A systematic review of attention-deficit/hyperactivity disorder in people living with cystic fibrosis.

There is a lack of research that has focused on attention-deficit hyperactivity disorder (ADHD) in people with cystic fibrosis (pwCF). Given ADHD is associated with executive functioning impairments, exploring ADHD in the context of living with cystic fibrosis (CF) is of great importance. The purpose of the current systematic review was to examine ADHD in pwCF across the lifespan in terms of its prevalence, its impact on various health outcomes, and treatments for managing ADHD. This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles reporting studies of any design that focused on ADHD in pwCF were included. Studies were excluded if they did not meet this criterion and if they were written in languages other than English. PsycINFO, MEDLINE, EMBASE, and CINAHL databases were searched. Search items were based on three concepts: (1) terms related to CF, (2) terms related to ADHD, and (3) terms related to age. Ten studies were included in this systematic review. Reported prevalence rates of ADHD in pwCF ranged from 5.26% to 21.9%. The reported relationships between ADHD and CF and other health outcomes is inconsistent. In terms of treatment considerations, pharmacological interventions and behavioural strategies for managing ADHD in the context of living with CF have been reported as being successful. Additional research is needed to further explore ADHD in the CF population and health variables that may be associated with CF prognosis.

Prevalence and Related Factors of Attention Deficit Hyperactivity Disorder in School-age Children With Atopic Dermatitis.

Context: Atopic dermatitis (AD) is a chronic inflammatory skin disease and commonly affects children. AD is associated with a high incidence of ADHD, the most common psychological and neurobehavioral disorder in children and adolescents. If clinicians don't identify ADHD and intervene early, preschool children can experience adverse effects. Objective: The study intended to investigate the prevalence of attention deficit hyperactivity disorder (ADHD) in preschool children with AD, analyze the associated factors, and provide insights for early identification of risk factors and the development of interventions to reduce the likelihood of ADHD occurrence. Design: The research team performed a prospective, observational, case-control study. Setting: The study took place at the Zhoushan branch of Ruijin Hospital at the Shanghai Jiaotong University School of Medicine in Zhoushan, Zhejiang, China. Participants: Participants were 80 school-aged children diagnosed with AD and admitted to the hospital between May 2019 and May 2023. Groups: Based on the presence or absence of ADHD, the research team divided the children into two groups: (1) the Simple AD group with 71 participants with AD only, and the AD + ADHD group, with 9 participants with AD and ADHD. Outcome Measures: The research team: (1) collected and analyzed participants' demographic and clinical data, including an assessment of the AD severity using the SCORing Atopic Dermatitis (SCORAD) scale and the presence of sleep disorders using the Children's Sleep Habits Questionnaire (CSHQ); (2) assessed the presence of ADHD using the Swanson, Nolan, and Pelham-IV rating scales (SNAP-IV); (3) analyzed the factors influencing the occurrence of ADHD in AD children, using univariate and multivariate logistic regression analysis. Results: Among the 80 school-age children with AD, 9 participants (11.25%) had received a diagnosis of ADHD. The AD + ADHD group's age (P < .001); body mass index (BMI), with P < .001; AD severity (P = .013); rate of sleep disorders (P = .001); and levels of serum interleukin 6 (IL-6), with (P < .001), interleukin 4 (IL-4), with (P < .001), and nerve growth factor (NGF), with (P < .001) were all significantly greater than those of the Simple AD group. The univariate logistic regression analysis indicated that age (P = .014), BMI (P = .024), AD severity (P = .022), sleep disorders (P = .042), and levels of IL-6 (P = .044), IL-4 (P = .045), and NGF (P = .046) were all significantly related to the development of ADHD in school-age children with AD. The multivariate logistic regression analysis revealed that sleep disorders (P = .018) and elevated levels of serum IL-6 (P = .032), IL-4 (P = .021), and NGF (P = .016 ) were independent risk factors for ADHD (OR = 2.651, 3.074, 2.686, 3.340). Conclusions: School-aged children with AD are more likely to develop ADHD, which is mainly associated with sleep disorders and elevated levels of serum IL-6, IL-4, and NGF. Clinicians should give attention to these risk factors and implement early interventions to reduce the risk of children with AD developing ADHD.

Are congenital heart defects connected to more severe attention-deficit/hyperactivity disorder?: A systematic review and meta-analysis.

BACKGROUND: Congenital heart defects (CHDs) are the most common cause of birth defect-related infant morbidity and mortality, affecting 1% of 40,000 births per year in the United States. On the other side, the etiology of attention-deficit/hyperactivity disorder (ADHD) is multifactorial. Multiple studies have found that cardiac surgery patients have higher morbidity of having this disorder. Many studies have investigated the prevalence of ADHD in different subtypes of CHD, but few have focused on the severity of ADHD symptoms. Thus, we conducted this systematic review and meta-analysis to investigate the severity of ADHD symptoms in CHD patients. METHODS: We searched PubMed, Embase, Scopus, and Web of Science were searched from inception to March 6, 2023 without any restrictions. We included observational studies published in English language that evaluated burden of symptom of ADHD in CHD patients. Moreover, the standardized mean difference (SMD) for continuous outcomes with 95% confidence interval (CI) was pooled. P-values <.05 are considered as significant, and we performed all statistical analyses using RevMan software Version 5.4.1. RESULTS: Eight studies were included in our review with a total number of 120,158 patients. CHD was associated with a statistically significant increase in both ADHD index T score and ADHD Hyperactivity-Impulsivity Subscale (informant) with (SMD = 0.65, 95% CI [0.40, 0.90], P < .00001, I2 = 81%) and (SMD = 0.16, 95% CI [0.04, 0.28], P = .008, I2 = 0%). Regarding ADHD Inattention Subscale (informant), the pooled data showed that a significant increase of this score in the CHD group (SMD = 0.25, 95% CI [0.13, 0.37], P < .001, I2 = 0%), and ADHD Combined Score (informant) showed a significant increase of this score in the CHD group (SMD = 0.23, 95% CI [0.11, 0.35], P = .0002, I2 = 0%). CONCLUSION: Our study revealed a strong association between CHD and not only ADHD, but also the severity of ADHD, making early diagnosis of ADHD in children with CHD a mandatory step in the clinical evaluation practice to improve these children on both clinical and psychological aspects.

Attention-deficit/hyperactivity disorder is not associated with overweight in adolescence but is related to unhealthy eating behavior and limited physical activity.

PURPOSE: The aim of the study was to examine the possible relation between adolescent ADHD and high BMI, studying also eating behavior and physical activity. METHODS: The data were collected from the Northern Finland Birth Cohort 1986. The follow-up at the age of 16 consisted of a self-assessment form and clinical examination where height and weight were measured and questionnaires on physical activity and eating habits was completed. ADHD diagnosis was based on a diagnostic interview with adolescents and parents according to DSM-IV-TR criteria. The participants were divided into the following study groups: individuals with adolescent ADHD (n = 90), those with only childhood ADHD (n = 40), and community controls (n = 269). RESULTS: Results showed no significant differences in BMI, but adolescents with ADHD seemed to have unhealthier eating habits than controls; they ate less often vegetables and breakfast, devoured more often, and consumed more fast food, soft drinks, sweets, and potato crisps daily. Individuals with adolescent ADHD reported light exercise more often but strenuous exercise more seldom than controls. Those with only childhood ADHD did not significantly differ from community controls regarding health behaviors. CONCLUSIONS: There was no relation between ADHD and high BMI but adolescents with ADHD had unhealthier eating habits than those without ADHD. It is conceivable that unhealthy eating behaviors in adolescence might be a risk factor for the development of later overweight; however, the longitudinal associations between ADHD, unhealthy eating behaviors and overweight have not been considered in the present study and remain to be examined further.

Epilepsy severity mediates association between mutation type and ADHD symptoms in tuberous sclerosis complex.

The association between attention-deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0-16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early-onset and severe epilepsy in the first 2 years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early-onset epilepsy across syndromic and non-syndromic populations.

The role of inflammation in the prospective associations between early childhood sleep problems and ADHD at 10 years: findings from a UK birth cohort study.

BACKGROUND: Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross sectional. We investigate (a) the association between early childhood sleep and probable ADHD diagnosis in childhood and (b) whether childhood circulating inflammatory markers mediate these prospective associations. METHODS: Data from the Avon Longitudinal Study of Parents and Children were available for 7,658 10-year-old children. Parent-reported sleep duration, night awakening frequency and regular sleep routines were collected at 3.5 years. The Development and Wellbeing Assessment was administered to capture children with clinically relevant ADHD symptoms, or probable ADHD diagnosis. Blood samples were collected at 9 years, from which two inflammatory markers were obtained [interleukin-6 (IL-6) and C-reactive protein (CRP)]. Logistic regression analyses were applied to investigate the associations between sleep variables at 3.5 years and probable ADHD diagnosis at 10 years. Further, path analysis was applied to examine the potential mediating role of inflammation at 9 years (as measured by CRP and IL-6) in the associations between early sleep and ADHD at 10 years. RESULTS: Less regular sleep routines (OR = 0.51, 95% CI = 0.28-0.93, p = .029), shorter nighttime sleep (OR = 0.70, 95% CI = 0.56-0.89, p = .004) and higher night awakening frequency (OR = 1.27, 95% CI = 1.06-1.52, p = .009) at 3.5 years were associated with higher odds of ADHD at 10 years. Further, IL-6 at 9 years, but not CRP, mediated the association between irregular sleep routines and ADHD (bias-corrected estimate, -0.002; p = .005) and between night awakening and ADHD (bias-corrected estimate, 0.002; p = .003). CONCLUSIONS: Several sleep problems in early childhood constitute a risk factor for probable ADHD diagnosis at 10 years. Further, these associations are partially mediated by IL-6 at 9 years. These results open a new research vista to the pathophysiology of ADHD and highlight sleep and inflammation as potential preventative targets for ADHD.

Diagnosis and treatment of intractable idiopathic orofacial pain with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with primary chronic pain syndromes, such as fibromyalgia, migraine, and chronic low back pain. Although idiopathic orofacial pain (IOP) is classified as burning mouth syndrome or persistent idiopathic facial or dentoalveolar pain and as a primary chronic pain, the association between IOP and ADHD has not been investigated. This retrospective cohort study investigated the severity of ADHD symptoms measured using the ADHD scale and the effects of treatment using ADHD drugs and the dopamine system stabilizer aripiprazole. The participants were 25 consecutive patients with refractory IOP referred to a psychiatrist and diagnosed with coexisting ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5. The ADHD scale scores were higher in patients with intractable IOP than those in the general population. Pharmacotherapy used in this study led to clinically significant improvements in pain, anxiety/depression, and pain catastrophizing. Intractable IOP and ADHD were shown to be associated. In the future, screening and pharmacotherapy for ADHD should be considered in the treatment of intractable IOP.

Association between attention deficit hyperactivity disorder and outcomes after metabolic and bariatric surgery: a nationwide propensity-matched cohort study.

BACKGROUND: The risks and benefits of metabolic and bariatric surgery for patients with attention deficit hyperactivity disorder (ADHD) remain to be investigated. OBJECTIVE: The aim of this study was to assess short- and long-term outcomes after metabolic and bariatric surgery in patients with previous ADHD compared with matched control individuals. SETTING: Registry based. METHODS: This 2-staged matched-cohort study included all adults with a body mass index of ≥30 kg/m2 who underwent primary Roux-en-Y gastric bypass or sleeve gastrectomy from 2007 until 2017 registered in the Scandinavian Obesity Surgery Registry. Patients with prescribed medication for ADHD were matched with control individuals without ADHD with a follow-up of up to 11 years after surgery. RESULTS: Among 1431 patients with ADHD and 2862 control individuals (mean body mass index, 42 kg/m2; mean age, 35 years), no difference in weight loss or follow-up attendance over 2 years was seen. ADHD was associated with a higher risk for early postoperative complications (odds ratio [OR] = 1.31; 95% confidence interval [CI], 1.05-1.63), self-harm (hazards ratio [HR] = 1.39; 95% CI, 1.11-1.75), and substance abuse (HR = 1.34; 95% CI, 1.16-1.55), while associations with overall mortality (HR = 1.42; 95% CI, .99-2.03), major adverse cardiovascular and cerebrovascular events (HR = 1.93; 95% CI, .98-3.83), and effects on obesity-related diseases were uncertain. ADHD was associated with a lower health-related quality of life in all aspects before surgery. These differences increased for mental and obesity-related aspects but remained unchanged over time for physical aspects. CONCLUSIONS: Compared with patients without ADHD, patients treated pharmacologically for ADHD experience similar weight loss and remission of obesity-related diseases without an increased risk for serious complications but report a lower health-related quality of life and have an increased risk of substance abuse and self-harm. This further emphasizes the need for close follow-up care for this group of individuals.

Psychiatric disorders and Type 2 diabetes mellitus: A bidirectional Mendelian randomization.

BACKGROUND: Extensive observational evidence put forward the association between psychiatric disorders and type 2 diabetes mellitus (T2DM). However, causal relationships between these two diseases required further research. Thus, we evaluated the bidirection casual effect between five psychiatric disorders and T2DM using two-sample mendelian randomization (MR). METHODS: By selecting single nucleotide polymorphisms associated with T2DM and five psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia, anxiety disorder and panic disorder), a bidirectional two-sample MR was applied to evaluate causality between these diseases. The inverse-variance weighted (IVW) method was used as the primary analysing approach for estimating possible causal effects. MR-Egger and weighted median were also conducted to verify the results. The funnel plot, Cochran's Q test and MR-Egger intercept test were used for sensitivity analyses. In addition, potential mediators were investigated by risk factor analyses. RESULTS: Genetic susceptibilities of ADHD and MDD would increase the risk of T2DM (ADHD: OR = 1.14, 95%CI 1.08-1.20; p = 5.7 × 10 - 6 ; MDD: OR = 1.22, 95%CI 1.09-1.36; p = 0.0004 ). In addition, genetic predisposition to T2DM was also associated with ADHD (OR = 1.09, 95%CI 1.04-1.14; p = 0.0004). Several risk factors of T2DM were implicated in the above causal associations, including smoking, high body mass index, waist-to-hip ratio and elevated serum triglycerides. CONCLUSION: Our studies indicated a causal effect of ADHD and MDD on increasing the risk of T2DM, which was potentially mediated by smoking and obesity-related phenotypes. Meanwhile, we found a causal effect of T2DM on ADHD. Thus, prevention strategies for T2DM should also include mental health and vice versa.

Attention-deficit/hyperactivity disorder and ischemic stroke: A Mendelian randomization study.

BACKGROUND: Observational studies have found an association between attention-deficit/hyperactivity disorder (ADHD) and ischemic stroke. AIMS: The purpose of this study was to investigate whether genetic liability to ADHD has a causal effect on ischemic stroke and its subtypes. METHODS: In this two-sample Mendelian randomization (MR) study, genetic variants (nine single-nucleotide polymorphisms; P < 5 × 10-8) using as instrumental variables for the analysis was obtained from a genome-wide association study of ADHD with 19,099 cases and 34,194 controls. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium, with 40,585 cases and 406,111 controls. MR inverse variance-weighted method was conducted to investigate the effect of genetic liability to ADHD on ischemic stroke and its subtypes. Sensitivity analyses (median-based methods, MR-Egger, MR-robust adjusted profile scores, MR-pleiotropy residual sum and outlier) were also utilized to assess horizontal pleiotropy and remove outliers. Multivariable MR (MVMR) analyses were conducted to explore potential mediators. RESULTS: Genetically determined ADHD (per 1 SD) was significantly associated with a higher risk of any ischemic stroke (AIS) (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.05-1.25, P = 0.002) and large-artery atherosclerotic stroke (LAS) (OR = 1.40, 95% CI = 1.10-1.76, P = 0.005). The significant association was also found in sensitivity analyses and MVMR analyses. CONCLUSIONS: Genetic liability to ADHD was significantly associated with an increased risk of AIS, especially LAS. The association between ADHD and LAS was independent of age of smoking initiation but mediated by coronary artery disease.

The Effects of Attention Deficit Hyperactivity Disorder and Other Psychiatric Comorbidities to Outcomes in Trauma Patients.

BACKGROUND: Psychiatric illnesses affect outcomes in trauma. Studies have examined the relationship between depression, schizophrenia, post-traumatic stress disorder, and other mental disorders with trauma, yet few have examined attention-deficit-hyperactivity disorder (ADHD). Attention-deficit-hyperactivity disorder has been suggested to increase the risk of injury, but severity and outcomes of the injury are not frequently studied. The relationship of additional psychiatric disorders in patients with ADHD to traumatic injury was also examined in this study. METHODS: A 5-year retrospective analysis was performed using the trauma registry of an urban ACS verified level 1 trauma center. Patients with ADHD were separated into ADHD Only and ADHD+ (having additional psychiatric comorbidities) and compared to a matched population of non-ADHD patients and patients with non-ADHD psychiatric disorders to analyze their demographics and outcomes. Descriptive statistics were used to analyze the data as appropriate. RESULTS: Seventy-three patients with ADHD were identified, with over half having additional psychiatric comorbidities (58.9%). The majority of ADHD patients were White (54.8%) vs Black (61.6%) at admission. At admission non-ADHD patients had significantly fewer psychiatric comorbidities (11%) compared to ADHD patients (58.9%). ADHD with psychiatric comorbidities patients had significantly higher ISS and longer hospital LOS. However, GCS and ICU LOS were not different between the two groups. CONCLUSIONS: Patients with ADHD were significantly more likely to have psychiatric comorbidities and experience worse outcomes compared to patients without ADHD.

Iron Deficiency in Infancy and Sluggish Cognitive Tempo and ADHD Symptoms in Childhood and Adolescence.

OBJECTIVE: To determine whether iron deficiency in infancy is associated with sluggish cognitive tempo (SCT) or attention-deficit/hyperactive-impulsive (AD-HI) symptoms in childhood and adolescence, and whether such behaviors contribute concurrently and predictively to lower verbal and mathematical abilities. METHOD: Chilean children (N = 959; 50% male, of Spanish or indigenous descent from working-class backgrounds) were rated by mothers for SCT or AD-HI symptoms at ages 5, 10, and 16 years. Children completed standardized tests assessing verbal and mathematical abilities at ages 5, 10, and 16. At ages 12 and 18 months, children were assessed for iron deficiency. RESULTS: Adjusting for a comprehensive panel of covariates, greater severity of iron deficiency in infancy was associated with more frequent SCT and AD-HI symptoms at all ages studied. Most effects of iron deficiency on children's verbal and math skills were indirect, mediated through AD-HI behaviors. Children's AD-HI symptoms related to lower verbal and math test scores within age and across age. CONCLUSIONS: The long-term associations found between infant iron deficiency and SCT and AD-HI behaviors suggest that the neurodevelopmental alterations that stem from postnatal iron deficiency might play an etiological role in the development of ADHD. Screening for early-life nutritional deficiencies among children with SCT or ADHD symptoms might prove useful, and behavioral screening of children with a history of iron deficiency seems warranted. Interventions that support brain development after early nutritional deprivation also would be beneficial.

Association between history of attention-deficit/hyperactivity disorder diagnosis and cardiovascular disease in U.S. adults.

OBJECTIVE: To examine the association between attention-deficit/hyperactivity disorder (ADHD) and cardiovascular disease (CVD) in a nationally representative population sample of adults in the United States. METHOD: We included adults aged 18 years or older who participated in the National Health Interview Survey 2007 and 2012, because information about ADHD diagnosis among adults was only available in these two cycles. Physician-diagnosed ADHD and CVD were defined based on an affirmative response in the questionnaire during a household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of CVD. RESULTS: This analysis included 57,728 adults (weighted mean age 46.20 years; 47.66% males). Among them, 1,790 reported physician-diagnosed ADHD, 7,906 had CVD, 4,061 had coronary heart disease (CHD), and 1,749 had stroke. The age-adjusted prevalence of CVD was 19.72% (95% CI [16.56%, 22.88%]) among individuals with ADHD, and 12.09% (95% CI [11.75%, 12.43%]) among those without ADHD. After adjustment for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of CVD, CHD and stroke in association with ADHD was 2.06 (95% CI [1.58, 2.68]), 1.88 (95% CI [1.31, 2.69]), and 1.75 (95% CI [1.07, 2.86]), respectively. CONCLUSIONS: In a nationally representative sample of U.S. adults, we found a significant, positive association between a history of ADHD diagnosis and CVD. Further investigation is needed to replicate our findings and determine the underlying mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Sluggish cognitive tempo profiles in survivors of childhood cancer as compared to children with attention-deficit/hyperactivity disorder.

PURPOSE: Neurocognitive late effects including problems with attention have been reported in pediatric oncology survivors. While some researchers have characterized these late effects as similar to symptoms of attention-deficit/hyperactivity disorder, inattentive presentation (ADHD-I), there remains some controversy as to whether these concerns in oncology patients are best conceptualized according to an ADHD-I or sluggish cognitive tempo (SCT) framework. The aim of this study was to describe SCT symptoms in children with ADHD-I or oncology diagnoses; identify groups of SCT symptoms among children with brain tumors (BT), acute lymphoblastic leukemia (ALL), or ADHD-I; and identify whether specific SCT profiles are associated with these diagnoses. METHODS: The sample was comprised of 364 youth (146 BT, 149 ADHD-I, 69 ALL) referred for a neuropsychological evaluation at an academic medical center. Caregivers completed the SCT scale as part of the clinical evaluation. RESULTS: Groups differed on mean scores for the SCT scales (Total, Sleepy/sluggish, Low initiation, and Daydreamy) by diagnosis (all p < 0.05), with the ADHD-I group having higher SCT symptoms on all scales. Latent profile analysis showed significant differences between latent SCT classes according to ADHD-I versus cancer diagnosis. The ADHD-I group was significantly more likely to be in the high SCT class compared to the oncology groups. CONCLUSION: Findings add to the understanding of SCT symptoms in pediatric oncology survivors. There is utility in applying the SCT framework to the oncology population; however, pediatric survivors are likely to be rated differently than youth with ADHD-I. Implications and future directions are discussed.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study.

STUDY QUESTION: Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER: Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY: Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION: This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006-2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present). MAIN RESULTS AND THE ROLE OF CHANCE: The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4-8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16-1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01-1.17) in the OI/IUI group and 1.12 (95% CI 1.04-1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION: Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(S): This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

New insights into precocious puberty and ADHD: a nationwide cohort study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children; however, studies delineating the association between ADHD and central precocious puberty are limited. This study aimed to understand whether children with ADHD are at a higher risk of central precocious puberty. METHODS: This population-based retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan to investigate the association between ADHD and the incidence of central precocious puberty between 2000-2015. We identified ADHD individuals treated with methylphenidate, atomoxetine or not. The control cohort consisted of individuals without ADHD. The outcome measure was central precocious puberty diagnosis. RESULTS: Among 290,148 children (mean age: 5.83 years), central precocious puberty incidence was 4.24 and 1.95 per 105 person-years in the ADHD and control groups, respectively. Children with ADHD treated with medication had a higher risk than those without ADHD. However, medication use did not affect the incidence of central precocious puberty among children with ADHD. CONCLUSION: This study showed an association between ADHD and a higher risk of central precocious puberty. Early referral of children with ADHD to a pediatric endocrinologist for evaluation may facilitate correct diagnoses and early interventions. IMPACT: ADHD is associated with a higher risk of central precocious puberty. This study provides relevant findings, as it is the first nationwide, population-based cohort study to investigate the association between ADHD and the risk of central precocious puberty with a 15-year follow-up. Early referral of children with ADHD to a pediatric endocrinologist for the evaluation of suspected precocious puberty could facilitate correct diagnosis. Early intervention treatment with gonadotropin-releasing hormone agonist might improve final height in children with central precocious puberty.

Nutritional complexity in children with ADHD related morbidities in China: A cross-sectional study.

BACKGROUND AND OBJECTIVES: To assess the general and nutritional health of children with attention deficit/ hyperactivity disorder (ADHD). METHODS AND STUDY DESIGN: The National Multicenter Sleep Research Database for 23791 school-age children in grades 1-6 from 9 cities in China was accessed. Children with a specialist diagnosis of ADHD or not (non-ADHD) in 2005 were studied. National anthropometric growth standards for children aged 2-18 years classified children as underweight, wasted, stunted (short stature presumed nutritional), or overweight/obesity. Independent variables were preterm birth, sleep quality and prior disease and ADHD was the dependent variable. Binary logistic regression models were developed along with interaction analyses for associated disorder or disease on overweight/obesity, and stunted. RESULTS: Some 18731 records were analyzed for 808 children with ADHD. The comparative prevalences for ADHD with non-ADHD children were stunted 9.8% vs 5.9% (p<0.001) and overweight/ obesity (32.6% vs 29.6%, p=0.002) respectively. ADHD boys were more often underweight (7.5% vs 5.3%, p=0.027), but not in girls. ADHD likelihood Odds Ratios, ORs (with 95%CI) were for premature birth 1.838, (1.393-2.423), allergic diseases 1.915 (1.526-2.399), otitis media 1.54 (1.118- 2.146), tonsillar or adenoid hypertrophy1.662 (1.348-2.050), gastroesophageal reflux 3.008(1.792-1.792-5.049), and sleep disorder 2.201(1.847-2.623) were ADHD risk factors. Only poor sleep quality and ADHD exhibited an interaction for stunted with OR=0.409 (0.233-0.719). CONCLUSIONS: Compromised and complex nutritional health in ADHD children challenges clinical nutrition with a range of health problems, albeit coherent with the needed nutritional emphasis in the 'first 1000 days'.

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno por déficit de atención con hiperactividad y un diagnóstico comórbido de trastorno por uso de sustancias.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

La evidencia actual confirma la alta comorbilidad entre el trastorno por déficit de atención con hiperactividad (TDAH) y trastorno por uso de sustancias (TUS). Esta revisión resume las intervenciones farmacológicas y psicosociales que se han evaluado en pacientes con TDAH y TUS, y ofrece recomendaciones mediante el enfoque GRADE. Nuestros resultados sugieren: 1) En pacientes con TDAH y trastorno por uso de alcohol, la atomoxetina es recomendable para reducir los síntomas de TDAH (recomendación débil) y el craving de alcohol (recomendación débil). 2) En pacientes con TDAH y trastorno por uso de cannabis, la atomoxetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de cannabis (recomendación débil). 3) En pacientes con TDAH y trastorno por uso de cocaína, el metilfenidato no es recomendable para mejorar los síntomas de TDAH o para reducir el uso de cocaína (recomendación débil). 4) En pacientes con TDAH y trastorno por uso de nicotina, es recomendable el metilfenidato para mejorar los síntomas de TDAH (recomendación débil). Los psicoestimulantes, como metilfenidato o lisdexanfetamina, no son recomendables para reducir el uso de nicotina (recomendación débil). 5) Respecto de los pacientes con TDAH y cualquier TUS, el uso de los psicoestimulantes es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). En estos pacientes, el uso de atomexetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). La atomoxetina y los psicoestimulantes parecen ser seguros en pacientes con cualquier TUS (recomendación fuerte). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multicéntricos y de mayor tamaño muestral para proporcionar más evidencia definitiva y concluyente.

Attention and Motor Learning in Adult Patients with Neurofibromatosis Type 1.

OBJECTIVE: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities, including attention and motor learning problems. These disabilities have been extensively studied in children with NF1 but limited studies have been performed in adults. METHOD: Attention, motor learning and intellectual performance were studied with neuropsychological tasks in 32 adults with NF1 and 32 controls. RESULTS: The NF1 and control group performed similarly on attention and motor learning tasks, although controls had shorter reaction times than adults with NF1 during the motor learning task (t[60] = -2.20, p = .03). Measures of attention or motor learning were not significantly associated with reduced intellectual performance in NF1. CONCLUSION: In contrast to many studies in children with NF1, our findings did not provide evidence for presence of attention or motor learning problems in adults with NF1 in neuropsychological tasks. Our observations may be of clinical importance to determine treatment focus in adults with NF1.