempted to fill in this gap by harnessing representative information from a large health insurance database. In general, ADHD children experience less severe consequences to risky behaviors and are less likely to develop prevention strategies and safety rules . It is aith ADHD , i.e., Aith ADHD . In our ith ADHD . Income ith ADHD . In our However, there are also differences in other studies. Davidson  reviewedAnalyzing the characteristics of injury yields a different result in this study. Several studies reported that the forms of injuries among ADHD children were different from those of non-ADHD children ,29, suchp = 0.017 and p < 0.001, respectively) during the spring and fall (when schools are in session). Carla et al. [In terms of the seasons, there is a significant difference in the risk of injury between ADHD children and non-ADHD children . There are two reasons for the reduction in the number of injuries in ADHD children with increasing age. First, ADHD children were often treated with medication to prevent injury. However, the evidence regarding prevention of injuries with medication is inconclusive [Moreover, the frequency of accidents could be predicted by ADHD, gender, and age . Figure nclusive . Moreovenclusive . Second,nclusive . Consequnclusive .In this study, we discovered that while ADHD does increase the risk of injury in children, as the patients get older, the difference in the risk of injury between ADHD and non-ADHD children gradually becomes smaller or even disappears completely. The injury incidence rate, average length of hospital stays, and average medical cost for ADHD children are all higher than for non-ADHD children. Additionally, among ADHD children, the low-income group has a higher incidence of injury than the non-low-income group. In comparing various causes of injury, ADHD children may suffer a higher risk in intentional injuries than non-ADHD children, but ADHD children actually experience a lower risk of injuries related to traffic incidents and falls. These findings will help develop new protocols and diagnostic criteria so that physicians are able to identify and report ADHD associations with injuries in a timelier manner. This issue is of great importance; nevertheless, it is simultaneously important to work with the latest and most accurate information. Future studies should investigate any changes in the observational period (every ten years) from 2011 to 2020, in areas such as awareness, organization, and support of ADHD children in any way, etc.


Background: Topographic memory is the ability to reach various places by recognizing spatial layouts and getting oriented in familiar environments. It involves several different cognitive abilities, in particular executive functions (EF), such as attention, working memory, and planning. Children with attention deficit hyperactivity disorder (ADHD) show impairments in inhibitory control, regulation of attention, planning, and working memory.Aim: The aim of this study was to evaluate the topographic memory in children with ADHD-combined subtype (ADHD-C).Method: Fifteen children (8–10 years) with a diagnosis of ADHD-C (DSM-5) (ADHD-C group) were compared to 15 children with typical development (TD group) of the same age. All children performed Raven's colored progressive matrices (CPM) test to obtain a measure related with cognitive functioning. The walking Corsi test , a large-scale version of the Corsi block-tapping test, was used to assess topographic memory in experimental environment.Results: A higher impairment was observed in ADHD-C than TD with significant differences in the WalCT, in particular on the topographic short-term memory (TSTM) task, on the topographic learning (TL) task, and on the repetition number (RN) task during the TL task. Perseverative errors were reported in performing the square-sequence in the WalCT. Zero-order correlations showed a positive correlation between TSTM and auditory attention, and memory of design of NEPSY-II and digit span of WISC-IV. No statistically significant differences were found between the ADHD-C group and TD group in the TL task in the WalCT condition.Conclusion: In ADHD-C, initial topographic learning was compromised whereas the long-term retention of learned topographical material seemed to not be impaired. In particular, these impairments seem to be linked with difficulties in sustained attention, in spatial memory for novel visual materials, in a poor working memory, and in perseverative behaviors. Human spatial cognition is a fundamental ability in humans. The visual and tactile world consists of objects situated in space, so it is essential from the first months of life to understand the characteristics of the surrounding area and object positions in it. This knowledge allows children to mentally and physically organize objects in their world. Indeed spatial awareness and spatial relations allow children to locate objects and navigate successfully in their environment, while spatial language allows children to express specific needs and describe the world .Topographic memory is one component of spatial cognition that corresponds to the ability to reach various places in the environment, recognize spatial layouts, orient in familiar environments , 3, and Topographic memory involves several cognitive processes and skills such as the ability to retain the spatial layout of an environment, to memorize and recognize complex visuo-spatial configurations, to find a shortcut between two locations, or to create an interconnected network among different paths –8. For aIndeed, human navigation develops gradually at distinct time points , 13, in Successful navigation is known to be strictly connected with the activity of several brain areas such as parieto-medial temporal networks , the posIn this regard, the investigation of the spatial navigation in children, presenting this selective impairment, may shed light on those factors causative of the development of navigational skills. For this purpose, the study of topographic memory in children with attention deficit hyperactivity disorder (ADHD) could be crucial as a disorder of EFs, which are proposed to be a core deficit of this pathology , 33. Wilexecutive functions could also affect learning processes. In particular, several studies and clinical evidence (Attention and executive functions (EF), in particular inhibition and VSWM, play a critical role in the development of topographic memory, so it is important to investigate the development of topographic memory in children with ADHD that tend to fail in tasks both requiring an attentional load and involving EF –46. Furtevidence –50 showeTo investigate the development of navigational skills in ADHD children, it is important to consider that the age period of 8–10 years represents a crucial developmental phase for both executive functions and navigational skills e.g., , 51–54].–54.51–54The aim of this study was to evaluate the topographic memory in children with ADHD-C compared with a group of typical developmental (TD) children. To this purpose, we used the WalCT , 65, 66,Does the ADHD-C group perform poorly on the topographic short-term memory task compared to TD children?Based on previous studies that confirmed a strong relationship between working memory and navigation , 67–74 aDoes the ADHD-C group perform poorly on topographic learning task compared to TD children?To our knowledge, this study is the first that assesses, in children with ADHD-C, not only some aspects of topographic short-term memory, but also the ability to learn new paths. It is known that sustained attention and flexibility in problem solving play an important role in learning and that these abilities seem to be compromised in children with ADHD , 49, 50.Does the ADHD-C group perform poorly on the topographic delayed recall (TDR) task compared to TD children? Few studies have assessed long-term memory  in children with ADHD. A recent meta-analysis  found thAre there any correlations between topographic memory and executive function performances in the ADHD-C group?Topographic memory involves several different cognitive abilities, in particular executive functions (EFs), such as attention and working memory , 22, 24.It is important to note that some navigational tasks might be impaired in both groups (children with ADHD and TD) because of age/stage of development. In particular, we considered the ability to use cognitive maps. Indeed, Lehnung et al.  showed tIn addition, the relation-place strategies required for cognitive mapping start to develop around 7 or 8 years of age and are fully functional by the age of 10 –60. TherFor this study, we assessed a sample of 100 children and adolescents (aged between 5.1 and 15.4 years), that had been referred to the Department of Human Neuroscience with a diagnostic suspicion of ADHD by parents, teachers, or a pediatrician. All children and parents underwent an initial interview with a child neuropsychiatrist who recorded the child's medical history, followed by an evaluation performed by a multidisciplinary team of experts constituted by a neuropsychiatrist and four psychologists. For the diagnosis, several neuropsychological and emotional tests were administered see .After this assessment, for the ADHD-C group, patients needed to meet the following criteria for hyperkinetic disorder (HKD) for ICD-10  and ADHDWe conducted an informal interview with parents of children that took part in the study as the control group (TD group) before the enrolment screening. None of these children had ever been previously reported for emotional, behavioral, or learning difficulties. No primary visual and hearing impairments, neurological and organic disease, or other neurodevelopmental issues were described. The individuals included in the study as TD had to meet the following criteria of inclusion: age 8–10, an average score on Raven's colored progressive matrices (percentile rank ≥ 37.5 = category average) , no emotWe administered Raven's colored progressive matrices to both groups to obtain a measure of non-verbal intelligence and to exclude the presence of a visuospatial deficit. All subjects were of Caucasian origin and came from families with middle-class socio economic status , confirmed during the interview with parents. TD children were recruited from primary schools, describing the study protocol individually to their parents. An informed written consent form, requiring active consent from caregivers, was signed. Each child, before taking part in the study, give an informed verbal assent. This research has been revised and approved by the Local Ethics Committees (Protocol number:416/16) in accordance with the tenets of the latest Declaration of Helsinki.All children in both the groups performed Raven's CPM to obtain a cognitive functioning measurement. The CPM is internationally recognized as a culture-fair test of non-verbal intelligence , 85 desiThe WalCT , 65, 66 It was set up in a wide room of the Department of Human Neuroscience. It was composed of nine green squares (30 × 30 cm) that were placed on a carpet on the floor, reproducing the same standard positions as used in the CBT see . In thisFollowing standard procedures , 65, 66,Topographic short-term memory (TSTM), in which a square span was obtained, that is, the number of squares in the longest sequence of squares that a child was able to repeat in the correct order immediately after the presentation.During the task, the number of squares to be reproduced gradually increased in length (from a 2-square sequences to a 9-square sequences). Children were required to reproduce the square sequences shown by the examiner by actually stepping on the green squares included in the sequence previously shown by the examiner.Topographic learning (TL), in which participants were asked to learn a fixed supra-span sequence (a path), which was calculated by considering the square span of the child + 2 squares according to standard procedures  of the supra-span sequence, in which 5 min later , participants were required to show the learned sequence. The examiner did not remind the child of the sequence and the child had to reproduce what he/she remembered of the long previously learnt sequence.At the end of the TDR task, the children had to use a felt-tip marker to retrace the pathway they had learned on the outline map of the WalCT .The whole protocol was administered in a single session on ~30 min at the Department of Human Neuroscience.For the aim of this study, descriptions and scores of the “attention and executive function” and “memory and learning” domains of NEPSY II  and the In NEPSY II , the subAnimal sorting (AS): assessing the ability to formulate basic concepts, to sort those concepts into categories, and to shift from one concept to another.Auditory attention (AA): assessing selective auditory attention and the ability to sustain it (vigilance).Visual attention (VA): assessing the ability to sustain selective visual attention.Response set (RS): the first task assesses the ability to shift and maintain a new and complex set involving both the inhibition of previously learned responses and correctly responding to matching or contrasting stimuli. In the second task, the child listens to a series of words and touches the appropriate circle when he/she hears a target word.Design fluency (DS): assessing the child's ability to generate unique designs by connecting up to five dots, presented in two arrays: structured and random.Inhibition (IN): assessing the ability to inhibit automatic responses in favor of novel responses and the ability to switch between response types (se types .The scores of the children with ADHD on the “attention and executive function” subtests of NEPSY II  are repoIn NEPSY II  the subtList memory (LM): assessing verbal learning and memory, rate of learning, and the role of interference in recall for verbal material.Memory for designs (MFD): assessing the spatial memory for novel visual material.Memory for faces (MFF): assessing the ability to encode facial features, as well as face discrimination and recognition.Memory for names (MFN): assessing the ability to learn the names of children over three trials.Narrative memory (NM): assessing the memory for organized verbal material under free recall, cued recall, and recognition conditions.Sentence repetition (SR): assessing the ability to repeat sentences of increasing complexity and length.Word list interference (WLI): assessing the verbal working memory, repetition, and word recall following interference : The examiner reads a series of numbers and the child has to repeat them. Then, the examiner again reads a series of numbers but this time the child is required to say them back in reverse order.Letter number sequencing (LNS): The examiner reads a series of letters and numbers and the child is required to repeat them back with the letters in alphabetical order and the numbers in numerical order . 2) test. Zero-order correlation was conducted to measure the strength and direction of association that exists between the ADHD-C group's performances in the WalCT and the performances in NEPSY II (To compare the performances of the two groups (ADHD-C vs. TD group) in the WalCT, we used the g formula of Hedges and Olkin , which cNEPSY II   based on the effect size, sample size, and parameter estimate from the data set, which found the following observed power for the variables considered: TSTM (0.93), TL (0.67), RN (0.76), OM (0.26), WalCT perseverative errors (0.88).To our current knowledge, this is the first study evaluating topographic memory in children with ADHD-C of a school age (ranging from 8 to 10 years) thus we conducted a Regarding the control variables of age and Raven score, the two groups were balanced for age but not for Raven score with a moderate Hedges' g .p > 0.05]. All children of both groups were of Caucasian origin and came from families with middle-class socio economic status.However, in examining the 95% CI for the effect size, for the Raven score, a mean difference of −3 with a 95% CI = −1.40 to 0.07 was not statistically significant because the CI included zero. Furthermore, the two groups were balanced for gender; the ADHD group was composed of three girls and 12 boys and the TD group consisted of five girls and 10 boys . In particular, the ADHD group committed a significantly higher number of perseverative errors than the TD group in the WalCT , and the memory of design task  of NEPSY II, and the digit span task  of WISC-IV  of NEPSY II was found (Zero-order correlations showed a positive correlation between the topographic short-term memory (TSTM) task and auditory attention (AA) task . It assessed the selective auditory attention and the ability to maintain concentrated attention over prolonged periods of time (vigilance or sustained attention). Children with ADHD-C could show a lower TSTM than TD because they could not sustain their concentration during the presentation of the sequences by the examiner. So, they were able to repeat only the first squares presented. To support of this hypothesis, Tucha et al.  assessedEventually, TSTM appears to be correlated with the memory for designs (MFD) task of NEPSY II that assessed spatial memory for novel visual material. In memory for designs, the child is shown a grid with four to ten designs on a page, which is then removed impeding the child from seeing the material to remember. The child then selects the designs from a set of cards and places the cards on a grid in the same location as previously shown .A low score on MFD may suggest difficulty with route memorization for details, with location of visual stimuli details in the two-dimensional space and with learning for visuospatial information. Although there are few studies using tests to assess visuo-spatial working memory (VSWM) in children with ADHD-C, our findings are consistent with Westerberg et al. , who shoFurthermore, children with ADHD-C performed significantly worse than controls in topographic learning (TL), they made more mistakes in executing the square-sequence path and needed a significantly higher number of repetitions to learn the path than children with typical development.It is known that the maintenance of attention and cognitive flexibility play an important role in learning , 49, 50.Furthermore, Robaey et al.  based onUnlike previous studies , 121, weWe did not find significant differences between the two groups on the WalCT outline map task. Generally, all children of both groups showed difficulties in reproducing the learned path on the map. This finding is consistent with previous studies that showed how some aspects of human navigation are acquired later mainly because the neural bases underlying different processes have different maturational rates. Indeed, the neural structures that allow path integration and reorientation are already fully developed in toddlers, whereas more complex navigational skills require the activity of neural areas  which present a prolonged development, continuing into adolescence , 54.Based on our findings it would seem that children with ADHD-C have a poor topographic span and a specific impairment in learning a new path, but when it is acquired, they have no difficulty in keeping it in their memory and repeating it after 5 min. In fact, children with ADHD-C presented significantly worse performances than controls in the topographic short-term memory (TSTM) and topographic learning (TL) tasks but not in topographic delayed recall (TDR). These impairments are probably due to the difficulty of maintaining their attention over prolonged periods of time (sustained attention), a spatial memory for novel visual material, poor working memory and visuo-spatial working memory, and perseverative behaviors. In regard to perseverative behaviors, children with ADHD-C tend to repeat the committed errors even if feedback suggests that their response is ineffective or maladaptive. Based on these results and on the conducted studies by Monfardini et al. , it woulThis study presents some limitations: the sample size does not allow for generalizations about findings and for such a reason we could not investigate the presence of individual differences (such as gender) on topographic memory in our sample, although previous studies found no gender differences in children aged 4–11 years on WalCT performance . We follFurther studies should compare different subtypes of ADHD [predominantly inattentive ADHD (ADHD/I) vs. hyperactive-impulsive subtype (ADHD/HI) vs. ADHD-C] to evaluate if there are differences between these groups in topographic memory and to better understand the role of attention, hyperactivity, and impulsivity in navigational performances.Eventually, several previous studies showed cortical maturation delay in ADHD children, particularly in prefrontal regions, relevant for the attention, planning, and navigational abilities that often disappear during adolescence [e.g., , 126–129The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee Of Policlinico Umberto I, Rome, Italy (Protocol number:416/16). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.MV recorded clinical data. NF conducted the research and wrote the manuscript with LP. SR and DA analyzed clinical data and conducted the statistical analysis. VG, GN MR, and CG coordinated and supervised the work and critically reviewed the manuscript. VB revised the English language editing. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Is prenatal analgesic opioid exposure associated with attention-deficit/hyperactivity disorder (ADHD) in children?In this cohort study of 73 480 children, with a mean follow-up of 11 years, no association between timing of analgesic opioid exposure during pregnancy and ADHD was found. The risk of ADHD diagnosis was elevated after exposure to opioids for 5 or more weeks compared with exposure for 4 weeks or less.The increased risk of ADHD observed in this study may be driven by longer duration of exposure; however, the role of residual or unmeasured confounding cannot be excluded, and this finding requires further study. This cohort study examines the association of timing and duration of prenatal analgesic opioid exposure with attention-deficit/hyperactivity disorder (ADHD) in children. Prior studies have reported that the use of illicit opioids during pregnancy is associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring; however, evidence regarding the association of analgesic opioids is limited.To examine the association of timing and duration of prenatal analgesic opioid exposure with ADHD in children.This cohort study uses data from the Norwegian Mother, Father and Child Cohort study (1999-2008), a nationwide birth cohort study linked to national health registries, with a mean (SD) follow-up of 10.8 (2.2) years. A total of 73 784 live-born singleton children born to 62 013 mothers who reported a pain-related condition before and/or during pregnancy were included, with 2 comparator groups: (1) mothers who did not use any opioids and (2) mothers who used opioids before pregnancy only. Data were analyzed from June to December 2020.Maternal self-report of analgesic opioid use during pregnancy, by timing (early and middle and/or late) and duration (≥5 weeks vs ≤4 weeks).Diagnosis of ADHD or filled prescription for ADHD medication in children and symptoms of ADHD at child age 5 years, measured by Conners’ Parent Rating Scale–Revised. Inverse probability of treatment weights were used to control for measured confounding. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs.The analyses of ADHD diagnosis and ADHD symptoms included 73 480 children  and 31 270 children , respectively. Overall, 1726 children in the ADHD diagnosis sample (2.3%) and 667 children in the ADHD symptom sample (2.1%) were exposed to an analgesic opioid at least once during gestation. No associations between timing of prenatal analgesic opioid exposure and ADHD diagnosis or symptoms was found. Exposure for 5 or more weeks was associated with an increased risk of ADHD diagnosis  compared with exposure for 4 weeks or less; however, there was no such association for the risk of ADHD symptoms.In this cohort study, a slightly elevated risk of ADHD diagnosis after prenatal analgesic opioid exposure for 5 or more weeks was found compared with exposure for 4 weeks or less. This result may be driven by longer duration of use; however, the role of residual or unmeasured confounding cannot be excluded. This finding needs to be replicated in other studies. Currently, there is a knowledge gap regarding the association of prenatal analgesic opioid exposure with ADHD. This study sought to fill this gap by focusing specifically on women using analgesic opioids for pain management. The aim of this study was to examine the association between timing and duration of prenatal analgesic opioid exposure and (1) ADHD diagnosis and/or filled prescription for ADHD medications and (2) ADHD symptoms at child age 5 years.Associations of prenatal opioid exposure with ADHD have been observed; however, prior studies have mainly been done in selected populations, such as women receiving opioid maintenance treatment or among women with opioid dependence.STROBE) reporting guideline was followed.This study used data from the Norwegian Mother, Father and Child Cohort study (MoBa) (data version 9), the Medical Birth Registry of Norway (MBRN), the Norwegian Prescription Database (NorPD), and the Norwegian Patient Registry (NPR), linked via the woman’s personal identification number and pregnancy sequence  17 or 18. The initial participation rate was 41%, and the cohort now includes 114 500 children, 95 200 mothers, and 75 200 fathers. Mothers were followed up by paper-based questionnaires during pregnancy (in GW 17 [Q1] and 30 [Q3]) and after the child was born .MoBa is a prospective population-based pregnancy cohort conducted by the Norwegian Institute of Public Health.24 The NorPD contains information about all prescribed medications (irrespective of reimbursement) to individuals in ambulatory care since 2004.25 The NPR contains records on admission to hospitals and specialist health care on an individual level since 2008.26 The data include date of admission and discharge as well as primary and secondary diagnosis and cover all government-owned hospitals and outpatient clinics and all private health clinics that receive governmental reimbursement. Diagnostic codes in the NPR follow the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).MBRN includes information on pregnancy, delivery, and neonatal health for all births from GW 12 in Norway.27 The list of included pain conditions is found in eTable 1 in the We included live-born singletons with a record in MBRN, born to women who completed the 2 prenatal questionnaires  in MoBa. Women with unknown timing of analgesic opioid exposure as well as women who reported a drug used for opioid maintenance treatment were excluded. We restricted the population to women reporting an underlying indication for treatment with analgesic opioids, ie, pain conditions, to emulate the design of a hypothetical clinical trial.28 The exposed group included children of women who reported use of analgesic opioids in pregnancy, defined as reporting of ATC code N02A. Individual substances included in the exposure definition appear in eTable 2 in the Information about medication use was obtained from MoBa Q1, Q3, and Q4. Women reported the name of the medication taken along with timing of use  according to listed indications. All medications were coded according to the Anatomical Therapeutic Chemical (ATC) classification system.First, we examined the association of ever use of analgesic opioids in pregnancy and ADHD. Then, we examined the association of timing and duration of analgesic opioid exposure. Timing was categorized as early pregnancy (first trimester) and middle and/or late pregnancy (second and/or third trimester), while duration of exposure was defined according to whether a single interval (use in ≤4 weeks) or multiple 4-week intervals (use in ≥5 weeks) were indicated on the questionnaires.Among women with pain ailments before and/or during pregnancy, we defined 2 comparison groups; first, a broad group consisting of children of women who did not report use of analgesic opioids  and, second, a narrower comparison group consisting of children of women who used analgesic opioids prior to pregnancy only (prepregnancy users only). The second comparator group was included to minimize residual confounding, given that these children have mothers whose confounder distribution may be more similar to the mothers of children exposed to opioids during pregnancy.ICD-10 code, F90) from 2008 to 2015 and/or at least 1 filled prescription for an ADHD medication  in NorPD between 2004 and 2016. The ICD-10 code F90 (hyperkinetic disorder) requires the combination of both inattentive and hyperactive symptoms. The drugs listed are licensed in Norway and used for treatment of ADHD. Diagnosis and treatment are started in the specialist health care service, and 80% of children with an ADHD diagnosis receive pharmacotherapy. There is no lower age limit for receiving a F90 diagnosis; however, it is rare in children younger than 5 years.30 Most children in MoBa were born in 2004 or later, and children born from 1999 to 2003 have available outcome data from age 4 years at the latest  included in the MoBa questionnaire at Q–5 years. Thus, the sample was further restricted to those with available outcome data at 5 years. Mean scores were calculated and standardized. Higher 33 We included the following covariates in our analyses: maternal age, marital status, maternal education, maternal income, parity, prepregnancy body mass index , folic acid supplement, smoking habits, alcohol use, illicit drug use, maternal chronic conditions in early pregnancy, symptoms of anxiety and depression (measured by a short version of the Hopkins Symptoms Checklist34 in Q1), number of pain episodes and comedications during pregnancy, and familial risk of ADHD . Additional factors  were considered under alternative model specifications –based methods with inverse probability of treatment weights (IPTW).P < .05, and all tests were 2-tailed. All statistical analysis were performed using Stata MP version 16.1 (StataCorp). Data were analyzed from June to December 2020.To estimate the hazard ratio (HR) for ADHD, we performed crude and weighted Cox regression analysis with robust standard errors. We used child age in years as the time scale and a quadratic term for year of birth. The follow-up period started at birth and ended on the date of ADHD diagnosis, date of first drug prescription for ADHD, or December 31, 2016, whichever came first. To estimate standardized mean differences in ADHD symptoms, we fit crude and weighted generalized linear models with robust standard errors. Statistical significance was set at 40 In a subsample of women with data available in both MoBa and NorPD (2004-2009), we crosschecked maternal self-reported opioid use with NorPD data and looked at the average defined daily dose (DDD) dispensed to describe the amount of opioids. More information and additional sensitivity analyses are presented in the eMethods in the We performed several subgroup and sensitivity analyses. First, we conducted separate models for all exposure definitions that considered additional parental and child factors under alternate model specifications .We had 73 480 children of 61 753 mothers with data on ADHD diagnosis  and 31 270 children of 26 017 mothers with data on ADHD symptoms  . Most chIn total, 2211 children (3.0%) had ADHD, and We found no associations between ever exposure to analgesic opioids during pregnancy and symptoms of ADHD at child age 5 years  compared with no exposure. No associations were found in analyses of timing or duration  .The point estimates under alternative model specifications were generally consistent with main findings  or symptoms  compared with no exposure. We found no associations between children exposed to analgesic opioids not in combination with paracetamol and ADHD diagnosis  or ADHD symptoms  compared with no exposure during pregnancy  for receiving a diagnosis of hyperkinetic disorder following ever exposure in pregnancy and an HR of 2.20  for ADHD diagnosis following exposure to paracetamol for more than 29 days during pregnancy. Whether this association is causal or due to bias is a debated topic.46 The combined product of paracetamol and codeine may be used under circumstances that are more heterogeneous than stronger opioids, and our latter finding may indicate that confounding might play a larger role on our findings.The most reported substance among opioid exposed women was the combined product of codeine and paracetamol, and our results are most representative for this substance. Therefore, disentangling the sole association of opioids may be challenging. We tried to address this by excluding women using the combined product in a sensitivity analysis, and we found no associations with ADHD or symptoms among children with vs without exposure. Prior studiesLonger duration of use may be indicative of a more severe pain condition. We tried to address this by including number of reported pain episodes in our models as a proxy of pain severity. We acknowledge the lack of data of how severe this pain was, and we cannot rule out unmeasured confounding by pain severity.47 and we tried to address this by including information about proxies of parental ADHD  in all models and maternal ADHD traits in a subsample. This did not substantially change our main estimates; however, we cannot exclude the role of unmeasured genetic factors in this study.48ADHD and its symptoms are highly heritable,48 discuss several early-life exposures  associated with neurodevelopmental risk alleles. None of these factors was of an order of magnitude that could account for our observed association. However, we cannot exclude a possible role of residual or unmeasured confounding on our results.To evaluate unmeasured confounding, we found that an E value of 2.58 was required to explain our association in the duration analysis. Leppert et alIf the association between prenatal analgesic opioid exposure and ADHD were causal, we would have expected a higher proportion of children displaying ADHD symptoms at age 5 years and a positive association in our positive control analysis of opioid-containing cough medications. However, we cannot rule out that loss of follow-up in the MoBa study have affected our findings on ADHD symptoms. Future studies on the long-term safety of analgesic opioids should include measures of dose and pain severity and include more domains of neurodevelopment, including cognition.23 Although association measures have been shown to be valid in MoBa in relation to immediate birth outcomes,50 we cannot rule the impact of selection bias on our results regarding ADHD symptoms when children were aged 5 years. Furthermore, the ADHD symptoms were parent reported,51 and although outcome misclassification cannot be ruled out, this was probably nondifferential. Also, the internal consistency of the CPRS-R is high (Cronbach α = 0.9). Due to low sample size, it was not possible to study the associations of individual opioids. We were not able to identify whether a clear duration association was in place due to low power, which prevented us from looking at more granular duration groups. Another limitation is that we did not have information regarding dosage or duration of use of opioids in MoBa. A mother who had reported use of opioids during one 4-week interval may have used the drug only once or possibly every day. However, mothers who reported use during 2 or more 4-week periods  are more likely to have consumed a higher total dose. This assumption is supported by results from the DDD analysis that showed that mothers who reported opioids in 4 or fewer weeks were dispensed an average of 8.6 DDD, and mothers who reported use in 5 or more weeks were dispensed on average 37.2 DDD. However, any conclusions with regard to duration should be interpreted with caution, as this is representative for only a subsample and not all prescribed medications are actually taken.52This study has limitations. The MoBa study has a moderate participation rate (41%), with a possibility of self-selection of the healthiest women into the cohort.In this cohort study, we found no associations between the timing of analgesic opioid exposure during pregnancy and ADHD, both as diagnosis and symptoms. The risk of ADHD was slightly increased after exposure for 5 or more weeks compared with exposure for 4 or fewer weeks. This result may be associated with longer duration of use, but we cannot exclude the potential role of residual or unmeasured confounding. This finding needs to be replicated in other studies. Adequate pain management in pregnancy should be discussed on an individual patient level, bearing in mind the benefits and risks of different analgesic therapies.