Comparación de dos métodos para identificar los factores asociados al inicio del consumo de cannabis en un estudio de cohortes

ResumenObjetivoComparar la utilidad de 2 métodos analíticos multivariados, el análisis como casos y controles (CC) y como casos y controles anidados (CCa) en una cohorte, para identificar los factores asociados al inicio del consumo de cannabis.MétodosEstudio longitudinal con una muestra de 1.056 alumnos de primer curso de Educación Secundaria Obligatoria (ESO), seguidos anualmente hasta cuarto de ESO. En el análisis como CC se consideraron casos los que declararon, en el cuarto año, haber consumido cannabis y controles los que no habían consumido nunca, estimando modelos de regresión logística (RL). En el análisis como CCa, se compararon los casos de cada año de seguimiento con una muestra aleatoria de controles de riesgo en ese mismo año, estimando modelos de RL condicional.ResultadosEn el análisis como CC, se identificaron 6 variables en los chicos y 9 en las chicas en los modelos bivariados, y 3 en los chicos y 4 en las chicas en los multivariados. En el análisis como CCa se obtuvieron 17 variables en los modelos bivariados y 4 en los multivariados, tanto en los chicos como en las chicas. Los estimadores del análisis como CC tenían 1,2 veces más variabilidad.ConclusionesEl análisis como CCa permitió identificar un mayor número de factores asociados al consumo de cannabis y los estimadores fueron más precisos. El CCa puede ser una alternativa más eficiente frente al análisis como CC.AbstractObjectiveTo compare the utility of two multivariate analytic methods, case-control (CC) analysis and nested case-control (NCC) analysis in a cohort, to identify the factors associated with the onset of cannabis use.MethodsA longitudinal cohort study of a sample of secondary school students (n = 1,056) in the first year of secondary school was carried out. Participating students were followed-up annually until the fourth year of secondary school. In the CC analysis, students in the fourth year who reported having consumed cannabis at some time were considered cases and those who had never consumed cannabis were considered controls. Logistic regression (LR) models were estimated. In the NCC analysis, cases in each year of follow-up were compared with a random sample of controls at risk in the same year and conditional LR models were estimated. IResultsIn the CC analysis, 6 variables in boys and 9 variables in girls in bivariate models and 3 variables in boys and 4 variables in girls in multivariate models were identified. In the NCC analysis, 17 variables in univariate models and 4 in multivariate models were obtained in both boys and girls. The estimators of the CC analysis showed an average of 1.2-fold more variability.ConclusionsA higher number of factors associated with cannabis use were identified in the NCC analysis and the estimators were more precise. NCC could be a more efficient option than CC analysis

Air pollution exposure during pregnancy and childhood, APOE ε4 status and Alzheimer polygenic risk score, and brain structural morphology in preadolescents

Apolipoprotein E; Genetic modifiers; NeurodevelopmentApolipoproteïna E; Modificadors genètics; NeurodesenvolupamentApolipoproteína E; Modificadores genéticos; NeurodesarrolloBackground Air pollution exposure is associated with impaired neurodevelopment, altered structural brain morphology in children, and neurodegenerative disorders. Differential susceptibility to air pollution may be influenced by genetic features. Objectives To evaluate whether the apolipoprotein E (APOE) genotype or the polygenic risk score (PRS) for Alzheimer's Disease (AD) modify the association between air pollution exposure during pregnancy and childhood and structural brain morphology in preadolescents. Methods We included 1186 children from the Generation R Study. Concentrations of fourteen air pollutants were calculated at participants’ home addresses during pregnancy and childhood using land-use-regression models. Structural brain images were collected at age 9–12 years to assess cortical and subcortical brain volumes. APOE status and PRS for AD were examined as genetic modifiers. Linear regression models were used to conduct single-pollutant and multi-pollutant (using the Deletion/Substitution/Addition algorithm) analyses with a two-way interaction between air pollution and each genetic modifier. Results Higher pregnancy coarse particulate matter (PMcoarse) and childhood polycyclic aromatic hydrocarbons exposure was differentially associated with larger cerebral white matter volume in APOE ε4 carriers compared to non-carriers (29,485 mm3 (95% CI 6,189; 52,781) and 18,663 mm3 (469; 36,856), respectively). Higher pregnancy PMcoarse exposure was differentially associated with larger cortical grey matter volume in children with higher compared to lower PRS for AD (19436 mm3 (825, 38,046)). Discussion APOE status and PRS for AD possibly modify the association between air pollution exposure and brain structural morphology in preadolescents. Higher air pollution exposure is associated with larger cortical volumes in APOE ε4 carriers and children with a high PRS for AD. This is in line with typical brain development, suggesting an antagonistic pleiotropic effect of these genetic features (i.e., protective effect in early-life, but neurodegenerative effect in adulthood). However, we cannot discard chance findings. Future studies should evaluate trajectorial brain development using a longitudinal design.The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. A.N. was supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (024.001.003, Consortium on Individual Development), a grant of the Canadian Institutes of Health Research team, and by the Research Foundation Flanders (FWO). S.A. was supported by the Programa Talen_UAB-Banc de Santander. The geocodification of the addresses of the study participants and the air pollution estimations were done within the framework of a project funded by the Health Effects Institute (HEI) (Assistance Award No. R-82811201). We received funding from the Spanish Institute of Health Carlos III (CPII18/00018), the EU Commission (733,206, 824,989), and the Agence Nationale de Securite Sanitaire de l’Alimentation de l’Environnement et du Travail (EST-18 RF-25). We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program”

Sleep problems at ages 8–9 and ADHD symptoms at ages 10–11:evidence in three cohorts from INMA study

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8–9 represent an alarm sign for presenting ADHD problems at ages 10–11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8–9) with the sleep items of the Child’s Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner’s Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10–11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10–1.19), 1.20 (1.14–1.26), 1.18 (1.11–1.25), and 1.18 (1.13–1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded. Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme.</p

Air Pollution and Birth Outcomes:Health Impact and Economic Value Assessment in Spain

Air pollution is considered an ongoing major public health and environmental issue around the globe, affecting the most vulnerable, such as pregnant women and fetuses. The aim of this study is to estimate the health impact and economic value on birth outcomes, such as low birthweight (LBW), preterm birth (PTB), small for gestational age (SGA), attributable to a reduction of PM10 levels in Spain. Reduction based on four scenarios was implemented: fulfillment of WHO guidelines and EU limits, and an attributable reduction of 15% and 50% in annual PM10 levels. Retrospective study on 288,229 live-born singleton children born between 2009-2010, using data from Spain Birth Registry Statistics database, as well as mean PM10 mass concentrations. Our finding showed that a decrease in annual exposure to PM10 appears to be associated with a decrease in the annual cases of LBW, SGA and PTB, as well as a reduction in hospital cost attributed to been born with LBW. Improving pregnancy outcomes by reducing the number of LBW up to 5% per year, will result in an estimate associated monetary saving of 50,000 to 7,000,000 euros annually. This study agrees with previous literature and highlights the need to implement, and ensure compliance with, stricter policies that regulate the maximum exposure to outdoor PM permitted in Spain, contributing to decreased environmental health risk, especially negative birth outcomes

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

Identifying Sensitive Windows of Exposure to NO2 and Fetal Growth Trajectories in a Spanish Birth Cohort

Background: We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth. Methods: We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0-12 weeks), mid (12-20 weeks), and late (20-34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman's residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 mu g/m(3) increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags. Results: We identified weeks 5-12 as a sensitive window for NO2 exposure on late EFW (cumulative beta = -3.0%; 95% CI = -4.1%, -1.9%). We identified weeks 6-19 as a sensitive window for late growth in BPD (cumulative beta = -2.0%; 95% CI = -2.7%, -1.4%) and weeks 8-13 for AC (cumulative beta = -0.68%; 95% CI = -0.97%, -0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy. Conclusions: Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation.K.W.W. and E.S. were partially supported by the P30 Environmental Health Sciences Core Center grant P30ES030285 from the National Institute

Susceptible windows of prenatal and postnatal fine particulate matter exposures and attention-deficit hyperactivity disorder symptoms in early childhood

Few prior studies have explored windows of susceptibility to fine particulate matter (PM2.5) in both the prenatal and postnatal periods and children's attention-deficit/hyperactivity disorder (ADHD) symptoms. We analyzed data from 1416 mother-child pairs from the Spanish INMA (INfancia y Medio Ambiente) Study (2003–2008). Around 5 years of age, teachers reported the number of ADHD symptoms (i.e., inattention, hyperactivity/impulsivity) using the ADHD Diagnostic and Statistical Manual of Mental Disorders. Around 7 years of age, parents completed the Conners' Parent Rating Scales, from which we evaluated the ADHD index, cognitive problems/inattention, hyperactivity, and oppositional subscales, reported as age- and sex-standardized T-scores. Daily residential PM2.5 exposures were estimated using a two-stage random forest model with temporal back-extrapolation and averaged over 1-week periods in the prenatal period and 4-week periods in the postnatal period. We applied distributed lag non-linear models within the Bayesian hierarchical model framework to identify susceptible windows of prenatal or postnatal exposure to PM2.5 (per 5-μg/m3) for ADHD symptoms. Models were adjusted for relevant covariates, and cumulative effects were reported by aggregating risk ratios (RRcum) or effect estimates (βcum) across adjacent susceptible windows. A similar susceptible period of exposure to PM2.5 (1.2–2.9 and 0.9–2.7 years of age, respectively) was identified for hyperactivity/impulsivity symptoms assessed ~5 years (RRcum = 2.72, 95% credible interval [CrI] = 1.98, 3.74) and increased hyperactivity subscale ~7 years (βcum = 3.70, 95% CrI = 2.36, 5.03). We observed a susceptibility period to PM2.5 on risk of hyperactivity/impulsivity symptoms ~5 years in gestational weeks 16–22 (RRcum = 1.36, 95% CrI = 1.22, 1.52). No associations between PM2.5 exposure and other ADHD symptoms were observed. We report consistent evidence of toddlerhood as a susceptible window of PM2.5 exposure for hyperactivity in young children. Although mid-pregnancy was identified as a susceptible period of exposure on hyperactivity symptoms in preschool-aged children, this association was not observed at the time children were school-aged.</p

The use of lower of 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

Prenatal Exposure to Residential Air Pollution and Infant Mental Development: Modulation by Antioxidants and Detoxification Factors

Background: Air pollution effects on children’s neurodevelopment have recently been suggested to occur most likely through the oxidative stress pathway