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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. [ABSTRACT FROM PUBLISHER]

Abstract: There is little evidence about exposure to currently used insecticides during early life periods and adverse effects on child neuropsychological development. The aim of this study is to examine the association between residential insecticide use during pregnancy and infancy, and the development of children. Study subjects were participants in the INMA (Environment and Childhood) Project, a Spanish multicenter birth cohort study. Prenatal and postnatal use of indoor insecticides and other variables were obtained from personal interview during pregnancy and infancy. Mental and psychomotor development was assessed around 14months using the Bayley Scales of Infant Development. The associations were analyzed by linear regression models. 54% of women used indoor insecticides at home during pregnancy and 47% postnatally. 34% of women used insecticide sprays and 33% used plug-in devices during pregnancy. During infancy, the percentage of women who used insecticide sprays decreased (22%), but the use of plug-in devices was similar to the prenatal period (32%). The use of insecticide sprays during pregnancy was associated with a decrement in psychomotor development (β=−1.9; 95%CI: −3.4, −0.5) but postnatal use did not associate with mental and psychomotor development. The negative effect was enhanced according to some modifying factors, such as being female, higher levels of prenatal exposure to PCB and mercury and belonging to the lowest social class. We found certain evidence about the adverse effect of using insecticide sprays during pregnancy on the psychomotor development of children. Some socio-demographic factors and other exposures could enhance that effect. [Copyright &y& Elsevier]

Background In utero tobacco exposure has been associated with adverse pregnancy outcomes but few studies have used longitudinal ultrasound measurements to asses the effects on fetal growth. The aim of this study was to examine the impact of active and passive smoking during pregnancy on fetal biometry in a cohort of Spanish women. Methods Biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) were evaluated in each trimester of pregnancy. Detailed information on smoking and potential confounders was assessed by questionnaire. SD scores were calculated from longitudinal growth curves adjusted for gestational age and potential determinants of growth. Size was assessed by means of unconditional SD scores at 12, 20, 32 and 38 weeks of pregnancy, while growth between these points was assessed by means of conditional SD scores. The association between smoking and fetal growth was investigated by regression models and adjusted for sociodemographic and lifestyle-related variables. Results Maternal smoking was inversely associated with size of all parameters at weeks 32 and 38 and with growth in 20--32, 12--32 and 12--38 week intervals. In 32--38 weeks the effect was significant for AC and EFW. Environmental tobacco smoke (ETS) exposure was inversely associated with growth in BPD in all the intervals except 32--38 weeks. Conclusions Active smoking during pregnancy was associated with a reduction in BPD, AC, FL and EFW from mid-gestation. ETS adversely affected BPD from early pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: To compare the risk of preterm and low birth weight among newborns from native and immigrant women and to assess the role of prenatal care in the association between the ethnic origin of the women and their reproductive outcomes. Methods: Cross-sectional study of 21,708 women giving birth between 1997 and 2008 in a region of Spain. Multinomial logistic regression models were adjusted to evaluate associations between mother’s area of origin and adverse reproductive outcomes and to assess the role of prenatal care in the occurrence of adverse reproductive results. Results: Our results indicate a worse prenatal control in immigrants than in natives. Very preterm birth (VPTB) and very low birth weight (VLBW) were greater among immigrants (odds ratio [OR], 1.78; 95% confidence interval [95% CI], 1.14−2.79 for VPTB and OR, 1.73; 95% CI, 0.89−3.33 for VLBW) but after adjustment for prenatal care the differences were substantially reduced (OR, 1.43; 95% CI 0.85−2.42 for VPTB and OR 1.15; 95% CI 0.53−2.52 for VLBW). Conclusions: Given the positive impact of prenatal care on reproductive results, strategies to improve it among immigrant women should be implemented. The difference found in the direction of the association between area of origin and different categories of low birth weight and preterm suggest that very and moderate categories should be analyzed separately in immigrant studies. [Copyright &y& Elsevier]

Vulnerability of the central nervous system to mercury is increased during early development. This study aimed to evaluate whether cord blood total mercury levels may have a negative effect on both mental and psychomotor development in a maternal-birth cohort from moderate-high fish consumption areas. Study subjects were 1,683 child participants in the INMA (Environment and Childhood) Project from 4 areas of Spain between 2003 and 2010. Cord blood total mercury levels were analyzed by atomic absorption spectrometry. Infant neurodevelopment was assessed around age 14 months by the Bayley Scales of Infant Development. Sociodemographic, lifestyle, and dietary information was obtained by questionnaire during pregnancy. The geometric mean of total mercury levels was 8.4 µg/L (95% confidence interval (CI): 8.1, 8.7). In multivariate analysis, a doubling in total mercury levels did not show an association with mental (β = 0.1, 95% CI: −0.68, 0.88) or psychomotor (β = −0.05, 95% CI: −0.79, 0.68) developmental delay; however, stratified findings by sex suggest a negative association between prenatal exposure to total mercury and psychomotor development among female infants (β = −1.09, 95% CI: −2.21, 0.03), although follow-up is required to confirm these results. [ABSTRACT FROM AUTHOR]

Abstract: Numerous studies have focused on the effects of exposure to air pollution on health; however, certain subsets of the population tend to be more exposed to such pollutants depending on their social or demographic characteristics. In addition, exposure to toxicants during pregnancy may play a deleterious role in fetal development as fetuses are especially vulnerable to external insults. The present study was carried out within the framework of the INMA (Infancia y Medio Ambiente or Childhood and the Environment) multicenter cohort study with the objective of identifying the social, demographic, and life-style factors associated with nitrogen dioxide (NO2) exposure in the subjects in the cohort. The study comprised 785 pregnant women who formed part of the INMA cohort in Valencia, Spain. Outdoor levels of NO2 were measured at 93 sampling sites spread over the study area during four different sampling periods lasting 7 days each. Multiple regression models were used for mapping outdoor NO2 throughout the area. Individual exposure was assigned as: 1) the estimated outdoor NO2 levels at home, and 2) the average of estimated outdoor NO2 levels at home and work, weighted according to the time spent in each environment. The subjects’ socio-demographic and life-style information was obtained through a questionnaire. In the multiple linear analyses, the outdoor NO2 levels assigned to each home were taken to be the dependent variable. Other variables included in the model were: age, country of origin, smoking during pregnancy, parity, season of the year, and social class. These same variables remained in the model when the dependent variable was changed to the NO2 levels adjusted for the subjects’ time-activity patterns. We found that younger women, those coming from Latin American countries, and those belonging to the lower social strata were exposed to higher NO2 levels, both as measured outside their homes as well as when time-activity patterns were taken into account. These subgroups also have a higher probability of being exposed to NO2 levels over 40 μg/m3, which is the annual limit for maximum safe exposure, as established by European Directive 2008/50/EC. [Copyright &y& Elsevier]

Abstract: Background: Research has shown that prenatal exposure to air pollutants may have a detrimental effect on fetal development, with the strength of the relationship depending on the effect being studied. The evidence to date, however, is insufficient to establish a direct causal link between such exposure and preterm delivery. This study evaluates the specific effect of prenatal exposure to NO2 and benzene on preterm births. Methods: The population under study comprised 785 pregnant women who formed part of the INMA cohort in Valencia, Spain (2003–2005). Multiple regression models were used for mapping outdoor nitrogen dioxide (NO2) and benzene levels throughout the area. Individual exposure was assigned as the estimated outdoor levels at each woman’s home measured during each trimester as well as throughout the entire pregnancy. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in order to assess the association between preterm birth and exposure to NO2 and benzene. The shape of the exposure–response curve between air pollution and the risk of preterm birth was analyzed with a flexible approach, introducing a natural cubic spline for air pollution levels into the model. Results: Pregnant women exposed to NO2 and benzene have an increased risk of preterm birth. This risk was shown to be significant when women were exposed to NO2 levels >46.2μg/m3 during the second and third trimesters as well as throughout the entire pregnancy and to benzene levels >2.7μg/m3 throughout the entire pregnancy. Conclusion: These results suggest that maternal exposure to traffic-related air pollution is associated with preterm birth. [ABSTRACT FROM AUTHOR]

It has been suggested that prenatal exposure to some organochlorine compounds (OCs) may adversely affect thyroid function and may, therefore, impair neurodevelopment. The main aim of this study was to examine the relationship of cord serum levels of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (4,4′-DDT), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4′-DDE), β-hexachlorocyclohexane (β-HCH), hexachlorobenzene (HCB), four individual polychlorobiphenyl (PCB) congeners (118, 138, 153, and 180), and their sum, with neonatal thyroid stimulating hormone (TSH) levels in blood samples in a mother-infant cohort in Valencia, Spain. This study included 453 infants born between 2004 and 2006. We measured OC concentrations in umbilical cord serum and TSH in blood of newborns shortly after birth. Associations between neonatal TSH levels and prenatal OC exposure adjusted for covariates were assessed using multivariate linear regression analyses. Neonatal TSH levels tended to be higher in newborns with β-HCH levels in umbilical cord above 90th percentile (104 ng/g lipid) than in those with levels below the median (34 ng/g lipid), with an adjusted increment in neonatal TSH levels of 21% (95% confidence interval=−3, 51; P=0.09). No statistically significant association was found between the remaining OCs and TSH at birth. Prenatal exposure to β-HCH may affect neonatal thyroid hormone status and its function in neurological development. [ABSTRACT FROM AUTHOR]

Background: Spain has become a principal destination for immigrants and delivery is the major reason for hospitalization in this population. However, research about inequities between native and immigrant women regarding the quality of the care received during pregnancy and delivery is still scarce. One of the indicators used to evaluate the quality of the obstetric care is the rate of caesarean sections (CSs). Methods: A cross-sectional study of 215 379 single deliveries from Spanish and immigrant women from Latin America, East Europe and Maghreb was carried out in Spain in 2005–06. Prevalence of CS according to maternal and neonatal characteristics was calculated by geographical origin. Two associations were explored by means of multiple logistic regression analysis. First, the association between geographical origin and the risk of CS in public or private hospitals separately, and, second, the risk of CS for women from the same geographical origin depending on whether they delivered at public or private hospitals. Results: Overall, the risk of CS was lower for immigrants as a whole than for native women (odds ratio (OR) = 0.83 95% confidence interval (CI) = 0.80–0.85), but the risk varied markedly by area of origin, being higher for Latin Americans (OR = 1.09 95% CI = 1.05–1.13) and lower for East Europeans (OR = 0.61 95% CI = 0.57–0.66) and Maghrebians (OR = 0.60 95% CI =0.57–0.63). Public hospitals followed the overall pattern of risk. CS risk was higher in private than in public hospitals for all groups. However, the increase in risk was higher for immigrant than for natives. Conclusion: Immigrants in Spain are a heterogeneous population regarding the risk of CS. Geographical origin and type of hospital are key aspects underlying such a risk. [ABSTRACT FROM AUTHOR]

Introduction: Several epidemiological studies have reported that some organochlorine compounds (OCs), such as polychlorobiphenyls (PCBs) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4′-DDE), may alter thyroid function. Objective: The aim of the present study was to investigate the association of maternal serum OC concentrations of 4,4′-DDE and the sum of seven PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) with thyroid hormone (TH) status. Methods: We measured OC concentrations in 157 maternal serum samples at 12 weeks of pregnancy in a cohort from Valencia (Spain). Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4) were measured as biomarkers of thyroid function in the same samples. Linear and logistic regression analyses were performed between OCs and TH levels, and variables were log transformed. Results: Mothers with higher levels of 4,4′-DDE had higher odds of having TSH levels >2.5mIU/L (OR=2.53; 95% CI=1.36; 4.73; p=0.004), and we found a significant negative association between serum 4,4′-DDE concentrations and FT4 levels (β=−0.03; 95% CI=−0.05; 0.00; p=0.050) after adjustment for covariates and total lipids. No association was found between sum of PCBs and TH levels. Conclusion: Serum concentrations of 4,4′-DDE were associated with increased TSH and reduced FT4 but not TT3 levels. Our results suggest that some environmental chemicals may interfere with the thyroid system of pregnant women. The major role that maternal THs may play in fetal neurodevelopment makes these findings especially relevant. [Copyright &y& Elsevier]

We examined the relationship between consumption of fruit and vegetables during pregnancy and anthropometric measures at birth in a general population mother-infant cohort in Valencia, Spain. A total of 787 infants born between May 2004 and February 2006 were included. Fruit and vegetable consumption during pregnancy was assessed by a FFQ administered using an in-person interview. We used multiple linear regression to assess associations between fruit and vegetable intake (in quintiles) and birth weight and length adjusted for sex and gestational age, and logistic regression to assess being small for gestational age (SGA) in weight and SGA in length, defined as adjusted birth weight or length below the 10th percentile. A linear relationship was found between vegetable consumption and having a SGA (weight) and SGA (length) baby. Women in the lowest quintile of vegetable intake during the first trimester had a higher odds of having a SGA (weight) baby than women in the highest quintile odds ratio (OR), 3.7; 95% Cl: 1.5-8.9; P-trend < 0.0011 and had a higher odds of having an SGA (length) baby in the third trimester (OR, 5.5; 95% Cl: 1.7-17.7; P-trend = 0.04) in multivariate analysis. We found a nonmonotonic relationship between adjusted birth weight and length and vegetable consumption during the first trimester; newborns in the 2 lowest quintiles of intake had a significantly lower weight and length than those in the 4th quintile. There was no association between fruit consumption and birth outcomes. Our findings indicate that vegetable consumption throughout pregnancy may have a beneficial effect on fetal growth. [ABSTRACT FROM AUTHOR]

1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs). PAHs are pollutants produced by the combustion of organic material, and could be found both indoors and outdoors. Prenatal exposure to these compounds has been associated with retarded intrauterine growth and respiratory problems in children. The objective of this study is to describe the 1-OHP levels in urine in pregnant women in the INMA cohort in Valencia, and to study the association with socio-demographic and lifestyle variables, as well as with indicators of air pollution. The study population is a sub-sample (n: 204) of a cohort of pregnant women in the multicentre INMA project in Valencia (Spain). Urine samples were taken in week 12 of gestation, and 1-OHP was analyzed, and adjusted for creatinine. Socio-demographic and lifestyle information was collected using a questionnaire. Data from the monitoring stations in Valencia were used to assign levels of exposure to nitrogen dioxide (NO2), sulphur dioxide (SO2), total suspended particulates (TSP) and carbon monoxide (CO). The median 1-OHP level was 0.061 μmol/mol of creatinine. Women who smoked had higher 1-OHP levels (0.095 μmol/mol of creatinine) than non-smokers (0.050 μmol/mol of creatinine). The variables predicting 1-OHP levels on linear multivariate analysis were: tobacco consumption, consumption of fried and smoked foods. There was also a significant association with NO2 levels 4 and 5 days before the samples were taken. The 1-OHP levels found in pregnant women in Valencia were higher than those found among women in reports in USA. 1-hydroxypyrene could be a good marker of exposure to PAHs from tobacco and diet, and also a useful marker of short term exposure to air pollution. [Copyright &y& Elsevier]

The INMA (INfancia y Medio Ambiente [Environment and Childhood]) is a population-based cohort study in different Spanish cities, that focuses on prenatal environmental exposures and growth, development and health from early fetal life until childhood. The study focuses on five primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) asthma and allergies; (4) sexual and reproductive development; and (5) environmental exposure pathways. The general aims of the project are: (1) to describe the degree of individual prenatal exposure to environmental pollutants, and the internal dose of chemicals during pregnancy, at birth and during childhood in Spain; (2) to evaluate the impact of the exposure to different contaminants on fetal and infant growth, health and development; (3) to evaluate the role of diet on fetal and infant growth, health and development; and (4) to evaluate the interaction between persistent pollutants, nutrients and genetic determinants on fetal and infant growth, health and development. Extensive assessments will be carried out on 3100 pregnant women and children. Data will be collected by physical examinations, questionnaires, interviews, ultrasound and biological samples. Pregnant women are being assessed at 12, 20 and 32 weeks of gestation to collect information about environmental exposures and fetal growth. The children will be followed until the age of 4 years. [ABSTRACT FROM AUTHOR]

• Association between postnatal Hg and behaviour was assessed among Spanish children. • Hair 9-years old THg associated with worse scores on the CBCL internalizing and total problems scales. • Factors such as sex and genetics seem to play a role in this relationship. • Boys obtained worse scores in the behaviour scales with increasing THg compared to girls. • Effect interactions were also observed for polymorphisms in the GSTP1 , BDNF and APOE genes. Mercury (Hg) is an environmental neurotoxicant whose main route of exposure in humans is the consumption of seafood. The aim of this study was to explore the relationship between Hg exposure at 9 years old and behaviour assessed at 9 and 11 years old. Study subjects were mother–child pairs participating in the INMA (Environment and Childhood) Project in Valencia (Spain). Total Hg (THg) was measured in hair samples from the children at 9 years old. Behaviour and emotions were assessed at 9 (n = 472) years and 11 (n = 385) years of age using the Child Behaviour Checklist test (CBCL) and the Conners Parents Rating Scale-Revised: Short Form (CPRS-R:S). Furthermore, the attention function was assessed by the Attention Network Test at 11 years old. Socio-demographic, lifestyle and dietary information was collected through questionnaires during pregnancy and childhood. Polymorphism in BDNF , APOE and GSTP1 were genotyped in cord blood DNA. Multivariable negative binomial regression models were built in order to study the association between THg concentrations and the scores obtained by the children at 9 and 11 years old. Effect modification by sex and genetic polymorphisms was assessed. The association between Hg levels and CBCL scores was positive (worse neurobehavioural development) for the CBCL internalizing and total problem scales (Incidence Rate Ratio [95% confidence interval] = 1.07 [1.01, 1.13] and 1.05 [0.99, 1.11], respectively). The association between Hg and the externalizing and total problems CBCL scales and the Attention Deficit Hyperactivity Disorder (ADHD) index of the CPRS-R:S was different according to sex, with boys obtaining worse scores with increasing Hg, compared to girls. Statistically significant interactions were also observed for genetic polymorphisms affecting the association between early exposure to Hg and both CBCL and CPRS-R:S scores. In conclusion, postnatal Hg exposure is associated with poorer neurobehavioural development in 9- and 11-year-old children. Sex and the presence of certain genetic polymorphisms modified this association. [ABSTRACT FROM AUTHOR]

Background: 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., Material and Methods: 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., Results: 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., Conclusions: 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.

Socioeconomic position (SEP) may have different effects on cognitive development and family context could play a role in this association. This work aimed to analyse the role of socioeconomic positions, measured via various indicators collected longitudinally, in cognitive development at 7-11 years of age, evaluating the role of family context as a potential mediator. The study sample included 394 and 382 children from the INMA Gipuzkoa and Valencia cohorts, respectively. SEP indicators were assessed during pregnancy (family social class, parental education, employment, and disposable income) and at 7 (Gipuzkoa) and 11 (Valencia) years of age (At Risk of Poverty or Social Exclusion (AROPE)). Family context and cognitive development were measured with the Haezi-Etxadi Family Assessment Scale 7-11 (HEFAS 7-11) and Raven's Coloured Progressive Matrices (Raven's CPM), respectively. Linear regression models were developed to assess the relationships between (a) SEP-family context, (b) SEP-cognitive development, and (c) family context-cognitive development, adjusting for a priori-selected confounders. Simple and multiple mediation analyses were performed to explore the role of family context in the SEP-cognitive development relationship. Lower SEP was related with a lower cognitive score, this association being particularly robust for family social class. SEP indicators were related to subscales of family context, in particular those regarding cognitive stimulation, parental stress, and parenting. A relationship was also found between these three subscales and child cognitive development, mediating the effect of family social class on child cognition by 5.2, 5.5, and 10.8%, respectively, and 12.0% jointly.    Conclusion: Both family SEP and context contribute to a child's cognitive development. Equalising policies and positive parenting programmes could contribute to improving cognitive development in children. What is Known: • Parental social class, education, and employment status have been widely employed to measure socioeconomic position. What is New: • This work focuses on standard measurements of socioeconomic position but also other economic indicators such as the EHII and AROPE, and their effect on child cognitive development and family context. • Promotion of cognitive and linguistic development, parental stress and conflict, and parental profile fostering child development mediated the effect of family social class on cognitive development., (© 2024. The Author(s).)

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p  < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p  < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p  < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p  < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8-9 represent an alarm sign for presenting ADHD problems at ages 10-11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8-9) with the sleep items of the Child's Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner's Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10-11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10-1.19), 1.20 (1.14-1.26), 1.18 (1.11-1.25), and 1.18 (1.13-1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded.   Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme., (© 2023. The Author(s).)

Introduction: There is a high prevalence of mental health problems among university students. Better prediction and treatment access for this population is needed. In recent years, short-term dynamic factors, which can be assessed using experience sampling methods (ESM), have presented promising results for predicting mental health problems., Methods and Analysis: Undergraduate students from five public universities in Spain are recruited to participate in two web-based surveys (at baseline and at 12-month follow-up). A subgroup of baseline participants is recruited through quota sampling to participate in a 15-day ESM study. The baseline survey collects information regarding distal risk factors, while the ESM study collects short-term dynamic factors such as affect, company or environment. Risk factors will be identified at an individual and population level using logistic regressions and population attributable risk proportions, respectively. Machine learning techniques will be used to develop predictive models for mental health problems. Dynamic structural equation modelling and multilevel mixed-effects models will be considered to develop a series of explanatory models for the occurrence of mental health problems., Ethics and Dissemination: The project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and has been approved by the IRB Parc de Salut Mar (2020/9198/I) and corresponding IRBs of all participating universities. All respondents are given information regarding access mental health services within their university and region. Individuals with positive responses on suicide items receive a specific alert with indications for consulting with a health professional. Participants are asked to provide informed consent separately for the web-based surveys and for the ESM study. Dissemination of results will include peer-reviewed scientific articles and participation in scientific congresses, reports with recommendations for universities' mental health policy makers, as well as a well-balanced communication strategy to the general public., Study Registration: osf.io/p7csq., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives?, Setting: Western Europe and Australia., Participants: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents., Primary and Secondary Outcome Measures: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad., Results: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives., Conclusion: The immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs)., Methods: We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates using random-effects meta-analyses., Results: Approximately 24% of women were exposed to at least one EDC group, but exposure to most individual EDC groups was low (<5%). Maternal organic solvent exposure was associated with lower quantitative scores among children (-5.8 points, 95% confidence interval: -11.0, -0.5). Though statistically non-significant, exposures to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds, and miscellaneous chemicals were associated with poorer offspring performance for most or all cognitive domains., Conclusions: This study found limited evidence for a role of maternal occupational EDC exposures on child cognition. Further research is needed to better characterize exposures among pregnant workers., Impact: Using data from a prospective birth cohort, we help fill an important research gap regarding the potential consequences of work-related exposure to endocrine-disrupting chemicals (EDCs) among pregnant women on child neurodevelopment. We expand on existing literature-largely limited to pesticide and organic solvent exposures-by using a job-exposure matrix to estimate exposure to several EDC groups. We found limited evidence of an association between maternal occupational EDC exposure and children's overall cognition. We did observe specific associations between exposure to organic solvents and lower quantitative reasoning scores., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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.

Objective: Describe 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)., Method: Families 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., Results: For 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., Conclusion: There 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., (Copyright © 2019 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Quality of the family context has an important role in the physical and mental health of children; that is why it is important to have reliable and updated tools. This study aims to design and validate a new tool, the Haezi Etxadi Family Assessment Scale 7-11 (HEFAS 7-11), to assess family context quality in middle childhood. A sample of two cohorts of 772 Spanish families with children aged between 7 and 11 (M = 9.39 years; SD = 1.57; 51.2% girls), participated in the study. Results showed good psychometric properties for the instrument and the confirmatory factor analysis showed a five individual subscales structure: 1. Promotion of Cognitive and Linguistic Development (α = 0.79); 2. Promotion of Socio Emotional Development (α = 0.83); 3. Organization of Physical Environment and Social Context (α = 0.73); 4. Parental Stress & Conflict (α = 0.75); and 5. Parental Profile Fostering Child Development (α = 0.80). The association between HEFAS 7-11 and Trial Making Test was also analyzed to determine the concurrent validity of the instrument. The new scale shows its potential in the fields of research, social and educational, to know those variables that need to be promoted under the approach of positive parenting from a public health perspective.

We assessed the association between the use of lower- and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4-5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400-999 (recommended dose), and ≥1000 μg/day. Child attentional function was assessed by Conners' Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 μg/day was associated with higher risk of omission errors-IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 μg/day and ≥1000 μg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 μg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 μg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4-5, particularly in boys.

Background: Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight., Methods: In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496., Findings: We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT 4 ]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT 4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p interaction =0·10). Each 1 SD increase in FT 4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second., Interpretation: Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT 4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy., Funding: Netherlands Organization for Scientific Research (grant 401.16.020)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 4-5 years old children (n = 1252) participant in the Spanish INMA Project. Total Hg was measured in cord blood and in hair samples taken at 4 years 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 0.98 µg/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.

Objective: Assessing the association between socioeconomic gradient and cognitive development among children of a Spanish birth cohort aged 5-6 years from a gender perspective., Method: Cognitive development was assessed on 525 children aged 5-6 years in the INMA-Valencia cohort, with the Global Cognitive Score (GCS) from McCarthy Scales of Children's Abilities. Information on social class, education level and employment was collected for both parents in addition to other sociodemographic factors, parental, family and child characteristics. The relationship between maternal and paternal socioeconomic gradient and cognitive development was assessed by linear regressions and comparing the variance explained by each indicator measured in the mother and father., Results: Maternal socioeconomic gradient indicators explained more variance on GCS than paternal. Maternal education and paternal social class had an important individual effect that stayed after adjusting by other parental, child and family determinants. In the multivariable analysis, maternal education, age and intelligence, paternal social class and the child's age and sex were significantly associated with cognitive development., Conclusions: Diverse socioeconomic gradient factors have an important influence on cognitive development, maternal education being the strongest determinant. Policies should be implemented to mitigate the negative effects of this gradient on child development., (Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age., Study Design: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates., Results: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria., Conclusions: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years., Methods: We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr)., Results: Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI -6.18 to -1.69) general cognitive scores lower than the reference (150-249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: -1.36; 95% CI -2.12 to -0.61; per one daily milk serving)., Conclusions: We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child's neurodevelopment at 4-5 years., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder., Objectives: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population., Methods: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PM(coarse)), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis., Results: A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score., Conclusions: Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies., Citation: Guxens M, Ghassabian A, Gong T, Garcia-Esteban R, Porta D, Giorgis-Allemand L, Almqvist C, Aranbarri A, Beelen R, Badaloni C, Cesaroni G, de Nazelle A, Estarlich M, Forastiere F, Forns J, Gehring U, Ibarluzea J, Jaddoe VW, Korek M, Lichtenstein P, Nieuwenhuijsen MJ, Rebagliato M, Slama R, Tiemeier H, Verhulst FC, Volk HE, Pershagen G, Brunekreef B, Sunyer J. 2016. Air pollution exposure during pregnancy and childhood autistic traits in four European population-based cohort studies: the ESCAPE Project. Environ Health Perspect 124:133-140; http://dx.doi.org/10.1289/ehp.1408483.

Background: A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries., Methods: Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts., Results: Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied., Conclusions: This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.

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.

Objectives: Scant evidence is available on effects of air pollution on longitudinally measured fetal biometry, and thus it remains unclear as to whether there are critical windows of exposure or specificity of effects. Our objective was to examine the association between exposure to nitrogen dioxide (NO2) during pregnancy and fetal and neonatal anthropometry in a cohort of Spanish women., Methods: Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses. Biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) were evaluated in each trimester by ultrasound. As neonatal outcomes, weight, length and head circumference were analysed. SD scores adjusted by gestational age, mother characteristics and fetus sex were calculated at 12, 20 and 32 weeks of gestation as well as at birth. The association between fetal growth and average exposure to NO2 in the relevant windows was investigated using regression models, adjusted for socio-demographic and lifestyle-related variables., Results: Exposure to NO2 was inversely associated with BPD, AC and EFW at week 32 and with growth in these parameters in weeks 20-32. BPD and FL were also affected earlier, at week 20. NO2 levels above the median (38 μg/m3) reduced size at week 32 by around 9% in all parameters except for FL (6%). The critical windows of exposure were in early pregnancy, before 20 weeks. Exposure in this period was also inversely associated with neonatal length and head circumference., Conclusions: Maternal exposure to NO2 is associated with impaired fetal growth from mid-gestation onwards.