0000000000254798
AUTHOR
Loreto Santa-marina
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions…
Association between trans fatty acid intake and overweight including obesity in 4 to 5-year-old children from the INMA study
Background: Trans fatty acid (TFA) intake has been positively associated with obesity in adults, although the evidence in children is scarce. There is growing evidence that TFA of industrial or natural origin may have different effects. Objectives: We aimed to explore the association between total, industrial, and natural TFA intake and overweight including obesity in 4 to 5-year-old Spanish children. Methods: We cross-sectionally analyzed data of 1744 children aged 4 to 5 from the INMA study, a prospective mother-child cohort study in Spain. We estimated the intake of total, industrial, and natural TFA in grams per day (g/day) using a validated food frequency questionnaire and expressed it…
Factors associated with second-hand smoke exposure in non-smoking pregnant women in Spain: self-reported exposure and urinary cotinine levels.
The aim of this study was to evaluate the main sources of and sociodemographic factors associated with second-hand smoke (SHS) exposure, assessed both by questionnaire and by urinary cotinine (UC) levels, in non-smoking pregnant women. We conducted a cross-sectional study in pregnant women from 4 different regions in Spain. A total of 1783 non-smoking pregnant women completed a questionnaire about their previous smoking habit and SHS exposure in their 3rd trimester of pregnancy and provided a urine sample for measuring UC levels. We used logistic regression models to assess the relationship between several sociodemographic variables and some potential sources of SHS exposure. In addition, w…
Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis
BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of e…
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 indicato…
Prenatal exposure to perfluoroalkyl substances and cardiometabolic risk in children from the spanish INMA birth cohort study
BACKGROUND: Perfluoroalkyl substances (PFAS) may affect body mass index (BMI) and other components of cardiometabolic (CM) risk during childhood, hut evidence is scarce and inconsistent. OBJECTIVES: We estimated associations between prenatal PFAS exposures and outcomes relevant to cardiometabolic risk, including a composite CM risk score. METHODS: We measured perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in maternal plasma (first trimester). We assessed weight gain from birth until 6 mo. At 4 and 7 y, we calculated the age- and sex-specific z-scores for BMI, waist circumference (WC), and blood pres…
Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder: An Individual-Participant Meta-Analysis
Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation…
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 d…
Prenatal exposure to fluoride and neuropsychological development in early childhood: 1-to 4 years old children
[EN]BACKGROUND: Cross-sectional and prospective studies have provided evidence of the neurotoxic effect of early exposure to fluoride (F) in pregnancy. It has been negatively associated with cognitive development during childhood, with most research conducted in areas with high F levels in community drinking water (CDW). METHOD: Data from 316 to 248 mother-child pairs from the Infancia y Medio Ambiente (Childhood and Environment, INMA) birth cohort project with maternal urinary F level adjusted for creatinine (MUFcr) measurements in the first and third trimesters of pregnancy. Children's cognitive domains and intelligence indexes were evaluated using the Bayley Scales (age of 1) and the McC…
Inorganic arsenic exposure and neuropsychological development of children of 4-5 years of age living in Spain
This study was funded by grants from Spanish Institute of Health Carlos III-Ministry of Economy and Competitiveness (INMA Network G03/176, CB06/02/0041, and FIS-FEDER: PI03/1615, PI04/1436, PI08/1151, PI04/2018, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI09/02647, PS09/00090, PI09/02311, MS11/0178, PI13/1944, PI13/2032, PI14/00891, PI16/1288, and PI17/00663). Miguel Servet-FEDER: MSII16/ 00051, CP14/00108 & PI16/00261 (Co-funded by European Regional Development Fund “A way to make Europe”), FEDER funds, MS13/00054. Generalitat de Catalunya-CIRIT 1999SGR 00241, JCI2011–09771–MICINN, Generalitat Valenciana (Conselleria de Sanitat048/2010 and 060/…
Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts
BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. OBJECTIVE: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. METHODS: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We u…
Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors
AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…
Prenatal exposure to perfluoroalkyl substances and birth outcomes in a Spanish birth cohort
BACKGROUND: Prenatal perfluorooctanoate (PFOA) exposure has been associated with reduced birth weight but maternal glomerular filtration rate (GFR) may attenuate this association. Further, this association remains unclear for other perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA). We estimated associations between prenatal PFAS exposure and birth outcomes, and the influence of GFR, in a Spanish birth cohort. METHODS: We measured PFHxS, PFOS, PFOA, and PFNA in 1st-trimester maternal plasma (years: 2003-2008) in 1202 mother-child pairs. Continuous birth outcomes included standardized weight, length, he…
Drinking water disinfection by-products during pregnancy and child neuropsychological development in the INMA Spanish cohort study.
Background: Disinfection by-products (DBPs) constitute a complex mixture of prevalent chemicals in drinking water and there is evidence of neurotoxicity for some of them. Objectives: We evaluated the association between estimates of DBP exposure during pregnancy and child neuropsychological outcomes at 1 and 4–5 years of age. Methods: We conducted a population-based mother-child cohort study in Spain with recruitment at first trimester of gestation (INMA Project, 2003–2008). Neuropsychological development was measured at 1 year of age using the Bayley Scales of Infant Development and at 4–5 years with the McCarthy Scales of Children's Abilities. Modeled tap water concentrations of trihalome…
The association between passive and active tobacco smoke exposure and child weight status among Spanish children
This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-97/1102, FIS07/0252,FIS-PS09/00362, 97/0588, 00/0021-2, PI061756, PS0901958, PI14/00677 incl. FEDER funds, FIS-PS09/00090, PI041436, FIS-PI042018, FIS-PI06/0867,PI081151 incl. FEDER funds, FIS-PI09/02311, and FIS-PI13/02187 and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/0178, 11/02591, 11/02038, PI12/01890 incl. FEDER funds, 13/1944, 13/2032, FIS-PI13/02429, 14/0891, 14/1687, and CP13/00054 incl. FEDER funds), Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds), CIBERES…
The Association of Mediterranean Diet during Pregnancy with Longitudinal Body Mass Index Trajectories and Cardiometabolic Risk in Early Childhood.
Objective To evaluate the associations between maternal adherence to the Mediterranean diet during pregnancy and their offspring's longitudinal body mass index (BMI) trajectories and cardiometabolic risk in early childhood. Study design We included mother-child pairs from the Infancia y Medio Ambiente (INMA) longitudinal cohort study in Spain. We measured dietary intake during pregnancy using a validated food frequency questionnaire and calculated the relative Mediterranean diet score (rMED). We estimated offspring's BMI z score trajectories from birth to age 4 years using latent class growth analyses (n = 2195 mother-child pairs). We measured blood pressure, waist circumference, and cardio…
Variability of perfluoroalkyl substance concentrations in pregnant women by socio-demographic and dietary factors in a Spanish birth cohort
Background: Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; but maternal determinants of PFAS exposure are unclear. We evaluated the socio-demographic and dietary factors of prenatal PFAS concentrations in a Spanish birth cohort. Methods: We analyzed perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 1216 plasma samples collected during the 1ST trimester of pregnancy (2003–2008). We used multivariable linear regressions to assess the geometric mean (GM) ratios of PFAS concentrations by socio-demographic and dietary factors. We used analysis of variance (ANOVA) to asse…
Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study
10 p. Objectives: To estimate the prevalence and factors associated with smoking and misclassification in pregnant women from INMA (INfancia y Medio Ambiente, Environment and Childhood) project, Spain, and to assess the optimal cut-offs for urinary cotinine (UC) that best distinguish daily and occasional smokers with varying levels of second-hand smoke (SHS) exposure.-- Design: We used logistic regression models to study the relationship between sociodemographic variables and self-reported smoking and misclassification (self-reported non-smokers with UC >50 ng/ml). Receiver operating characteristic (ROC) curves were used to calculate the optimal cut-off point for discriminating smokers. The…
Urban environment and cognitive and motor function in children from four European birth cohorts
[EN]Background: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-e…
Second-hand smoke exposure in 4-year-old children in Spain: Sources, associated factors and urinary cotinine
Introduction Second-hand smoke exposure (SHS) in children remains as a major pollution problem, with important consequences for children's health. This study aimed to identify the sources of exposure to SHS among 4-year-old children, comparing self-reports to a urinary biomarker of exposure, and characterize the most important variables related to SHS exposure in this population. Methods 4-year-old children's exposure to SHS was assessed by a parental-reported questionnaire and by urinary cotinine (UC) measurements in 1757 participants from 4 different areas of the Spanish INMA (INfancia y Medio Ambiente – Environment and Childhood) Project. The questionnaire about SHS included information …
Serum metal levels in a population of Spanish pregnant women
Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. Method: Cross-sectional study with 1279 participants from the INMA cohorts. Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p = 0.026), for cop-per with excess body weight (p 71 g/day) (p = 0.014) and having been born in Spain (p = 0.001). Further, lower iron levels were associated with being overweight (p = 0.021) or obese (p <…
Association between exposure to organochlorine compounds and maternal thyroid status: Role of the iodothyronine deiodinase 1 gene.
Introduction: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action. Aim: To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes. Methods: The study population (n = 1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003–2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4´-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (T…
Maternal sleep duration and neonate birth weight: A population-based cohort study.
Objective Sleep duration is an important health indicator. Our aim was to investigate the association between maternal sleep duration and infant birthweight. Methods The study included 2,536 mother-infant pairs of a Spanish birth cohort (2004-2006, INMA project). The exposures were questionnaire-based measures of sleep duration before and during pregnancy. The primary outcome was infant birthweight score (g) standardized to 40 weeks of gestation. Results In women sleeping less than 7 hours per day before pregnancy, each additional hour of sleep increased birthweight score by 44.7 g (p = 0.049) in the minimally-adjusted model, although findings were not statistically significant after consid…
Early childhood growth is associated with lung function at 7 years: a prospective population-based study
Previous studies have related early postnatal growth with later lung function but their interpretation is limited by the methods used to assess a child's growth. We aimed to assess the association of early childhood growth, measured by body mass index (BMI) trajectories up to 4 years, with lung function at 7 years.We included 1257 children from the Spanish Infancia y Medio Ambiente population-based birth cohort. Early childhood growth was classified into five categories based on BMI trajectories up to 4 years previously identified using latent class growth analysis. These trajectories differed in birth size ("lower", "average", "higher") and in BMI gain velocity ("slower", "accelerated"). W…
Prenatal ambient air pollution exposure, infant growth and placental mitochondrial DNA content in the INMA birth cohort
Background: The association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association. Objective: In a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO2) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association. Finally, the mediation role of placental mitochondrial DNA content in this association was assessed. Methods: In 336 INMA children, relative placental mtDNA content was measured. L…
Correction: Santa-Marina et al. Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA-INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study. Int. J. Environ. Res. Public Health 2020, 17, 7704
Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children's ADHD-like symptoms at ages 4-5 years were assessed using the ADHD Rating Scale-IV. The count model of the zero-inflated Poisson regression model showed a significant inverse association between ferritin (continuous variable) and inattention, β = -0.19 …
Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy
BACKGROUND: We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. METHODS: DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We ex…
Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta
BACKGROUND: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes…
Riesgo de pobreza infantil y exclusión social en dos regiones españolas: determinantes sociales y familiares
espanolObjetivo Describir el riesgo de pobreza y exclusion social en ninos/as de 8-11 anos de Gipuzkoa y Valencia (Espana), mediante los indicadores AROPE (At Risk Of Poverty or Social Exclusion), y evaluar sus factores asociados en el Proyecto INMA (Infancia y Medio Ambiente). Metodo Familias de Gipuzkoa y Valencia (394 y 382, respectivamente) completaron un cuestionario en 2015-2016. Se estimaron la baja intensidad de trabajo (BIT), el riesgo de pobreza (RP) y la privacion material (PM). AROPE consistio en cumplir cualquiera de estos subindicadores. Se consideraron caracteristicas sociodemograficas, familiares y parentales. Se usaron diagramas de Venn, los test de Ji-cuadrado y Fisher en …
Maternal Ferritin Levels during Pregnancy and ADHD Symptoms in 4-Year-Old Children: Results from the INMA–INfancia y Medio Ambiente (Environment and Childhood) Prospective Birth Cohort Study
Ferritin status during prenatal brain development may influence the risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. We investigated the association of maternal ferritin in pregnancy and ADHD-like symptoms in offspring. A total of 1095 mother-child pairs from three birth cohorts of the INMA Project (Spain) were studied. Maternal plasma ferritin in pregnancy was measured at 11.57 weeks of gestation. Children&prime
Prenatal exposure to cooking gas and respiratory health in infants is modified by tobacco smoke exposure and diet in the INMA birth cohort study
Background: Studies that have evaluated the association between exposure to gas appliances emissions at home with respiratory health in children obtained heterogeneous and limited results. The aim of this study is to analyze the association between the use of gas cooking at home during pregnancy and respiratory problems in children during their first year of life. Methods: In the years 2003 through 2008 pregnant women were enrolled in 4 Spanish areas and visited in different age-points following a common protocol. Outcomes studied (from a questionnaire) were any episode of lower respiratory tract infection (LRTI), wheezing, persistent cough, chestiness and otitis. The association between ex…
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 iod…