Sabrina Llop

Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children

BACKGROUND Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects. OBJECTIVES To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project. METHODS One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols. RESULTS Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education. CONCLUSIONS Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class.

Air pollution exposure during pregnancy and reduced birth size: a prospective birth cohort study in Valencia, Spain

BackgroundMaternal exposure to air pollution has been related to fetal growth in a number of recent scientific studies. The objective of this study was to assess the association between exposure to air pollution during pregnancy and anthropometric measures at birth in a cohort in Valencia, Spain.MethodsSeven hundred and eighty-five pregnant women and their singleton newborns participated in the study. Exposure to ambient nitrogen dioxide (NO2) was estimated by means of land use regression. NO2 spatial estimations were adjusted to correspond to relevant pregnancy periods (whole pregnancy and trimesters) for each woman. Outcome variables were birth weight, length, and head circumference (HC), along with being small for gestational age (SGA). The association between exposure to residential outdoor NO2 and outcomes was assessed controlling for potential confounders and examining the shape of the relationship using generalized additive models (GAM).ResultsFor continuous anthropometric measures, GAM indicated a change in slope at NO2 concentrations of around 40 μg/m3. NO2 exposure >40 μg/m3 during the first trimester was associated with a change in birth length of -0.27 cm (95% CI: -0.51 to -0.03) and with a change in birth weight of -40.3 grams (-96.3 to 15.6); the same exposure throughout the whole pregnancy was associated with a change in birth HC of -0.17 cm (-0.34 to -0.003). The shape of the relation was seen to be roughly linear for the risk of being SGA. A 10 μg/m3 increase in NO2 during the second trimester was associated with being SGA-weight, odds ratio (OR): 1.37 (1.01-1.85). For SGA-length the estimate for the same comparison was OR: 1.42 (0.89-2.25).ConclusionsPrenatal exposure to traffic-related air pollution may reduce fetal growth. Findings from this study provide further evidence of the need for developing strategies to reduce air pollution in order to prevent risks to fetal health and development.

Preterm birth and exposure to air pollutants during pregnancy

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 NO(2) 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 (NO(2)) and benzene levels throughout the area. Individual exposure was assigned as the estimated outdoor levels at each womans 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 NO(2) 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 NO(2) and benzene have an increased risk of preterm birth. This risk was shown to be significant when women were exposed to NO(2) levels >46.2 μg/m(3) during the second and third trimesters as well as throughout the entire pregnancy and to benzene levels >2.7 μg/m(3) throughout the entire pregnancy. CONCLUSION These results suggest that maternal exposure to traffic-related air pollution is associated with preterm birth.

Circulating 25-Hydroxyvitamin D3 in Pregnancy and Infant Neuropsychological Development

OBJECTIVE: To investigate whether circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy is associated with neuropsychological development in infants. METHODS: The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5±2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11–23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D3 were calculated by using linear regression analysis. RESULTS: The median plasma value of 25(OH)D3 in pregnancy was 29.6 ng/mL (interquartile range, 21.8–37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D3 concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D3 concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63–4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36–4.28) in comparison with those of mothers with 25(OH)D3 concentrations <20 ng/mL. CONCLUSIONS: Higher circulating concentration of maternal 25(OH)D3 in pregnancy was associated with improved mental and psychomotor development in infants.

Residential exposure to outdoor air pollution during pregnancy and anthropometric measures at birth in a multicenter cohort in Spain.

Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.

Prenatal Exposure to Mercury and Infant Neurodevelopment in a Multicenter Cohort in Spain: Study of Potential Modifiers

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.

Gender differences in the neurotoxicity of metals in children

Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on potential neurodevelopment effects in children due to mercury exposure is available, but, a clear pattern regarding gender differences in neurotoxicity is not elucidated. There is also abundant available information on the gender-specific health effects of lead, and exposure to this metal seems to affect boys more than girls. Information regarding gender differences in susceptibility of manganese, cadmium, and arsenic is still too scarce to draw any definite conclusion. More research is highly warranted about this matter. Environmental epidemiological studies should be designed to quantify differential gender-based exposures and outcomes, and this may provide new insights into prevention strategies.

Polybromodiphenyl ethers in mothers and their newborns from a non-occupationally exposed population (Valencia, Spain)

Polybromodiphenyl ethers (PBDEs) were analyzed in blood serum of pregnant women and in cord blood serum of their newborns from a general population cohort (n = 174; Valencia, Spain). The most abundant PBDE congeners identified were BDE 47, BDE 99, BDE 153, BDE 154 and BDE 209. Their cord blood serum concentrations were about 45% of those in maternal serum but after lipid normalization about the same concentrations were observed in both types of samples. Thus, median of total PBDEs was 9.6 ng/g lipid in cord serum (range between not detected and 140 ng/g lipid) and 9.6 ng/g lipid in maternal serum (range between not detected and 120 ng/g lipid). The distributions of these compounds were dominated by BDE 47 in both cases. In cord blood serum the decreasing order of abundance was BDE 47>BDE 99>BDE 209>BDE 153>BDE 154. The congener composition in maternal serum followed a similar trend: BDE 47>BDE 153>BDE 154>BDE 209>BDE 99. The congener concentrations exhibited a higher degree of correlation in cord blood than in maternal serum. Use of the maternal determinants for categorization of the observed maternal and fetal PBDE concentrations only showed significant associations for the levels in umbilical cord. Neonates from rural areas exhibited statistically significantly lower concentrations than those from urban, semi-urban or metropolitan sites. Maternal serum also showed this difference but the higher dispersion of the concentrations in maternal serum did not afford its recognition with statistical significance. The lower qualitative and quantitative variability in the PBDE concentrations of cord blood serum than maternal serum suggest that the latter is reflecting PBDE contributions from a wider diversity of sources than the former whereas cord blood sera seem to represent the long term standing stock of these compounds accumulated in the maternal tissues.

Prenatal mercury exposure in a multicenter cohort study in Spain

BACKGROUND Mercury is a ubiquitous heavy metal that may negatively affect human health. It is desirable to investigate mercury exposure in vulnerable populations. OBJECTIVE To determine the concentrations of total mercury (T-Hg) in cord blood and to evaluate the role of maternal fish consumption in a Spanish mother and child cohort. METHODS A total of 1883 mother and child pairs from a population-based cohort were included between 2004 and 2008. T-Hg concentrations were measured in whole cord blood and maternal seafood consumption was ascertained by means of a food-frequency questionnaire. Linear regression was used in stratified analyses, while a joint model was adjusted using a mixed-effects linear model. RESULTS Maternal daily seafood consumption was 78g/d and the geometric mean for T-Hg was 8.2μg/L. Maternal fish intake during pregnancy, mothers age, country of origin, educational level, employment status and parity, as well as area of study and season of delivery, were associated with cord blood T-Hg levels. A doubling in consumption of large oily fish was associated with an increase of 11.4% (95%CI: 3.8 to 19.6%) in cord blood T-Hg levels, followed by an increase of 8.4% (95%CI: 5.7 to 11.2%) in the case of canned tuna and 8.3% (95%CI: 5.5 to 11.1%) in that of lean fish. CONCLUSION A high proportion of newborns had elevated concentrations of cord blood T-Hg according to the current US-EPA reference dose (5.8μg/L for methylmercury). Mercury concentrations were related to maternal fish consumption, with large oily fish being the main contributor.

Prenatal exposure to persistent organic pollutants and rapid weight gain and overweight in infancy

To examine the effects of prenatal exposure to persistent organic pollutants (POPs) on rapid growth in the first 6 months of life and overweight at 14 months of age.