Temporal trends and geographical variability of the prevalence and incidence of attention deficit/hyperactivity disorder diagnoses among children in Catalonia, Spain

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% (95%CI 4.03, 4.10) in 2017, being 5.81% (95%CI 5.75, 5.87) for boys and 2.20% (95%CI 2.16, 2.24) for girls, the highest prevalence being in 13-to-17-year-olds (7.28% (95%CI 7.20, 7.36)). 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

Determinants of organophosphate pesticide exposure in pregnant women: A population-based cohort study in the Netherlands

Background: In the Netherlands organophosphate (OP) pesticides are frequently used for pest control in agricultural settings. Despite concerns about the potential health impacts of low-level OP pesticides exposure, particularly in vulnerable populations, the primary sources of exposure remain unclear. The present study was designed to investigate the levels of DAP metabolites concentrations across pregnancy and to examine various determinants of DAP metabolite concentrations among an urban population of women in the Netherlands. Method: Urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined at 25 weeks of pregnancy in 784 pregnant women participating in the Generation R Study (between 2004 and 2006), a large population-based birth cohort in Rotterdam, the Netherlands. Questionnaires administered prenatally assessed demographic and lifestyle characteristics and maternal diet. Linear mixed models, with adjustment for relevant covariates, were used to estimate associations between the potential exposure determinants and DAP metabolite concentrations expressed as molar concentrations divided by creatinine levels. Results: The median DAP metabolite concentration was 311 nmol/g creatinine for the first trimester, 317 nmol/g creatinine for the second trimester, and 310 nmol/g creatinine for the third trimester. Higher maternal age, married/living with a partner, underweight or normal weight (BMI of <18.5 and 18.5-<25), high education, high income, and non-smoking were associated with higher DAP metabolite concentrations, and DAP metabolite concentrations tended to be higher during the summer. Furthermore, fruit intake was associated with increased DAP metabolite concentrations. Each 100 g/d difference in fruit consumption was associated with a 7% higher total DAP metabolite concentration across pregnancy. Other food groups were not associated with higher DAP metabolite concentrations. Conclusions: The DAP metabolite concentrations measured in the urine of pregnant women in the Netherlands were higher than those in most other studies previously conducted. Fruit intake was the main dietary source of exposure to OP pesticides in young urban women in the Netherlands. The extent to which DAP metabolite concentrations reflect exposure to the active parent pesticide rather than to less toxic metabolites remains unclear. Further research will be undertaken to investigate the possible effects of this relatively high level OP pesticides exposure on offspring health

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

BACKGROUND: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. OBJECTIVES: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. METHODS: This was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g-in all mother-child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation-with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. RESULTS: UI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status. CONCLUSIONS: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits

Prenatal exposure to NO2 and ultrasound measures of fetal growth in the Spanish INMA cohort

__Background:__ Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability. __Objective:__ The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study. Methods: Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis. __Results:__ A 10-μg/m3 increase in average exposure to NO2 during weeks 0-12 was associated with reduced growth at weeks 0-12 in AC (-2.1%; 95% CI: -3.7, -0.6) and EFW (-1.6%; 95% CI: -3.0, -0.3). The same exposure was inversely associated with reduced growth at weeks 20-34 in BPD (-2.6%; 95% CI: -3.9, -1.2), AC (-1.8%; 95% CI: -3.3, -0.2), and EFW (-2.1%; 95% CI: -3.7, -0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers. __Conclusi

Association of maternal iodine status with child IQ: a meta-analysis of individual-participant data

Dataset, supplement to the article (to be added later

Dietary intake of trans fatty acids in children aged 4–5 in Spain: The INMA cohort study

Trans fatty acid (TFA) intake has been identified as a health hazard in adults, but data on preschool children are scarce. We analyzed the data from the Spanish INMA Project to determine the intake of total, industrial and natural TFA, their main sources and the associated socio-demographic and lifestyle factors in children aged 4–5 (n = 1793). TFA intake was estimated using a validated Food Frequency Questionnaire, and multiple linear regression was used to explore associated factors. The mean daily intakes of total, industrial and natural TFA were 1.36, 0.60, and 0.71 g/day, respectively. Ten percent of the children obtained >1% of their energy intake from TFA. The main sources of industrial TFA were fast food, white bread and processed baked goods. Milk, red and processed meat and processed baked goods were the main sources of natural TFA. Having parents from countries other than Spain was significantly associated with higher natural TFA (in mg/day) intake (β 45.5) and television viewing was significantly associated with higher industrial TFA intake (β 18.3). Higher fruits and vegetables intake was significantly associated with lower intakes of all TFAs, whereas higher sweetened beverages intake was significantly associated with lower total and natural TFA intake. Thus, total and industrial TFA intake was associated with less healthy food patterns and lifestyles in Spanish preschool children

The use of lower or higher than recommended doses of folic acid supplements during pregnancy is associated with child attentional dysfunction at 4–5 years of age in the inma project

We assessed the association between the use of lower-and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4–5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400–999 (recommended dose), and ≥1000 µg/day. Child attentional function was assessed by Conners’ Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 µg/day was associated with higher risk of omission errors—IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 µg/day and ≥1000 µg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 µg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 µg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4–5, particularly in boys

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Background: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10-8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10-8, n = 577) and sleep onset latency (p = 8.8 × 10-9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539). Conclusion: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available

A genome-wide association meta-analysis of attention-deficit/hyperactivity disorder symptoms in population-based pediatric cohorts

OBJECTIVE: The aims of this study were to elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. METHOD: Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (<13 years of age) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. RESULTS: SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46 × 10(-6) and 2.66 × 10(-6)). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. CONCLUSION: The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture, and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and to improve statistical power for identifying genetic variants.This study was funded by grants from the Spanish Instituto de Salud Carlos III (CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PI061756, PI091958, and PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931 , 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, CP11/0178 and MS13/00054), Spanish Ministry of Science and Innovation (SAF2008-00357), European Commission (ENGAGE project and grant agreement HEALTH-F4-2007-201413, HEALTH.2010.2.4.5-1, FP7- ENV-2011 cod 282957), Fundació La Marató de TV3, Generalitat de Catalunya-CIRIT 1999SGR 00241, and Conselleria de Sanitat Generalitat Valenciana. N. Vilor-Tejedor thanks the Agència de Gestió d’Ajuts Universitaris i de Recerca - Generalitat de Catalunya for her pre-doctoral grant (2015 FI_B 00636