Sociodemographic, lifestyle, and environmental determinants of vitamin D levels in pregnant women in Spain.

INTRODUCTION: Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the mother and the fetus. This study aims to evaluate the sociodemographic, lifestyle, and environmental determinants associated with circulating vitamin D levels in Spanish pregnant women. METHODS: We used data from the Spanish INMA ("Infancia y Medio Ambiente") prospective birth cohort study from the regions of Gipuzkoa, Sabadell, and Valencia. 25-hydroxyvitamin D3 (25(OH)D3) was measured in plasma collected in the first trimester of pregnancy. Information on 108 determinants was gathered: 13 sociodemographic, 48 lifestyle including diet, smoking and physical activity, and 47 environmental variables, representing the urban and the chemical exposome. Association of the determinants with maternal 25(OH)D3 levels was estimated in single- and multiple-exposure models. Machine learning techniques were used to predict 25(OH)D3 levels below sufficiency (30 ng/mL). RESULTS: The prevalence of < 30 ng/mL 25(OH)D3 levels was 51 %. In the single-exposure analysis, older age, higher socioeconomic status, taking vitamin D, B12 and other sup*plementation, and higher humidity, atmospheric pressure and UV rays were associated with higher levels of 25(OH)D3 (IQR increase of age: 1.2 [95 % CI: 0.6, 1.8] ng/mL 25(OH)D3). In the multiple-exposures model, most of these associations remained and others were revealed. Higher body mass index, PM2.5 and high deprivation area were associated with lower 25(OH)D3 levels (i.e., Quartile 4 of PM2.5 vs Q1: -3.6 [95 % CI: -5.6, -1.5] ng/mL of 25(OH)D3). History of allergy and asthma, being multiparous, intake of vegetable fat, vitamin B6, alcohol consumption and molybdenum were associated with higher levels. The machine learning classification model confirmed some of these associations. CONCLUSIONS: This comprehensive study shows that younger age, higher body mass index, higher deprived areas, higher air pollution and lower UV rays and humidity are associated with lower 25(OH)D3 levels.

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

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

Pre and postnatal exposure to mercury and respiratory health in preschool children from the Spanish INMA Birth Cohort Study.

Effects of mercury on maturing immune system have been reported, however the association with respiratory and allergy problems during infancy remains unclear. The aim of this study is to evaluate the association between pre and postnatal mercury exposure and respiratory and allergy problems among preschool children and to examine the role of potential modifying factors. Study subjects were children participant in Spanish Childhood and Environment Project (INMA, 2003-2008). We measured total mercury levels in cord blood (n = 1868) and hair at 4 years of age (n = 1347). Respiratory outcomes (wheezing, severe wheezing, chestiness, persistent cough, eczema and otitis) were obtained by questionnaires administered to parents. Associations were investigated by logistic regression adjusted for socio-demographic and lifestyle-related variables in each cohort and subsequent meta-analysis. We tested effect modification by factors related to individual susceptibility, diet and co-exposure with other pollutants. The geometric mean of cord blood and hair total mercury was 8.20 µg/L and 0.97 µg/g, respectively. No statistically significant association between pre or postnatal mercury exposure and respiratory and allergy outcomes was found. Notwithstanding, lower maternal intake of fruits and vegetables increased the risk of some respiratory outcomes due to the prenatal exposure to mercury (pint < 0.05). Moreover, an inverse association between prenatal mercury exposure and some respiratory outcomes was observed among children with higher maternal exposure to organocholorine compounds or smoking (pint < 0.05). Also, sex and postnatal smoking exposure modulated mercury postnatal effects on persistent cough (pint < 0.05). In conclusion, no association between pre and postnatal mercury exposure and respiratory and allergy problems among the whole population at study was found. However, diet and other toxicants could modulate this relation, especially during prenatal period. More research on this topic is warranted due to the limited evidence.

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

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.

Association of Lifestyle Factors and Neuropsychological Development of 4-Year-Old Children.

BACKGROUND: We aimed to assess how lifestyle factors such as diet, sleep, screen viewing, and physical activity, individually, as well as in a combined score, were associated with neuropsychological development in pre-school age children. METHODS: We conducted a cross-sectional study in 1650 children of 4 years of age, from the Environment and Childhood Project (INMA) population-based birth cohorts in four regions of Spain. Children were classified per a childhood healthy lifestyle score (CHLS) with a range of 0 to 4 that included eating in concordance with the Mediterranean diet (1 point); reaching recommended sleep time (1 point); watching a maximum recommended screen time (1 point); and being physically active (1 point). The McCarthy Scales of Children's Abilities (MSCA) were used to test neuropsychological development. Multi-adjusted linear regression models were created to assess the association with the lifestyle factors individually and as a combined score. RESULTS: CHLS was not associated with MSCA general cognitive score (1-point increment = -0.5, 95% CI: -1.2, 0.2). Analyzed by separate lifestyle factors, physical activity had a significant negative association with MSCA score and less TV/screen time had a negative association with MSCA score. CONCLUSION: In this cross-sectional study, a combined score of lifestyle factors is not related to neuropsychological development at pre-school age.

First-trimester maternal concentrations of polyfluoroalkyl substances and fetal growth throughout pregnancy.

BACKGROUND: Several studies have investigated the possible association between prenatal exposure to perfluoroalkyl substances (PFASs) and birth anthropometry. However, none has assessed fetal size longitudinally. We studied the possible association between PFASs and fetal biometry. METHODS: In 1230 mother-child pairs of three cohorts from the Spanish INMA-Project, we analyzed perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in first-trimester maternal plasma (collection: 2003-2008). We measured abdominal circumference (AC), femur length (FL), biparietal diameter (BPD), and estimated fetal weight (EFW) by ultrasounds at 12, 20, and 34 gestational weeks. We conducted multivariable linear regression analyses between log2-transformed (PFASs) and SD-scores of fetal parameters in each cohort and subsequent meta-analysis. We also assessed effect modification by sex and maternal smoking. RESULTS: PFHxS, PFOA, PFOS, and PFNA medians were: 0.58, 2.35, 6.05, and 0.65 ng/mL, respectively. There were no associations for the whole population in any trimester of pregnancy. However, we found an indication that maternal smoking modified the effect in different directions depending on the PFAS. Among smokers (31%), we found negative associations between both PFOA and PFNA and FL or EFW at week 20 (% change ranging between -6.8% and -5.7% per twofold PFAS increase) and positive associations between PFHxS or PFOS and BPD at week 34 (6.8% and 6.3%, respectively). CONCLUSIONS: Results did not suggest an overall association between prenatal PFASs and fetal growth. The results among smokers should be taken with caution and further studies are warranted to elucidate the possible role of smoking in this association.

Social Factors Associated with Non-initiation and Cessation of Predominant Breastfeeding in a Mother-Child Cohort in Spain.

Objective The aim of the study was to identify factors associated with non-initiation and cessation of predominant breastfeeding (PBF) in a mother-child cohort from Spain. Materials and Methods The analysis included 2195 mother-infant from birth to 14 months post- delivery recruited between 2004 and 2008. Maternal characteristics were collected during the pregnancy. Lactation data were obtained at 6 and 14 months after delivery. PBF was defined as intake of breast milk plus liquids like juices or water. The PBF cessation was calculated using the date that women started PBF and the date that she reported to start giving infant formula and/or food. The relationship between maternal variables and PBF initiation and cessation was modeled using logistic and Cox proportional hazards regression analysis. Results The prevalence of PBF at hospital discharge was 85.3, 53.4% at 3 months, 46.1% at 4 months and 7.2% at 6 month. Only two women continued PBF at 12 months and none at 14 months. The initiating of PBF was associated with higher levels of maternal education, being a first-time mother and worked in a non-manual occupation. Higher level of physical activity, not smoking and having a healthy BMI, were also positively associated with PBF initiation. PBF cessation was higher in young, obese women, who had had complications during the pregnancy, and who had lower levels of education and smoked. The employment status of women, in week 32 of pregnancy and also in month 14 post-delivery, determined likelihood of PBF cessation. Conclusions Healthier habits and education positively influenced PBF initiation and duration. Decrease in PBF duration rates in Spain can be interpreted in part as a consequence of women returning to work.

Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study.

BACKGROUND: Prenatal exposure to organophosphate pesticides (OPs) has been associated with impaired child development. Pesticide exposure determinants need to be studied in order to identify sources and pathways of pesticide exposure. The aim of this paper is to describe prenatal exposure to OPs and evaluate the associated factors in pregnant women. METHODS: The study population consisted of pregnant women (n = 573) who participated in the INMA birth cohort study in Valencia (Spain, 2003-2006). OP metabolites were analyzed in maternal urine at the 32nd week of gestation using a liquid chromatography-high resolution mass spectrometry method. The analysis included non-specific (diethyl phosphate [DEP], diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4-pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para-nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the sociodemographic, environmental, and dietary characteristics was obtained by questionnaire. The association between log-transformed OPs and covariates was analyzed using multivariable interval censored regression. RESULTS: The detection frequencies were low, DMTP and TCPY being the most frequently detected metabolites (53.8% and 39.1%, respectively). All the OP metabolites were positively associated with maternal intake of fruits and vegetables. Other maternal characteristics related to the OPs were body mass index (BMI) before pregnancy and smoking habit during pregnancy. Women with lower BMI and those who did not smoke presented higher OP concentrations. Moreover, mothers who had a yard or garden with plants at home or who lived in an urban area were also more exposed to OPs. CONCLUSIONS: The OP detection frequencies and the concentrations observed in our study population were low, compared with most of the previously published studies. Given the high vulnerability of the fetus to neurotoxicant exposure, further research on the determinants of the body burden of OPs during pregnancy would be necessary. The knowledge gained from such studies would enhance the effectiveness of public health control and future recommendations in order to reduce the risk to both the health of pregnant women and the health and development of their children.

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 examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach. RESULTS: Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) < 0.05]. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight. CONCLUSIONS: We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome.

Prevalencia de obesidad en escolares en dos comunidades rurales / 25 Rev. Cient. Esc. Univ. Cienc. Salud, Volumen 3 / Año 3 / No. 1: 25-29 Artículos Originales Prevalence of obesity in school children in two rural communities

El continuo incremento de la obesidad en niños constituye un importante problema de salud que requiere de la identificación precisa de su magnitud y tendencias. Objetivo: Establecer la prevalencia de obesidad en escolares del Centro Básico Ingeniero Luis Bográn (CBILB) y el Centro de Educación Básica Marco Aurelio Pinto (CEB-MAP) en el mes de agosto del año 2015. Pacientes y métodos: Se realizó un estudio descriptivo, de corte transversal, durante el mes de agosto del año 2015, en escolares de dos Centros Básicos simultáneamente, el Centro Básico Ingeniero Luis Bográn, ubicado en la comunidad de Gualjoco, Santa Bárbara y el Centro de Educación Básica Marco Aurelio Pinto, ubicado en la comunidad de El Coowle, San Manuel, Cortés. Mediante mues- treo probabilístico aleatorio estratificado se obtuvo 154 y 93 escolares respectivamente, los cuales fueron evaluados antropométricamente. Los datos se analizaron mediante PASSW Statistics 18. Resultados: Se encontró que la prevalencia de obesidad en CBILB fue de 12.3%, siendo más frecuente en mujeres (7.14%) y en edades entre 9-11 años (7.79%) y en el CEBMAP fue de (6%), siendo más frecuente en hombres (7%). Conclusiones: La prevalencia de obesidad en escolares es significativa y varía según sexo y edad...(AU)

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 about smoking habits at home by household members, and about exposure to SHS in other places including other homes, bars, restaurants or transportation. The association between quantified UC levels (>4ng/ml) and sociodemographic variables and the different sources of SHS exposure was examined using logistic regression. RESULTS: Based on parental reports, 21.6% of the children were exposed to SHS at home and 47.1% elsewhere; making a total 55.9% of the children exposed to SHS. In addition, 28.2% of the children whose parents reported being not regularly exposed to SHS had quantified UC values. Children from younger mothers (<34 vs. ≥39.4 y) had a higher odds of exposure to SHS [OR (95% CI): 2.28 (1.70-3.05) per year], as well as from families with a lower educational level [OR secondary: 2.12 (1.69-2.65); primary or less: 2.91 (2.19-3.88)]. The odds of quantifiable UC in children dropped after the smoking ban in public places [OR=0.59 (0.42-0.83)]. Regarding the sources of SHS exposure we observed that quantifiable UC odds was increased in children whose parents smoked at home in their presence [OR mother occasionally: 13.39 (7.03-25.50); mother often: 18.48 (8.40-40.66); father occasionally: 10.98 (6.52-18.49); father often: 11.50 (5.96-22.20)] or in children attending other confined places, mainly other houses where people smoked [OR: 2.23 (1.78-2.80)]. CONCLUSIONS: Children's SHS exposure is nowadays an unresolved major public health problem in Spain. After the ban of smoking in public places health care professionals should put more emphasis to the parents on the importance of controlling the exposure of their children in private spaces.

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, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. CONCLUSION: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.

Prenatal Exposure to NO2 and Ultrasound Measures of Fetal Growth in the Spanish INMA Cohort.

BACKGROUND: Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability. OBJECTIVE: The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study. METHODS: Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis. RESULTS: A 10-µg/m(3) increase in average exposure to NO2 during weeks 0-12 was associated with reduced growth at weeks 0-12 in AC (-2.1%; 95% CI: -3.7, -0.6) and EFW (-1.6%; 95% CI: -3.0, -0.3). The same exposure was inversely associated with reduced growth at weeks 20-34 in BPD (-2.6%; 95% CI: -3.9, -1.2), AC (-1.8%; 95% CI: -3.3, -0.2), and EFW (-2.1%; 95% CI: -3.7, -0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers. CONCLUSIONS: Maternal exposure to NO2 in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth.

Use of high doses of folic acid supplements in pregnant women in Spain: an INMA cohort study.

OBJECTIVES: We examined the use of low (<400 µg/day, including no use) and high folic acid supplement (FAS) dosages (≥1000 µg/day) among pregnant women in Spain, and explored factors associated with the use of these non-recommended dosages. DESIGN: Population-based cohort study. SETTING: Spain. PARTICIPANTS: We analysed data from 2332 pregnant women of the INMA study, a prospective mother-child cohort study in Spain. MAIN OUTCOME MEASURES: We assessed usual dietary folate and the use of FAS from preconception to the 3rd month (first period) and from the 4th to the 7th month (second period), using a validated food frequency questionnaire. We used multinomial logistic regression to estimate relative risk ratios (RRRs). RESULTS: Over a half of the women used low dosages of FAS in the first and second period while 29% and 17% took high dosages of FAS, respectively. In the first period, tobacco smoking (RRR=1.63), alcohol intake (RRR=1.40), multiparous (RRR=1.44), unplanned pregnancy (RRR=4.20) and previous spontaneous abortion (RRR=0.58, lower use of high FAS dosages among those with previous abortions) were significantly associated with low FAS dosages. Alcohol consumption (RRR=1.42), unplanned pregnancy (RRR=2.66) and previous spontaneous abortion (RRR=0.68) were associated with high dosage use. In the second period, only tobacco smoking was significantly associated with high FAS dosage use (RRR=0.67). CONCLUSIONS: A high proportion of pregnant women did not reach the recommended dosages of FAS in periconception and a considerable proportion also used FAS dosages ≥1000 µg/day. Action should be planned by the Health Care System and health professionals to improve the appropriate periconceptional use of FAS, taking into consideration the associated factors.

Time trends in serum organochlorine pesticides and polychlorinated biphenyls in the general population of Biscay, Spain.

Despite the measures adopted, levels of organochlorine compounds (OCs) are still being detected in the human body. This study aimed to explore factors related to changes in the concentrations of polychlorinated biphenyls (PCBs) and pesticide OCs in blood samples obtained from a general population cohort. Two cross-sectional samples were taken from 162 adults (2-75 years of age), with a gap of 2 years, from four areas in Biscay (Spain). More than 75 % had quantifiable levels of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene, and PCBs 138 153 and 180. During this time, significant changes were observed: PCB 180 and HCB levels increased, and PCB 138 and ß-HCH levels decreased. Regarding age, this study shows a decrease suggesting a cohort effect. The period was not related to the decrease of levels in all age intervals, but a statistically significant increase of PCBs in older people was found. High body mass index was associated with lower PCB 180 levels and greater HCH levels. Inversely, greater levels of HCB and ß-HCH were in those who had lost weight before the study. Levels of HCB and ß-HCH were also greater in women who had had children, although they were lower in those who breastfed. Levels of these same OCs were greater in fish consumers, whereas those of PCBs 138 and 153 were greater in those who consumed local produce; all of these trends were close to significance. Efforts should continue to decrease exposure to these pollutants and to assess their influence on general population.

In utero exposure to mixtures of xenoestrogens and child neuropsychological development.

BACKGROUND: To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. METHODS: Cumulative prenatal exposure to xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1-2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4-5 years of age. Interactions with sex were investigated. RESULTS: After adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1-2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found. CONCLUSIONS: Our results suggest that boys' early motor development might be more vulnerable to prenatal exposure to mixtures of xenoestrogens, but associations do not persist in preschool children.

Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta.

BACKGROUND: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. OBJECTIVES: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. METHODS: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. RESULTS: A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value<0.001), while no significant effects were found in girls (p-value=0.134). CONCLUSIONS: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.

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, we analysed the association of several sociodemographic variables and the SHS exposure according to UC levels, using Tobit regression analysis. More than half of women (55.5%) were exposed to SHS in their 3rd trimester of pregnancy. The following variables were associated with SHS exposure: having smoked previously, low educational level, and being primiparous. Data collection after the first law banning smoking in public places was associated with lower risk of SHS exposure in restaurants and at work. UC levels were higher among women exposed to more than one source. Having a partner who smoked at home was the source of SHS with the greatest impact on UC levels, followed by having a partner who smoked but not at home, other people smoking in the household, being exposed during leisure time, at work and at restaurants. The most important source of SHS exposure was exposure at home. Prevention of SHS exposure should be addressed not only with pregnant women but also with their families.

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.

Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study.

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 cut-offs were also calculated after stratification among non-smokers by the number of sources of SHS exposure. The cut-off points used to discriminate smoking status were the level of UC given by Youden's index and for 50 and 100 ng/ml for daily smokers, or 25 and 50 ng/ml for occasional smokers. PARTICIPANTS: At the third trimester of pregnancy, 2263 pregnant women of the INMA Project were interviewed between 2004 and 2008 and a urine sample was collected. RESULTS: Prevalence of self-reported smokers at the third trimester of pregnancy was 18.5%, and another 3.9% misreported their smoking status. Variables associated with self-reported smoking and misreporting were similar, including born in Europe, educational level and exposure to SHS. The optimal cut-off was 82 ng/ml (95% CI 42 to 133), sensitivity 95.2% and specificity 96.6%. The area under the ROC curve was 0.986 (95% CI 0.982 to 0.990). The cut-offs varied according to the SHS exposure level being 42 (95% CI 27 to 57), 82 (95% CI 46 to 136) and 106 ng/ml (95% CI 58 to 227) for not being SHS exposed, exposed to one, and to two or more sources of SHS, respectively. The optimal cut-off for discriminating occasional smokers from non-smokers was 27 ng/ml (95% CI 11 to 43). CONCLUSIONS: Prevalence of smoking during pregnancy in Spain remains high. UC is a reliable biomarker for classifying pregnant women according to their smoking status. However, cut-offs would differ based on baseline exposure to SHS.