INMA Cohort Research Articles

Exposure to noise at home, emotional behaviour, and attention deficit hyperactivity disorder in 9-year-old children

The purpose of this study was to assess the relationship between noise disturbance at home, sleep disturbance, and neurodevelopmental problems in 9-year-old children. Noise exposure (frequency) perceived by 430 9-year-old children from the INMA cohort in Valencia, Spain, were reported by their mothers. The risk of developing attention deficit hyperactivity disorder, as well as internalizing and externalizing problems, were assessed using the Child Behaviour Checklist. The risk of internalizing (18%) and externalizing problems (11.7%) was higher compared to the risk of developing attention deficit hyperactivity disorder (1.4%) and were more prevalent in boys than in girls. The most common and bothersome noise exposures were generated at home (50.8-55.3%) and by neighbours (24.5%). The risk of neurodevelopmental problems was associated with sleep disturbances, particularly in relation with attention deficit hyperactivity disorder (16.1 vs 4%; p<0.001), with no differences observed between sex. Sleep disturbances were significantly more common in children exposed to noise from household or neighbours. High levels of noise exposure from street traffic and neighbours were linked to an increased risk of attention deficit hyperactivity disorder, while noise from other children at home was associated with a higher risk of internalizing and externalizing problems. These effects remained consistent even after adjusting for sleep disturbances. High levels of noise annoyance from various sources perceived at home are differently associated with the risks of different neurodevelopmental problems in 9-year-old boys and girls, with sleep disturbances not influencing this relationship.

Preconception and/or preimplantation exposure to a mixture of environmental contaminants altered fetoplacental development and placental function in a rabbit model

Pregnant women are daily exposed to environmental contaminants, including endocrine disruptors that can impact the offspring's health. This study aimed to evaluate the effects of maternal oral exposure to a mixture of contaminants at a dose mimicking women's exposure, during folliculogenesis and/or preimplantation period (FED and ED groups, respectively) on the fetoplacental phenotype in a rabbit model. The mixture (DEHP, pp’DDE, β-HCH, HCB, BDE-47, BPS, PFOS, PFOA) was defined based on data from HELIX and INMA cohorts. FED and ED females or unexposed females (control) were inseminated, their embryos were collected and transferred to unexposed control recipient rabbits at 80 h post-insemination. The effects of maternal FED and ED exposure were evaluated on fetoplacental growth and development by ultrasound, fetoplacental biometry, fetal metabolism, placental structure and function. The results demonstrated that the mixture weakly affected ultrasound measurements, as only placental volume increased significantly in FED vs ED. Analysis of placental structure demonstrated that the volume fraction of the maternal blood space was increased in FED vs control. Pre- and/or periconception exposure did not affect biometric at the end of gestation, but affected FED fetal biochemistry. Plasma triglyceride concentration was reduced compared to control. However, total cholesterol, urea, ASAT and ALAT in fetal blood were affected in both exposed groups. Multiple factor analysis, including biometric, biochemical, and stereological datasets, indicated that the three groups were significantly different. Additionally, several placental genes were differentially expressed between groups, compared two by two, in a sex-specific manner, with more difference in females than in males. The differentially expressed genes were involved in lipid, cholesterol, and drug/xenobiotic metabolism in both sexes. These results indicate that maternal exposure to environmental contaminants during crucial developmental windows only mildly impaired fetoplacental development but disturbed fetal blood biochemistry and placental gene expression with potential long-term effects on offspring phenotype.

Latent Childhood Exposure to Mixtures of Metals and Neurodevelopmental Outcomes in 4–5-Year-Old Children Living in Spain

Neurodevelopmental disorders are increasing globally, and metal exposure may play a significant role as an environmental factor. This cross-sectional study aimed to identify metal mixture patterns and assess their impact on children’s neurodevelopment. Data from 962 children (aged 4–5 years) participating in the Spanish INMA cohort study were analysed. Urinary metal concentrations (cobalt (Co), copper (Cu), molybdenum (Mo), selenium (Se), lead (Pb), zinc (Zn), and arsenic speciation) were used as exposure biomarkers. Principal component analysis (PCA) revealed four latent exposure variables representing uncorrelated metal mixture patterns. Linear regression analyses examined the associations between these variables and children’s neuropsychological functions assessed through the McCarthy Scales of Children’s Abilities. The first latent exposure variable (Cu, Se, Pb, Zn) and the second (inorganic arsenic, monomethylarsonic acid) showed negative associations with verbal executive function (ß = − 1.88, 95% confidence interval (CI) = − 3.17 to − 0.59) and gross motor function (ß = − 1.41, 95% CI = − 2.36 to − 0.46), respectively. Conversely, the third variable (Mo, Co) and the fourth (arsenobetaine) exhibited positive associations with visual and verbal span functions (ß = 1.14, 95% CI = 0.16 to 2.12) and fine motor function (ß = 1.01, 95% CI = 0.11 to 1.92), respectively. This study suggests that even relatively low levels of metal latent exposures, notably inorganic arsenic and a mixture of metals including Pb, adversely affect children’s neuropsychological development function scores, while exposure to arsenobetaine and a mixture of Co and Mo has a positive impact.

Association between mediterranean diet and metal(loid) exposure in 4-5-year-old children living in Spain.

Even relatively low levels of metals exposure may impact health, particularly among vulnerable populations such as infants and young children. However, little is known about the interplay between simultaneous metal exposures, common in real-life scenarios, and their association with specific dietary patterns. In this study, we have evaluated the association between adherence to Mediterranean diet (MD) and urinary metal concentrations individually and as an exposure mixture in 713 children aged 4-5-years from the INMA cohort study. We used a validated food frequency questionnaire to calculate two MD indexes scores: aMED and rMED. These indexes gather information on various food groups within the MD and score differently. To measure urinary concentrations of cobalt, copper, zinc, molybdenum, selenium, lead, and cadmium as exposure biomarkers, we used inductively coupled plasma mass spectrometry (ICP-MS), coupled with an ion chromatography (IC) equipment for arsenic speciation analysis. We applied linear regression and quantile g-computation, adjusted for confounders, to analyse the association between MD adherence and exposure to the metal mixture. High adherence to MD such as the quintile (Q) 5 MD was associated with higher urinary arsenobetaine (AsB) levels than Q1, with β values of 0.55 (confidence interval - CI 95% 0.01; 1.09) for aMED and 0.73 (CI 95% 0.13; 1.33) for rMED. Consumption of fish was associated with increased urinary AsB but reduced inorganic arsenic concentrations. In contrast, the aMED vegetables consumption increased urinary inorganic arsenic content. A moderate level of adherence to MD (Q2 and Q3) was associated with lower copper urinary concentrations than Q1, with β values of −0.42 (CI 95% −0.72; −0.11) for Q2 and -0.33 (CI 95% −0.63; −0.02) for Q3, but only with aMED. Our study, conducted in Spain, revealed that adhering to the MD reduces exposure to certain metals while increasing exposure to others. Specifically, we observed increase in exposure to non-toxic AsB, highlighting the significance of consuming fish/seafood. However, it is crucial to emphasize the necessity for additional efforts in reducing early-life exposure to toxic metals, even when adhering to certain food components of the MD.

The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood.

The increasing global burden of respiratory diseases over the last decades raises questions about the impact of environmental factors during industrialisation and urbanisation. Although the knowledge of environmental epidemiology is growing, it is still unclear what the most critical exposure windows are for respiratory health. In addition, the relationships between different environmental exposures can be complex. The exposome approach investigating all non-genetic factors on health has been developed in recent years but has been little applied in respiratory health to date. This journal club article reviews three recent publications investigating the effects of environmental exposures, considered separately or in an exposome approach with different exposure windows, on respiratory health outcomes. These three studies highlight targets for action in primary and secondary prevention. Two studies, using data from the INMA and RHINESSA cohorts, support the regulation and reduction of phthalates and air pollution, respectively. Moreover, the exposome approach conducted in the NutriNet-Santé cohort emphasises that risk reduction must involve a multi-interventional approach targeting both specific early-life risk factors and promotion of a healthy lifestyle in adulthood. These three articles also present research perspectives in environmental epidemiology.

Exploration of thyroglobulin as a biomarker of iodine status in iodine-sufficient and mildly iodine-deficient pregnant women

PurposeUrinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency.MethodsStored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg.ResultsMedian serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated.ConclusionThe association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed.

Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010–2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS). Associations between pesticide metabolites and odds of being in stage 2+ for breast development (girls), genital development (boys), pubic hair growth (girls and boys), and/or overall puberty onset, gonadarche, and adrenarche (PDS for girls and boys) were examined by mixed-effect logistic regression. Effect modification by BMI was explored by interaction terms and stratified analysis. In girls, DETP and ETU concentrations>75th percentile (P75) were associated with higher odds of overall puberty development (OR [95%CI] = 1.86 [1.07–3.24] and 1.71 [1.03–2.83], respectively, for > P75 vs. undetected concentrations), while ETU > P75 was also associated with higher odds of breast development (OR [95%CI] = 5.55 [2.83–12.91]), particularly in girls with underweight/normal weight (OR [95%CI] = 10.08 [2.62–38.76]). In boys, detection of TCPy (40%) and 3-PBA (34%) was associated with higher odds of genital development (OR [95%CI] = 1.97 [1.08–3.57] and 2.08 [1.15–3.81], respectively), and the association with 3-PBA was observed in boys with overweight/obesity alone. In addition, ETU > P75 was associated with higher odds of genital development in boys with underweight/normal weight (OR [95%CI] = 2.89 [1.08–7.74]) but higher DETP with lower odds of puberty in boys with overweight/obesity (OR [95%CI] = 0.94 [0.89–0.99] per log-unit increase in concentration). Results suggest an association of childhood exposure to ETU and certain insecticides with earlier puberty in girls and boys that may be modified by child BMI.

Association between the Use of Folic Acid Supplements during Pregnancy and Children's Cognitive Function at 7-9 Years of Age in the INMA Cohort Study.

This study investigated the association between maternal low (<400 μg/day) or high (≥1000 μg/day) folic acid supplements (FAs) use during pregnancy and the attentional function and working memory in boys and girls at age 7–9. A longitudinal analysis based on 1609 mother–child pairs from the Spanish Infancia y Medio Ambiente Project was carried out. Multivariable regression analyses revealed that, compared to the recommended FAs use, a low FAs use during the second period of pregnancy was associated with a lower alertness in all children (β = 18.70 ms; 95% CI: 7.51; 29.89) and in girls (β = 30.01 ms; 95% CI: 12.96; 47.01), and with a lower N-back Task performance in boys (d’ number 2-back (β = −0.25; 95% CI: −0.49; 0.01)). A high FAs use throughout the two periods of pregnancy was associated with a better N-back Task performance only in girls (d’ number 2-back (β = 0.28; 95% CI: 0.01; 0.56) and d’ number 3-back (β = 0.32; 95% CI: 0.08; 0.56)). The maternal use of FAs beyond the periconceptional period may affect children’s attentional function and working memory at age 7–9 differently for boys and girls.

Prevalence of inattention and hyperactivity symptoms in children from the INMA cohorts of Gipuzkoa, Sabadell, and Valencia.

Prevalence of inattention and hyperactivity symptoms in children from the INMA cohorts of Gipuzkoa, Sabadell, and Valencia.

Adherence to Mediterranean diet and metal exposure during childhood in the INMA study

BACKGROUND AND AIM The Mediterranean diet (MD) has been shown to have beneficial effects in children. A greater adherence to this pattern has been associated with a lower risk of developing obesity, diabetes, and cardiovascular disease. Yet, the contribution of the MD to the ingestion of essential and non-essential elements during childhood is unknown. Here, it is investigated the association between children’s adherence to the MD and exposure to essential and non-essential elements. METHODS Our study population of 714 children come from the INMA cohort study (INfancia y Medio Ambiente). Urinary concentrations of essential (Co, Cu, Zn, Se, and Mo) and non-essential (As, Pb and Cd) elements were measured as exposure biomarkers. Urinary arsenic speciation was also determined, and concentrations were adjusted for urine dilution. The MD dietary indexes rMED (relative Mediterranean Diet Score) and aMED (alternate Mediterranean Diet Score) were calculated based on the information gathered with a validated food frequency questionnaire (FFQ). The urine samples and data from FFQ were collected at 4 years of age. RESULTS The median urinary concentrations of Co, Cu, As, Se, Mo, Cd, Pb and Zn were 0.78, 7.64, 24.45, 23.07, 92.76, 0.08, 0.37 and 377.39 &amp;#x3bc;g/L, respectively. Urinary arsenic species concentrations (median) included arsenobetaine (10.83 &amp;#x3bc;g/L), monomethylarsonic acid (0.36 &amp;#x3bc;g/L), dimethylarsinic acid (3.00 &amp;#x3bc;g/L), and inorganic arsenic (1.17 &amp;#x3bc;g/L). An increased adherence to MD was associated with higher Mo, As and lower Co concentrations. The non-toxic arsenobetaine was associated with fish consumption in both indexes, but vegetables consumption was related to the inorganic arsenic exposure only in aMED index. CONCLUSIONS These findings suggest that the level of adherence to the MD is associated with exposure to essential but also non-essential elements. Efforts should aim to reduce toxic dietary exposures while preserving beneficial nutrients in children’s dietary patterns. KEYWORDS Mediterranean Diet, Metals, Childhood

Pre and postnatal exposure to mercury and sexual development in 9-year-old children in Spain: The role of brain-derived neurotrophic factor

Early exposure to mercury has been related to endocrine disruption. Steroid hormones play a crucial role in neural cell migration, differentiation, etc., as well as protecting against several neurotoxic compounds.We investigate the relation between mercury exposure and children's sexual development, and we evaluate the possible influence of different brain-derived neurotrophic factor (BDNF) polymorphisms on this association.Our study sample comprised 412 9-year-old children participating in the INMA cohort (2004–2015). Mercury concentrations were measured at birth (cord blood) and at 4 and 9 years of age (hair). Sexual development was assessed by levels of sex steroid hormones (estradiol and testosterone) in saliva and the Tanner stages of sex development at 9 years (categorized as 1: prepuberty and >1: pubertal onset). Covariates and confounders were collected through questionnaires during pregnancy and childhood. Polymorphisms in the BDNF gene were genotyped in cord blood DNA. Multivariate linear regression analyses were performed between mercury levels and children's sexual development by sex. Effect modification by genetic polymorphisms and fish intake was assessed.We found marginally significant inverse associations between postnatal exposure to mercury (at 9 years) and testosterone levels (β[95%CI] = -0.16[-0.33,0.001], and −0.20[-0.42,0.03], for boys and girls, respectively). Additionally, we found that prenatal mercury was negatively associated with Tanner stage >1 in boys. Finally, we found significant genetic interactions for some single nucleotide polymorphisms in the BDNF gene.In conclusion, pre and postnatal exposure to mercury seems to affect children's sexual development and BDNF may play a role in this association, but further research would be needed.

Effects of residential greenness on attention in a longitudinal study at 8 and 11–13 years

In an urbanizing world, with 55% of the population living in cities, it is essential to design friendly and healthy ones. An emerging body of evidence has associated greenspace exposure with improved cognitive development, including attentional function; however, the longitudinal studies looking at the association with attentional function are still scarce. Therefore, the objective of this study was to analyze the association of the exposure to greenspace and attention in school children. This study was based on 751 participants at 8 years and 598 at 11–13 years of two sub-cohorts of the INMA cohort study in Gipuzkoa and Asturias, Spain. Greenspace exposure at home was characterized using four indicators: (i) average of Normalized Difference Vegetation Index (NDVI) and (ii) Vegetation Continuous Field (VCF) in buffers of 100 m, 300 m, and 500 m around the residential address, (ii) availability of a green space within 300 m from the residential address, and (iv) residential distance to green spaces. Participants’ attention was characterized twice at ages of 8 and 11 years, using the computerized Attentional Network Test (ANT). General linear models were used for the cross-sectional analyses and linear mixed effects model for the longitudinal analyses. Our cross-sectional analyses showed a statistical significant protective association between average NDVI at 300 m and inattentiveness (−7.20, CI 95%: 13.74; −0.67). In our longitudinal analyses, although we generally observed beneficial associations between greenspace exposure and attention, none attained statistical significance. No statistically significant indirect effect were seen for NO2. Our findings add to the emerging body of evidence on the role of green spaces in neurodevelopment, which can provide the evidence base for implementing intervention aimed at promoting neurodevelopment in urban children.

Influence of gestational weight gain on the organochlorine pollution content of breast milk

BackgroundTransplacental transfer and breastfeeding are the main transport routes of organic pollutants into children at the beginning of life. Although pollutant transmission through these mechanisms primarily depends on the maternal pollution burden, its impact may be modulated by physiological effects. ObjectivesWe have examined whether gestational weight gain (GWG) exerts an influence on the content of lipophilic low volatile pollutants in breast milk. ResultsColostrum from mothers from the INMA cohorts of Sabadell and Gipuzkoa (n = 256 and 119, respectively) with low GWG as defined by the Institute of Medicine (IOM) from the US National Academies of Sciences, Engineering and Medicine had significantly higher concentrations of polychlorobiphenyls (PCBs) and 4,4′-DDE than colostrum in mothers who gained weight within IOM recommendations or in those who exceeded this threshold. Statistically significant differences were also found in the colostrum:maternal serum ratios of these compounds. Women with low GWG retained higher pollutant amounts in colostrum. These observations are consistent with previously described higher concentrations of these pollutants in infant cord blood from mothers with low GWG by IOM standards. They indicate that mobilization of lipophilic organic pollutants by metabolic pregnant changes not only leads to higher fetal transfer but to higher accumulation into the mammary system upon low GWG. Conclusions: The present results show that insufficient GWG, besides increasing in utero exposure, also enhances pollutant transfer to infants during breastfeeding which considerably extends the significance of this physiological change for the pollutant children intake in early life.

Serum metal levels in a population of Spanish pregnant women

ObjectiveTo describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. MethodCross-sectional study with 1279 participants from the INMA cohorts. ResultsThe concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). ConclusionsOur results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Dietary inflammatory index of mothers during pregnancy and Attention Deficit-Hyperactivity Disorder symptoms in the child at preschool age: a prospective investigation in the INMA and RHEA cohorts.

Inflammation provides a substrate for mechanisms that underlie the association of maternal diet during pregnancy with Attention Deficit-Hyperactivity Disorder (ADHD) symptoms in childhood. However, no previous study has quantified the proinflammatory potential of maternal diet as a risk factor for ADHD. Thus, we evaluated the association of maternal dietary inflammatory index (DII®) scores during pregnancy with ADHD symptoms in 4-year-old children born in two Mediterranean regions. We analyzed data from two population-based birth cohort studies-INMA (Environment and Childhood) four subcohorts in Spain (N = 2097), and RHEA study in Crete (Greece) (N = 444). The DII score of maternal diet was calculated based on validated food frequency questionnaires completed during pregnancy (12th and/or 32nd week of gestation). ADHD symptoms were assessed by ADHD-DSM-IV in INMA cohort and by ADHDT test in RHEA cohort, with questionnaires filled-out by teachers and parents, respectively. The associations between maternal DII and ADHD symptoms were analysed using multivariable-adjusted zero-inflated negative binomial regression models in each cohort study separately. Meta-analysis was conducted to combine data across the cohorts for fitting within one model. The DII was significantly higher in RHEA (RHEA = 2.09 [1.94, 2.24]) in comparison to INMA subcohorts (Asturias = -1.52 [-1.67, -1.38]; Gipuzkoa = -1.48 [-1.64, -1.33]; Sabadell = -0.95 [-1.07, -0.83]; Valencia = -0.76 [-0.90, -0.62]). Statistically significant reduced risk of inattention symptomatology (OR = 0.86; CI 95% = 0.77-0.96), hyperactivity symptomatology (OR = 0.82; CI 95% = 0.72-0.92) and total ADHD symptomatology (OR = 0.82; CI 95% = -0.72 to 0.93) were observed with increased maternal DII in boys. No statistically significant associations were observed in girls between maternal DII and inattention, hyperactivity and total ADHD symptomatology. We found reduced risk of ADHD symptomatology with increased DII only in boys. This relationship requires further exploration in other settings.

Are low fluoride levels in drinking water really detrimental for neuropsychological neurodevelopment in childhood?

Methods: Fluoride was measured in drinking water (DW) and in urine (1st and 3rd trimesters of pregnancy). The 369 mother-children pairs of the Spanish INMA cohort participating in the study reported their drinking water habits (Fluorinated DW, non-Fluorinated DW or bottled water (BW)). Maternal urine fluoride creatinine adjusted (MUFcr) levels at both trimesters were determined and neuropsychological assessment at 1 and 4 years of age was performed. For neuropsychological assessment the Bayley Scales (1 y) and the McCarthy Scales (4-5 years) were used. Multivariate linear regression models were built with the following neuropsychological domains as outcomes: Mental Index (Bayley) and Verbal, Perceptive-Manipulative, Numeric, Memory and General Cognitive (McCarthy)). Results: The percentage of mothers drinking FDW, NFDW and BW was 23.9%, 35% and 39.8% respectively. Fluoride mean levels were 0.81, 0.1-0.25 and &lt;0.1-0.48 mg/L in FDW, non-FDW and BW, consecutively. MUFcr mean levels of entire pregnancy (mg F/g creatinine) (mean; 95% CI) were different (p&lt;0.001) for those drinking FDW ((0.91 (0.83, 0.99), NFDW (0.45 (0.41, 0.49)) and BW (0.64 (0.6, 0.69)). No association was detected between MUFcr levels and Mental Index (Bayley). An increase of 1 unit in MUFcr during the entire pregnancy was related to a higher score on the perceptual-manipulative (5.13 (0.52, 9.74)) and the general cognitive (4.8 (0.13, 9.47)) McCarthy scales., MUFcr levels at 32th week of pregnancy were associated with higher verbal, memory and general cognitive scores in boys (p for interaction &lt;0.05). Conclusions: Positive associations between fluoride levels during pregnancy and neuropsychological development at 4 years of age were found. Detrimental effects of fluoride in neurodevelopment were not supported by our data.

Association of placental concentrations of phenolic endocrine disrupting chemicals with cognitive functioning in preschool children from the Environment and Childhood (INMA) Project

Aim: To examine the association of placental concentrations of several phenolic endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Methods: Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children’s Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. Results: PB compounds were detected in &gt;71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in &lt;9%. After adjustment for confounders, BPA was associated with greater odds of scoring lower (&lt;20th percentile) in the verbal area (odds ratio [OR]= 2.78, 95% confidence interval [CI]=1.00; 5.81 for upper vs. first tertile, p-trend=0.05), whereas PrPB was inversely associated with scores in memory (β=-4.96, 95%CI=-9.54; -0.31 for detected vs. undetected), span memory (OR=2.50, 95%CI=0.95; 6.92 and 2.71, 95%CI=0.97; 6.64, respectively for middle and upper tertiles, p-trend=0.03), and motor function (β=-5.15, 95%CI=-9.26; -0.01 for upper vs. first tertile, p-trend=0.04). EtPB and total PB concentrations (∑PBs) in the middle tertile were also inversely associated with visual function of posterior cortex and quantitative scores, respectively, but linear trends were not statistically significant. Conclusions: These associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenols is associated with impaired cognitive development.

Association of placental concentrations of phenolic endocrine disrupting chemicals with cognitive functioning in preschool children from the Environment and Childhood (INMA) Project.

Developmental exposure to bisphenol A (BPA) and other phenolic endocrine disrupting chemicals (EDCs) may affect child neurodevelopment, but data on the effects of prenatal exposure to phenols on cognitive function remain sparse. Our aim was to examine the association of placental concentrations of several phenolic EDCs, including BPA, parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in 490 placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. PB compounds were detected in more than 71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in <9% of the samples. Because of the low detection frequency of BzP compounds, only 4-OH-BzP was included in the exposure-outcome analyses. After adjustment for confounders, BPA was associated with greater odds of scoring lower (below the 20th percentile) in the verbal (third vs. first exposure tertile: odds ratio [OR]=2.78, 95% confidence interval [CI]=1.00; 5.81, p-trend=0.05) and gross motor (detected vs. undetected: OR=1.75, 95%CI=1.06; 9.29) areas, and these associations were only significant for boys. Regarding PB compounds, PrPB was associated with lower scores in memory (detected vs. undetected: β=-4.96, 95%CI=-9.54; -0.31), span memory (OR=2.50, 95%CI=0.95; 6.92 and 2.71, 95%CI=0.97; 6.64, respectively for second and third tertiles, p-trend=0.03), and motor function (β=-5.15, 95%CI=-9.26; -0.01 for third vs. first exposure tertile, p-trend=0.04). EtPB and total PBs concentrations in the second tertile were also associated with poorer visual function of posterior cortex and worse quantitative performance, respectively, but linear trends were not statistically significant. The associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenolic EDCs is associated with impaired cognitive development.

High adherence to a mediterranean diet at age 4 reduces overweight, obesity and abdominal obesity incidence in children at the age of 8.

A higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8. We analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0-6), medium (7-10), and high (11-16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4-8 years of age. In cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21-0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05-0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12-0.73; p = 0.008) at the age of 8. This study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages.

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.