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Background: Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD. Methods: POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models. Results: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (β = −0.28, 95% confidence interval [CI]: −0.51, −0.04) and PBDE-153 (β = −0.61, 95% CI: −1.11, −0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females. Conclusions: Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity. [ABSTRACT FROM AUTHOR]

Background and objectives: The vitamin D deficiency during pregnancy has been associated with adverse events during pregnancy and the postnatal child development. In this study we examined plasma levels of vitamin D [25(OH)D3] and factors associated with plasma deficiency and insufficiency in pregnant women in northern Spain. Methods: We analyzed data from 453 pregnant women participating in the INMA-Asturias cohort in which was determined 25(OH)D3 by high resolution liquid chromatography. Dietary intake of vitamin D was estimated through a food frequency validated questionnaire. We estimated the prevalence of deficiency [25(OH)D3 <20 ng / ml] and insufficiency [20 to 29.9 ng / ml] of vitamin I) and analyzed the distribution of 25(OH)D3 per month extraction and other factors. Results: The mean concentration of 25(OH)D3 was 27.7 ng/ml (range 6.4 to 69.5). 27.4% of pregnant women had deficient levels and 35.3% inssuficient. Levels of 25(OH)D3 were higher in the summer months (median 34.1 ng/ml). There was a higher percentage of deficiency in pregnant women with overweight/obesity (34.5%) and under 25 years (47.8%). The average daily intake of vitamin D was 5.48 mg / day (SI) 2.82 range 1.09 to 32.52). Intake during the months of October to May was associated with levels of 25(OH)D3. 8.6% reported taking supplements of vitamin I). Conclusions: We detected a high proportion of pregnant women with deficient or insufficient vitamin D levels, especially in the months of October to May, in pregnant women with overweight and obesity, and the youngest. [ABSTRACT FROM AUTHOR]

The health-related quality of life (HRQOL) of adolescents with end-stage renal disease (ESRD) is an important marker of disease burden. Our aims were to investigate HRQOL in a group of children and adolescents with ESRD and to compare them with the reference population norms. Ours was a cross-sectional study of 81 patients aged 10 years to 21 years with ESRD (68 with kidney transplants and 13 on dialysis) at five Spanish paediatric nephrology centres. HRQOL was investigated with the Spanish version of the child health and illness profile, adolescent edition (CHIP-AE). Clinical variables such as underlying diagnosis, number of rejection episodes, pre-emptive transplantation, anaemia and height were also analysed. No differences were found between patients with kidney transplants and their healthy peers in any domain or sub-domain of CHIP-AE. The group on dialysis scored lower than healthy controls and patients with transplants for satisfaction with health. Discomfort was higher in patients with transplants who had suffered one rejection episode. Physical discomfort was increased in anaemic patients with transplants. Short patients scored less in the satisfaction domain, with lower self-esteem and lower satisfaction with health. Adolescents with kidney transplants had better satisfaction with health than the group on dialysis, which matched the level of a healthy population. Further long-term prospective research is warranted. [ABSTRACT FROM AUTHOR]

Background: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children.Methods: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex.Results: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß = -0.065, 95% CI: -0.096, -0.035, second tertile; ß = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß = -0.029, 95% CI: -0.059, -0.000, second tertile; ß = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile).Conclusions: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females. [ABSTRACT FROM AUTHOR]

Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4–5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children's Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (β = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (β = 3.85; 95% CI = −0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child's health, including cognitive functions such as working memory. [ABSTRACT FROM AUTHOR]

Identifying cardiovascular-related measures that track from early childhood into later ages may help inform early prevention targets for cardiovascular disease. In this study, the tracking of triglycerides (TG), high-density cholesterol (HDL-c), atherogenic coefficient (AC), waist circumference to height ratio (WC/Height), mean arterial pressure (MAP), and homeostatic model assessment of insulin resistance (HOMA-IR) was examined in the INMA-Asturias cohort between 4 and 8 years of age. The analysis was conducted in 307 children who participated in the INMA-Asturias cohort (Spain) at 4 and at 8 years of age. Quantile regression models were used to evaluate tracking between measures at both ages, with each measure at 8 years as the dependent variable and the rank transformation of the same measure at 4 years as the independent variable. We found a positive association between HDL-c rank at 4 years and higher quantiles of the HDL-c distribution at 8 years, with an increase of 2.93 mg/dL (95% CI: 1.98, 3.87) per decile in the 0.9 quantile. A positive association was also found for WC/Height, with an increase of 0.008 (95% CI: 0.004, 0.012) per decile in the 0.9 quantile. We observed that tracking for AC increased in the higher quantiles of the distribution at 8 years, with an increase of 0.11 (95% CI: 0.09, 0.14) in the 0.6 quantile compared to an effect of 0.15 (95% CI: 0.09, 0.21) in the 0.9 quantile. Conclusions: Adult markers of dyslipidemia and central obesity tracked between ages 4 and 8 years. For AC, tracking increased in the higher quantiles of the distribution. What is Known: • Atherosclerosis begins in early life, so preventive efforts that start in childhood may delay progression to clinical disease. Determine what cardiovascular risk factors track into time since childhood bring the opportunity to identified those subjects at risk for later cardiovascular disease. • The study of risk factors in health populations and, particularly in children, copes with not clear and/or controversial thresholds definition. This makes it challenging to study tracking in pediatric ages. What is New: • Quantile regression is a useful tool for assessing the tracking of risk factors for which there are no clinically meaningful thresholds. The increasing trend observed in the tracking of dyslipidemia suggests the possible difficulty that children with abnormal values at 4 years of age might have in normalizing them in future years. • The findings of this article may help to determine which cardiovascular-related measures could be screened and followed-up in children. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate whether there are subgroups of children with different clusters of cardiovascular disease (CVD) risk factors at 4 and 8 years of age, and their patterns of change between these two time points. Methods: The analysis was conducted in 332 children who participated in the INMA-Asturias cohort (Spain) at 4 and at 8 years of age. The CVD risk factors were central obesity, dyslipidaemia, hyperglycaemia, and hypertension. Latent transition analysis was used to identify the different clusters and their probabilities of change. Results: At 4 years, three subgroups were identified: no disorders (prevalence of 55.9%); some disorders (21.2%), and central obesity (22.9%). Three distinct subgroups were identified at 8 years: no disorders (59.8%); hypertension (17.9%), and central obesity (22.3%). Central obesity at 4 years tends to appear simultaneously with dyslipidaemia, while at 8 years it tends to appear simultaneously with dyslipidaemia and/or hypertension. Children aged 4 years with no disorders had a 93.7% probability of remaining in the same status at 8 years of age. Children aged 4 who had some disorders had a 67.7% of probability of having only hypertension and a 32.3% of probability of having central obesity. Children aged 4 in the central obesity subgroup had a 32.4% of probability of having no disorders at 8 years of age, while 67.6% still had central obesity. Conclusions: These exploratory findings suggest that children who do not present any disorder at 4 years of age tend to remain in that state at 8 years of age. And also that central obesity may play a major role in the development of other disorders, as the number of disorders with which it concomitantly occurs increases between the ages of 4 and 8 years. [ABSTRACT FROM AUTHOR]

During pregnancy, women are commonly exposed to several endocrine-disrupting chemicals, including persistent organic pollutants (POPs). These compounds can transfer to the fetus through the placenta. Prenatal POP exposure is related to altered fetal genital and reproductive tract development. However, the relationship between exposure to POP mixtures and anogenital distance (AGD) is poorly investigated. This study investigated the association between prenatal exposure to POP mixtures and AGD in 8-year-old children. Data were collected from the INMA-Asturias cohort. Maternal serum POP concentrations were measured during the first trimester of pregnancy. Anoscrotal distance (AGD AS) and anopenile distance (AGD AP) in males and anofourchetal distance (AGD AF) and anoclitoral distance (AGD AC) in females were recorded in 362 8-years-olds. Conventional linear regression, and the novel weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) models were applied to assess the relationships between AGD and POPs exposure stratified by sex. Among males, in the linear regression, b-hexachlorocyclohexane, PCB138, PCB153, and PCB180 were inversely associated with the anogenital index (AGI) AS (−0.06 mm/kg (95% confidence interval [CI]: –0.11, −0.02), −0.07 mm/kg (95% CI: –0.14, −0.01), −0.07 mm/kg (95% CI: –0.13, −0.01), and −0.08 mm/kg (95% CI: –0.14, −0.02), respectively). Among females, polybrominated diphenyl ether (PBDE)47 and PBDE154 were positively associated with increased AGI AF (0.02 mm/kg (95% CI: 0.00, 0.03) and 0.09 mm/kg (95% CI: 0.01, 0.17), respectively). BKMR confirmed these associations. WQSR found a negative combined effect of the POP mixture on AGD, and PCB138, PCB153, and PCB180 (weighted 0.18, 0.13, and 0.09, respectively) were identified as the most impacting chemicals. In females, WQSR found a positive combined effect and determined PBDE47 (weighted 0.35) as the most impacting. Maternal exposure to a POP mixture was negatively associated with AGD in male children and positively associated with AGD in female children, thus providing evidence of the adverse effects of POPs on genital development. • The joint effect of 18 POPs exposure on AGD was assessed through linear regression, WQSR and BKMR statistical approaches. • Co-exposure to POPs is related to a reduced AGD in male children and to an increase of AGD in female children at 8 years. • Exposure to POPs with anti-androgenic effects during pregnancy may hamper normal masculinization of the reproductive system. [ABSTRACT FROM AUTHOR]

The objective is to investigate the relation between cord blood mercury concentrations and child neurobehavioural functioning assessed longitudinally during childhood until pre-adolescence. The study involves mothers and their offspring engaged in the Spanish INMA birth cohort (n = 1147). Total mercury (THg) was determined in cord blood. Behavioural problems were assessed several times during childhood using the ADHD-DSM-IV at age 4, SDQ at ages 7 and 11, CPRS-R:S and the CBCL at ages 7, 9 and 11. Covariates were obtained through questionnaires during the whole period. Multivariate generalised negative binomial (MGNB) models or mixed-effects MGNB (for those tests with information at one or more time points, respectively) were used to investigate the relation between cord blood THg and the children's punctuations. Models were adjusted for prenatal fish intake. Effect modification by sex, prenatal and postnatal fish intake, prenatal fruit and vegetable intake, and maternal polychlorinated biphenyl concentrations (PCBs) was assessed by interaction terms. The geometric mean ± standard deviation of cord blood THg was 8.22 ± 2.19 μg/L. Despite adjusting for fish consumption, our results did not show any statistically significant relationship between prenatal Hg and the children's performance on behavioural tests conducted between the ages of 4 and 11. Upon assessing the impact of various factors, we observed no statistically significant interaction. Despite elevated prenatal THg exposure, no association was found with children's behavioural functioning assessed from early childhood to pre-adolescence. The nutrients in fish could offset the potential neurotoxic impact of Hg. Further birth cohort studies with longitudinal data are warranted. • The Spanish INMA cohort presented elevated prenatal exposure to Hg. • No relation was found between Hg and child behaviour from ages 4 to 11. • No influence of fish, fruit, and vegetable intake, sex or prenatal PCBs was observed. [ABSTRACT FROM AUTHOR]

Inorganic arsenic (i-As) has been related to wide-ranging health effects in children, leading to lifelong concerns. Proportionally, dietary i-As exposure dominates in regions with low arsenic drinking water. This study aims to investigate the relation between rice and seafood consumption and urinary arsenic species during childhood and to assess the proportion of urinary i-As metabolites. Urinary arsenic species concentration in 400 4-year-old children living in four geographical areas of Spain, in addition to repeated measures from 100 children at 7 years of age are included in this study. Rice and seafood products intake was collected from children's parents using a validated food frequency questionnaire (FFQ). At 4 years of age, children's urine i-As and monomethylarsonic acid (MMA) concentrations increased with rice product consumption ( p -value = 0.010 and 0.018, respectively), and urinary arsenobetaine (AsB) with seafood consumption ( p = 0.002). Four-year-old children had a higher consumption of both rice and seafood per body weight and a higher urinary %MMA ( p -value = 0.001) and lower % dimethylarsinic acid (DMA) ( p -value = 0.017). This study suggests increased dietary i-As exposure related to rice product consumption among children living in Spain, and the younger ones may be especially vulnerable to the health impacts of this exposure also considering that they might have a lower i-As methylation capacity than older children. In contrast, seafood consumption did not appear to influence the presence of potentially toxic arsenic species in this population of children. [ABSTRACT FROM AUTHOR]

Background Results regarding the association between mercury exposure and anthropometry at birth, gestational length and placental weight are inconsistent, as is the role of seafood intake in these associations. Objective We assessed whether prenatal mercury exposure is associated with anthropometry at birth, placental weight and gestational length in a population with a relatively high exposure to mercury from seafood consumption. Methods Total mercury (T–Hg) was determined in cord blood from 1869 newborns with birth outcome measures, within the Spanish multicenter INMA cohort from 2004 to 2008. We adjusted cohort specific linear and Cox regression models to evaluate the association between T–Hg and birth anthropometry (weight, length, and head circumference), placental weight and gestational length. Non-spontaneous labor was taken to be censoring in the survival analysis. Final estimates were obtained using meta-analysis. Results Geometric mean T–Hg was 8.2 μg/L. A doubling of T–Hg was associated with a 7.7 g decrease in placental weight (95% CI: −13.6, −1.8) and marginally with head circumference (beta: −0.052 cm, 95% CI: −0.109, 0.005). T–Hg was also inversely related to weight and length, although with weaker estimates. Mercury exposure was not associated with the length of gestation. The inverse relation between T–Hg and growth was enhanced when the intake of different seafood groups was adjusted for in the models. Conclusions Prenatal mercury exposure may be associated with reduced placental and fetal growth. Confounding by fish intake should be considered when assessing these relationships. [ABSTRACT FROM AUTHOR]

Focal dermal hypoplasia (FDH) is a rare multisystem disorder characterized by abnormalities in tissues derived from the meso-ectoderm, mainly affecting the skin, eyes, teeth and skeleton. We present the case of a young girl with FDH due to de novo mutation c.1061T>C (p.Leu354Pro) in the PORCN gene, responsible for defects in bone, eyes, skeleton, heart, maxillary and anus/rectum malformation. At birth, an infectious etiology and cutaneous syndromes that produce similar skin lesions were ruled out. Clinical manifestations led to the diagnosis of FDH, subsequently confirmed by genetic studies during the neonatal period. Early diagnosis allows organizing a detailed and personalized follow-up, which makes interventions more effective. This has contributed to satisfactory development to date in our patient. These patients present a host of possible complications requiring the coordinated effort of a multidisciplinary medical team from the start, all coordinated by a pediatrician. [ABSTRACT FROM AUTHOR]

Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4–5 years of age. We used urine metal concentrations as biomarkers of exposure in 328 children enrolled in the Spanish INMA-Asturias cohort. Anthropometric measurements (arm, head, and waist circumferences, standing height, and body mass index) and parental sociodemographic variables were collected through face-to-face interviews by trained study staff. Linear regressions were used to estimate the independent effects and were adjusted for each metal in the mixture. We applied Bayesian kernel machine regression to examine non-linear associations and potential interactions. In linear regression, urinary levels of cadmium were associated with reduced arm circumference (β adjusted = −0.44, 95% confidence interval [CI]: −0.73, −0.15), waist circumference (β adjusted = −1.29, 95% CI: −2.10, −0.48), and standing height (β adjusted = −1.09, 95% CI: −1.82, −0.35). Lead and cobalt concentrations were associated with reduced standing height (β adjusted = −0.64, 95% CI: −1.20, −0.07) and smaller head circumference (β adjusted = −0.29, 95% CI: −0.49, −0.09), respectively. However, molybdenum was positively associated with head circumference (β adjusted = 0.22, 95% CI: 0.01, 0.43). BKMR analyses showed strong linear negative associations of cadmium with arm and head circumference and standing height. BKMR analyses also found lead and cobalt in the metal mixture were related to reduce standing height and head circumference, and consistently found molybdenum was related to increased head circumference. Our findings suggest that exposure to metal mixtures impacts growth indicators in children. • Co-exposure to metals was related to childhood anthropometry at 4 years of age. • Cd and Pb may affect children's anthropometry differently depending on levels of the other metals. • Large head circumference is shown to be related with higher levels of Mo. • 4-year-old children seem to have smaller head circumference when the levels of Co are low. • High Cd exposure was associated with a decrease in children's growth measures. [ABSTRACT FROM AUTHOR]

Presents a survey of informed consent for registration of congenital anomalies in Europe. Description of the survey's participants; Methods and results of the survey; Statistics related to the survey; Reports that the primary concern of most patients is not the use of their data for research but inappropriate access to medical data.