Exposure to road traffic noise and cognitive development in schoolchildren in Barcelona, Spain: A population-based cohort study.

BACKGROUND: Road traffic noise is a prevalent and known health hazard. However, little is known yet about its effect on children's cognition. We aimed to study the association between exposure to road traffic noise and the development of working memory and attention in primary school children, considering school-outdoor and school-indoor annual average noise levels and noise fluctuation characteristics, as well as home-outdoor noise exposure. METHODS AND FINDINGS: We followed up a population-based sample of 2,680 children aged 7 to 10 years from 38 schools in Barcelona (Catalonia, Spain) between January 2012 to March 2013. Children underwent computerised cognitive tests 4 times (n = 10,112), for working memory (2-back task, detectability), complex working memory (3-back task, detectability), and inattentiveness (Attention Network Task, hit reaction time standard error, in milliseconds). Road traffic noise was measured indoors and outdoors at schools, at the start of the school year, using standard protocols to obtain A-weighted equivalent sound pressure levels, i.e., annual average levels scaled to human hearing, for the daytime (daytime LAeq, in dB). We also derived fluctuation indicators out of the measurements (noise intermittency ratio, %; and number of noise events) and obtained individual estimated indoor noise levels (LAeq) correcting for classroom orientation and classroom change between years. Home-outdoor noise exposure at home (Lden, i.e., EU indicator for the 24-hour annual average levels) was estimated using Barcelona's noise map for year 2012, according to the European Noise Directive (2002). We used linear mixed models to evaluate the association between exposure to noise and cognitive development adjusting for age, sex, maternal education, socioeconomical vulnerability index at home, indoor or outdoor traffic-related air pollution (TRAP) for corresponding school models or outdoor nitrogen dioxide (NO2) for home models. Child and school were included as nested random effects. The median age (percentile 25, percentile 75) of children in visit 1 was 8.5 (7.8; 9.3) years, 49.9% were girls, and 50% of the schools were public. School-outdoor exposure to road traffic noise was associated with a slower development in working memory (2-back and 3-back) and greater inattentiveness over 1 year in children, both for the average noise level (e.g., ‒4.83 points [95% CI: ‒7.21, ‒2.45], p-value < 0.001, in 2-back detectability per 5 dB in street levels) and noise fluctuation (e.g., ‒4.38 [‒7.08, ‒1.67], p-value = 0.002, per 50 noise events at street level). Individual exposure to the road traffic average noise level in classrooms was only associated with inattentiveness (2.49 ms [0, 4.81], p-value = 0.050, per 5 dB), whereas indoor noise fluctuation was consistently associated with all outcomes. Home-outdoor noise exposure was not associated with the outcomes. Study limitations include a potential lack of generalizability (58% of mothers with university degree in our study versus 50% in the region) and the lack of past noise exposure assessment. CONCLUSIONS: We observed that exposure to road traffic noise at school, but not at home, was associated with slower development of working memory, complex working memory, and attention in schoolchildren over 1 year. Associations with noise fluctuation indicators were more evident than with average noise levels in classrooms.

Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children.

OBJECTIVE: Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems. METHODS: Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8-12 years underwent brain MRI on the same 1.5 T MR unit over a 1.5-year period (October 2012-April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5) levels were retrospectively estimated at the mothers' residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5 exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers' smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV. RESULTS: Prenatal PM2.5 levels ranged from 11.8 to 39.5 µg/m3 during the third trimester of pregnancy. An interquartile range increase in PM2.5 level (7 µg/m3) was significantly linked to a decrease in the body CC volume (mm3) (ß = -53.7, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers' smoking status during the third trimester of pregnancy. A 50 mm3 decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR) = 1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons. CONCLUSIONS: Prenatal exposure to PM2.5 may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.

Poor mothers, unhealthy children: the transmission of health inequalities in the INMA study, Spain.

BACKGROUND: The health of pregnant women and their fetuses are especially sensitive to socioeconomic conditions. This study analyzes the impact of maternal socioeconomic status (SES), evaluated by occupation and maternal education level, in preterm births (PTBs) and in small for gestational age (SGA) fetuses, considering the effect of the potential mediating factors on the SES and birth outcomes. METHODS: A total of 2497 mother/newborn dyads from the INMA-Spain project were studied. We examined maternal occupation and education in relation to PTB and SGA along with covariate data, using logistic regression analysis. Adjusted models for each of the outcome variables in relation to SES indicators were estimated, considering potential mediating factors. RESULTS: About 4.7% of babies were PTB and 9.7% SGA. Full adjusted logistic regression models showed similar odds ratio (OR) for SGA in both SES indicators. Manual working women or without university studies had higher risk of SGA than their counterpart groups (OR = 1.39% CI = 1.03-1.88 and OR = 1.39% CI = 1.00-2.00, respectively). Likewise, mothers with a manual occupation were at more risk of PTB than those with a non-manual occupation (OR = 1.74 95% CI = 1.13-2.74), but there was no association between education and PTB. Smoking, pre-pregnancy BMI and underweight gain during pregnancy were significantly associated to SGA births. The mother's age, presence of complications and overweight gain during pregnancy were related to PTB. CONCLUSION: The mother's socioeconomic disadvantage was consistently associated with birth outcomes giving rise to intergenerational transmission of health inequalities. Reducing inequalities requires eliminating the upstream causes of poverty itself.

Comparison of urinary iodine levels in women of childbearing age during and after pregnancy.

PURPOSE: Median urinary iodine concentration (UIC) is used to describe the iodine status of a population. However, the link between UIC and iodine intake may vary during pregnancy. The aim of this study was to compare UIC during and after pregnancy, adjusting for factors that affect iodine intake. METHODS: Two repeated measures of UIC and data on maternal iodine intake estimated through questionnaires were collected during pregnancy and 1-4 years after pregnancy in a subsample of women (n = 598) from a mother and child cohort study in Spain. Random-effects interval regression was used to assess the changes in UIC according to pregnancy status. RESULTS: Median UIC was similar during (133 µg/L) and after pregnancy (139 µg/L). After adjusting for iodised salt, iodine supplement consumption, and socio-demographic related variables, UIC was 24.0% (95% CI 11.3, 38.2) higher after than during pregnancy. This difference was maintained in a subsample of women with exhaustive information on diet (n = 291): 26.2%, 95% CI 10.3, 44.4. CONCLUSIONS: In an iodine sufficient area for the general population, iodine excretion was lower during than after pregnancy when factors affecting iodine intake were controlled for. Current recommendations of median UIC during pregnancy are based on the equivalence between iodine intake and UIC estimated from studies in non-pregnant populations, which might lead to overestimation of iodine deficiency during gestation. Further studies should evaluate the equivalence between iodine intake and its urinary excretion during pregnancy.

Green spaces and cognitive development in primary schoolchildren.

Exposure to green space has been associated with better physical and mental health. Although this exposure could also influence cognitive development in children, available epidemiological evidence on such an impact is scarce. This study aimed to assess the association between exposure to green space and measures of cognitive development in primary schoolchildren. This study was based on 2,593 schoolchildren in the second to fourth grades (7-10 y) of 36 primary schools in Barcelona, Spain (2012-2013). Cognitive development was assessed as 12-mo change in developmental trajectory of working memory, superior working memory, and inattentiveness by using four repeated (every 3 mo) computerized cognitive tests for each outcome. We assessed exposure to green space by characterizing outdoor surrounding greenness at home and school and during commuting by using high-resolution (5 m × 5 m) satellite data on greenness (normalized difference vegetation index). Multilevel modeling was used to estimate the associations between green spaces and cognitive development. We observed an enhanced 12-mo progress in working memory and superior working memory and a greater 12-mo reduction in inattentiveness associated with greenness within and surrounding school boundaries and with total surrounding greenness index (including greenness surrounding home, commuting route, and school). Adding a traffic-related air pollutant (elemental carbon) to models explained 20-65% of our estimated associations between school greenness and 12-mo cognitive development. Our study showed a beneficial association between exposure to green space and cognitive development among schoolchildren that was partly mediated by reduction in exposure to air pollution.

Traffic-related Air Pollution and Attention in Primary School Children: Short-term Association.

BACKGROUND: Although air pollution's short-term effects are well understood to be marked and preventable, its acute neuropsychological effects have, to our knowledge, not yet been studied. We aim to examine the association between daily variation in traffic-related air pollution and attention. METHODS: We conducted a follow-up study from January 2012 to March 2013 in 2,687 school children from 265 classrooms in 39 schools in Barcelona (Catalonia, Spain). We assessed four domains of children's attention processes every 3 months over four repeated visits providing a total of 10,002 computerized tests on 177 different days using the child Attention Network test (ANT). Ambient daily levels of nitrogen dioxide (NO2) and elemental carbon (EC) in particulate matter <2.5 µm (PM2.5) filters were measured at a fixed air quality background monitoring station and in schools. RESULTS: Daily ambient levels of both NO2 and EC were negatively associated with all attention processes (e.g., children in the bottom quartile of daily exposure to ambient NO2 levels had a 14.8 msecond [95% confidence interval, 11.2, 18.4] faster response time than those in the top quartile, which was equivalent to a 1.1-month [0.84, 1.37] retardation in the natural developmental improvement in response speed with age). Similar findings were observed after adjusting for the average indoor (classroom) levels of pollutants. Associations for EC were similar to those for NO2 and robust to several sensitivity analyses. CONCLUSIONS: The short-term association of traffic-related air pollutants with fluctuations in attention adds to the evidence that air pollution may have potential harmful effects on neurodevelopment. See video abstract at, http://links.lww.com/EDE/B158.

Video gaming in school children: How much is enough?

OBJECTIVE: Despite extensive debate, the proposed benefits and risks of video gaming in young people remain to be empirically clarified, particularly as regards an optimal level of use. METHODS: In 2,442 children aged 7 to 11 years, we investigated relationships between weekly video game use, selected cognitive abilities, and conduct-related problems. A large subgroup of these children (n = 260) was further examined with magnetic resonance imaging approximately 1 year later to assess the impact of video gaming on brain structure and function. RESULTS: Playing video games for 1 hour per week was associated with faster and more consistent psychomotor responses to visual stimulation. Remarkably, no further change in motor speed was identified in children playing >2 hours per week. By comparison, the weekly time spent gaming was steadily associated with conduct problems, peer conflicts, and reduced prosocial abilities. These negative implications were clearly visible only in children at the extreme of our game-playing distribution, with 9 hours or more of video gaming per week. At a neural level, changes associated with gaming were most evident in basal ganglia white matter and functional connectivity. INTERPRETATION: Significantly better visuomotor skills can be seen in school children playing video games, even with relatively small amounts of use. Frequent weekly use, by contrast, was associated with conduct problems. Further studies are needed to determine whether moderate video gaming causes improved visuomotor skills and whether excessive video gaming causes conduct problems, or whether children who already have these characteristics simply play more video games. Ann Neurol 2016;80:424-433.

Longitudinal association between air pollution exposure at school and cognitive development in school children over a period of 3.5 years.

INTRODUCTION: Recently, we showed that exposure to traffic-related air pollutants (TRAPs) at school was negatively associated with cognitive development, specifically working memory and inattentiveness, in primary schoolchildren during a course of 12 months. The persistence of such associations over longer periods remains as an open question. OBJECTIVE: To study the longitudinal association between TRAPs at school and cognitive development over a period of 3.5 years. METHODS: Indoor and outdoor levels of TRAPs (elemental carbon (EC), dioxide nitrogen (NO2), particulate matter (PM2.5) from traffic sources and ultrafine particles (UFP)) were measured at 39 schools across Barcelona during 2012/2013. Working memory, as a measure of cognitive development, was evaluated 4 times in 2012/2013 assessment and was re-evaluated one more time in 2015 using computerized n-back test (3-back d' as main outcome). Linear mixed effects models were used to test the association between TRAPs and 3-back d', adding child and school as random effects to account for the multilevel nature of the data, and school air pollutants levels (one at a time) as predictor. RESULTS: We found detrimental associations between all TRAPs and annual change in 3-back d' (working memory) (i.e. slower development of working memory in children attending schools with higher levels of air pollution). The associations (per one interquartile range increase in exposure) were strongest for outdoor NO2 (Coefficient (Coef) = - 4.22, 95% confidence interval (CI), - 6.22, - 2.22) and indoor UFP (Coef = - 4.12, 95%CI, - 5.68, - 1.83). These reductions were equivalent to - 20% (95%CI, - 30.1, - 10.7) and - 19.9% (95%CI, - 31.5, - 8.4) change in annual working memory development associated with one interquartile range increase in outdoor NO2 and indoor UFP, respectively. CONCLUSION: Our findings suggest the persistence of the negative association between TRAPs exposure at school and cognitive trajectory measured by n-back test over a period of 3.5 years.

Green spaces and spectacles use in schoolchildren in Barcelona.

Myopia is one of the major causes of low visual acuity during childhood, and hence of the need for spectacles. It is generally more prevalent in urban areas where children are often less exposed to green spaces than in rural areas. This study evaluated the association between exposure to green space and use of spectacles (as a surrogate measure for myopia) in a cohort of 2727 schoolchildren (7-10 years old) recruited from 39 primary schools in Barcelona (2012-2015). We assessed exposure to green spaces by characterizing outdoor surrounding greenness at home and school and during commuting using satellite data on greenness (Normalized Difference Vegetation Index). We also obtained data on the annual average time children spent playing in green spaces through questionnaires. Cross-sectional analyses were conducted based on prevalent cases of spectacles use at baseline data collection campaign and longitudinal analyses based on incident cases of spectacles use during the three-year period between the baseline and last data collection campaigns. An interquartile range (IQR) increase in exposure to green space at home (500m buffer) and school and during commuting was associated with respectively 14% (95% CI: 2%, 26%), 27% (95% CI: 6%, 44%), and 20% (95% CI: 5%, 33%) decrease in spectacles use in cross-sectional analyses. In longitudinal analyses, we observed a reduction of 23% (95% CI: 4%, 39%) and 34% (95% CI: 2%, 55%) associated with an IQR increase in greenness at home and school, respectively. Moreover, an IQR increase in time playing in green spaces was associated with a 28% (95% CI: 7%, 45%) reduction in the risk of spectacles use in the longitudinal analysis. Our observed reduced risk of spectacles use associated with higher contact with green space calls for more refined studies of the association between green spaces and refractive errors of visions.

Traffic pollution exposure is associated with altered brain connectivity in school children.

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain.

Physical Activity and Cognitive Trajectories in Schoolchildren.

PURPOSE: The evidence regarding the role of physical activity (PA) habits on cognitive development in children is still scarce. Our study aimed to assess the association between PA habits and cognitive growth patterns, including working memory (WM) and inattentiveness in a large sample of primary schoolchildren. METHOD: This study included 2,897 children between 7 and 10 years old. WM was measured using the n-back task (2- and 3-back) and inattentiveness was measured using the attentional network task (ANT) on four occasions during one year. Parents completed a questionnaire with data about the extracurricular exercise of their child, commuting to school and other sociodemographic information at the first visit. RESULTS: Exercising twice per week or more was associated with better 2-back, 3-back and inattentiveness scores at baseline, as compared with the once per week or less category. Active commuting for more than 50 min was associated with better 3-back scores at baseline, as compared with passive commuting. No consistent associations were found between PA and cognitive growth. CONCLUSION: Overall, although children with high levels of PA performed better in cognitive tasks at baseline, PA levels had no clear effects on cognitive growth trajectories.

Association between traffic-related air pollution in schools and cognitive development in primary school children: a prospective cohort study.

BACKGROUND: Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development. METHODS AND FINDINGS: We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10-700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%-8.8%] versus 11.5% [95% CI 8.9%-12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%-23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation. CONCLUSIONS: Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.

Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain.

BACKGROUND: Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery. METHODS: We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4 < 5 th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4 > 95 th percentile and TSH normal), and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery. RESULTS: An inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (ß = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes. CONCLUSIONS: High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range.

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women.

OBJECTIVE: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. METHODS: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. RESULTS: The geometric means of TSH, TT3, FT4 and mercury were 1.1µU/L, 2.4nmol/L, 10.5pmol/L and 7.7µg/L, respectively. Mercury levels were marginally significantly associated with TT3 (ß: -0.05; 95%CI: -0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (-0.08; 95%CI: -0.15, -0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. CONCLUSION: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed.

Iodine supplementation during pregnancy and infant neuropsychological development. INMA Mother and Child Cohort Study.

Iodine supplementation during pregnancy is a common practice in developed countries. However, scant evidence is available regarding the safety and effectiveness of maternal iodine supplementation with regard to child neuropsychological development. We previously reported an inverse association between iodine supplementation and the psychomotor development of infants in a birth cohort from Valencia, Spain. In the present study, we assessed this association in a wider sample of mother and child pairs from 3 other regions in Spain. Neuropsychological development was assessed using the Bayley Scales of Infant Development in 1,519 infants (median age, 16 months) between 2006 and 2009. In multivariate analyses, maternal consumption of 150 µg/day or more of iodine from supplements was related to a 1.5-fold increase in the odds of a psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7-fold increase in the odds of a mental score less than 85 (95% confidence interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were only partially verified. The results of the present study suggest that, at least in these regions, iodine supplementation does not improve infant neuropsychological development at 1 year of age. Further research is needed on the risks and benefits of supplementary iodine for both maternal thyroid function and child neurodevelopment.

Maternal smoking during pregnancy and fetal biometry: the INMA Mother and Child Cohort Study.

In utero tobacco exposure has been associated with fetal growth restriction, but uncertainty remains about critical windows of exposure and specific effects on body segments. In the present study, we aimed to examine the association of maternal smoking with fetal biometry in different stages of pregnancy. The study population comprised 2,478 fetuses from a Spanish birth cohort study that was established between 2003 and 2008. Biparietal diameter, femur length, abdominal circumference, and estimated fetal weight were evaluated at 12, 20, and 34 weeks of gestation. Fetal size and growth were assessed by standard deviation scores adjusted by maternal and fetal characteristics. Maternal smoking was assessed using questionnaire and a sample of urinary cotinine at week 32 of gestation. Associations were estimated using multiple regression analysis. Smokers at week 12 of gestation showed decreased fetal growth as reflected by all growth parameters at 20-34 weeks, leading to a reduced fetal size at week 34. The reduction was greatest in femur length, at -9.4% (95% confidence interval -13.4, -5.4) and least in abdominal circumference, at -4.4% (95% CI: -8.7, -0.1). Fetuses of smokers who quit smoking before week 12 showed reduced growth only in femur length (-5.5; 95% CI: -10.1, -0.9). Dose-response curves for smoking versus fetal growth parameters (abscissa: log2 cotinine) were linear for biparietal diameter and femur length.

Thyroxine levels during pregnancy in healthy women and early child neurodevelopment.

BACKGROUND: The fetus depends on maternal thyroid hormones during pregnancy for normal brain development. Little is known about the effects of subclinical hypothyroidism and mild hypothyroxinemia during pregnancy on neurodevelopment of the child. METHODS: We evaluated a population-based birth cohort in Spain. A total of 1761 children and their mothers were included in the main analyses. Serum levels of free thyroxine and thyrotropin were measured in pregnant women. Mental and psychomotor development of their children was assessed using the Bayley Scales of Infant Development during the second year of life. RESULTS: Low free thyroxine levels (<5th percentile) and self-reported prepregnancy thyroid disorder without medical treatment were associated with a decrease of mental scores (Beta = -3.4 [95% confidence interval= -6.7 to -0.2]) and -5.5 [-8.9 to -2.0], respectively). No association between thyrotropin levels and mental scores or psychomotor scores was observed. CONCLUSIONS: Low free thyroxine levels in healthy pregnant women are related to a moderate delay in child neurodevelopment. The impairment is similar in magnitude to that observed in mothers with untreated prepregnancy thyroid disorder. The value of screening pregnant women for thyroid function requires further assessment, particularly in mildly iodine-deficient areas.

Maternal C-reactive protein levels in pregnancy are associated with wheezing and lower respiratory tract infections in the offspring.

OBJECTIVE: We assessed whether maternal C-reactive protein (CRP) levels during pregnancy and CRP gene variations are associated with wheezing and lower respiratory tract infections (LRTIs) in offspring. STUDY DESIGN: Information on wheezing and LRTIs in the offspring at 6 and 14 months of age, and maternal CRP levels and genotype was obtained from a population-based birth cohort. RESULTS: A total of 63 children (12.5%) experienced recurrent wheezing and 61 (12.4%) a recurrent diagnosis of LRTIs. Children in the highest tertile of maternal CRP levels had a higher risk of experiencing recurrent wheezing (adjusted odds ratio, 2.87; 95% confidence interval, 1.23-6.71) and being diagnosed with recurrent LRTIs (odds ratio, 2.37; 95% confidence interval, 1.01-5.55), as compared with children in the lowest tertile. The rs1205 polymorphism influenced maternal serum CRP levels but not the risk of the offspring outcomes. CONCLUSION: Higher CRP levels in pregnancy are associated with wheezing and LRTIs in offspring. However, genetic variation in CRP influencing maternal levels is not related to these phenotypes.

Iodine intake and maternal thyroid function during pregnancy.

BACKGROUND: An adequate iodine intake during pregnancy is essential for the synthesis of maternal thyroid hormones and normal brain development in the fetus. Scant evidence is available on the effects and safety of iodine supplementation during pregnancy in areas with adequate or mildly deficient iodine intake. We examined the association of maternal iodine intake and supplementation with thyroid function before 24 weeks of gestation in population-based samples from 3 different areas in Spain. METHODS: A cross-sectional study of 1844 pregnant women (gestational age range 8-23 weeks) was carried out in 3 areas in Spain (Guipúzcoa, Sabadell, Valencia), during the period 2004-2008. We measured levels of free thyroxine and thyroid-stimulating hormone (TSH) in serum, iodine in a spot urine sample, and questionnaire estimates of iodine intake from diet, iodized salt and supplements. Adjusted associations were assessed by multiple linear regression and logistic regression analyses. RESULTS: There was an increased risk of TSH above 3 muU/mL in women who consumed 200 microg or more of iodine supplements daily compared with those who consumed less than 100 microg/day (adjusted odds ratio = 2.5 [95% confidence interval = 1.2 to 5.4]). We observed no association between urinary iodine and TSH levels. Pregnant women from the area with the highest median urinary iodine (168 microg/L) and highest supplement coverage (93%) showed the lowest values of serum free thyroxine. (geometric mean = 10.09 pmol/L [9.98 to 10.19]). CONCLUSIONS: Iodine supplement intake in the first half of pregnancy may lead to maternal thyroid dysfunction in iodine-sufficient or mildly iodine-deficient populations.

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.