INMA Project Research Articles

Prenatal Manganese Exposure and Long-Term Neuropsychological Development at 4 Years of Age in a Population-Based Birth Cohort.

Background: Manganese (Mn) is an essential micronutrient for humans, the diet being the main source of exposure. Some epidemiological studies describe a negative association between prenatal Mn and later neuropsychological development, but results are inconsistent. The aim of this study was to explore the association between prenatal Mn exposure and neuropsychological development assessed at 4 years of age. Methods: Study subjects were 304 mother-child pairs from the Gipuzkoa cohort of the INMA (Environment and Childhood) Project. Mn was measured in newborns’ hair. Children’s neuropsychological development was assessed at 4 years of age using the McCarthy Scales of Children’s Abilities. Multivariate linear regression models were built. Stratified analysis by sex was performed. Generalized additive models were used to assess the shape of the relation. Results: The median Mn concentration in newborns’ hair was 0.42 μg/g (95% CI = 0.38, 0.46). The association between Mn levels and the neuropsychological development was not statistically significant for the general cognitive scale (β [95% CI] = 0.36 [−5.23, 5.95]), motor scale (β [95% CI] = 1.9 [−3.74, 7.55]) or any of the other outcomes. No sex-specific pattern was found. The best shape describing the relationship was linear for all the scales. Conclusion: Our results suggest that prenatal Mn concentrations measured in newborns’ hair do not affect cognitive or motor development at 4 years of age in boys or in girls at the observed Mn levels.

Postnatal exposure to mercury and neuropsychological development among preschooler children.

The objective of this study was to describe the postnatal exposure to Hg and to evaluate its association with neuropsychological development among preschool children. The study population are 4-5years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4years of age (2008-2012). Neuropsychological development was assessed using the McCarthy Scales of Children's Abilities (MSCA). Information on covariates and possible confounders was obtained by questionnaires during pregnancy and childhood. Generalized additive and linear regression models were built in order to assess the relationship between MSCA scores and Hg exposure. We also evaluated the magnitude of the possible bias generated from measurement error in seafood intake estimate from questionnaire and Hg determination. The geometric mean of hair Hg was 0.98µg/g [95% confidence interval (CI) 0.94, 1.03]. In the regression analysis, the association between Hg and the MSCA scores was positive for all the scales and statistically significant for the verbal (β = 0.89; 95%CI 0.38, 1.39), memory (β = 0.42; 95%CI 0.09, 0.76) and general cognitive scales (β = 1.35; 95%CI 0.45, 2.25). However, these associations were clearly attenuated when we adjusted by the children's fish intake variables or when took into account theoretical scenarios of low precision in fish intake and Hg measurements. Hg levels in this Spanish population were high in comparison with other European countries; however, we did not observe adverse effects on child neuropsychological development associated with this postnatal exposure to Hg.

Risk of child poverty and social exclusion in two Spanish regions: social and family determinants

ObjectiveDescribe the risk of poverty and social exclusion in children aged 8-11 years from Gipuzkoa and Valencia (Spain), through AROPE (At Risk Of Poverty or Social Exclusion) indicators, and evaluate their associated factors in the INMA Project (Childhood and Environment). MethodFamilies in Gipuzkoa and Valencia (394 and 382, respectively) completed a questionnaire in 2015-2016. Low work intensity (LWI), at risk of poverty (RP) and material deprivation (MD) were estimated. AROPE consisted in meeting any of the previous sub-indicators. Socio-demographic, family and parental characteristics were considered. Frequencies, Venn's diagrams, and chi-square and Fisher tests were used in bivariate analysis and logistic regression in multivariate analysis. ResultsFor LWI, RP, MD and AROPE, prevalence of 2.5%, 5.6%, 2.3% and 7.2% were obtained in Gipuzkoa, and 8.1%, 31.5%, 7.8% and 34.7% in Valencia, respectively. In the multivariate analysis, the AROPE was associated in both areas with maternal social class and non-nuclear families. In Gipuzkoa, it was also related to maternal education. In Valencia, other factors were the mother's foreign origin, and paternal education and smoking. ConclusionThere is higher AROPE prevalence in Valencia. Social class and family type were shared factors, but a differential pattern is observed in other social determinants. It is essential to implement social policies to reduce this axis of inequalities in health, especially in childhood.

Haurdunaldian amak izandako bizi-ohiturak, ingurumen-esposizioak, osasun-sistemaren ekimenak eta haurraren garapen neuropsikologikoa. INMA (Haurtzaroa eta Ingurumena-Infancia y Medio Ambiente) proiektuan argitaratutako lanen errebisioa

Osasunaren esparruan oro har, eta zehazki Osasun Publikoarenean, azken bi mendeetan ingurumenak osasunean duen eragina aztertzeak interesa piztu du. Marc Lalondek, 1974. urtean osasun-eredua garatu zuen, eta azpimarratu zuen bizi-ohiturek eta inguruko faktoreek osasunean zuten eragina. Artikulu honen helburu orokorra da faktore hauek haurraren garapen neuropsikologikoan nola eragiten duten aztertzea helburutzat duten INMA proiektuko hainbat lanen emaitza esanguratsuenak azpimarratzea. Hala nola, emakumeen bizi-estiloekin erlazionatutako gainpisu/obesitateak eta erretze-ohiturak asoziazio negatiboa erakutsi zuten haurraren garapen neuropsikologikoarekin. Elikadura-ohiturei dagokienez, ikusi zen arraina osasunerako onuragarriak zein kaltegarriak diren substantzien garraio dela. Emakume haurdunek jarraitzen zituzten ekimenei dagokienez, gure proiektuko emaitzek erakutsi zuten azido folikoaren dosi altuegi zein baxuegiek haurren garapen neuropsikologikoan eragin positiboak zituztela. Edoskitze naturalak autismoa bezalako jokabide-arazoentzat eragin babesgarria zuela erakutsi zuten gure ikerketek. Ingurumen faktoreek haurraren garapenean eta osasunean kalteak dakartzatela ikusi da. Berdeguneek duten eragina, ordea, onuragarria dela ikusi da. Lan honek haurdunaldian emakumeak jarraitzen dituen bizi-ohiturak eta osasun-sistemaren aholkuak zein emakumeak dituen ingurumen-esposizioak haurraren garapen neuropsikologikoan duen eragina erakutsi du.

Prenatal manganese exposure and neuropsychological development in early childhood in the INMA cohort.

Manganese (Mn) is an essential element, diet being its main source. Some epidemiological studies have found that a prenatal excess of Mn could negatively affect neuropsychological development during infancy, but the evidence is inconclusive. The aim of this study was to explore the relationship between maternal serum Mn concentrations and child neuropsychological development assessed at 1 year of age. study subjects were 1179 mother-child pairs from two Spanish cohorts (Valencia and Gipuzkoa) of the INMA (Environment and Childhood) Project. Mn was measured in serum samples collected during the first trimester of pregnancy. Child neuropsychological development was assessed using the Bayley Scales of Infant Development, composed of both mental and psychomotor scales. Sociodemographic, lifestyle and dietary information was collected through questionnaires during pregnancy and during the child's first year of life. Serum Mn was log-2 transformed. Multivariable linear regression models were built. Generalized additive models were used to assess the shape of the relation between prenatal exposure to Mn and the neuropsychological test scores. geometric mean and 95% confidence interval (95% CI) of maternal serum Mn was 1.50 (1.48-1.53) μg/L. Levels of Mn were higher among non-working mothers and in those with a higher consumption of nuts. The association between maternal Mn levels and child neuropsychological development was negative in the multivariable models for the mental (β [95% CI]=-0.39 [-2.73, 1.95]) and psychomotor scales (β [95% CI]=-0.92 [-3.48, 1.65]), although the coefficients were not statistically significant. The best shape describing the relationship between Mn and the Bayley scales was linear in both cases. This study shows a null association between maternal prenatal levels of Mn and neuropsychological development at one year after birth in two cohorts within the INMA study.

Impact of lifestyle behaviors in early childhood on obesity and cardiometabolic risk in children: Results from the Spanish INMA birth cohort study.

Identifying modifiable lifestyle behaviors linked to childhood obesity is necessary to develop preventive strategies. To estimate the association of five lifestyle behaviors in children aged 4years on obesity and cardiometabolic risk factors at age 4years and on obesity and blood pressure at age 7years. We used child lifestyle data from the INMA project at age 4years (n=1480). We constructed a child lifestyle score by summing five behaviors (physical activity, sleep time, television time, plant based foods and intake of ultra-processed foods) and we categorized it into tertiles. At ages 4 and 7 years, we calculated age- and sex-specific z-scores for BMI, waist circumference (WC), and blood pressure. At age 4, we also calculated age-, and sex-, specific z-scores for triglycerides and HDL. We used linear and logistic regression analyses. The lifestyle score was not associated with the outcomes at 4years, but it was negatively associated with BMI and WC z-scores at age 7 years. Children at age 4 years in the highest tertile of the score had lower risk of overweight or obesity at age 7 years (OR = 0.61; 95% CI 0.39; 0.96) and abdominal obesity (OR = 0.48; 95% CI 0.24; 0.96). Higher adherence to a healthy lifestyle at age 4years decreased risk of overweight, obesity and abdominal obesity at 7years.

Outdoor artificial light at night exposure during pregnancy and child cognitive and psychomotor development.

PDS 73: Neurological effects, Johan Friso Foyer, Floor 1, August 26, 2019, 10:30 AM - 12:00 PM Background/Aim: Exposure to artificial light at night (ALAN) has been related with a higher exposure to blue light spectrum that has been shown to suppress melatonin. We assessed whether residential outdoor ALAN exposure during pregnancy was associated with child cognitive and psychomotor development at 4 years of age. Methods: We used data of 477 children from Sabadell, Spain, as part of the INMA Project. Outdoor ALAN was estimated using images from the International Space Station of 2013. Exposure to remotely sensed upward visual light and to blue light spectrum for whole pregnancy period was calculated. Child cognitive and psychomotor development was assessed at 4 years of age by psychologists using the McCarthy Scales of Children’s Abilities. Linear regression models were adjusted for various socio-economic and lifestyle characteristics. Multiple imputation and inverse probability weighting were applied to correct for potential attrition bias. Results: Exposure to visual light of outdoor ALAN and in the blue light spectrum during pregnancy was not associated with child general cognition and global motor (e.g. 2.30 points of general cognition [95%CI: -0.67; 5.92) for higher vs. lowest tertile of visual light and 1.06 points of general cognition [95%CI:-2.03; 4.14] for highest vs. lowest tertile of blue light spectrum). However, exposure to outdoor ALAN in the blue light spectrum was associated with better child fine motors skills (3.93 points [95%CI: 0.66; 7.22] for higher vs. lowest tertile of blue light spectrum). Conclusions: Evidence on the effect of residential outdoor ALAN in the visual light or in the blue light spectrum exposure during pregnancy and cognitive and psychomotor development in children at 4 years old was not consistent. However, we found modest evidence between residential outdoor ALAN in the blue light spectrum exposure and child fine motor skills.

Exposure to mercury among 9-year-old Spanish children: Associated factors and trend throughout childhood

Mercury is considered a neurotoxicant and human exposure occurs mainly from the consumption of marine species. We aimed to describe total mercury concentrations (THg) and associated factors in 9-year old children, as well as to explore the trend in THg from 4 to 9 years of age. The study population consisted of 9-year-old children participating in the INMA (Environment and Childhood) birth cohort study in Valencia, Spain (n = 405, 2013–2014). THg in hair samples was measured by atomic absorption spectrometry at the age of 4 and 9 years. Sociodemographic and dietary data was obtained through questionnaires. Multiple linear regression was used to explore the association between THg and covariates.The geometric mean (95% confidence interval) of hair THg at 9 years old was 0.89 μg/g (0.81, 0.98). Thirteen percent of children had THg above the equivalent to the Provisional Tolerable Weekly Intake proposed by the World Health Organization. THg were higher among children whose mothers had a healthy body mass index before pregnancy. Children with non-smoker mothers and worker fathers had also higher THg. Children's fish intake at 9 years-old was positively associated with THg, being swordfish, canned tuna and lean fish (i.e. hake, sea bream and sole) the most associated categories. Levels decreased by around 22% between 4 and 9 years old.Birth cohort studies, such as the INMA Project, allow the longitudinal evaluation of Hg exposure and the possible effects on children's health. This information can be used to formulate diet recommendations in vulnerable populations.

Prenatal exposure to PM2.5 and NO2 and sex-dependent infant cognitive and motor development.

BackgroundPrenatal exposure to air pollutants including particulate matter (<2.5 μm of diameter,PM2.5)and nitrogen dioxide (NO2) has been identified as a potential risk factor for neuropsychological developmental and mental health disorders. ObjectiveThis study aimed to analyze the associations between prenatal PM2.5 and NO2 exposure and cognitive functions in children at 4–6 years of age, including sex differences, and the modification effect of the duration predominant breastfeeding these associations. DesignThis study was conducted as part of the INMA project, a population-based birth cohort study in Spain (n = 1119). Each of the pregnant mothers was assigned a prenatal exposure to PM2.5 and NO2 for their whole pregnancy based on their place of residence. At the 4-6 year-old follow-up, infants’ neuropsychological development was assessed using McCarthy scales: Verbal, Perceptive-Manipulative, Numeric, General Cognitive, Memory and Motor (gross and fine). Between 6 and 14 months of age, information concerning breastfeeding was gathered with a questionnaire. Regression analyses were performed to estimate the associations between exposure and outcomes, accounting for potential confounders. The analyses were stratified by child sex and breastfeeding duration. ResultsThe majority of coefficients for the different cognitive domains were negative either for PM2.5 and NO2, though none was statistically significant. After stratifying by sex, the associations become even more negative for boys, with some of the associations becoming statistically significant (memory both for PM2.5 and NO2), and global cognition and verbal for NO2. Duration of predominant breastfeeding was not found to have a modifying effect. ConclusionsThese findings suggest a sex-dependent effects on neuropsychological development at 4–6 years of age, with a greater vulnerability in boys, specifically in domains related to memory, verbal and general cognition. No modifying effect was observed for duration of predominant breastfeeding.

Does breastfeeding have a long-term positive effect on dental occlusion?

BackgroundBreastfeeding produces beneficial effects on a baby’s early growth and development, and general well-being. Some studies have associated breastfeeding with better occlusal development. The aim of this study was to assess the long-term effect of breastfeeding on occlusal development in children.Material and MethodsA retrospective cohort study was conducted to evaluate the occlusions of 320 children belonging to the Spanish INMA Project cohort, monitored from gestation onwards. The association between the duration of breastfeeding and different occlusal traits in mixed dentition (overjet, overbite, openbite, midline displacement, incisor crowding, incisor spacing, diastema, maximum maxillary and mandibular irregularity, anterior and posterior crossbite) at the age of 9 was assessed, as well as the orthodontic treatment need as determined by the “Index of Orthodontic Treatment Need” and the “Dental Aesthetic Index”.ResultsA statistically significant association between the duration of breastfeeding and posterior crossbite was found. The Odds Ratio for posterior crossbite was 2.52 (IC 95% 1.34-4.74) for children breastfed up to 16 weeks, 0.56 (IC 95% 0.29-1.08) for children breastfed 16 to 45 weeks, and for more than 45 weeks of breastfeeding it was 0.50 (IC 95% 0.19-1.32). No association was found between breastfeeding and the other examined occlusal traits, nor with the orthodontic treatment need.ConclusionsBreastfeeding for less than 4 months increases the risk of posterior crossbite. However, breastfeeding duration is not linked to other malocclusion traits nor is it linked to the orthodontic treatment need of nine-year-old children. Key words:Breastfeeding, occlusion, malocclusion, dental development.

Head circumference and child ADHD symptoms and cognitive functioning: results from a large population-based cohort study

The aim of this study is to understand the association between prenatal, newborn and postnatal head circumference (HC) and preschool neurodevelopment in a large population-based birth cohort. The INMA project followed 1795 children from 12weeks of pregnancy to preschool years. HC measurements were carried out prospectively, and following a standardized protocol during pregnancy (12, 20 and 34weeks), birth, and child ages of 1-1.5 and 4years old; and z-scores were further estimated. Prenatal head growth was assessed using conditional z-scores between weeks 12-20 and 20-34. Several neuropsychological tests [MSCA (cognition), CPT (attention)] and behavioral rating scales [DSM-IV-ADHD, CAST (autism), CPSCS (social competence)] were carried out during the last follow-up (5years old). Multivariable models adjusted for family and child characteristics were applied to analyze associations between HC and neurodevelopment. In fully adjusted models, prenatal HC and head growth showed little or no associations with the neurodevelopment outcomes. Independent associations were observed between HC z-scores at birth, 1-1.5years and 4years and MSCA global cognitive scores and DSM-IV inattention symptoms. Specifically, z-score at birth was positively associated with general cognitive scores [β 1.22, 95% confidence interval (CI) 0.59, 1.85], and we observed a protective association with ADHD-DSM-IV total symptoms, mean ratio (MR) 0.85 (0.75, 0.96). Prenatal HC and head growth measurements gave little information about child cognitive abilities and behavior at preschool years. However, HC at birth and early childhood was positively associated with a range of neuropsychological outcomes, including protective associations with ADHD symptoms.

High doses of folic acid in the periconceptional period and risk of low weight for gestational age at birth in a population based cohort study.

We investigated the association between maternal use of folic acid (FA) during pregnancy and child anthropometric measures at birth. We included 2302 mother-child pairs from a population-based birth cohort in Spain (INMA Project). FA dosages at first and third trimester of pregnancy were assessed using a specific battery questionnaire and were categorized in non-user, < 1000, 1000-4999, and ≥ 5000µg/day. Anthropometric measures at birth (weight in grams, length and head circumference in centimetres) were obtained from medical records. Small for gestational age according to weight (SGA-w), length (SGA-l) and head circumference (SGA-hc) were defined using the 10th percentile based on Spanish standardized growth reference charts. Multiple linear and logistic regression analyses were used to explore the association between FA dosages in different stages of pregnancy and child anthropometric measures at birth. In the multiple linear regression analysis, we found a tendency for a negative association between the use of high dosages of FA (≥ 5000µg/day) in the periconceptional period of pregnancy and weight at birth compared to mothers who were non-users of FA (β = -73.83; 95% CI -151.71, 4.06). In the multiple logistic regression, a greater risk of SGA-w was also evident among children whose mothers took FA dosages of 1000-4999 (OR = 2.21; 95% CI 1.17, 4.19) and of ≥ 5000µg/day (OR = 2.32; 95% CI 1.06, 5.08) compared to mothers non-users of FA in the periconceptional period of pregnancy. Our findings suggest that a high dosage of FA (≥ 1000µg/day) may be associated with an increased risk of SGA-w at birth.

Prenatal co-exposure to neurotoxic metals and neurodevelopment in preschool children: The Environment and Childhood (INMA) Project

We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was associated with impaired neurodevelopment in preschool children from the Spanish Environment and Childhood (INMA) Project, using the placenta as exposure matrix. We measured metal levels in placenta tissue samples randomly selected from five of the seven population-based birth cohorts participating in the INMA Project, collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was carried through the use of the McCarthy Scales of Children's Abilities (MSCA) at the age of 4–5years. Data on placental metal levels, MSCA scores, and relevant covariates was available for 302 children. Mn was detected in all placental samples, Cd in nearly all placentas (99%) and As, Hg, and Pb in 22%, 58%, and 17% of the placentas, respectively. After adjusting for potential confounders, detectable As levels were associated with decrements in global and verbal executive functions and quantitative abilities; detectable Hg was associated with lower scores on the verbal function of posterior cortex in a dose-response manner, and non-linearly related to poorer motor function and gross motor skills; and Mn levels were associated with decrement in perceptual-performance skills in a dose-response manner but with better memory span and quantitative skills. A synergistic interactive effect was found between As and Pb with respect to the general cognitive score, whereas an antagonistic interaction was found between Mn and Hg. Prenatal exposure to As and Hg may be a risk factor for cognitive and motor impairment in children, while the effects of Cd and Mn on neurodevelopment are less clear. Future studies should examine combined and interactive effects of exposure to multiple metals during vulnerable periods of brain development prospectively.

Drinking water disinfection by-products during pregnancy and child neuropsychological development in the INMA Spanish cohort study

BackgroundDisinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. ObjectivesWe evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4–5years of age. MethodsWe conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003–2008). Neuropsychological development was measured at 1year of age using the Bayley Scales of Infant Development and at 4–5years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalomethanes (THM) were combined with personal ingestion, showering and bathing habits to estimate exposure as ingestion uptake, all route (showering, bathing, ingestion) uptake (μg/day) and crude levels (μg/l) in the residence. Chloroform, brominated THMs (bromodichloromethane, dibromochloromethane, bromoform) and total THMs (chloroform and brominated THMs) were analysed separately. Nine haloacetic acids levels were available in one of the areas. Linear regression was used to estimate associations in 1855 subjects adjusting for covariables. ResultsThe median concentration of total THMs, chloroform, brominated THMs, total haloacetic acids, dichloroacetic acid, and trichloroacetic acid were, respectively 30.3μg/L, 9.4μg/L, 11.6μg/L, 10.5μg/L, 2.7μg/L, and 3.1μg/L. The associations between THM exposure and neuropsychological outcomes were null, except for total and brominated THM uptake though all routes and the general cognitive score at 4–5years, with a decrease in −0.54 points (95%CI −1.03, −0.05) and −0.64 (95%CI −1.16, −0.12), respectively, for doubling total and brominated THM uptake. A positive association found between dichloroacetic acid and the mental score at 1year did not persist at 4–5years. ConclusionsMinor associations observed between DBP exposure during gestation and child neuropsychological development at 1year disappeared at 4–5years. Although a suggestive association is identified for exposure to brominated THMs and the cognitive score at 4–5years, chance cannot be ruled out.

Prenatal exposure to mercury and longitudinally assessed fetal growth: Relation and effect modifiers

BackgroundPrenatal mercury exposure has been related to reductions in anthropometry at birth. Levels of mercury have been reported as being relatively elevated in the Spanish population. ObjectiveTo investigate the relation between prenatal exposure to mercury and fetal growth. MethodsStudy subjects were pregnant women and their newborns (n:1867) participating in a population-based birth cohort study set up in four Spanish regions from the INMA Project. Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were measured by ultrasounds at 12, 20, and 34 weeks of gestation. Size at and growth between these points were assessed by standard deviation (SD) scores adjusted for constitutional characteristics. Total mercury (T-Hg) was determined in cord blood. Associations were investigated by linear regression models, adjusted by sociodemographic, environmental, nutritional – including four seafood groups – and lifestyle-related variables in each sub-cohort. Final estimates were obtained using meta-analysis. Effect modification by sex, seafood intake and polychlorinated biphenyl (PCB) congener 153 concentration was assessed. ResultsGeometric mean of cord blood T-Hg was 8.2μg/L. All the estimates of the association between prenatal Hg and growth from 0 to 12 weeks showed reductions in SD-scores, which were only statistically significant for BPD. A doubling of cord blood T-Hg was associated with a 0.58% reduction in size of BPD at week 12 (95% confidence interval -CI-: − 1.10, − 0.07). Size at week 34 showed estimates suggestive of a small reduction in EFW, i.e., a doubling of T-Hg levels was associated with a reduction of 0.38% (95% CI: − 0.91, 0.15). An interaction between PCB153 and T-Hg was found, with statistically significant negative associations of T-Hg with AC and EFW in late pregnancy among participants with PCB153 below the median. ConclusionsExposure to mercury during pregnancy was associated with early reductions in BPD. Moreover, an antagonism with PCB 153 was observed with noteworthy reductions late in pregnancy in AC and EFW in the group with lower PCB153.

Evening salivary cortisol and alpha-amylase at 14 months and neurodevelopment at 4 years: Sex differences

Stress system activity in early life can have long-term effects on neurodevelopment. The main aim of this study was to assess the association of child evening salivary cortisol and alpha-amylase basal levels at 14months of age with longer-term neuropsychological development at 4years in a low-risk population-based birth cohort derived from the INMA (Environment and Childhood) project in Spain. We included 186 parent-children pairs with information on both stress system activity and neurodevelopment. Both stress markers at 14months of age showed an association with neuropsychological development at 4years. Salivary cortisol showed a sex-specific pattern of association. In girls, cortisol levels at 14months were negatively associated with cognitive development [long-term declarative memory (β=−17.8, p=0.028; 95% CI=−33.2 to −2.5); executive function (β=−9.8, p=0.08; 95% CI=−21 to 1)] and gross motor development (β=−13; p=0.022; 95% CI=−24 to −2), whereas in boys cortisol levels were negatively associated with socioemotional development [autistic-like behaviours: Incidence Rate Ratio (IRR)=1.6, p=0.039; 95% CI=1.01 to 2.41]. Salivary alpha-amylase was positively associated with socioemotional development in boys only [social competence (β=2.11, p=0.013; 95% CI=0.47 to 3.72), autistic-like behaviours (IRR=0.93, p=0.042; 95% CI=0.87 to 0.99) and hyperactivity symptoms (IRR=0.81, p=0.021; 95% CI=0.69 to 0.97)]. These results suggest that stress system activity in early life is associated with longer-term neurodevelopment and that sex is an important factor in this relationship.

Association between exposure to organochlorine compounds and maternal thyroid status: Role of the iodothyronine deiodinase 1 gene

Introduction: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action.Aim: To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes.Methods: The study population (n=1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003–2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4´-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) were measured in serum samples taken during the first trimester of pregnancy (mean [standard deviation (SD)]: 13.5 [2] weeks of gestation). Polymorphisms in DIO1 (rs2235544) and DIO2 (rs12885300) were genotyped in maternal DNA. Sociodemographic and dietary characteristics were obtained by questionnaire.Results: A 2-fold increase in HCB was associated with lower TT3 (% change=−1.48; 95%CI: −2.36, −0.60). Women in the third tertile for b-HCH had lower TT3 (% change=−3.19; 95%CI: −5.64, −0.67). The interactions between DIO1 rs2235544 and PCB153 and b-HCH were statistically significant. The inverse association between PCB153 and TT3 was the strongest among women with AA genotype. Women with CC genotype presented the strongest inverse association between b-HCH and FT4.Conclusion: Exposure to HCB and b-HCH was associated to a disruption in maternal TT3. The DIO1 rs2235544 SNP modified the association between exposure to some of the OCs (specifically b-HCH and PCB153) and maternal thyroid hormone levels. These results strengthen the hypothesis that DIO enzymes play a role in explaining the disruption of thyroid hormones in relation to exposure to OCs.

The INMA-INfancia y Medio Ambiente-(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research.

In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that children's environmental health research will face in the coming years. The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children.

Reproducibility and Validity of a Food Frequency Questionnaire Designed to Assess Diet in Children Aged 4-5 Years.

BackgroundThe food frequency questionnaire (FFQ) is the most efficient and cost-effective method to investigate the relationship between usual diet and disease in epidemiologic studies. Although FFQs have been validated in many adult populations worldwide, the number of valid FFQ in preschool children is very scarce. The aim of this study was to evaluate the reproducibility and validity of a semi-quantitative FFQ designed for children aged 4 to 5 years.Materials and methodsIn this study, we have included 169 children aged 4–5 years from the INMA project in Valencia, a population-based prospective cohort study of mothers and children in Spain. The 105-items FFQ was administered twice to the parents or care-givers of children over a 9-month period. Reproducibility was explored by comparing intake of nutrients by the FFQs, while validity was examined by comparing the nutrient values from the FFQs with the average nutrient values of three 24 hour dietary recall (24hDR) taken in the period, and also, with the concentration in blood specimens for several vitamins (carotenoids, folate, vitamin B12, vitamin C and α-tocopherol). Pearson correlation coefficients and de-attenuated correlation coefficients were calculated and we also evaluated misclassification by quintile distribution.ResultsAll correlation coefficients for reproducibility for nutrients and major food groups were statistically significant; the average correlation coefficients for daily intake were 0.43 for food groups and 0.41 for nutrients. The average correlation coefficients for validity for daily intakes against 24hDR was r = 0.30, and the average for de-attenuated correlation coefficients was r = 0.44. When evaluating validity against the blood concentration of vitamins, statistically significant correlations were observed for vitamin C (0.35), lycopene (0.31), β-Cryptoxantin (0.40), and vitamin E (0.29); the average of correlation coefficients was r = 0.21.ConclusionDespite some low to moderate correlations for reproducibility and validity, overall this study suggests that the FFQ may be a good method for assessing a wide range of food groups and nutrients intake in children aged 4–5 years.

Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain.

Several studies have related longer breastfeeding duration to better intellectual performance in children. By contrast, few studies have investigated the potential protective effects of breastfeeding against behavioral problems such as attention deficit hyperactivity disorder (ADHD) symptoms, and even fewer on autism spectrum disorders (ASD) traits. We examined the association between breastfeeding duration and cognitive development, attention, ADHD symptoms, and autistic traits using data from the INMA Project, a Spanish multicenter birth-cohort study, and taking into account the intensity of breastfeeding. Duration of any, predominant, and exclusive breastfeeding was documented during infancy through maternal questionnaires. Children (N = 1,346; mean age = 4.9 y) were assessed using the McCarthy Scales of Children's Abilities, Conners' Kiddie Continuous Performance Test, criteria of the DSM-ADHD symptoms form list, and the Childhood Autism Spectrum Test. After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits. This study provides further evidence of a positive association of breastfeeding with cognitive function apart from socio-environmental factors, and also suggests a protective role against autistic traits. Results are in agreement with recommendations for prolonged breastfeeding duration to promote child development.