Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort.
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ABSTRACT:
SUBMITTER: Garcia-Villarino M
PROVIDER: S-EPMC8124891 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort.
García-Villarino Miguel M Fernández-Iglesias Rocío R Riaño-Galán Isolina I Rodríguez-Dehli Cristina C Babarro Izaro I Fernández-Somoano Ana A Tardón Adonina A
International journal of environmental research and public health 20210429 9
Smoking by women is associated with adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, low birth weight, infertility, and prolonged time to pregnancy. Anogenital distance (AGD) is a sensitive biomarker of prenatal androgen and antiandrogen exposure. We investigated the effect of smoking and passive smoke exposure during pregnancy on anogenital distance in offspring at 4 years in the INMA-Asturias cohort (Spain). Women were interviewed during pregnancy to collect informati ...[more]
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Project description:BackgroundExposure 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.MethodsWe 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.ResultsIn linear regression, urinary levels of cadmium were associated with reduced arm circumference (βadjusted = -0.44, 95% confidence interval [CI]: -0.73, -0.15), waist circumference (βadjusted = -1.29, 95% CI: -2.10, -0.48), and standing height (βadjusted = -1.09, 95% CI: -1.82, -0.35). Lead and cobalt concentrations were associated with reduced standing height (βadjusted = -0.64, 95% CI: -1.20, -0.07) and smaller head circumference (βadjusted = -0.29, 95% CI: -0.49, -0.09), respectively. However, molybdenum was positively associated with head circumference (βadjusted = 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.ConclusionOur findings suggest that exposure to metal mixtures impacts growth indicators in children.
| S-EPMC8671344 | biostudies-literature
Project description:Considerable attention has been paid to reproductive toxicity of fine particulate matter (PM2.5). However, the relationship between prenatal PM2.5 exposure and anogenital distance (AGD) has not been well studied. We aim to investigate the potential effects of prenatal exposure to PM2.5 on newborn AGD. Prenatal PM2.5 exposure of 2332 participates in Shanghai (2013-2016) was estimated using high-performance machine learning models. Anoscrotal distance (AGDas) in male infants and anofourchette distance (AGDaf) in female infants were measured by well-trained examiners within 3 days after birth. We applied multiple linear regression models and multiple informant models to estimate the association between prenatal PM2.5 exposure and AGD. Multiple linear regression models showed that a 10 μg/m3 increase in PM2.5 exposure during full pregnancy, the second and third trimesters was inversely associated with AGDas (adjusted beta = - 1.76, 95% CI: - 2.21, - 1.31; - 0.73, 95% CI: - 1.06, - 0.40; and - 0.52; 95% CI: - 0.87, - 0.18, respectively) in males. A 10 μg/m3 increase in PM2.5 exposure during the full pregnancy, the first, second, and third trimesters was inversely associated with AGDaf (adjusted beta = - 4.55; 95% CI: - 5.18, - 3.92; - 0.78; 95% CI: - 1.10, - 0.46; - 1.11; 95% CI: - 1.46, - 0.77; - 1.45; 95% CI: - 1.78, - 1.12, respectively) in females after adjusting for potential confounders. Multiple informant models showed consistent but slightly attenuated associations. Our study observed a significant association between gestational PM2.5 exposure during pregnancy and shortened AGD in newborns, and provided new evidence on potential reproductive toxicity of prenatal PM2.5 exposure.
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Project description: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.
| S-EPMC10570156 | biostudies-literature
Project description:Study questionWhat is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW?Summary answerIntrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age.What is already knownThe increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism.Study design, size, durationProspective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire.Participants/materials, setting, methodMothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants.Main results and the role of chanceParacetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent.Limitations, reasons for cautionConfounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error.Wider implications of the findingsOur observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development.Study funding/competing interestsThis work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.
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Project description: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 exposure to gas cooking at home and respiratory outcomes was assessed using logistic regression and adjusting by confounding variables. Some potential effect modifiers (i.e. smoking, fruit and vegetables consumption) were examined. RESULTS: Among the 2003 children included in the study, a total of 731 (36.6%) had a LRTI episode, 693 (34.6%) experienced wheezing, 302 (15.5%) a persistent cough, 939 (47.4%) chestiness and 620 (31.2%) had an episode of otitis during their first year of life. Gas cookers were present in 45.5% of homes. Exposure to gas cooking in homes was not associated with respiratory outcomes Odds Ratios (OR) were close to 1 and not statistically significant. However, a positive association was found for otitis among infants whose mothers reported low intakes of fruit and vegetables during pregnancy [OR (95% CI) = 1.38 (1.01-1.9)] and also wheezing and chestiness were associated with gas cookers among those children whose mothers smoked during pregnancy. CONCLUSIONS: In susceptible subjects (those whose mothers smoke and consumed below average fruit and vegetables) we found an association between exposure to gas cooking during pregnancy and risk of wheezing, chestiness and otitis during the first year of life. But more research is needed regarding not only gas cooking and respiratory health but also the possible effect modifier role of diet and tobacco.
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Project description:AimThis 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.MethodsThe 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.ResultsAt 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.ConclusionsThese 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.
| S-EPMC10096221 | biostudies-literature
Project description:Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003-2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12-20 and 20-34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We conducted multivariate linear regression analyses between PBDE congeners and their sum (ΣPBDEs) and outcomes. We found statistically significant inverse associations between ΣPBDEs and AC, EFW, and BPD at weeks 20-34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20-34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size.
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Project description: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.The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study.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.A 10-?g/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.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.
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Project description:Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3-5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.
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Project description:Epigenetic alterations may mechanistically explain the developmental origins of adult disease, namely the hypothesis that many complex adult chronic diseases originate as a result of conditions encountered in utero. If true, epigenetically regulated imprinted genes, critical to normal growth and development, may partially mediate these outcomes. We determined the influence of in utero exposure to cigarette smoking on methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) and H19, and how this might relate to birth weight of infants born to 418 pregnant women. Smoking status was ascertained through self-report and medical records. Bisulfite pyrosequencing was used to measure methylation in umbilical cord blood DNAs. Least squares DNA methylation means at each DMR and birth weight were compared between infants of smokers and non-smokers, using generalized linear models. While there were no significant differences at the H19 DMR, infants born to smokers had higher methylation at the IGF2 DMR than those born to never smokers or those who quit during pregnancy (49.5%, SD=8.0 versus 46.6%, SD=5.6 and 45.8%, SD=6.3, respectively; p=0.0002). The smoking-related increase in methylation was most pronounced in male offspring (p for sex interaction=0.03), for whom approximately 20% of smoking-related low birth weight was mediated by DNA methylation at the IGF2 DMR. Our findings suggest that IGF2 DMR plasticity is an important mechanism by which in utero adjustments to environmental toxicants are conferred. Larger studies to replicate these findings are required.
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