Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorders in childhood and adolescence, affecting 2.2 to 17.8% of all school-aged children and adolescents. ADHD in children has been associated with a wide range of developmental deficits including limitations of learning or control of executive functions as well as global impairments of social skills. However, no review has been conducted to report the consolidated magnitude of ADHD in children and adolescents in Africa. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of ADHD in Africa.Q- and the I2-test. We assessed potential publication bias using Egger's test and visual inspection of the symmetry in funnel plots.Following the PRISMA guideline, we systematically reviewed and meta-analyzed studies that investigated the prevalence of ADHD in Africa from three electronic databases . We also looked at the reference lists of included studies to include other relevant studies. Subgroup and sensitivity analysis was carried out based on the study setting, tools used to measure ADHD, sex of participants, and the subtype of ADHD. Heterogeneity across the studies was evaluated using Cochran's In the present meta-analysis, 7452 articles were initially identified and evaluated. Of these, 12 studies that met the inclusion criteria were included in the final analysis. The pooled prevalence of ADHD in children and adolescents in Africa was 7.47% (95% CI 60–9.26). The prevalence of ADHD was apparently greater in boys (10.60%) than in girls (5.28%) with a male:female ratio of 2.01:1. In our subgroup analysis, the predominantly inattentive type (ADHD-I) was found to be the most common subtype of ADHD, followed by hyperactive–impulsive type (ADHD-HI) and the combined type (ADHD-C) with the prevalence of 2.95%, 2.77%, and 2.44% respectively. The predominantly inattentive type (ADHD-I) was the most common type of ADHD in both boys (4.05%) and girls (2.21%). The funnel plot and Egger's regression tests provided no evidence of substantial publication bias in the prevalence of ADHD.Our systematic review suggested a higher prevalence of ADHD (7.47%) in children and adolescents in Africa, indicating that ADHD is a serious public health problem in children and adolescents in Africa. The prevalence of ADHD was considerably greater in males than in females. The predominantly inattentive type (ADHD-I) was the most common type of ADHD in both males and females. Greater attention needs to be paid to the prevention and treatment of ADHD. The Diagnostic Statistical Manual of fifth revision, DSM-5, defines ADHD as a neurodevelopmental disorder characterized by impairing levels of inattention, disorganization, and/or hyperactivity–impulsivity . InattenIn childhood, ADHD frequently overlaps with other mental disorders including oppositional defiant disorder and conduct disorder , 4. ADHDIn DSM-5, three main nominal subtypes of ADHD are identified which are mainly based on the differential elevation of two dimensions of inattention symptoms and hyperactivity–impulsivity symptoms. The first one is the predominantly inattentive type (ADHD-I) which describes individuals with maladaptive levels of inattention, but not hyperactivity–impulsivity; the second is the predominantly hyperactive–impulsive type (ADHD-H) which is characterized by maladaptive levels of hyperactivity–impulsivity, but not inattention, and finally, the combined type (ADHD-C) which describes individuals who exhibit significant symptoms of both inattention and hyperactivity–impulsivity .In a recent meta-analysis which included 179 ADHD prevalence estimates, the pooled prevalence estimate of ADHD in children and adolescents was 7.2%  [According to evidence from different worldwide scientific studies, among the three nominal subtypes of ADHD, the predominantly inattentive type (ADHD-I) is the most common subtype of ADHD, followed by combined (ADHD-C) and hyperactive–impulsive type (ADHD-HI) , 10–15. To our knowledge, this is the first systematic and meta-analytic review that aimed to estimate the prevalence of ADHD in children and adolescents in Africa. We hypothesized that the prevalence of ADHD is notably high in children and adolescents in Africa. Therefore, the purposes of this meta-analysis are (1) estimate the overall prevalence of ADHD in Africa; (2) determine the prevalence of specific subtypes of ADHD in Africa; (3) formulate recommendations for future clinical practice and research as well as provide evidence for planners and policymakers in the area.We conducted this review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . We usedAn article was included if it met the following criteria: first, the study was conducted in children, (2) study design was observational studies , (3) the outcome of interest was ADHD, and (4) conducted in Africa. We excluded editorials, reviews, nonhuman subjects, and not published in the English language. We screened titles and abstracts using the prespecified inclusion and exclusion criteria before the retrieval of full-text articles for further screening. Two reviewers (KY and MA) independently performed the screening. In the second step, the two reviewers independently read the full-texts of the articles that are not excluded in the initial stage, then selected the studies that met the inclusion criteria. Any disagreements were resolved by consensus or after discussing it with a third reviewer.Two authors (KY and MA) independently extracted the information from the included studies. We used a specific data extraction form particularly designed to extract data for this systematic review and meta-analysis. Data from the included studies were extracted to summary tables containing information on the study population, sample size, s year of publication, study design, study setting, authors, and the tools used for assessment of ADHD. Information from the included studies was extracted as depending on the assessment template prepared as recommended by PRISMA guidelines .We used a modified version of the Newcastle–Ottawa Scale (NOS) to evaluate the quality of the studies included in our final analysis . The NOSIn this study, the definition of our outcome variable (ADHD) was based on validated standard instruments designed to measure ADHD in children and adolescents. Hence, studies included in the final analysis used the following standard tools to assess ADHD: Disruptive Behavior Rating Scale (DBRS) , ConnersQ and I2 statistics [I2 statistics assess the proportion of total variance across the included studies that contributed to the observed heterogeneity. In this study, the I2 statistic value of zero indicates true homogeneity, whereas the values 25, 50, and 75% were considered to represent low, medium, and high, respectively [For the studies that reported suitable statistics, a meta-analysis with a random-effects model was conducted to calculate pooled prevalence, and 95% CIs . We usedatistics . The I2 ectively . For theA total of 7484 articles were identified using electronic search engines and strategies. An additional eight relevant studies were found through a manual search of the reference lists of the remaining papers. Of these, 7452 were excluded due to duplicate and during the review of abstract and titles as they did not meet the inclusion criteria Fig. . 40 artiTwelve studies were included in the systematic review and meta-analysis. The characteristics of these studies are summarized in Table The quality of the studies was assessed using the Newcastle–Ottawa Scale with some modifications. Ten studies were good in quality , one moderate 31), and one poor (34) . The pooled prevalence was based on the random effect model due to the observed heterogeneity across the studies.A meta-analysis of 12 prevalence studies  performed in Africa between 2005 and 2017, and revealed that the pooled prevalence of ADHD in children and adolescents was 7.47% (95% CI 6.00–9.26)  in males and it was 5.28% (95% CI 4.38–6.36%) in females. The difference between the groups was statistically significant  was found to be the most common subtype of ADHD, followed by hyperactive–impulsive type (ADHD-HI) and combined (ADHD-C) with the prevalence of 2.95%, 2.77%, and 2.44%, respectively, although the difference across the groups was not statistically significant , hyperactive–impulsive type (ADHD-HI), and combined (ADHD-C) with the prevalence of 4.05%, 3.61%, and 3.62%, respectively, as compared to the corresponding prevalence in females of 2.21%, 1.5%, and 1.52%. The difference was statistically significant for inattentive and combined type but not for hyperactive type  for studies conducted in a community-based setting and it was 8.74% (95% CI 5.66–13.27%) for studies conducted in hospital-based setting (see Table P = 476)  as compared to other instruments 7.62%), although the observed difference across the tools used to measure ADHD was not statistically significant , the magnitude of ADHD was 7.04% (95% CI 5.61–8.79) and was 11.25% (95% CI 7.61–16.33) for both moderate and poor-quality studies combined  , the funnel plot was symmetric and quantitatively, Egger’s regression tests provided no evidence of substantial publication bias for the prevalence of ADHD in children and adolescents in Africa . We observed a wide variation in the prevalence of ADHD across the countries ranging from 1.49 in Ethiopia to 11.75% in Uganda. The observed substantial variation in the prevalence of ADHD across the countries could be due to the methodological differences, the age of the child, perinatal complications, the instruments used to measure ADHD, sex of the participants, culture, and the sociodemographic status of the family as well as other comorbid mental and neurologic conditions.The finding of the current meta-analysis (7.47%) was consistent with the 9.2% worldwide pooled prevalence estimate of ADHD reported by Ramtekkar et al.  in 2010 P = 476). Moreover, the study population differed in a number of mental health-related and other environmental factors such as maternal substance used during and before pregnancy, the age of the child, perinatal complications, culture, other psychological and social factors as well as the sociodemographic status of the family and other comorbid mental and neurologic conditions among the study participants that are consistently associated with increased rates of ADHD in children and adolescent might contribute to the difference in the observed variation.However, our pooled prevalence estimates of ADHD in children and adolescents in Africa exceed the 5.3% worldwide prevalence estimate of ADHD reported in 2007 by Polanczyk et al. . The posAs expected, our stratified analysis showed that the estimate of ADHD in males (10.60%) was considerably higher than the estimates in females (5.28%) with a male:female ratio of 2.01:1. This ratio was lower than those reported by Ramtekkar et al.  which prConsistent with the previous meta-analytic study, the predominantly inattentive type (ADHD-I) is the most common subtype of ADHD in our meta-analysis . The conMoreover, the current meta-analysis ADHD is more prevalent among males in all three subtypes including the predominantly inattentive type (ADHD-I), hyperactive–impulsive type (ADHD-HI), and combined (ADHD-C). This is consistent with other study findings that ADHD is more prevalent among males in all three subtypes , 16–18. In the present meta-analysis, the variant among the 12 studies included in the final analysis led to a high level of heterogeneity. The methodological difference, sample size, the setting, the tools used, and the study populations differed on a number of characteristics, which may contributed to the variance in prevalence rates of ADHD in children and adolescents in Africa. For the purpose of further investigating the potential source of heterogeneity in the analysis of the prevalence rates of ADHD in children and adolescents in Africa, extensive sensitivity analysis based on the sex of participants, the tools used, the setting, and the quality of studies was done. This analysis revealed that the major causes for the variation across the studies were the sex of the participants and the subtypes of ADHD. Moreover, to make the results of our meta-analysis meaningful, we employed a random-effects model where summary effect estimates are more conservative than fixed-effects summaries in epidemiologic meta-analysis.The current systematic review and meta-analysis has several strengths: first, to minimize the possible reviewer bias, data extraction and quality assessment were performed by two independent reviewers and we used a predefined search strategy to identify the possible studies to include in the study; second, to identify the small study effect and the risk of heterogeneity, we performed sensitivity and subgroup analysis; and third, we evaluated the quality of the included studies and the result from the assessment of the study quality indicated that the methodological quality was generally good. Nevertheless, we identified considerable heterogeneity among the studies which we considered as limitations of the current study.In summary, results from this systematic review and meta-analysis suggest that (1) the prevalence of ADHD (7.47%) was high; (2) the prevalence of ADHD was considerably greater in males than females with a male:female ratio of 2.01:1; (3) the predominantly inattentive type (ADHD-I) is the most common subtype of ADHD followed by ADHD-impulsive type (ADHD-HI) and combined (ADHD-C); (4) ADHD is more prevalent among males in all three subtypes; (5) among the three types of ADHD, the prevalence of the predominantly inattentive type (ADHD-I) was greater in both males and females; (6) future studies should assess the possible reasons for gender difference in epidemiology of ADHD as well as the low male:female ratio in Africa as compared to worldwide findings. Finally, more attention should be paid to the prevention and treatment of ADHD in children and adolescents in Africa.


Scientists are struggling to enhance the efficiencies of these systems by maximizing their light absorption, engineering more stable redox couples, and discovering new O2 and H2 evolutions co-catalysts. In this work, Au decorated WO3/g-C3N4 Z-scheme nanocomposites are fabricated via wet-chemical and photo-deposition methods. The nanocomposites are utilized in photocatalysis for H2 production and 2,4-dichlorophenol  degradation. It is investigated that the optimized 4Au/6% WO3/CN nanocomposite is highly efficient for production of 69.9 and 307.3 µmol h−1 g−1 H2 gas, respectively, under visible-light (λ > 420 nm) and UV–visible illumination. Further, the fabricated 4Au/6% WO3/CN nanocomposite is significant  for 2,4-DCP degradation under visible light and highly stable in photocatalysis. A significant 4.17% quantum efficiency is recorded for H2 production at wavelength 420 nm. This enhanced performance is attributed to the improved charge separation and the surface plasmon resonance effect of Au nanoparticles. Solid-state density functional theory simulations are performed to countercheck and validate our experimental data. Positive surface formation energy, high charge transfer, and strong non-bonding interaction via electrostatic forces confirm the stability of 4Au/6% WO3/CN interface.A typical Z-scheme system is composed of two photocatalysts which generate two sets of charge carriers and split water into HThe online version of this article (10.1007/s40820-019-0345-2) contains supplementary material, which is available to authorized users. Hydrogen could play a vital role in low-carbon future, facilitating a more clean, low cost, and pollution free energy. Hence, counter-balancing the electricity as a zero-carbon energy carrier for storage and transportation, and reducing global CO2 emission to two-thirds  termination exhibit low surface formation energy and therefore represent the most stable phase of WO3 [−2) and electrostatic potential. A single layer of CN is considered for simulations, where three gold atoms are dispersed on the surface of Au/CN to generate 4% Au decorated CN. H2 atoms are employed to passivate the systems, especially for the monolayers of CN, Au/CN and their corresponding heterojunctions. The generalized gradient approximation (GGA) with Perdew–Burke–Ernzerhof (PBE) exchange correlation function and double-zeta polarized (DZP) basis-set is used for the crystal structure and energy optimization because of its superior over hybrid pseudo-potentials [3 unit cell, while a 5 × 5 × 1 k-point-mesh is used for WO3 slabs. Thus, 7 × 7 × 7 Monkhorst–Pack k-grid and energy-cutoff of 900 eV is used for monolayers of CN, WO3/CN, and Au/CN, and 5 × 5 × 1 k-point-mesh with 1200 eV cutoff-energy for 6WO3/CN and 4Au/6WO3/CN heterostructures. We tried many methods for band-structure simulations such as GGA/PBE, meta-GGA, SGGA, and GGA + U. Due to ferromagnetic nature  of W, the GGA + U method can accurately reproduce its electronic properties, especially band structure, etc. Thus, the band-structure calculations were completed with GGA + U, where the U value is set to accurately represent the experimental data. Partial density of states (PDOS), band-structure and electrostatic potential maps are also designed. The DFT-occupied and unoccupied DOS are regarded as the VB and CB edges, respectively [DFT simulations were completed with Quantum-ATK  and resuf P2_1/c , 43 is ue of WO3 . The statentials . In thistentials . A 5 × 5ectively .3, and xWO3/CN photocatalysts are provided in Fig. S1a. It is clear that CN exhibits two distinct diffraction peaks located at 2θ = 13.0° and 27.7°, respectively, which can be indexed to the characteristic (100) and (002) planes of g-C3N4 [θ = 27.7° is ascribed to the inter-layer stacking interaction of conjugated rings with an inter-layer distance of 0.325 nm [3 display a monoclinic-phase constitution with prominent diffraction peaks at 2θ of 23.17°, 24.40°, 33.50°, and 36.22°, indexed to the characteristic planes (002), (200), (022), and (202), respectively, (JCPDS No. 72-1465) [3 does not influence the crystal structure of CN, while the characteristic (002) peak of WO3 appeared in the xWO3/CN composites and its intensity gradually enhanced with the increase in WO3 content. Further, it can be seen that the characteristic (002) peak of CN significantly decreased in the xWO3/CN composites, which may be due to the high dispersion of monoclinic WO3 over the surface of CN [yAu/6WO3/CN composites are shown in Fig. θ values of 38.2° and 44.4° can be observed in the yAu/6WO3/CN composites. These peaks are ascribed to the face-centered cubic structure of Au with (111) and (200) crystal planes, respectively [The XRD patterns of pristine CN, WOf g-C3N4 . The str0.325 nm . The XRDce of CN –53. The 3, and xWO3/CN photocatalysts are provided in Fig. S1b. The band gap energies of CN, WO3, and xWO3/CN photocatalysts were predicted from intercept of tangents to plots of (αhν)1/2 versus hν as displayed in Fig. S1c. As obvious, pure WO3 and CN photocatalysts exhibit band gap energies of 2.82 and 2.7 eV, respectively. It is worth noting that coupling of WO3 does not influence the band gap of CN. The absorption spectra of yAu/6WO3/CN nanocomposites are shown in Fig. 3/CN nanocomposite, the absorption spectra of yAu/6WO3/CN composites exhibit an additional absorption peak occupying a wavelength range of 500–650 nm, centering at 560 nm. This absorption band corresponds to the SPR effect of Au, confirming that Au is successfully deposited on the CN surface [3/CN composite. In fact, the SPR absorption can induce a strong local electric field around the interface that enhances the light absorption of the surrounding molecules and accelerates the separation rate of photo-induced charges leading to the enhanced photocatalytic activities [The UV–visible absorption spectra of CN, WO surface . It can tivities .3, and xWO3/CN photocatalysts. Figure S2a reveals that CN exhibit stacked layers of ultra-thin flat surface nanosheets with thickness in the range of 80–100 nm. Figure S2b reveals that monoclinic WO3 exhibit nanoplates like morphology with thickness in the range of 30–50 nm. Figure S2c–f shows the SEM micrographs of xWO3/CN composites. The adhering of WO3 particles on the surface of CN nanosheets can be clearly observed. To investigate the elemental-distribution morphology of 6WO3/CN photocatalyst, energy-dispersive spectroscopy (EDS) elemental-mapping analysis was carried out as shown in Fig. S3a–e. The red, magenta, cyan, and green colors correspond to the distribution of C, N, W, and O elements, respectively, which further confirmed the existence of C, N, W, and O elements and their respective atomic percentage composition is shown in Fig. S3f inset. The SEM micrographs of yAu/6WO3/CN nanocomposites  show that Au nanoparticles are successfully deposited on the surface of 6WO3/CN nanocomposite. Furthermore, EDS spectrum of 4Au/6WO3/CN nanocomposite shows the presence of C, N, W, O, and Au elements . To explore the distribution morphology of the optimized 4Au/6WO3/CN nanocomposite, EDS elemental-mapping analysis was carried out as shown in Fig. S5a–f. The elements C, N, W, O, and Au are evenly distributed in the composite.SEM images were taken to examine the morphology of CN, WO3/CN, 4Au/6WO3/CN, and WO3 photocatalysts are shown in Fig. 3/CN nanocomposite  plane of WO3. The TEM image of 4Au/6WO3/CN nanocomposite  plane of WO3.TEM and high resolution TEM images of CN, 6WOite Fig. b inset site Fig. b shows tto the 00 plane ofto the 00 plane ofto the 00 plane ofto the 00 plane of3/CN, and 4Au/6WO3/CN photocatalysts were explored by BET N2 adsorption–desorption technique. As shown in Fig. S6a, the adsorption isotherm curves of all photocatalysts exhibit a type-IV behavior with H3 hysteresis loops, signifying mesoporous structures. The observed specific surface areas of CN, 6WO3/CN, and 4Au/6WO3/CN photocatalysts are 45.6, 51, and 54 m2 g−1, respectively. The pore diameter values of the photocatalysts were calculated by Barrett–Joyner–Halenda (BJH) models, and the plots are provided in Fig. S6b. The pore diameter distribution curves of the photocatalysts show that the average pore diameters of the photocatalysts are in the range of 2 nm. The BET results reveal that surface area of the photocatalysts may not be the key factor affecting the catalytic activities of the photocatalysts [The BET surface area and pore volume of CN, 6WOatalysts .3, and xWO3/CN photocatalysts are shown in Fig. S6C. As obvious, pure CN exhibit characteristic absorption peaks at 810, 1242, 1307, 1410, 1463, 1562, 1641, and 3200–3500 cm−1. The absorption peak at 810 cm−1 is ascribed to the out-of-plane bending modes of triazine-units. The peaks in range of 1240–1590 cm−1 correspond to stretching-mode of C–N heterocycles. The peaks at 1307 and 1641 cm−1 are assigned to the C–N and C=N stretching-modes in CN, respectively. The broad peak in the region of 3200–3500 cm−1 can be ascribed to the NH stretching-modes and the surface-adsorbed OH− groups [3 shows characteristic absorption peaks in the region of 500–900 cm−1, which corresponds to the (O–W–O) stretching vibrations in a monoclinic-type WO3. The absorption peak at 1625 cm−1 is due to the (O–H) bending-vibration modes of the coordinated water and the broad band in the region of 3200–3500 cm−1 is due to the stretching-vibration mode of the surface-adsorbed OH− groups [xWO3/CN composites, the characteristic absorption band of WO3 does not appear which may be due to its low content. Further, Au deposition does not influence the structural morphology of 6WO3/CN composite .To reveal about the chemical composition of photocatalysts, FT-IR spectra were obtained. The FT-IR spectra of CN, WO− groups . The pur− groups . In case3/CN is composed of C, N, W, and O elements, while that of 4Au/6WO3/CN contains C, N, W, O, and Au elements. The high-resolution C 1s XPS  and tertiary (N–(C)3) groups, respectively [s XPS peaks of 6WO3/CN and 4Au/6WO3/CN composites are little shifted toward high energy side due to the electron delocalization effect. The high-resolution O 1s XPS spectra of 6WO3/CN and 4Au/6WO3/CN composites  groups, respectively [f XPS spectra of 6WO3/CN and 4Au/6WO3/CN composites  simulations have been carried out. The optimized relaxed geometries (models) of WO3, 6WO3/CN, and 4Au/6WO3/CN are shown in Fig. S8. In these heterojunctions, both CN and Au decorated CN have strong non-bonding interactions with the surface atoms of WO3. These models are further employed for the electronic properties simulations. The geometric parameters of the simulated relaxed crystal structure of the unit cell are compared with the already reported crystallographic parameters of WO3, which conclude that PBE/GGA accurately reproduces the experimental data. Moreover, the applied theoretical protocol was counterchecked from the simulated per atom cohesive formation energy of W, O, C, H, Au, and N. The calculated band gap and formation energy of WO3 are 2.80 eV and 0.38 J m−2, respectively, which has nice correlation with the already reported work [In order to well understand the structure, binding, and the electronic properties of 4Au/6WOted work . All theted work , 64.3 are given in Figs. S9a and S10. It can be seen that VB and CB positions of WO3 are located at − 7.72 and − 4.9 eV, respectively, (vs. vacuum). The occupied 5d band of W is lower in energy than that of the O 2p band which consequence O 2p VB at − 7.72 eV and W 5d CB at − 4.9 eV with a band gap of 2.82 eV (vs. vacuum) . Thus, the VB is dominated by oxygen atoms while W dominates CB of WO3. Moreover, the PDOS of CN along with band structure is shown in Figs. S9b and S11. In this case, the VB and CB are located at − 5.9 and − 3.2 eV, respectively, (vs. vacuum). The band edge positions of both of WO3 and CN are consistent with the already reported work that validates our theoretical methods.The density of state (DOS) and partial DOS (PDOS) plots along with band structure of WO3 surface produces some inter-bands in the band gaps of 6WO3/CN . This statement also corroborates our experimental data. This strong interaction between WO3 and CN and Au/CN with WO3, enhances the overall catalytic activity of resulted material (vide infra). The reason behind this is the strong hybridizations of the bonding and anti-bonding orbitals of W, O, C, N, H, and Au . At Fermi energy of 5.09 eV, the vacuum-phase VBM and CBM values of WO3/CN are slightly changed as that of parent WO3. However, the N and C of CN have produced some extra bands in the band gap of WO3 as can be seen from Fig. S12a, b. These extra bands  can trap the electron–hole recombination which consequently enhances the photocatalytic activity.The interaction of CN and Au/CN with that of WO3/CN are given in Fig. S16. The bonding and anti-bonding orbitals of W, O, C, N, H, and Au constitute band gap and band edge positions. Again, similar but severe behavior of Au/CN is observed in 4Au/6WO3/CN photocatalyst. Figure S16a, b shows that both the bonding and anti-bonding orbitals of Au/CN are prominent compared to that of the CN in 6WO3/CN system. In addition, the VBM and CBM of 4Au/6WO3/CN are moved toward more positive potentials, aligned with the reduction potential of water to efficiently reduce H2O and produce H2. The strong hybridizations and perturbation of these edges positions validate our experimentally proposed Z-scheme behavior of 4Au/6WO3/CN system (vide infra).The PDOS and DOS plots of 4Au/6WO3, CN, Au/CN, 6WO3/CN, and 4Au/6WO3/CN heterojunction were calculated from difference of vacuum-energy (Evac) and Fermi energy level (EF). Evac is the energy of a stationary electron in vacuum nearby the surface. The simulated electrostatic potential maps of WO3, CN, Au/CN, 6WO3/CN, and 4Au/6WO3/CN heterojunction along the Z-direction are shown in Figs. S17–S19. The work functions of WO3, CN, Au/CN, 6WO3/CN, and 4Au/6WO3/CN photocatalysts are 6.30, 4.38, 4.24, 5.09, and 4.95 eV, respectively. A large difference in work functions and band-edge potentials (VBM and CBM) of CN and WO3 led us to predict that photo-generated electrons of CN cannot transfer thermodynamically to the CB of WO3 in 6WO3/CN heterojunction. Instead, the excited holes in the VB of CN recombine with the photo-generated electrons of WO3 which consequently enhance charge carriers separation and photo-reduction ability of CN.Moreover, the band alignment of WO3/CN composite (5.09 eV). So, in case of 4Au/6WO3/CN heterojunction, the photo-generated electrons (CB) of CN will transfer to the surface of Au nanoparticles. Meanwhile, the excited holes of CN will recombine to the excited electrons of WO3, which significantly promote charge carriers separation and photocatalytic activity. Comparative analysis of Fig. S17C, D led us to conclude that work function of 4Au/6WO3/CN (4.95 eV) is lower than that of the 6WO3/CN (5.09 eV). So, it is inferred that Au has accepted electronic cloud density of CN (donor).According to our previous report , the wor3/CN and 4Au/6WO3/CN heterojunctions is calculated from charge-density difference (CDD), as shown in Fig. 3/CN and 4Au/6WO3/CN heterojunctions. In addition, we can see that bulk region of WO3 has no appreciable change, especially the far side area of the interface. So, we can predict, this type of charge distribution may result a strong interaction between Au/CN and WO3. Analysis of charge redistribution at the interfaces of these species led us to conclude that electrons (CB) of CN and Au/CN directly reduce water while its holes recombine with the excited electrons of WO3. So, holes at VBM of WO3 oxidize H2O and produce O2 while the electrons at CN, especially, at Au/CN surface reduce water and generate H2. The amount of charge density difference between 6WO3/CN and 4Au/6WO3/CN heterojunctions is ~ 0.073 and 0.091 electrons, respectively, . The higher charge transformation in 4Au/6WO3/CN compared to that of the 6WO3/CN can also be visualized from the EDD maps (green shaded areas), as shown in Fig. 3/CN heterojunction, which consequently separate electrons and holes (vide supra).Finally, inter-charge transfer in 6WOxWO3/CN, and yAu/6WO3/CN photocatalysts, SPV and PL characterizations were carried out. The SPV is a sensitive and non-destructive technique mainly used to explore the photo-physics of photo-generated charges in the semiconductor nanomaterials. The SPV signals for nanomaterials mainly originate from photo-generated charge carriers separation via the diffusion phenomenon [3, and xWO3/CN photocatalysts measured under air condition are shown in Fig. S20a. The low-intensity SPV signal of CN mainly resulted from the fast recombination rate of photo-generated charges. It is important to note that the SPV response of CN is drastically improved after coupling WO3 and the intense signal is detected for 6WO3/CN photocatalyst. Worth noting, the SPV signal intensity of 8WO3/CN photocatalyst is greatly reduced because of the over the excess amount of WO3 that covers the CN surface and acts as a charge recombination center. As shown in Fig. 3/CN composite is further improved after photo-deposition of Au nanoparticles, and the highest intensity signal is detected for the amount optimized 4Au/6WO3/CN composite. Based on the SPV signals, it is concluded that loading proper amount of WO3 and Au could greatly enhance the charge carrier’s separation of CN, leading to the superior photocatalytic performance.To reveal the photo-generated charge carrier’s properties of CN, enomenon . In fact3, and xWO3/CN photocatalysts are displayed in Fig. S20b. In fact, the stronger PL signal reveals high charge carrier’s recombination rate and vice versa. Notably, CN shows strong PL signal with emission peak centering at 460 nm. This is ascribed to the band–band transition in bare CN. Thus, it is clear that charge carrier’s recombination rate in CN is quite fast. Obviously, the PL intensity of CN is drastically reduced after coupling WO3 and the low-intensity signal is detected for 6WO3/CN photocatalyst. This confirms that charge carrier’s recombination rate is greatly suppressed by the synergistic effect of the two components system. Interestingly, Fig. 3/CN composite is further decreased after photo-deposition of Au nanoparticles and the lowest intensity signal is detected for 4Au/6WO3/CN composite. The PL results are in accordance with the SPV results.Further, the charge carrier’s separation is confirmed by the PL measurement. The PL is a highly sensitive technique used to investigate surface-properties of nanomaterials. Generally, it tells us about the photo-generated charge carriers trapping, migration, transfer, oxygen vacancies, active sites, and surface defects in semiconductor nanomaterials –68. The ·OH amount could effectively reveal the charge separation in photocatalysis. Thus, the fluorescence spectra of CN, WO3, xWO3/CN, and yAu/6WO3/CN photocatalysts were measured to further confirm the improved charge carriers separation. For this, the coumarin-fluorescent technique was used to measure the ·OH amount. As widely accepted, the coumarin reacts with ·OH and generate luminescent 7-hydroxycoumarin which has a characteristic fluorescence emission peak at about 450 nm wavelength. Figure S20c shows that CN exhibit weak fluorescence signal which reflects the negligible amount of ·OH generated. Further, the fluorescence intensity peak of xWO3/CN composites become stronger with an increase in percentage composition of WO3 especially that of the amount optimized 6WO3/CN composite. Interestingly, as can be seen from Fig. 3/CN composite becomes stronger and the highest fluorescence intensity peak is recorded for 4Au/6WO3/CN composite, which is in accordance to the SPV and PL results.As mentioned in the previous report , the fluI–V curves analysis of CN, 6WO3/CN, and 4Au/6WO3/CN photocatalysts were performed in Na2SO4 electrolyte (0.5 M) at 0.4 V bias versus the Ag/AgCl electrode as shown in Fig. I–V curves result, it can be concluded that the photocurrent density of CN is not obvious. However, compared to the CN, an abrupt increment in the photocurrent density response is observed for 6WO3/CN composite. Interestingly, the photocurrent density of 4Au/6WO3/CN photocatalyst is much stronger signifying that charge carrier separation is drastically enhanced.To further reveal the improved charge carriers separation, photoelectrochemical rolyte 0. M at 0.43/CN, and 4Au/6WO3/CN photocatalysts as shown in Fig. S20d. The EIS Nyquist plots arc radius of 4Au/6WO3/CN photocatalyst is significantly reduced compared to that of the 6WO3/CN composite and bare CN. These results demonstrate that the 4Au/6WO3/CN photocatalyst has a higher separation rate of photo-generated charges than the 6WO3/CN composite and bare CN, which is in accordance to the PL, SPV, FL, and I–V results.The photo-generated electron–hole pair’s separation was further investigated by the measurement of electrochemical-impedance spectra of CN, 6WOxWO3/CN and yAu/6WO3/CN photocatalysts were evaluated for H2 production under UV–visible and visible-light illumination. As obvious from Fig. 2 (6.87 μmol h−1 g−1) under visible-light illumination. It should be noted that the amount of H2 produced over xWO3/CN composites is remarkably enhanced and the 6WO3/CN composite produced 38.77 μmol h−1 g−1 of H2. Figure 3/CN composite produced 69.9 μmol h−1 g−1 of H2. The quantum efficiencies of the CN, 6WO3/CN, and 4Au/6WO3/CN photocatalysts for H2 evolution at wavelength 420 nm are calculated to be 0.68%, 3.0%, and 4.17%, respectively. The quantum efficiency yield of 4Au/6WO3/CN composite is much higher than the reported correlated systems as shown in Table S1. The H2 production activities were further evaluated under UV–visible illumination. Figure 2 production activities of CN and xWO3/CN photocatalysts under UV–visible illumination. One can see that CN produced 16.87 μmol h−1 g−1 of H2 under UV–visible light which is much higher than that produced under visible light. The activity of xWO3/CN composite for H2 production under UV–visible illumination is greatly improved and the amount optimized 6WO3/CN composite produced 53.32 μmol h−1 g−1 of H2. It must be noted from Fig. 2 production over yAu/6WO3/CN composites under UV–visible illumination is much significant and the amount optimized 4Au/6WO3/CN is capable of producing 307.36 μmol h−1 g−1 of H2. Thus, the significantly improved photocatalytic activities of the amount optimized 4Au/6WO3/CN composite pointing out the favorable synergetic effect of the well-designed three-component photocatalyst. The photocatalytic stability and recyclability tests of the amount optimized 4Au/6WO3/CN composite for H2 evolution were also carried out under UV–visible and visible-light irradiation. Figure 3/CN composite before and after four consecutive photocatalytic cycles of H2 evolution under visible-light irradiation, XRD patterns were measured as shown in Fig. S21. As can be seen, there is no obvious change in the crystal structure before and after the photocatalytic reaction. The result specifies excellent recycling performance and stability of the 4Au/6WO3/CN composite.The catalytic activities of CN, 3/CN, and 4Au/6WO3/CN photocatalysts was 2.2%, 7.9%, and 14.5%, respectively, as shown in Fig. S22a. It is clear from Fig. S22b that degradation rate of 2,4-DCP over CN photocatalyst under visible-light irradiation is 26%. However, the degradation rate is remarkably enhanced after coupling WO3, and the optimized 6WO3/CN composite degraded 71% of the 2,4-DCP in 2 h. It should be noted from Fig. S22c that the degradation rate of 2,4-DCP over yAu/6WO3/CN photocatalysts is much significant and 4Au/6WO3/CN is capable of degrading 100% 2,4-DCP in 2 h. Thus, it is confirmed that the significantly enhanced photoactivities for H2 production and 2,4-DCP degradation are ascribed to the remarkably improved charge carriers separation as investigated by the above photophysical and photochemical results.To test the improved photocatalytic performance, 2,4-DCP photodegradation was also carried out under visible-light irradiation. In heterogeneous photocatalysis, the adsorption of pollutants on the semiconductor surfaces also plays a vital role. Thus, the photocatalytic system was kept in dark under stirring for half an hour to reach the adsorption equilibrium and then irradiated under visible light for 2 h. The adsorption of 2,4-DCP over the optimized CN, 6WO3/CN heterojunction is proposed as depicted in Fig. 3 and CN photocatalysts are located at 0.4 and − 1.3 eV, respectively. Thus, due to the more negative conduction-band potential of CN, its photo-generated electrons can reduce the O2 molecules to superoxide radicals (·O2−), while due to the more positive conduction-band potential of WO3, its electrons mcan not reduce the O2 molecules to ·O2−. The reason is that the standard redox potential of O2/·O2− is − 0.046 eV [3 and CN photocatalysts are located at 3.22 and 1.4 eV, respectively. Hence, the valence band potential of WO3 can oxidize the OH− to ·OH as confirmed by the fluorescence results, while that of the CN can not oxide because the standard redox potential of OH−/·OH is 2.7 eV [·OH formation, the EPR spectroscopy analysis of the optimized 4Au/6WO3/CN photocatalyst was carried out in dark and under visible-light irradiation in the presence of trapping reagent DMPO. As shown in Fig. S22d, no characteristic peaks of DMPO-·OH can be observed in dark. However, under visible-light irradiation, the characteristic peaks of DMPO-·OH can be clearly observed and their intensities steadily increased with the increase in irradiation period, i.e., 5, 10, 15, and 20 min. These results further specify that ·OH plays a vital role in the degradation of 2,4-DCP.According to the above results, a schematic mechanism for charge carriers generation, separation and transfer and the photocatalytic activities over Au deposited Z-scheme WO0.046 eV . In conts 2.7 eV . To furt3 and CN directs a Z-scheme heterojunction. Based on the above facts, it is concluded that when Au deposited WO3/CN Z-scheme heterojunction is fabricated and irradiated under UV–visible and/or visible light, photo-generated charge carriers are produced. Meanwhile, the electrons are excited to the conduction bands while leaving photo-generated-holes in valence bands. Thus, the excited electrons in the conduction band of WO3 and the holes left in the valence band of CN quickly recombine at the interface. On the other hand, the photo-excited electrons in the conduction band of CN would transfer to Au and the excited holes left in the valence band of WO3 would transfer to its surface, resulting in the drastically improved carrier’s separation. Subsequently, the electrons on the surface of Au would induce water reduction to evolve H2 and the photo-generated holes on the surface of WO3 would oxidize OH− to generate ·OH. The generated ·OH will directly oxidize the 2,4-DCP pollutant molecules. The above results reveal that decoration of Au on WO3/CN Z-scheme heterojunction can significantly promote charge carriers separation and transfer leading to the drastically promoted photocatalytic performance for water reduction and pollutant oxidation.Thus, the composite of WO3N4 can produce a little amount of H2 due to its suitable reduction potential for water reduction. However, WO3 cannot commence water reduction reactions because its conduction-band potential is more positive than the standard reduction potential value of H2O  versus the normal hydrogen electrode (NHE). In addition, the composite of WO3 and CN can remarkably improve the photocatalytic H2O reduction to evolve H2, especially the Au decorated WO3/g-C3N4 composite. In this case, the VB of WO3 causes photo-oxidation of water and CB of g-C3N4 is responsible for photo-reduction of water and produce H2. The experimentally observed and theoretically simulated band edge positions of these materials have strong correlation with each other and their energy levels nicely satisfy the Z-scheme system.In brief, the individual g-C3/CN Z-scheme heterojunctions have been successfully fabricated for the first time that exhibited superior photocatalytic performance for solar H2 production and 2,4-DCP degradation. The enhanced photocatalytic performance is ascribed to the promoted charge separation by constructing Z-scheme heterojunction and to the SPR effect of Au nanoparticles. The calculated quantum efficiency for H2 evolution at a wavelength 420 nm was 4.17%. Finally, our theoretical and experimental data have a nice correlation with each other that further confirms and validates the enhanced photocatalytic performance of 4Au/6WO3/CN nanocomposite. This work would be helpful for the future development of CN-based highly proficient catalysts and will be of great significance to meet the energy and environmental demands.In summary, Au decorated WOSupplementary material 1 (PDF 2340 kb)Below is the link to the electronic supplementary material.


Attention deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood. According to a recent systematic review, the worldwide estimate of ADHD prevalence is 7.2% in children. This study aims to assess the prevalence of ADHD diagnoses in 2017 and the incidence of ADHD diagnoses in 2009–2017 in children living in Catalonia, Spain, as well as their temporal and geographical variability, and stratifying by sex and age. We used administrative data for all children aged 4 to 17 years who were insured in the public Catalan Health System in 2009–2017. We identified all ADHD cases diagnosed in 2009–2017 (ICD-9 code 314). We estimated the prevalence of ADHD diagnoses in 2017 and the overall annual incidence of ADHD diagnoses in 2009–2017. We used Poisson regression models to assess temporal trends in the incidence. We estimated a prevalence of ADHD diagnoses of 4.06%  in 2017, being 5.81%  for boys and 2.20%  for girls, the highest prevalence being in 13-to-17-year-olds ). We did not observe a statistically significant increase of the incidence of ADHD diagnoses during the study period. Geographical differences were found across the healthcare areas in both prevalence and annual incidence and constant during the study period. In conclusion, the prevalence of ADHD diagnoses observed in this study was 4.06%, which was lower than the estimates reported in previous systematic reviews, but in line with the prevalence estimates from other recent European studies. The prevalence was higher in boys than girls, with a sex ratio consistent with previous studies. We did not observe an increase in the temporal trend of incidence of ADHD diagnoses in recent years, but we found geographical differences. ADHD is commonly characterized by a persistent pattern of inattention, hyperactivity and/or impulsivity. These manifestations can cause a significant impairment in school as well as in the activities of daily life2. ADHD appears to have a complex etiology including environmental and genetic risk factors3.Attention deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood and adolescence4. Most of the ADHD prevalence studies were conducted in Europe  and within school populations . The studies included in this review have reported highly variable rates worldwide, ranging from 0.2% to 34.5%. Globally, ADHD prevalence estimates are higher in the Middle East and North America regions and lower in African and Asian countries. Regarding sex differences, most previous studies have shown a higher ADHD prevalence in boys than in girls with an overall sex ratio boy/girl of 2:1 in children5. Although ADHD symptoms can be reliably diagnosed since 4 years old5, there is no homogeneous evidence among studies about the most prevalent age group of diagnosis. Some studies have reported higher ADHD prevalence in children aged 6–12 years8. However, some other studies have reported higher ADHD estimates at older age groups11.In the past decade, several systematic reviews have been conducted to estimate the prevalence of ADHD. According to a recent systematic review conducted with 175 studies across the world, the overall pooled estimate of ADHD prevalence was 7.2% in children15. Only few studies have reported annual incidence estimates of diagnosed ADHD for an extensive period of time allowing for time trend analysis, but most of them showed an increase in the incidence during the study period15. Overall, higher incidence was detected in boys and ADHD diagnosis for both boys and girls was greater in children aged 6–11years14 and specially among 7–9 years old13.ADHD incidence in children was also assessed in some studies16. Among the ADHD prevalence studies, only two studies have been conducted in Catalonia over the last years and both among preschoolers18. However, little is known about the distribution of the prevalence of ADHD diagnoses in other age groups of children in that region and whether the incidence of ADHD diagnoses is still increasing as other studies have reported. Additionally, there is no study conducted in Spain that has evaluated the geographical variability of the prevalence and incidence of ADHD diagnoses. These data are crucial for service planning, resource allocation, training and research priorities, and prevention and treatment programming. Therefore, this study aims to assess the prevalence of ADHD diagnoses in 2017, and its incidence between 2009 and 2017 among the child population of the Catalonia region in Spain, as well as their temporal and geographical variability. Also, this study aims to assess the differences of the prevalence and incidence of ADHD diagnoses by sex and age.To our knowledge, very few studies with the aim of studying the prevalence of ADHD have been carried out in Spain and there are no studies on the ADHD incidence over an extended period of timeIn 2017, 1,114,226 children aged 4 to 17 years were covered in the Catalan Health Service, of whom 45,260 had a diagnosis of ADHD. We observed an overall prevalence of ADHD diagnoses of 4.06%  in 2017 . The incidence of new ADHD cases followed an oscillating nonlinear pattern from 0.51%  in 2009 to 0.58%  in 2017 Table . HoweverThis study assessed the prevalence of ADHD diagnoses in 2017 and the incidence of ADHD diagnoses between 2009 and 2017, as well as their temporal and geographical variability and sex and age differences, among children aged 4 to 17 years in the Catalonia region in Spain. The prevalence of ADHD diagnoses in 2017 was estimated at 4.06%, with a sex ratio boy/girl of 2.8:1, and with the highest prevalence in the 13 to 17 age group. We did not observe an increase in the incidence of ADHD diagnoses between 2009 and 2017 although we found a higher number of new cases diagnosed with ADHD among boys and children aged 7 to 12 years. Regarding the geographical analyses, we found differences between healthcare areas in the prevalence of ADHD diagnoses in 2017 and in the annual incidence but the incidence of ADHD diagnoses was almost constant in most healthcare areas during the study period from 2009 to 2017.1 and 7.20%4 in some systematic reviews. However, our findings are in line with the prevalence estimates from other European studies conducted in recent years21, which showed lower prevalence estimates than North American studies4. The prevalence of ADHD diagnoses found in our study was also lower than the overall ADHD pooled-prevalence of 6.8% reported in a systematic review with studies conducted in Spain16. The inconsistency in the prevalence estimates among this systematic review and our study could be explained by some of the following reasons: i) our study included general population of children between 4 and 17 years old while most studies included in the systematic review (78.6%) were conducted using school population with children between 6 and 12 years old, ii) methodology used was different; our study is based on registry data with ADHD diagnoses confirmed by specialized clinicians instead of ADHD confirmation from symptoms referred by parents and teachers as in most of the studies included in the systematic review (64.3%), and iii) our study used ICD-9 code based on DSM-V criteria while most of the studies included in the systematic review using diagnostic criteria applied the DSM-III-R and DSM-IV (71.5%). Overall, the reasons of the variability in the estimates of the ADHD prevalence between and within countries remain poorly understood but age, gender, study design, study period, diagnostic criteria, population assessed, the informant-patient reporting symptoms, sociodemographic factors, and health care access are factors that could have an influence11. The different methodologies used in the studies make the comparison of ADHD prevalence estimates very challenging.Epidemiological studies on ADHD prevalence during childhood and adolescence have reported highly variable estimates worldwide ranging from 0.2% to 34.5%. In the present study, the prevalence of ADHD diagnoses was estimated at 4.06%, indicating a lower estimate than previously reported worldwide values of 5.29%22. However, it is difficult to compare estimates of ADHD incidence from different studies because they may not have been conducted homogeneously: differences in the time periods, geographical locations, and methodological issues. In order to explain the overall changes in the temporal trends of ADHD incidence, some researchers have hypothesized that they might be due to i) an overdiagnosis of ADHD23, ii) clinicians that do not follow strictly the diagnostic manuals24, iii) changes in ADHD diagnosis criteria that occurred over the study period, iv) an increased awareness in the last years among the parents, teachers, psychiatrists, and pediatricians about ADHD.With regard to the overall incidence of ADHD diagnoses, incidence estimates have not been on a continuous upwards over the study period from 2009 to 2017. It is unclear whether the increase observed between 2016 and 2017 is just a random variation of the incidence or will be maintained in the following years. Epidemiological studies on the ADHD incidence are published less frequently than those of prevalence, but most of them showed an increasing temporal trend during their respective study periods5 in children. In our study, we estimated a sex ratio boy/girl of 2.8:1 in the prevalence of ADHD diagnoses in 2017, which is near to the sex ratio reported in the DSM-V. Despite the heterogeneity of the sex ratio reported among different studies, our results are also similar to two studies conducted in 2016 with similar age group populations, in which they found a sex ratio boy/girl of 3.1:111 and 2.3:125, respectively. The organizational effects of sexual hormones such as testosterone during the intrauterine period may influence the development of ADHD predominantly in boys, maybe by acting on the dopaminergic neural system in the prefrontal cortex and striatum influencing the clinical manifestations and severity of ADHD26. Emerging evidence however indicates that the stress hormones and sex chromosome genes (i.e X-and Y-linked genes) are also biological mechanisms contributing to sex differences in ADHD27. Moreover, girls may be underidentified and underdiagnosed mostly due to differences in the expression of the ADHD symptoms. Girls tend to present more inattentive symptoms and fewer hyperactive/impulsive symptoms as well as fewer disruptive behaviors when compared with boys with ADHD.ADHD seems to be a predominantly male disorder with a reported sex ratio of approximately 2:1et al. found that ADHD prevalence in 2015–2016 in US children and adolescents was higher among adolescents aged 12 to 17 years than children aged 4 to 11 years 9. A study conducted among children and adolescents aged 3 to 17 years diagnosed with ADHD in Germany found that prevalence estimates increased from 1.5% during preschool to 5.3% during elementary school and further increased to 7.1% in secondary school, being the ADHD prevalence higher at older ages10. However, our findings differ from some studies that found the highest ADHD prevalence among children aged 6 to 12 years7. Additionally, we found a lower prevalence of ADHD diagnoses in age group of 4 to 6 years old compared to other studies that reported estimates of 2% to 5%18. The lower prevalence estimates found in our study in the youngest age group might be explained by reticence among clinicians to label children with ADHD at very young ages or by lack of enough training for health professionals to improve the early diagnosis. Our findings of the incidence of ADHD diagnoses by age groups are consistent with some previous studies carried out in United Kingdom, Canada, Denmark, and Taiwan14. As expected, in our study there was a greater diagnosis of new cases of ADHD over all the study period among children aged 7 to 12 years, which corresponds to the elementary school period where ADHD symptoms tend to be notice and more detectable28. These results might be explained by the transition from preschool to elementary schools which involves new demands on child’s organizational skills and reveals difficulties with controlling attention that might have been hidden previously. However, it would be recommended to put more efforts into an early diagnosis and intervention that could significantly reduce the lifelong costs of care for ADHD person. The average estimated total cost of ADHD per year per child was 5732.64€ among Spanish population including medical and non-medical costs29.The noticeable beginning of ADHD symptoms is often early in childhood, being the behavioral and hyperactivity symptoms those that might already be detected after 4 years old. However, before the age of 4, ADHD symptoms are challenging to diagnose because children have more difficulties to self-regulate their behavior and it is complicated to distinguish ADHD symptoms from normative behaviors. In our study, the highest prevalence of ADHD diagnoses in 2017 was observed in the group of children aged 13 to 17 years with a prevalence of 7.28%. Some studies have also shown higher ADHD prevalence at older age groups. Xu 30. The results of the prevalence of ADHD diagnoses are also in agreement with the results of the geographical variability of the population between 6 to 17 years old that takes medication for ADHD31. However, these results should be interpreted with caution since other factors may be associated and affect the geographical variability of ADHD, such as socio-economic factors that might influence the awareness of the disease and therefore the consultation with the specialist, the likelihood of the use of private health versus public health services of each healthcare area, or the different diagnostic and treatment procedures of the medical teams across healthcare areas. Unfortunately, we did not have information of these potential factors that might have influenced the geographical variability of the prevalence and incidence of ADHD and could not investigate the reasons of this variability. Future research to understand the reasons of this variability is warranted in order to develop and implement specific measures aimed at reduce the variability and to improve the diagnostic and treatment procedures in all the region.In the geographical analysis, we found similar results to the study of the prevalence and incidence of ASD diagnoses in children in Catalonia, with a greater incidence of ADHD diagnoses in the central and southern regionsThe main strengths of our study are the design, which is based on administrative data, and the large sample size included. It is one of the few studies carried out in Southern Europe based on register data. Our study also included data from a relatively long period of time allowing a thorough temporal trend analysis. Finally, we studied the differences in prevalence and incidence of ADHD diagnoses by sex, age group, and across healthcare areas.32. Most of the children covered in the Catalan Health Service follow this program even if they benefit from double health coverage. Therefore, we expect that most ADHD cases have at least one contact with the public healthcare centers in relation to their ADHD diagnosis or for other health issues and that their ADHD diagnosis would be registered. Furthermore, our study is based on register data which only capture individuals who accessed the healthcare services. As a result, participants with the disorder who are not in contact with these services are yet unidentified and not included as cases, leading to a possible underestimation of the prevalence and incidence estimations. In addition, since we are using administrative data we cannot confirm that the ADHD diagnosis assessment has been made in a standard way for all ADHD cases and it could be variation in ADHD diagnostic practices. Although all cases have been identified with ICD-9 code, diagnostic practices might have differed between different facilities or even between healthcare professionals. This potentially contributed to the variation between healthcare areas. It is also possible that in those healthcare areas with higher socioeconomic status, private health services are used more frequently and this could represent an underestimation of the ADHD cases registered. However, as far we known, there are no specific features that may influence the ADHD diagnosis in Catalonia. It has been reported that the percentage of mental health disorders (including ADHD) in Catalonia does not differ from the average of Spain. Other disadvantage is linked to the already defined covering population, time periods, and variables, so it is not possible to include other relevant research questions to the study such as in survey data based studies. Also, data on variables of lesser importance in administrative terms may be of lower quality. Administrative data often lacks any documentation and information about the quality of the data. To our knowledge, no efforts are made by the data provider to perform a case validation of the ADHD cases in the register we used in our study, which precludes us from knowing whether we have an under- or overestimation of the ADHD diagnosis. Further studies focusing on case validation as well as on evaluating the completeness of the data are warranted. However, while we recognize that there are limitations in using a register methodology, other study designs have also important limitations that must be recognized including a low and selected participation of families in the study that would lead to bias estimations or studies relying solely on parental reports may be prone to recall bias6. Thus, a methodology using administrative data is less costly and more time-efficient and may provide very large and representative samples of individuals for longtime periods which are not achievable financially or logistically through any survey method. The administrative datasets allow good opportunities for obtaining regional statistics and longitudinal series. Finally, another limitation is that we could not stratify the analyses by the three different subtypes of ADHD recognized, the predominantly inattentive, the predominantly hyperactive/impulsive, and the combined with characteristics of the first two subtypes, since they are not considered in the ICD-9 classification.Our study has also some limitations. The main limitation is that only ADHD cases from the public healthcare centers that are under the Catalan Health Department were considered. We were unable to access data of those children diagnosed in two other type of centers: i) the private healthcare centers and ii) the Child Development and Early Care Centers that are under the Catalan Welfare Deparment. However, in Catalonia the “Healthy Childhood” program is implemented and visits to the pediatrician are scheduled regularly during the whole childhoodWe found a prevalence of ADHD diagnoses of 4.06% in 2017. This prevalence was higher in boys than girls with a sex ratio of 2.8:1, and was highest in the 13 to 17 years age group. We did not observe an increase in the incidence of ADHD diagnoses trends from 2009 to 2017. We observed geographical differences in the prevalence of ADHD diagnoses in 2017 and in the annual ADHD incidence between healthcare areas. ADHD incidence was almost constant within healthcare areas during the study period. This study provides new evidence of the prevalence and incidence of ADHD diagnoses in children in the South of Europe producing essential information for planning and evaluating the needs of the healthcare services as well as the educational services in the Catalonia region.33. Catalonia is an autonomous community on the northeastern of Spain. In 2018, the official population of Catalonia was 7,543,825 inhabitants, accounting for about 16.2% of the Spanish population. Catalonia consists of four provinces, Barcelona, Girona, Lleida, and Tarragona, which in turn are divided into 29 healthcare areas which are delimited based on geographic, socio-economic, and demographic factors.We used administrative data for children aged 4 to 17 years covered under the Catalan Public Health Service between 2009 and 2017. In this cohort, we identified children diagnosed with ADHD at public healthcare centers between 2009 and 2017, and we defined population-based denominators based on the total population of children in 2017, and the total population of children at risk for each year between 2009 and 2017, as detailed in the following sections. Spain’s National Health System provides universal access to health services for all native and foreign-born children. Therefore, the access to public healthcare centers is available to all children regardless of socioeconomic/financial status or racial/ethnic identificationth edition Text revision (DSM-IV-TR)34 and the Diagnostic and Statistical Manual of mental disorders 5th edition (DSM-V)5. However, when these diagnoses have to be registered in the MBDS register, they are coded according to the International Classification of Diseases 9th edition (ICD-9)35.In Catalonia, all children diagnosed with ADHD in a public healthcare center are registered by the Catalan Health Service in the Minimum Basic Data Set (MBDS) register. This population register collects information on the patients’ activity and health morbidity, and is populated using information provided by 4 different types of public healthcare centers: mental health centers, mental health outpatient clinics, primary care centers, and hospital discharges. These different centers started to register cases of ADHD at different years. The primary care centers started in 1990 but had good quality and reliable data since 2006, the hospital discharges started in 2005, and the mental health centers and mental health outpatient clinics started in 2008. In 2008, the first year that all centers had available data registered, we observed an expected artifact of high number of ADHD diagnoses registered. Thus we started this study in 2009 when the number of ADHD diagnoses became more stable. If a child was registered with an ADHD diagnosis before 2009, it was excluded from the dataset. The diagnostic procedure of ADHD in any of these centers is carried out following the criteria of the Diagnostic and Statistical Manual of mental disorders 45.Therefore, in this study ADHD cases were defined as those children aged 4 to 17 years with a diagnosis of ADHD between 2009 and 2017 based on the ICD-9 code 314 (hyperkinetic syndrome of childhood). ADHD cases might be duplicated when they are registered in different public healthcare centers or by different health professionals (which happened in 24% of the cases). For our study, we selected the first entry in the register as the first ADHD diagnosis as children have a unique identifier in all centers. We considered the subsequent registered diagnoses of the same child as the same case registered multiple times instead of different ADHD diagnoses. We excluded ADHD cases registered before the age of 4 because ADHD diagnosis before this age might not be reliableFor each child, we collected information about sex, healthcare area where ADHD was diagnosed, and age at two times: age at diagnosis and age in 2017. Age was stratified in three categories: 4–6 years, 7–12 years, and 13–17 years.st of January of each year. Both population-based denominators were also stratified by sex, age group, and healthcare areas, using the same category groups as those for the ADHD cases.We used the total population of children in 2017 and the total population of children at risk for each year between 2009 and 2017, as registered by the Catalan Health Service through the Central Register of Insured Persons. The total population of children was defined as the number of children aged 4 to 17 years in 2017, and the total population of children at risk as the number of children aged 4 to 17 years who were ADHD-free but still at risk of developing ADHD for each year between 2009 and 2017. For both population-based denominators, we used the population on 1We calculated the prevalence of ADHD diagnoses ) in 2017 by dividing the number of children aged 4 to 17 years with an ADHD diagnosis that year (numerator) by the total number of children in the same age range in the population in the studied year (denominator). The prevalence in 2017 was stratified by sex, age group (age in 2017), and healthcare area. The differences in prevalence between sexes and age groups were estimated using the Chi-squared test. We plotted the distribution of the prevalence of ADHD diagnoses by healthcare areas in a map. We categorized the distribution of the prevalence of ADHD diagnoses in equal intervals per each 0.50% increase.We calculated the annual incidence of ADHD diagnoses (95% CI) between 2009 and 2017 by dividing the number of newly diagnosed cases of ADHD among children aged 4 to 17 years (numerator) by the total population at-risk of children aged 4 to 17 years for each year (denominator). Annual incidence between 2009 and 2017 was stratified by sex, age group (at diagnosis), and healthcare area. As there is independence between the occurrences of ADHD events, i.e. one child does not predispose to the appearance of more cases of children diagnosed with ADHD, we used Poisson regression models to assess the temporal trend of the overall incidence between 2009 and 2017, and that for each sex and age group (at diagnosis). Finally, we also plotted in maps the distribution of incidence of ADHD diagnoses for each year and for each healthcare area. We categorized the distribution of the incidence of ADHD diagnoses into deciles.We used STATA  and OpenEpi  for the statistical analyses. We used QGIS  for creating the maps of the prevalence and incidence by healthcare areas.This study was reviewed and approved by the Clinical Research Ethics Committee of the Parc de Salut Mar that waived the need to obtain informed consent as this study did not involve contact with study subjects, authors only had access to anonymized data through registries. Adequate measures to ensure personal data protection and confidentiality were taken according to the Regulation (EU) 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and the Spanish Law of Personal Data Protection and Digital Rights Guarantee . National regulations on personal data protection were implemented to guarantee the highest standards in personal data management.The dataset analyzed during the present study is available from the corresponding author on reasonable request.Supplementary Material.


Attention-deficit-hyperactivity disorder (ADHD) is closely associated with deficits in cognitive control. It seems, however, that the degree of deficits strongly depends on the examined subprocess, with the resolution of stimulus–stimulus conflicts being particularly difficult for patients with ADHD. The picture is far less clear regarding stimulus–response conflicts. The current study provides multi-level behavioural and neurophysiological data on this type of conflict monitoring in children with ADHD compared to healthy controls. To account for the potentially strong effects of intra-individual variability, electroencephalogram (EEG) signal decomposition methods were used to analyze the data. Crucially, none of the analyses  show any differences between the ADHD group and the control group. Bayes statistical analysis confirmed the high likelihood of the null hypothesis being true in all cases. Thus, the data provide multi-level evidence showing that conflict monitoring processes are indeed partly intact in ADHD, even when eliminating possible biasing factors such as intra-individual variability. While stimulus–stimulus conflict processing has been shown to be consistently dysfunctional in ADHD, the resolution of stimulus–response conflicts is not deficient in this patient group. In comparison to other studies, the results provide novel theoretical insights into the nature of conflict control deficits in childhood ADHD. Attention-deficit-hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in adolescence and is associated with several deficits in executive functioning and cognitive control ,4,5,6,7.Overall, the monitoring and control of conflicts depends on an intricate neurophysiological processing architecture associated with the medial and inferior frontal cortices ,10. SpecThe norepinephrine system plays a central role in ADHD and in its treatment . FurtherIt cannot be ruled out that differences in conflict monitoring processes are more subtle in ADHD and can only be delineated when distinct neurophysiological coding levels are isolated in the EEG data. This is all the more likely considering the high intra-individual performance variability in ADHD ,29,30,31However, in addition to the above mentioned considerations relating to issues of intra-individual variability and neurophysiological aspects, cognitive-theoretical aspects also have to be considered: At present, the research on conflict monitoring in ADHD is largely inconsistent in relation to theoretical concepts and the different mechanisms underlying conflict monitoring. From a theoretical point of view, stimulus–response (S-R) conflicts have to be distinguished from stimulus–stimulus (S-S) conflicts . An S-S Interestingly, meta-analytic evidence suggests that there are stable conflict monitoring deficits in ADHD when these are examined using S-S conflicts  . The patRather different mechanisms and functional neuroanatomical structures seem to be involved in S-R conflicts ,51. SpecThus, it is the goal of the current study to examine modulations of neurophysiological processes underlying the resolution of S-R conflicts in ADHD in detail and to account for possible biasing effects of intra-individual variability in the neurophysiological data. Adding to existing studies, the results will provide valuable insights into the nature of conflict monitoring deficits in ADHD. Since a major result of the study could be that there are no deficits in ADHD, the study will also test the evidence for the non-occurrence of an effect/the evidence for the null hypothesis when appropriate. Accordingly, this study uses both classical significance tests and Bayes’ statistics to estimate the degree of evidence for the null hypothesis.2 = 0.04) in the important interaction “compatibility x group” with a power of 95%. In total, N = 69 participants were included in the study. All demographic data is presented in In the ADHD sample, diagnoses had been determined based on standard clinical procedures , audiometry, and vision testing). Parents rated  their children’s ADHD symptoms using the ADHD Symptom Checklist . As expeDuring the flanker task, vertically arranged visual stimuli (white arrowheads) were presented in the centre of a screen on a black background. Central target stimuli pointing to the left or right were preceded (200 ms) by two arrowheads above and below pointing in the same  or opposite  direction as the target stimulus. Target stimuli were displayed for 300 ms with flanker stimuli being switched off simultaneously. The response–stimulus interval was pseudo-randomized between 1400 and 1800 ms. To further increase the level of conflict, time pressure was administered since the participants were asked to respond within 450 ms for target onset. If responses occurred after this deadline, a warning tone  was given 1200 ms after the response. This principal stimulus setup was used in four blocks of 120 stimuli each .We recorded the EEG signals using an equidistant electrode setup . Impedances were kept below 5 kΩ. Offline data processing took place analogously to the procedure described in : data was down-sampled to 256 Hz and a band-pass filter  was applied. A manual raw data inspection was conducted to remove technical artifacts. Periodically occurring artifacts  were detected and removed using an independent component analysis. Data was segmented to the onset the target stimulus (−1000–2000 ms). Only trials with correct responses were analysed further. An automatic artefact rejection procedure  was used to remove any remaining artifacts. A current source density transformation was used to allow a reference-free evaluation of the EEG data . Data weUsing a data-driven approach, single-subject ERP-amplitudes were quantified as the mean amplitude in a defined time interval. The choice of electrodes and time windows was validated using a statistical procedure described in Mückschel et al. . The folhttp://cns.hkbu.edu.hk/RIDE.htm. It is important to note that the spatial filter properties of the current source density (CSD) transformation do not violate assumptions of RIDE as the decomposition is conducted separately for each single electrode channel [To account for intra-individual variability in the data, residue iteration decomposition (RIDE) was applied using established protocols ,14,37,56 channel . RIDE deSubsequently, the S-cluster is removed and the latency of the C-cluster is re-estimated based on a template matching approach. Information about the validity of the template matching approach used by the RIDE algorithm can be found elsewhere ,38,57. DThe choice of electrodes and time windows to quantify the RIDE clusters were also validated using a statistical procedure described in Mückschel et al. . For theThe C-cluster data was used to quantify activation in the N2 and P3 time windows. The C-cluster N2 RIDE component  was quantified at electrode Fz. The P3 RIDE was measured in the time window of 300–600 ms at electrode Pz. In the R-Cluster, relevant activation was quantified in a time interval of ±100 ms around the mean reaction time  at electrodes C3 and C4 (mean).p(H0/D). The entire dataset can be obtained from the In all analyses, means and standard errors are indicated as descriptive statistics. Pearson correlations were calculated in order to examine any associations between ADHD symptom severity and the other variables. Reaction times (RTs) in corrects trials were analyzed using repeated-measures ANOVA, using the within-subject factor Compatibility (compatible vs. incompatible) and the between-subject factor Group (controls vs. ADHD). The same statistical model was used to analyse the error rates (% of errors) as well as the neurophysiological data. The effect of Compatibility was not analysed for any flanker-related neurophysiological data, since this effect can only occur after presentation of a target stimulus. Greenhouse–Geisser correction was applied and post-hoc tests, as well as all correlational analyses, were Bonferroni-corrected when necessary. To substantiate the lack of significant effects, we performed Bayesian analysis  to calcup = 0.92; ηp2 = 0.0) between the groups . The repeated-measures ANOVA further showed significantly faster reaction times in compatible (331 ± 7.9 ms) than in incompatible (416 ± 10.0 ms) trials  = 238.1; p ≤ 0.001; ηp2 = 0.78). The interaction of Group * Compatibility was not significant  = 0.05; p = 0.82; ηp2 = 0.001), with Bayesian analysis showing p(H0/D) = 0.89. According to Raftery [p = 0.21; ηp2 = 0.02) between groups . Both groups committed significantly more errors in incompatible (44.0 ± 1.9%) than in compatible trials (17.1 ± 2.2%)  = 111.2; p ≤ 0.001; ηp2 = 0.62). The interaction of Group * Compatibility was not significant  = 0.55; p = 0.46; ηp2 = 0.008). Bayesian analysis revealed p(H0/D) = 0.86. Further, ADHD symptom severity was not correlated with task performance .Concerning reaction times (RTs), there were no significant differences  = 0.01;  Raftery , this shP1 and N1 components in response to the flanker and the target stimuli for both groups and both trial types are shown in p > 0.29, all ηp2 < 0.02). Concerning the target P1, we found a main effect of Compatibility  = 74.4, p ≤ 0.001, ηp2 = 0.5) There were no further significant main effects or interactions concerning target P1 amplitude . Concerning the target N1 amplitude, we found no significant main effects or interactions . Concerning the N2 . Analysis of P3 amplitude . All other effects were not significant . Using Bayesian analyses, we could show for the probability of the null hypothesis being true for all six non-significant Group * Compatibility to be p(H0/D) ≥ 0.78. ADHD symptom severity was not correlated with any of these measures .There were no significant main effects of the factor Group on flanker P1 or N1 amplitude , flanker N1-time window (flanker N1RIDE), the target P1-time window (target P1RIDE) and in the target N1-time window (target N1RIDE) for both groups and both trial types are shown in Components in the flanker P1-time window . Concerning the flanker N1RIDE amplitude, we also found no significant main effects or interactions . Analysis of the target P1RIDE amplitude revealed a significant main effect of Compatibility  = 73.9; p ≤ 0.001; ηp2 = 0.52), with incompatible trials resulting in significantly higher amplitudes (59.3 ± 5.0 µV/m2) than compatible trials (47.5 ± 4.6 µV/m2). All other main effects and interactions were not significant . No significant main effects or interactions were found for the target N1RIDE amplitude . Using Bayesian analyses, we could show for the probability of the null hypothesis being true for all four non-significant Group * Compatibility to be p(H0/D) ≥ 0.72. The waveform of the S-cluster in the N2-time window (N2 RIDE_S) for both groups and for compatible and incompatible trials is shown in There were no significant effects of the factor Group on the flanker P1RIDE_S amplitude revealed no main effects or interactions  were significant. Bayesian analyses showed for the probability of the null hypothesis being true for the non-significant Group * Compatibility to be p(H0/D) = 0.89. ADHD symptom severity was not correlated with any of these measures .The analyses of the N2RIDE_C) for both groups and for compatible and incompatible trials is shown in RIDE_C component revealed a main effect of Compatibility  = 6.5; p = 0.01; ηp2 = 0.09). Incompatible trials (−37.2 ± 3.5 µV/m2) resulted in significantly more pronounced N2 RIDE_C amplitudes than compatible trials (−31.1 ± 2.6 µV/m2). All other main effects and interactions were not significant . Bayesian analyses showed for the probability of the null hypothesis being true for the non-significant Group * Compatibility to be p(H0/D) = 0.83. The waveform of the C-cluster in the P3-time window (P3RIDE) at electrode Pz for both groups and for compatible and incompatible trials is shown in RIDE component revealed a main effect of Compatibility  = 29.8; p ≤ 0.001; ηp2 = 0.3). Incompatible trials (27.4 ± 2.9 µV/m2) resulted in significantly more pronounced P3RIDE amplitudes than compatible trials (17.4 ± 2.1 µV/m2). All other main effects and interactions were not significant . Bayesian analyses showed for the probability of the null hypothesis being true for the non-significant Group * Compatibility to be p(H0/D) = 0.86. ADHD symptom severity was not correlated with any of these measures .The waveform of the C-cluster in the N2-time window . Bayesian analyses showed for the probability of the null hypothesis being true for the non-significant Group * Compatibility to be p(H0/D) = 0.85. ADHD symptom severity was not correlated with R-Cluster activity .The waveform of the R-Cluster for both groups and for compatible and incompatible trials is shown in In the current study, we examined conflict monitoring processes in patients with ADHD using a Flanker task and neurophysiological methods. Dysfunctions in various cognitive control functions such as conflict processing are supposed to reflect a major aspect of ADHD ,4,5,6,7.The results show that ADHD is not associated with deficits in conflict monitoring when examined using a Flanker task. The study is well powered  and the lack of group differences is substantiated with a Bayesian analysis of the data. The latter provided positive evidence in favour for the null hypothesis, i.e., that there are no deficits in conflict monitoring in ADHD. This was the case for the behavioural and the neurophysiological data. Notably, we found strong evidence for the null hypothesis even when accounting for intra-individual variability in the data using RIDE, and when considering that different aspects of information processing during conflict monitoring are coded in distinct parts of the neurophysiological signal. Further, ADHD symptom severity was not correlated with any of these parameters. Thus, the data provide multi-level behavioural and neurophysiological evidence showing that conflict monitoring processes are indeed partly intact in ADHD. Importantly, when looking closer at the available evidence on conflict monitoring in ADHD in comparison to the current results, the nature of cognitive control deficits in ADHD becomes clearer:As mentioned above, previous evidence on conflict monitoring processes in ADHD is heterogenous ,29,30,31This apparent variation in conflict monitoring deficits depending on the approach  used to assess conflict monitoring provides insights into the boundary conditions under which conflict/interference monitoring is dysfunctional in ADHD. Response interference, as examined in the Flanker task or Simon task , involveFrom this cognitive-theoretical perspective, it seems that conflict monitoring is consistently dysfunctional in ADHD when it comes to the resolution of S-S conflicts , but noNotably, meta-analytic functional imaging data show that especially S-S conflicts modulate processes in the inferior frontal and anterior cingulate areas , i.e., aOverall, it has further been argued that deficits in ‘inhibitory control’ are at the core of cognitive control deficits in ADHD and carry a high clinical relevance ,70,71,72From a clinical perspective it seems that it is important to strengthen inhibitory control processes in ADHD. This is especially important as baseline impulsivity has been suggested to be a very good predictor of treatment response . InteresImportantly, only atomoxetine has been shown to increase prefrontal activation during a Stroop task . This efFuture studies should therefore evaluate whether there are differences in the treatment effects depending on whether S-R or S-S conflicts are examined in ADHD and whether such results should be included in the calculation of risk scores or information profiles, which might guide treatment decisions in the future . Importa


Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive.To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children.In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score.BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile , being stronger for girls . A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03).Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.The online version contains supplementary material available at 10.1186/s12940-021-00709-y. Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most common neurodevelopmental disorders in children . Both haDuring fetal life, the brain development is particular sensitive, and prenatal exposure to environmental chemicals is therefore of concern . BisphenA previous study in the Odense Child Cohort (OCC) found an association between prenatal BPA exposure and delayed language development, but no association with ADHD related symptoms at 2 years of age among 658 children . The lacN = 332) were excluded from this study.From 2010 to 2012, women residing in the municipality of Odense with a newly diagnosed pregnancy before 16 weeks of gestation were invited to participate in the prospective OCC, and 2874 agreed to participate . Twins aBPA was measured in maternal urine samples. An aliquot of 10–12 mL fasting urine was collected in the morning at approximately week 28 of pregnancy (range: week 26–34). Samples were stored in freezers at − 80 °C until chemical analysis , 37. TheTo account for urinary dilution, all BPA concentrations were adjusted for osmolality. In contrast to urinary creatinine adjustment, urine osmolality is directly related to the number of particles in solution and is unaffected by the molecular weight and size of these particles . Osmolalnot true, 1 = somewhat/sometimes true or 2 = very true/ often true. A standardized version of CBCL/1½-5 translated into Danish [The Child Behaviour Checklist; 1½-5 (CBCL/1½-5) is a parent rated questionnaire measuring emotional and behavioural problems in children between 1½ and 5 years of age. CBCL/1½-5 consists of 100 problem questions, which the parents are asked to rate on a 3-point Likert scale based on the preceding 2 months as: 0 = o Danish  was sentcannot concentrate, hyperactive, cannot stand waiting, demands met immediately, gets into everything, quickly shifts) with a scale-score between 0 and 12 points. Autistic symptoms were measured at the DSM-oriented ASD problem scale  scale), extracted from CBCL/1½-5. It contains 13 questions  with a possible scale-score between 0 and 26 points. Results were kept as raw scores and dichotomized at the 75th percentile to identify a subclinical population, and at the 90th percentile, since a score on the DSM-ADHD scale derived from CBCL/1½-5 above the 90th percentile is a predictor of a later ADHD diagnosis [We measured ADHD related symptoms at the DSM-oriented ADHD problem scale, extracted from CBCL/1½-5. It contains 6 questions  and smoking habits were obtained through questionnaires filled in during pregnancy. Birth information, including; maternal age, parity, birth weight, gestational age, and child sex was extracted from obstetric journals. Data on child’s health including duration of breastfeeding were obtained through questionnaires filled in, when the children were 3 and 18 months of age. Maternal ethnicity was obtained through data from the municipality. Finally, information regarding parental psychiatric diagnosis was extracted from the Danish National Patient Registry.. At 5 years of age respectively 20 and 26% of children had a score of ≥4 on the ASD and ADHD scale. Therefore, the children were dichotomized into ≤/> the 75th for ASD score and </≥ 75th percentile for ADHD score. BPA concentrations were not normally distributed, and 15% of concentrations were below LOD. Thus, we both divided BPA concentrations into tertiles, and kept it as an ln-transformed continuous variable. However, it should be noted that residuals did not fit the logistic model with ln-transformed continuous BPA, and thus results should be interpreted with caution. The characteristics of the included participants were compared to the excluded participants by the use of Chi2 test. Differences in urinary BPA concentration, ADHD and ASD scores (below and above 75th percentile) were examined according to maternal and child characteristics using non-parametric Kruskal Wallis test (BPA) and Chi2 test (ADHD and ASD).ADHD- and ASD scores were not normally distributed and scores of respectively below and above the 75th and 90th percentile was calculated for both scales. The 75th and 90th percentile dichotomization of the ADHD score corresponded to a score of ≥4 and ≥ 5, respectively, at 5 years of age. The 75th and 90th percentile dichotomization of the ASD score corresponded to a score of ≥3 and ≥ 4, respectively, at 2 years of age, and a score of ≥4 and ≥ 5, respectively, at 5 years. At 2 years of age, 26% of children had an ASD score ≥ 3, and were dichotomized into </≥ 75th percentileFirst, we used multiple logistic regression to calculate the Odds Ratio (OR) and 95% confidence intervals (95% CI) of having an ADHD or ASD problem score > 75th and ≥ 90th percentile across increasing maternal BPA exposure (continuous ln-transformed or divided into tertiles) and to test the trend across tertiles. Second, ASD- and ADHD-scores were analysed as ordinal data using negative binomial regression to estimate the relative change in ASD or ADHD-score expressed as ratio of risk between exposure groups. In addition, a sub-analysis was undertaken to calculate the odds ratio of having an ASD-score above the 75% percentile at both 2 and 5 years of age. Confounders were selected based on careful review of the literature, and if they varied by exposure and outcome status. Furthermore, covariates were included, if they changed the effect estimate of the independent variable with ≥10%. Possible confounders included in the final analyses were maternal educational level, parity, pre-pregnancy BMI and maternal age. Furthermore, we adjusted for child age at evaluation, as small differences in age could affect neuropsychological status. In addition, the unstratified analyses were also adjusted for child sex. A sensitivity analyses was performed for the 75th percentile additionally adjusting for the possible mediators breastfeeding and birth weight, as we were interested in the direct rather than the total effect of BPA on ADHD and ASD symptoms. Since previous research has found BPA to cause sexually dimorphic alterations in child behaviour , 34, allp-value < 0.05 was considered statistically significant.To evaluate the fit of the logistic regression models, goodness of fit was tested using Hosmer-Lemeshow test and accepted for all models. Results are presented with an Odds Ratio (OR) 95% confidence interval (CI), and a N = 1559), the included participants were less often smokers and breastfeed for a longer period of time  concentration of 1.2 ng/mL (0.5–2.6) (Table The median score (25–75%) on the ASD-scale was 1 (0–2) for girls, and 1 (0–3) for boys at 2 years of age and 1 (0–3) for girls, and 2 (1–3) for boys at 5 years of age. The median score (25–75%) on the ADHD scale was 2 (0–3) for girls, and 2 (1–4) for boys at 5 years of age. Higher ADHD/ASD scores were found among children of mothers, who were nulliparous, smokers, less educated, younger, among children with a psychiatric predisposition, children who had been exclusively breastfed for a shorter duration, children with lower birth weight, and children who were born prematurely  (p-trend = 0.06). For each doubling in BPA exposure the odds of a score ≥ 75th percentile increased with 38% ) compared to a score < 75th percentile  [Braun et al. (2017) [Braun et al. (2017) [Lim et al. (2017) [The association between maternal BPA exposure and child neurodevelopment has been investigated by several studies (reviewed in –35). To . (2011)  a signif. (2011) . However. (2011) , 45, our. (2011)  found an. (2011) . They me. (2017)  found st. (2017) , and in . (2017) . During . (2017) , 47. The. (2017)  might be. (2017)  also fouGrohs et al (2020) [In a previous publication from our cohort, no association between maternal BPA exposure and ADHD symptoms at age 2 years was found . These fl (2020)  suggesteThe ability of in utero BPA exposure to alter behaviour has been confirmed in several animal studies (reviewed in ). In rodOur study presents several strengths, including the relatively large study population and the prospective design. Furthermore, we were able to adjust for potential confounding factors. However, some limitations need mentioning. First, only a single urine sample was used as a proxy for fetal exposure to BPA. BPA is rapidly conjugated in the human body and almost fully excreted in urine within 24 h, and therefore temporal and diurnal variation in exposure patterns and excretion rates may occur –65. BPA Even though we adjusted for potential confounders, the possibility of additional confounding from e.g. maternal IQ cannot be dismissed. Furthermore, it is possible that other environmental chemicals in co-exposure with BPA could impact the findings. Finally, BPA was measured in gestational week 28, and brain development may be more vulnerable during early or late pregnancy or even during childhood, as studies have found childhood (preschool) BPA exposure is associated with behavioural alterations in children , 22–24. In conclusion, in this low exposed mother-child cohort, children of mothers within the highest tertile of BPA exposure had suggestive higher odds of having an ASD-score > 75th percentile at 5-years of age whereas no association was found at age 2 years. High scores may predict later ASD symptoms which may influence social and learning abilities, and it is therefore important to follow-up these children and measure their own BPA exposure to determine if these findings persist.Additional file 1: Supplementary table 1. Maternal and child characteristics according to included participants with BPA and CBCL1½-5 data at 2 years (N=658) and excluded participants (N=1559). Supplementary table 2. Multiple logistic regression analysis of the association between osmolality adjusted maternal BPA exposure divided into tertiles and the odds ratio (OR) and 95% confidence intervals (CI 95%) of an ASD and ADHD-score >75% compared to <75% (reference) at 2 and/or 5 years of age.