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OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.
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Aldosterona , Peso ao Nascer , Pressão Sanguínea , Idade Gestacional , Saliva , Humanos , Feminino , Gravidez , México , Aldosterona/sangue , Adulto , Saliva/química , Pressão Sanguínea/fisiologia , Recém-Nascido , Modelos Lineares , Adulto Jovem , Estudos de CoortesRESUMO
Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited. Methods: Our study included 601 mother-child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: "higher" if a BLL was at least once above the median (HPb) and "lower" if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status. Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32-0.86) and postnatally (OR = 0.59, 95%CI = 0.36-0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44-0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08-0.86), BMI (OR = 0.33, 95%CI = 0.11-0.99), SBP (OR = 0.53, 95%CI = 0.32-0.85), and DBP (OR = 0.57, 95%CI = 0.34-0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00-1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91-0.99). Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.
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Increased exposure to maternal psychosocial stress during gestation and adverse neonatal environments has been linked to alterations in developmental programming and health consequences in offspring. A programmed low nephron endowment, among other altered pathways of susceptibility, likely increases the vulnerability to develop chronic kidney disease in later life. Our aim in this scoping review was to identify gaps in the literature by focusing on understanding the association between life-course exposure to psychosocial stress, and the risk of reduced kidney function. A systematic search in four databases (PubMed, ProQuest, Wed of Science, and Scopus) was performed, yielding 609 articles. Following abstract and full-text review, we identified 19 articles meeting our inclusion criteria, reporting associations between different psychosocial stressors and an increase in the prevalence of kidney disease or decline in kidney function, mainly in adulthood. There are a lack of studies that specifically evaluated the association between gestational exposure to psychosocial stress and measures of kidney function or disease in early life, despite the overall evidence consistent with the independent effects of prenatal stress on other perinatal and postnatal outcomes. Further research will establish epidemiological studies with clear and more comparable psychosocial stressors to solve this critical research gap.
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Pregnancy is characterized by high bone remodeling and might be a window of susceptibility to the toxic effects of metals on bone tissue. The aim of this study was to assess associations between metals in blood [lead (Pb), cadmium (Cd)and arsenic (As)] and bone remodeling during pregnancy. We studied pregnant woman from the PROGRESS Cohort (Programming Research in Obesity, Growth, and Environment and Social Stress). We measured concentrations of metals in blood and obtained measures of bone remodeling by quantitative ultrasound (QUS) at the radius in the second and third trimester of pregnancy. To account for chronic lead exposure, we measured lead in tibia and patella one-month postpartum with K-shell X-ray fluorescence. We assessed cross-sectional and longitudinal associations between multiple-metal concentrations and QUS z-scores using linear regression models and linear mixed models adjusted for potential confounders. Third trimester blood Cd concentrations were marginal associated with lower QUS z-scores [-0.16 (95% CI: -0.33, 0.007); P-Value = 0.06]. Mixed models showed that blood Cd was longitudinally and marginally associated with an average of -0.10 z-score (95% CI: -0.21, 0.002; P-Value = 0.06) over the course of pregnancy. Associations for Pb and As were all inverse however none reached significance. Additionally, bone Pb concentrations in patella, an index of cumulative exposure, were significantly associated with -0.06 z-score at radius (95% CI: -0.10, -0.01; P-Value = 0.03) during pregnancy. Pb and Cd blood levels are associated with lower QUS distal radius z-scores in pregnant women. Bone Pb concentrations in patella were negatively associated with z-score at radius showing the long-term effects of Pb on bone tissue. However, we cannot exclude the possibility of reverse causality for patella Pb and radius z-score associations. Our results support the importance of reducing women's metal exposure during pregnancy, as metals exposure during pregnancy may have consequences for bone strength later in life. The main finding of our study is the association between Cd blood levels and radius z-score during pregnancy. Bone lead in patella was also negatively associated with radius z-scores.
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Arsênio , Metais , Remodelação Óssea , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , GravidezRESUMO
Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16-64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease.
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Background: Lead is a neurotoxic metal potentially affecting the developing brain. Children are particularly susceptible since they can absorb between 50% and 100% of ingested lead. There is no safe level for lead, therefore preventing exposure is crucial. We previously reported a positive association between lead concentrations found in candy and concurrent blood lead levels in Mexican children. This first report garnered media and the general public's attention. Objective: To conduct a follow-up study to assess lead concentrations in candy brands that we previously reported with concentrations ≥0.1ppm the U.S. Food and Drug Administration's recommended maximum lead level in candy likely to be consumed frequently by small children. Methods: In 2018 we analyzed 50 additional candy samples. Lead concentrations were analyzed by an inductively coupled plasma mass spectrometer and lead content per candy unit was calculated. Findings: We found concentrations were typically low, with a marked decrease from prior levels (2008). Nevertheless two candy units had concentrations of 0.1 ppm of lead. Conclusions: Candy may have lead concentrations up to 0.1 ppm and 1.2 µg per unit. This is a concern because candies are exported and consumed in many countries worldwide potentially resulting in human exposure. Continued public health surveillance is needed to protect populations especially vulnerable to lead exposure, especially children.
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Doces/análise , Contaminação de Alimentos/análise , Intoxicação por Chumbo/prevenção & controle , Chumbo/análise , Política Pública , Contaminação de Alimentos/legislação & jurisprudência , Contaminação de Alimentos/prevenção & controle , Humanos , México , Espectrofotometria AtômicaRESUMO
BACKGROUND: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 µm in diameter (PM2.5) exposure and children's BP at ages 4-6 years. METHODS: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM2.5 exposure and systolic and diastolic BP (SBP and DBP), adjusting for child's age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM2.5 exposure. RESULTS: We found that PM2.5 exposure between weeks 11-32 of gestation (days 80-226) was significantly associated with children's increased SBP. Similarly, PM2.5 exposure between weeks 9-25 of gestation (days 63-176) was significantly associated with increased DBP. To place this into context, a constant 10 µg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4-6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. CONCLUSIONS: Second and third trimester PM2.5 exposure may increase children's BP in early life. Further work investigating PM2.5 exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.
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Poluentes Atmosféricos , Poluição do Ar , Pressão Sanguínea , Exposição Materna , Material Particulado , Efeitos Tardios da Exposição Pré-Natal , Adulto , Poluentes Atmosféricos/toxicidade , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental , Feminino , Humanos , Masculino , México , Material Particulado/toxicidade , GravidezRESUMO
BACKGROUND: Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. OBJECTIVE: Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. DESIGN/METHODS: We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. RESULTS: Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) µg/L, maternal third trimester 0.75 (0.41) µg/L, maternal at delivery 0.85 (0.70) µg/L, and infant cord 0.78 (0.65) µg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman râ¯=â¯0.65, pâ¯<â¯0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. ORâ¯=â¯1.44, 95% CI: 1.08-1.93) and LGA (adj. ORâ¯=â¯2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. ORâ¯=â¯1.46, 95% CI: 0.67-3.12). CONCLUSION: We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.
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Arsênio/sangue , Peso ao Nascer , Poluentes Ambientais/sangue , Idade Gestacional , Exposição Materna/estatística & dados numéricos , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , México , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Trace metal concentrations may affect cardiometabolic risk, but the role of prenatal exposure is unclear. We examined (1) the relation between blood metal concentrations during pregnancy and child cardiometabolic risk factors; (2) overall effects of metals mixture (essential vs. nonessential); and (3) interactions between metals. METHODS: We measured 11 metals in maternal second-trimester whole blood in a prospective birth cohort in Mexico City. In children 4-6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N = 609); and plasma hemoglobin A1C (HbA1c), non-high-density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N = 411). We constructed cardiometabolic component scores using age- and sex-adjusted z scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (ß = -1.01 z score units per 1 unit ln(Se), 95% CI = -1.84, -0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (ß = -0.32 and 95% CI = -0.61, -0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardiometabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardiometabolic risk factors in childhood.
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Doenças Cardiovasculares/epidemiologia , Metais/sangue , Adiponectina/sangue , Tecido Adiposo , Adolescente , Adulto , Teorema de Bayes , Pressão Sanguínea , Índice de Massa Corporal , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Leptina/sangue , Metais/classificação , México/epidemiologia , Gravidez , Segundo Trimestre da Gravidez/sangue , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Adulto JovemRESUMO
Infants born prematurely or with low birth weights are more susceptible to kidney dysfunction throughout their lives. Multiple proteins measured in urine are noninvasive biomarkers of subclinical kidney damage, but few studies have examined the joint effects of multiple biomarkers. We conducted an exploratory study of 103 children in the Programing Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) longitudinal birth cohort, and measured nine proteins selected a priori in banked spot urine samples collected at ages 4-6. The goal of our study was to explore the combined effects of kidney damage biomarkers previously associated with birth outcomes. To do this, we generated kidney biomarker indices using weighted quantile sum regression and assessed associations with length of gestation or birth weight. A decile increase in each kidney biomarker index was associated with 2-day shorter gestations (ß = -2.0, 95% CI: -3.2, -0.9) and 59-gram lower birth weights (ß = -58.5, 95% CI: -98.3, -18.7), respectively. Weights highlighting the contributions showed neutrophil gelatinase-associated lipocalin (NGAL) (60%) and osteopontin (19%) contributed most to the index derived for gestational age. NGAL (66%) and beta-2-microglobulin (10%) contributed most to the index derived for birth weight. Joint analyses of multiple kidney biomarkers can provide integrated measures of kidney dysfunction and improved statistical assessments compared to biomarkers assessed individually. Additionally, shorter gestations and lower birth weights may contribute to subclinical kidney damage measurable in childhood.
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Peso ao Nascer , Idade Gestacional , Recém-Nascido Prematuro , Nefropatias/diagnóstico , Biomarcadores/urina , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Nefropatias/urina , Estudos Longitudinais , Masculino , MéxicoRESUMO
BACKGROUND: High blood pressure (BP) in childhood is frequently renal in origin and a risk factor for adult hypertension and cardiovascular disease. Shorter gestations are a known risk factor for increased BP in adults and children, due in part to a nephron deficit in children born preterm. As nephrogenesis is incomplete until 36â¯weeks gestation, prenatal lead exposure occurring during a susceptible period of renal development may contribute to programming for later life renal disease. The relationship between shorter gestation and children's BP has not yet been explored to identify i) critical windows using nonlinear piecewise models or ii) combined with other early life risk factors such as prenatal lead exposure. OBJECTIVES: (1) To evaluate the nonlinear relationship between lower gestational age and childhood BP measured at 4-6â¯years of age, and (2) to investigate modification by prenatal lead exposure. METHODS: In a prospective longitudinal birth cohort, we assessed 565 children between 4 and 6â¯years of age (mean: 4.8â¯years) in the PROGRESS cohort in Mexico City, Mexico. Gestational age at delivery was calculated using maternal report of last menstrual period (LMP) and confirmed with Capurro physical examination at birth. We measured pregnant women's blood lead levels (BLLs) in the second trimester via inductively coupled plasma-mass spectrometry and children's BP using an automated device. We performed both linear and nonlinear piecewise regression analyses to examine associations of gestational age with children's BP adjusting for children's age, sex, height, prenatal exposure to smoke, and maternal socioeconomic status. We stratified to assess modification by prenatal lead exposure, and used a data-adaptive approach to identify a lead cutpoint. RESULTS: Maternal second trimester BLLs ranged from 0.7 to 17.8⯵g/dL with 112 (20%) women above the CDC guideline level of 5⯵g/dL. In adjusted linear regression models, a one week reduction in gestational age was associated with a 0.5â¯mmâ¯Hg (95%CI: 0.2, 0.8) increase in SBP and a 0.4â¯mmâ¯Hg (95%CI 0.1, 0.6) increase in DBP. Our nonlinear models suggested evidence for different magnitude estimates on either side of an estimated join-point at 35.9â¯weeks' gestation, but did not reach statistical significance. However, when stratified by prenatal lead exposure, we identified a cutpoint lead level of concern of 2.5⯵g/dL that suggested an interaction between gestational age and blood lead. Specifically, for BLLsâ¯≥â¯2.5⯵g/dL, SBP was 1.6 (95%CI: 0.3, 2.9) mmâ¯Hg higher per each week reduction in gestational age among children born before 37.0â¯weeks; and among children born after 37.0â¯weeks, this relationship was attenuated yet remained significant [ß: 0.9, 95%CI (0.2, 1.6)]. At BLLs below 2.5⯵g/dL, there was no appreciable association between lower gestational age and SBP. CONCLUSIONS: Our findings suggest that shorter gestation combined with higher prenatal lead exposure contributes to a higher risk of increased SBP at 4-6â¯years of age, particularly among infants born <37â¯weeks gestation. Our results underscore the importance of preventing prenatal lead exposure - even levels as low as 2.5⯵g/dL - especially among pregnant women at risk for preterm birth. Given that high BP in childhood is a risk factor for adult hypertension and cardiovascular disease later in life, these results may have implications that extend across the life span.