Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms.

OBJECTIVE: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. STUDY DESIGN: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. RESULTS: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. CONCLUSIONS: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring.

Iodine sources and iodine levels in pregnant women from an area without known iodine deficiency.

OBJECTIVE: An adequate iodine intake during pregnancy is essential for normal development of the foetus. The World Health Organization (WHO) recommends that the median urinary iodine concentration (UIC) in a population of pregnant women should range between 150 and 249 microg/l. The aim of this study was to evaluate iodine status and to examine the main sources of iodine in pregnant women from an apparently iodine-sufficient area. METHODS: Six hundred pregnant women in the third trimester completed a food frequency questionnaire, and iodine was measured in urine samples. Urinary iodine concentrations were described in the whole population and in subgroups according to their frequency of intake of milk, fish, eggs, bread and iodized salt, as iodine supplements. RESULTS: The median UIC was 104 microg/l (n = 600), however, the median was higher among women who had a high milk intake (117 microg/l), used iodized salt (117 microg/l) or who were supplemented with iodine (141 microg/l). Women receiving iodine supplementation who also consumed more than one cup of milk per day had median UIC higher than 150 microg/l. In multivariate models, women with moderate and high milk intake had lower risk of having UIC below 150 microg/l [OR (95% CI): 0.42 (0.22-0.82) and 0.29 (0.15-0.55) respectively], after adjustment for potential confounders. CONCLUSIONS: On the basis of WHO criteria, the iodine status of pregnant women was inadequate in this area. Milk was the most important dietary source of iodine, and iodine supplementation was also an important source of iodine, although not enough to reach the current recommendations.

An evaluation of the sexual differences in the accumulation of organochlorine compounds in children at birth and at the age of 4 years.

This study of the body burden and serum concentrations of organochlorine compounds (OCs), represents a general population in a cohort from Menorca Island (birth 1997-1998) of children at birth and at 4 years of age; the study has shown that the concentrations of hexachlorobenzene (HCB), 4,4'-DDE, 4,4'-DDT, polychlorobiphenyl (PCB) congeners #153, #138 and #180 and total PCBs in sera collected at 4 years are much higher in breastfed children than in those fed with formula, e.g. HCB 0.48 vs 0.21 ng/ml, beta-HCH 0.32 vs 0.24 ng/ml, total DDTs 2.2 vs 0.57 ng/ml and total PCBs 1.4 vs 0.52 ng/ml. Comparison of gender differences in 4 years old children shows higher concentrations of all examined OCs in females than in males with the exception of HCB and PeCB in breastfed children, which are higher in males than in females, e.g. beta-HCH 0.34 vs 0.28 ng/ml, total DDTs 2.6 vs 1.7 ng/ml and total PCBs 1.6 vs 1.0 ng/ml for breastfed children and beta-HCH 0.23 vs 0.19 ng/ml, total DDTs 0.59 vs 0.48 ng/ml and total PCBs 0.58 vs 0.45 ng/ml for formula fed children. Gender comparison of the body burden between children fed with breastmilk or formula also shows higher concentrations in females than in males, e.g. beta-HCH 0.47 vs 0.35 microg, total DDTs 3.0 vs 1.8 microg and total PCBs 1.9 vs 1.2 microg for breastfed children, and beta-HCH 0.39 vs 0.17 microg, total DDTs 0.48 vs 0.27 microg and total PCBs 0.66 vs 0.55 microg for formula fed children. The results may suggest a higher capacity in female children for the retention of OCs incorporated through breastfeeding. However, these results should be taken with caution because the differences of the gender averages have low statistically significance when evaluated with the Student test.

Maternal use of folic acid supplements during pregnancy and four-year-old neurodevelopment in a population-based birth cohort.

The use of folic acid supplements during very early pregnancy is recommended in order to reduce the incidence of neural tube defects. Little is known about the possible benefits of folic acid on child neurodevelopment. A total of 420 children (87% of those eligible) from a birth cohort had complete data for final analyses at age 4 years. Information about folic acid and other over-the-counter dietary supplements was obtained prospectively using interviewer-administered questionnaires at the end of the first trimester of pregnancy. Psychological outcomes were assessed by two psychologists and teachers 4 years later. Low maternal socio-economic status, smoking, high parity and short duration of breast feeding were associated with lower prevalence of folic acid supplement use. Verbal (b = 3.98, SE = 1.69), motor (b = 4.54, SE = 1.66) and verbal-executive function (b = 3.97, SE = 1.68) scores, social competence (b = 3.97, SE = 1.61) and inattention symptom [OR = 0.46; 95% CI 0.22, 0.95] scores were associated with reported folic acid use. Reported folic acid supplement use during pregnancy was associated with improved neurodevelopment in children after adjusting for a number of sociodemographic and behavioural factors.

Maternal fish and other seafood intakes during pregnancy and child neurodevelopment at age 4 years.

OBJECTIVE: To analyse the relationship between maternal intakes of fish and other seafood during pregnancy and child neurodevelopment at age 4 years. Although pregnant women are advised to limit seafood intakes because of possible neurotoxin contamination, several studies suggest that overall maternal seafood intakes are associated with improved child neurodevelopment, perhaps because of higher DHA intakes. DESIGN: The study uses data from a prospective birth cohort study. Maternal seafood intakes were assessed using a semi-quantitative FFQ administered shortly after delivery. Multivariate linear regression was used to estimate associations between seafood consumption and scores on the McCarthy Scales of Children's Abilities (MCSA). Analyses were stratified by breast-feeding duration as breast milk is a source of DHA during the postnatal phase of the brain growth spurt. SETTING: Menorca, Spain, 1997-2001. SUBJECTS: Full-term children (n 392) with data on maternal diet in pregnancy, breast-feeding duration and neurodevelopment at age 4 years. RESULTS: Among children breast-fed for <6 months, maternal fish intakes of >2-3 times/week were associated with significantly higher scores on several MCSA subscales compared with intakes < or =1 time/week. There was no association among children breast-fed for longer periods. Maternal intakes of other seafood (shellfish/squid) were, however, inversely associated with scores on several subscales, regardless of breast-feeding duration. CONCLUSIONS: The study suggests that moderately high intakes of fish, but not other seafood, during pregnancy may be beneficial for neurodevelopment among children breast-fed for <6 months. Further research in other populations with high seafood intakes and data on additional potential confounders are needed to confirm this finding.

Brain Structure and Function in School-Aged Children With Sluggish Cognitive Tempo Symptoms.

OBJECTIVE: Sluggish cognitive tempo (SCT) is a cluster of symptoms associated with poor function in various domains of major life activities that may comprise a novel attention disorder distinct from attention-deficit/hyperactivity disorder (ADHD). Nevertheless, very little is known about the neural substrate of SCT in children. The present study aimed to examine associations between SCT symptoms and brain structure and function in school-aged children. METHOD: We performed a cross-sectional MRI study in 178 children 8 to 12 years old from primary schools in Barcelona, Spain. Data were collected between January 2012 and March 2013. Parents completed the Sluggish Cognitive Tempo-Child Behavior Checklist (SCT-CBCL). Participants underwent magnetic resonance imaging to assess regional brain volume, white matter integrity using diffusion tensor imaging, and functional connectivity in major neural networks. RESULTS: SCT symptoms were associated with altered anatomy of the frontal lobe in the form of increased regional volume. The anomalously large cortical regions were less mature in terms of functional connectivity. Importantly, all the anatomical and functional anomalies identified remained significant after adjusting the analyses for ADHD symptom scores. CONCLUSION: Our results suggest that SCT symptoms are associated with distinct features of brain structure and function that differ from the classical neural substrates described in ADHD.

Urinary porphyrin excretion in children is associated with exposure to organochlorine compounds.

BACKGROUND: Hexachlorobenzene (HCB) and other organochlorines induce porphyria cutanea tarda (PCT) in animal studies. Evidence in humans, however, is contradictory. In neonates and adults from a population historically highly exposed to HCB (Flix, Catalonia, Spain), no relation with PCT or with porphyrin excretion was found. OBJECTIVES: We aimed to analyze the association between urinary porphyrin excretion and exposure to HCB and other organochlorinated compounds in children 4 years of age. METHODS: Our birth cohort included all newborns from Flix and the five surrounding towns (where no airborne pollution occurred). Among the 68 children with porphyrins we measured in cord blood, 52 children 4 years of age provided blood to measure organochlorine compounds, hair for methylmercury, and urine for porphyrin excretion pattern. RESULTS: Quantitative porphyrin excretion was within the normal values. However, total porphyrins, coproporphyrin I (CPI), and coproporphyrin III (CPIII) adjusted to creatinine excretion increased with increasing levels of HCB, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT), and polychlorinated biphenyl congener 153 (PCB-153). We found no association with methylmercury. When we fitted multiple pollutant models, p,p'-DDE had the strongest association. We found these associations in children from both Flix and other towns, and they were independent of breast-feeding and of organochlorine and porphyrin levels at birth. CONCLUSION: HCB at current levels did not induce porphyria or increase uroporphyrins. However, the increase of urinary coproporphyrins suggests an incipient toxic effect of the organochlorines, especially for p,p'-DDE, on the hepatic heme-synthesis pathway that differs from the major effects seen in PCT.

Influence of glutathione S-transferase polymorphisms on cognitive functioning effects induced by p,p'-DDT among preschoolers.

BACKGROUND: Early-life exposure to p,p'-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p'-DDT. METHODS: We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children's Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms. RESULTS: p,p'-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p'-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p'-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms. CONCLUSIONS: Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p'-DDT exposure.

Thyroid disruption at birth due to prenatal exposure to beta-hexachlorocyclohexane.

OBJECTIVE: Thyroid hormones play an important role in human brain development, and some organochlorine compounds (OCs) act as thyroid disruptors. The objective of the present study was to evaluate the association between prenatal exposure to organochlorine compounds and thyroid function in newborns from a general population birth cohort in Menorca, with an a-priori specific focus on beta-HCH. METHODS: Levels of polychlorinated biphenyls (PCB congeners 28, 52, 101, 118, 138, 153 and 180), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), dichlorodiphenyl dichloroethylene (p'p'-DDE) and dichlorodiphenyl trichloroethane (p'p-DDT) in cord serum, and thyrotropin (TSH) concentration in plasma three days after birth were measured in 387 newborns from Menorca. The TSH concentration was categorized (high or low), except for 27 children whose TSH levels were quantified. RESULTS: Levels of beta-HCH and PCB-153 were positively related to TSH concentrations (gestational age-adjusted coefficient (p-value): 0.26 (p = 0.006) and 0.31 (p = 0.050), respectively). CONCLUSIONS: beta-HCH is potentially a new thyroid disrupting compound, deserving special interest in future studies given its high body burden in humans.

Monitoring concentrations of persistent organic pollutants in the general population: the international experience.

Assessing the adverse effects on human health of persistent organic pollutants (POPs) and the impact of policies aiming to reduce human exposure to POPs warrants monitoring body concentrations of POPs in representative samples of subjects. While numerous ad hoc studies are being conducted to understand POPs effects, only a few countries are conducting nationwide surveillance programs of human concentrations of POPs, and even less countries do so in representative samples of the general population. We tried to identify all studies worldwide that analyzed the distribution of concentrations of POPs in a representative sample of the general population, and we synthesized the studies' main characteristics, as design, population, and chemicals analyzed. The most comprehensive studies are the National Reports on Human Exposure to Environmental Chemicals (USA), the German Environmental Survey, and the Arctic Monitoring and Assessment Programme. Population-wide studies exist as well in New Zealand, Australia, Japan, Flanders (Belgium) and the Canary Islands (Spain). Most such studies are linked with health surveys, which is a highly-relevant additional strength. Only the German and Flemish studies analyzed POPs by educational level, while studies in the USA offer results by ethnic group. The full distribution of POPs concentrations is unknown in many countries. Knowledge gaps include also the interplay of age, gender, period and cohort effects on the prevalence of exposures observed by cross-sectional surveys. Local and global efforts to minimize POPs contamination, like the Stockholm convention, warrant nationwide monitoring of concentrations of POPs in representative samples of the general population. Results of this review show how such studies may be developed and used.

Prenatal exposure to mercury in a prospective mother-infant cohort study in a Mediterranean area, Valencia, Spain.

BACKGROUND: Mercury (Hg) is a ubiquitous pollutant that negatively affects fetal and child neurodevelopment at accidental high-dose exposure. Some studies indicate that Mediterranean populations could be at risk of prenatal exposure to mercury through fish consumption. OBJECTIVES: To assess the prenatal exposure to total mercury (T-Hg), both inorganic and organic, in newborns by analyzing the T-Hg concentration in cord blood, and to evaluate the role of maternal fish consumption in this exposure. METHODS: In the context of a multi-center project (INMA project), a prospective birth cohort was set up in Valencia, Spain, from 2005 to 2006. A total of 253 newborns were included in this study. We compared cord blood T-Hg concentration by levels of fish intake assessed by a food frequency questionnaire completed at 28-32 weeks of gestation. Maternal covariates were obtained through a questionnaire. RESULTS: The geometric mean of T-Hg at birth was 9.9 microg/L (95% CI: 9.0, 10.8). Seventy five percent of cord blood samples were above the estimated level assumed to be without appreciable harm (5.8 microg/L). Women who consumed a portion of large oily fish, lean fish, or mixed fried fish two or more times per week had mean cord blood levels 1.6, 1.4 and 1.3 times higher, respectively, than those who rarely or never consumed fish. Other factors such as the mother's age, country of origin, smoking and season of delivery were also significantly and independently associated with cord blood T-Hg concentrations. CONCLUSIONS: Newborns from a Mediterranean area presented elevated levels of T-Hg in cord blood. Higher concentrations of T-Hg were related to maternal fish intake, particularly in the case of large oily fish species.

Pentachlorobenzene, hexachlorobenzene, and pentachlorophenol in children's serum from industrial and rural populations after restricted use.

The study of a population of 4-year-old children born between 1997 and 1999 in an urban area under strong inputs of pentachlorobenzene (PeCB) and hexachlorobenzene (HCB) suggested that the measured concentrations of pentachlorophenol (PCP) in serum may essentially result from metabolism of these chlorinated hydrocarbons. In contrast, examination of a rural population of children where the same compounds were present at relatively low levels points to other inputs besides transformation of PeCB and HCB being responsible for the measured PCP concentrations. In both populations, the results showed that a major proportion of the organochlorine compounds present in these children's serum at 4 years of age was incorporated during the lactation period.

[Studies conducted in Spain on concentrations in humans of persistent toxic compounds]. / Estudios realizados en España sobre concentraciones en humanos de compuestos tóxicos persistentes.

No systematic review is available on studies conducted in Spain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrations of DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individuals may be over 200-fold higher than those of others. The actual magnitude of human contamination by PTS and their trends across Spain -as well as the geographic and social heterogeneity- remain largely unknown.

Beneficial effects of breastfeeding on cognition regardless of DDT concentrations at birth.

The authors previously reported that intrauterine exposure to background concentrations of p,p'-dichlorodiphenyltrichloroethane (DDT) reduces cognitive performance among preschoolers. Breastfeeding has been associated with both increased exposure to certain pollutants during infancy and better performance on cognitive tests. Thus, the authors examined the role of breastfeeding in cognitive function among preschoolers, taking prenatal DDT exposure into account. Two birth cohorts in Spain (Ribera d'Ebre and Menorca) were recruited between 1997 and 1999 (n = 391). Infants were assessed at age 4 years using the McCarthy Scales of Children's Abilities. Levels of organochlorine compounds were measured in umbilical cord serum. Information on type and duration of breastfeeding was obtained by questionnaire when the children were 1 year of age. Children who were breastfed for more than 20 weeks had better cognitive performance regardless of their in utero exposure to DDT. A linear dose response between breastfeeding and cognition was observed in all DDT groups (for children highly exposed to DDT, adjusted beta = 0.30 (standard error, 0.12) per week breastfed). Despite the possibility of harm from environmental contaminants in breast milk, breastfeeding for long periods should still be recommended as the best infant feeding method.

Exposure to hexachlorobenzene during pregnancy and children's social behavior at 4 years of age.

BACKGROUND: Hexachlorobenzene (HCB) is an organochlorine chemical that has been used in agriculture and industrial processes. Behavioral impairment after HCB exposure has been described in animal models, but little information is available in humans. OBJECTIVES: Our goal was to study the association of prenatal exposure to HCB with the social behavior of preschool children. METHODS: Two birth cohorts in Ribera d'Ebre and Menorca (Spain) were set up between 1997 and 1999 (n = 475). The California Preschool Social Competence Scale and the Attention-Deficit Hyperactivity Disorder (ADHD) were scored by each 4-year-old child's teacher. Organochlorine compounds were measured in cord serum. Children's diet and parental sociodemographic information were obtained through questionnaire. RESULTS: Children with concentrations of HCB > 1.5 ng/mL at birth had a statistically significant increased risk of having poor Social Competence [relative risk (RR) = 4.04; 95% confidence interval (CI), 1.76-9.58] and ADHD (RR = 2.71; 95% CI, 1.05-6.96) scores. No association was found between HCB and the cognitive and psychomotor performance of these children. CONCLUSIONS: Prenatal exposure to current concentrations of HCB in Spain is associated with a decrease in the behavioral competence at preschool ages. These results should be considered when evaluating the potential neurotoxicologic effects of HCB.

Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort.

BACKGROUND: Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children, but a few cohort studies measuring smoking data prospectively have studied its specific effects on the cognitive abilities of pre-schoolers. METHOD: A birth cohort was set up in Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A total of 420 (87% of those eligible) children had complete data for final analyses at age 4 years. Interviewer-administered questionnaires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child. A standardized version of the McCarthy Scales of Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive capabilities. Multivariable regressions were used with MCSA's assessed outcomes adjusting for: home location, maternal alcohol consumption, mother's social class and level of education during pregnancy, parity, marital status, father's education level, child's gender, birth weight and height, breastfeeding duration, passive smoking, school season, age during test administration and evaluator (psychologist). RESULTS: A high global consistency in maternal smoking habits was found (total agreement = 88.7%). Maternal social class and education level were inversely associated with maternal smoking behaviour. Maternal smoking during pregnancy (in cig./day) was associated with a decrease (in points) of children's global cognitive score [beta = -0.60, (95% CI: -1.10; -0.09)]; as well as global cognitive sub-areas like verbal score [beta = -0.59, (95% CI: -1.11; -0.07)]; quantitative score [beta = -0.57, (95% CI: -1.08; -0.06)]; executive function score [beta = -0.71, (95% CI: -1.23; -0.20)]; and working memory score [beta = -0.46, (95% CI: -0.92; -0.01)]. CONCLUSION: Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years.

The Spanish Environment and Childhood Research Network (INMA study).

Prenatal and early life exposure to environmental agents, including dietary exposure, is associated with child health and human development and predisposes to late adult effects. Children are more vulnerable than adults to chemical, physical and biological hazards in air, water and soil, because they are still growing and their immune system and detoxification mechanisms are not fully developed. The physical, social and intellectual development of children from conception to the end of adolescence requires a protected environment that is also protective of their health. Following WHO and European Union recommendations, the Cooperative Environment and Childhood Research Network was funded by the Spanish Ministry of Health to study effects of environment and diet on foetal and early childhood development in different geographical areas of Spain. This network integrates different multidisciplinary research groups and is comprised of six cohorts--three pre-existing and three de novo--which will prospectively follow up 3600 pregnant women from start of pregnancy until the children are 4-6-year old.

[Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA (Childhood and Environment Project)]. / Exposición a contaminantes atmosféricos durante el embarazo y desarrollo prenatal y neonatal: protocolo de investigación en el proyecto INMA (Infancia y Medio Ambiente).

INTRODUCTION: The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. METHODS: The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. CONCLUSION: This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential.

Is intensive home-treatment a real alternative to classical hospitalization for managing acute psychiatric processes? Insights from clinical practice / ¿Es la hospitalización domiciliaria una alternativa real a la hospitalización clásica para el tratamiento de los procesos psiquiátricos agudos? Reflexiones desde la práctica clínica

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